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Gupta A, Joshi R, Dewangan L, Shah K, Soni D, Patil UK, Chauhan NS. Capsaicin: pharmacological applications and prospects for drug designing. J Pharm Pharmacol 2025; 77:459-474. [PMID: 39657966 DOI: 10.1093/jpp/rgae150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 11/21/2024] [Indexed: 12/12/2024]
Abstract
OBJECTIVES A primary objective of this review is to summarize the evidence-based pharmacological applications of capsaicin, particularly its use to manage pain and treat various health conditions. A second goal of the review is to research how recent technological advances are improving the bioavailability and therapeutic index of capsaicin, as well as the development of novel capsaicin-mimetics that are able to enhance therapeutic responses in various human diseases. METHODS In the review, numerous human clinical trials and preclinical studies are examined to determine how effective, safe, and optimal dosages of capsaicin can be used in pain management and therapeutic applications. Furthermore, it discusses capsaicin's mechanisms of action, specifically its interactions with the transient receptor potential vanilloid 1 (TRPV1) channel. As a result of this review, the potential of nanotechnology systems for bypassing the limits of capsaicin's pungency is discussed. The review takes into account individual factors such as pain tolerance and skin sensitivity. KEY FINDINGS For topical applications, capsaicin is typically used in concentrations ranging from 0.025% to 0.1%, with higher concentrations being used under medical supervision for neuropathic pain. The formulation can come in the form of creams, gels, or patches, which provide sustained release over the course of time. A condition such as arthritis or neuropathy can be relieved with capsaicin as it depletes substance P from nerves. Neuropathy and osteoarthritis as well as musculoskeletal disorders have been treated successfully with this herbal medicine. A major mechanism through which capsaicin relieves pain is through activating TRPV1 channels, which induce calcium influx and neurotransmitter release. Additionally, it affects the transcription of genes related to pain modulation and inflammation, particularly when disease conditions or stress are present. There have been recent developments in technology to reduce capsaicin's pungency and improve its bioavailability, including nanotechnology. CONCLUSIONS It is proven that capsaicin is effective in pain management as well as a variety of therapeutic conditions because of its ability to deplete substance P and desensitize nerve endings. Although capsaicin is highly pungent and associated with discomfort, advancements in delivery technologies and the development of capsaicin-mimetics promise improved therapeutic outcomes. There is a great deal of complexity in the pharmacological action of capsaicin due to its interaction with TRPV1 channels and its ability to affect gene transcription. There is a need for further research and development in order to optimize capsaicin's clinical applications and to enhance its therapeutic index in a variety of human diseases.
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Affiliation(s)
- Anshita Gupta
- Rungta College of Pharmaceutical Sciences and Research, Raipur, 492009, C.G., India
| | - Renjil Joshi
- Rungta College of Pharmaceutical Sciences and Research, Bhilai, 490024, C.G., India
| | - Lokkanya Dewangan
- Shri Shankaracharya Institute of Pharmaceutical Sciences and Research (SSIPSR), Bhilai, 490020, C.G., India
| | - Kamal Shah
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, U.P., India
| | - Deependra Soni
- Faculty of Pharmacy, MATS University, Aarang, 493441, Chhattisgarh, India
| | - Umesh K Patil
- Phytomedicine and Natural Product Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, M.P., 470003India
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Talebi A, Bitarafan‐Rajabi A, Alizadeh‐asl A, Seilani P, Khajetash B, Hajianfar G, Tavakoli M. Machine learning based radiomics model to predict radiotherapy induced cardiotoxicity in breast cancer. J Appl Clin Med Phys 2025; 26:e14614. [PMID: 39704607 PMCID: PMC11969081 DOI: 10.1002/acm2.14614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/06/2024] [Accepted: 11/27/2024] [Indexed: 12/21/2024] Open
Abstract
PURPOSE Cardiotoxicity is one of the major concerns in breast cancer treatment, significantly affecting patient outcomes. To improve the likelihood of favorable outcomes for breast cancer survivors, it is essential to carefully balance the potential advantages of treatment methods with the risks of harm to healthy tissues, including the heart. There is currently a lack of comprehensive, data-driven evidence on effective risk stratification strategies. The aim of this study is to investigate the prediction of cardiotoxicity using machine learning methods combined with radiomics, clinical, and dosimetric features. MATERIALS AND METHODS A cohort of 83 left-sided breast cancer patients without a history of cardiac disease was examined. Two- and three-dimensional echocardiography were performed before and after 6 months of treatment to evaluate cardiotoxicity. Cardiac dose-volume histograms, demographic data, echocardiographic parameters, and ultrasound imaging radiomics features were collected for all patients. Toxicity modeling was developed with three feature selection methods and five classifiers in four separate groups (Dosimetric, Dosimetric + Demographic, Dosimetric + Demographic + Clinical, and Dosimetric + Demographic + Clinical + Imaging). The prediction performance of the models was validated using five-fold cross-validation and evaluated by AUCs. RESULTS 58% of patients showed cardiotoxicity 6 months after treatment. Mean left ventricular ejection fraction and Global longitudinal strain decreased significantly compared to pre-treatment (p-value < 0.001). After feature selection and prediction modeling, the Dosimetric, Dosimetric + Demographic, Dosimetric + Demographic + Clinical, Dosimetric + Demographic + Clinical + Imaging models showed prediction performance (AUC) up to 73%, 75%, 85%, and 97%, respectively. CONCLUSION Incorporating clinical and imaging features along with dose descriptors are beneficial for predicting cardiotoxicity after radiotherapy.
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Affiliation(s)
- Amin Talebi
- Department of Medical PhysicsSchool of MedicineIran University of Medical SciencesTehranIran
| | - Ahmad Bitarafan‐Rajabi
- Cardiovascular Intervention Research CenterRajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
- Echocardiography Research Center, Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
| | - Azin Alizadeh‐asl
- Rajaei Cardiovascular Medical and Research CenterCardio‐Oncology Research CenterIran University of Medical ScienceTehranIran
| | - Parisa Seilani
- Rajaei Cardiovascular Medical and Research CenterCardio‐Oncology Research CenterIran University of Medical ScienceTehranIran
| | - Benyamin Khajetash
- Department of Medical physicsIran University of Medical SciencesTehranIran
| | - Ghasem Hajianfar
- Division of Nuclear Medicine and Molecular ImagingGeneva University HospitalGenevaSwitzerland
| | - Meysam Tavakoli
- Department of Radiation Oncology, and Winship Cancer InstituteEmory UniversityAtlantaGeorgiaUSA
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3
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Zhang G, Jiang X, Xia Y, Qi P, Li J, Wang L, Wang Z, Tian X. Hyaluronic acid-conjugated lipid nanocarriers in advancing cancer therapy: A review. Int J Biol Macromol 2025; 299:140146. [PMID: 39842601 DOI: 10.1016/j.ijbiomac.2025.140146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 01/03/2025] [Accepted: 01/20/2025] [Indexed: 01/24/2025]
Abstract
Lipid nanoparticles are obtaining significant attention in cancer treatment because of their efficacy at delivering drugs and reducing side effects. These things are like a flexible platform for getting anticancer drugs to the tumor site, especially upon HA modification, a polymer that is known to target tumors overexpressing CD44. HA is promising in cancer therapy because it taregtes tumor cells by binding onto CD44 receptors, which are often upregulated in cancer cells. Lipid nanoparticles are not only beneficial in improving solubility and stability of drugs; they also use the EPR effect, meaning they accumulate more in tumor tissue than in healthy tissue. Adding HA to these nanoparticles expands their biocompatibility and makes them more accurate and specific towards tumor cells. Studies show that HA-modified nanoparticles carrying drugs such as paclitaxel or doxorubicin improve how well cells absorb the drugs, reduce drug resistance, and make tumor shrinking. These nanoparticles can respond to tumor microenvironment stimuli in targeted delivery. This targeted delivery diminishes side effects and improves anti-cancer activity of drugs. Thus, lipid-based nanoparticles conjugated with HA are a promising way to treat cancer by delivering drugs effectively, minimizing side effects, and giving us better therapeutic results.
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Affiliation(s)
- Guifeng Zhang
- Department of Neurology, Liaocheng People's Hospital and Liaocheng Hospital Affiliated to Shandong First Medical University, Liaocheng, Shandong, China
| | - Xin Jiang
- Department of Clinical Pharmacy, Baoying People's Hospital, Affiliated Hospital of Medical School, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yitong Xia
- Department of Oral Medicine, Jining Medical College, Jining, Shandong, China
| | - Pengpeng Qi
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Jie Li
- Department of Neurology, Liaocheng People's Hospital and Liaocheng Hospital Affiliated to Shandong First Medical University, Liaocheng, Shandong, China
| | - Lizhen Wang
- Department of Radiation Oncology Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong, China.
| | - Zheng Wang
- Department of Neurosurgery, Liaocheng City Hospital of Traditional Chinese Medicine, Liaocheng, Shandong, China.
| | - Xiuli Tian
- Department of Respiration, Liaocheng People's Hospital, Liaocheng, Shandong, China.
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4
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Chen KC, Yang SJ, Yang SH, Pai JA, Shieh MJ. Hyaluronan-coated gold nanoshells for enhanced synergistic effect and immunogenic cell response of chemo-photothermal therapy on lung cancer. Int J Biol Macromol 2025; 300:140114. [PMID: 39837437 DOI: 10.1016/j.ijbiomac.2025.140114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 01/09/2025] [Accepted: 01/18/2025] [Indexed: 01/23/2025]
Abstract
Lung cancer (LC) is the predominant cause of cancer-related fatalities globally, with the highest death rates in both genders, primarily attributed to smoking. The non-kinase transmembrane cell surface glycoprotein, CD44, enhances LC cell migration and invasion, leading to drug resistance and an unfavorable prognosis. This research formulated a cisplatin-loaded gold nanoshell (HCP@GNS) integrated with hyaluronan (HCP@GNS@HA) to enhance targeting capability and realize a synergistic effect of chemo-photothermal therapy (chemo-PTT) against LC. The coating of hyaluronic acid (HA) facilitated the uptake of HCP@GNS@HA into CD44-rich cancer cells, maintaining the superior photothermal conversion capacity of HCP@GNS nanoparticles for hyperthermia and photothermal eradication of tumor tissues under near-infrared exposure. As a nanocarrier, HCP@GNS@HA exhibited high biocompatibility and hemocompatibility, showing stronger cytotoxicity than either the free drug or photothermal therapy alone when combined with NIR irradiation, especially at high cis-diamminedichloroplatinum (II) (CDDP) concentrations. The chemo-PTT mediated by HCP@GNS@HA effectively curtailed tumor growth without adverse effects, significantly mobilizing B cells, DC cells, macrophages, natural killer (NK) cells, and NKT cells in the distal tumor against tumor growth. In conclusion, the developed hyaluronic acid (HA)-coated gold nanoshells could potentially serve as a promising candidate for nanomedicine, tackling both primary and distal LC growth.
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Affiliation(s)
- Ke-Cheng Chen
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
| | - Shu-Jyuan Yang
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
| | - Jui-An Pai
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan
| | - Ming-Jium Shieh
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
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5
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Li X, Wang Y, Ren M, Liu Q, Li J, Zhang L, Yao S, Tang L, Wen G, An J, Jin H, Tuo B. The role of chloride intracellular channel 4 in tumors. Cancer Cell Int 2025; 25:118. [PMID: 40140845 PMCID: PMC11948840 DOI: 10.1186/s12935-025-03737-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Tumors are among the most predominant health problems in the world, and the annual incidence of cancer is increasing globally; therefore, there is an urgent need to identify effective therapeutic targets. Chloride intracellular channel 4 (CLIC4) belongs to the family of chloride intracellular channels (CLICs), which are widely expressed in various tissues and organs, such as the brain, lung, pancreas, colorectum, and ovary, and play important roles in promoting apoptosis, promoting angiogenesis, maintaining normal proliferation of endothelial cells, and regulating the assembly and reconstruction of the cytoskeleton. The expression and function of CLIC4 in tumors varies. It has been reported that CLIC4 is low expressed in gastric cancer, skin cancer and prostate cancer, suggesting a tumor suppressor role. Interestingly, CLIC4 is overexpressed in pancreatic, ovarian and breast cancers, indicating a cancer-promoting role. CLIC4 expression is dysregulated in some solid tumors, which may be because CLIC4 is involved in the growth, migration or invasion of some cancer cells through various mechanisms. Regulation of CLIC4 expression may be a potential therapeutic strategy for some tumors. CLIC4 may be a promising therapeutic target and a biomarker for some cancers. In this study, we review the role of CLIC4 in several cancers and its value in the diagnosis and treatment of tumors.
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Affiliation(s)
- Xin Li
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Yongfeng Wang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Minmin Ren
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou Province, China
- Nursing School of Zunyi Medical University, Zunyi, 563003, Guizhou Province, China
| | - Qian Liu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Jiajia Li
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Li Zhang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Shun Yao
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Lulu Tang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Guorong Wen
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Jiaxing An
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China
| | - Hai Jin
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China.
- The Collaborative Innovation Center of Tissue Damage Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, 563003, China.
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, 563003, Guizhou, China.
- The Collaborative Innovation Center of Tissue Damage Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, 563003, China.
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Tazawa M, Nawa N, Yamauchi S, Tokunaga M, Fushimi K, Kinugasa Y, Fujiwara T. Impact of the coronavirus disease 2019 pandemic on the number of colorectal cancer surgeries performed: analysis of a nationwide inpatient database in Japan. Surg Today 2025; 55:247-256. [PMID: 39164425 DOI: 10.1007/s00595-024-02913-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 06/25/2024] [Indexed: 08/22/2024]
Abstract
PURPOSE This study examined the impact of the COVID-19 pandemic on the number of colorectal cancer surgeries performed in Japan. METHODS We selected patients who underwent colorectal cancer surgeries between January, 2017 and December, 2020 from the Diagnosis Procedure Combination database. The COVID-19 pandemic was divided into three waves. We evaluated the changes in the number of surgeries performed for colorectal cancer during each wave, stratified by cancer stage using Poisson regression. RESULTS During the first wave, the rate ratio (RR) for stage III colon cancer decreased significantly (RR, 0.94), whereas those for stages 0 to II (RR, 1.01) and stage IV (RR, 1.04) were not different. During the second and third waves, the RR for stage 0 to II colon cancer decreased significantly (RR, 0.96), that for stage IV increased (RR, 1.09), and that for stage III was not different (RR, 0.97). During the first wave, the RR for stage 0 to II rectal cancer increased significantly (RR, 1.09), that for stage IV decreased (RR, 0.84), and that for stage III was not different (RR, 0.97). CONCLUSIONS The number of colorectal cancer surgeries changed during the pandemic and varied according to the stage of disease.
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Affiliation(s)
- Miyako Tazawa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Nobutoshi Nawa
- Department of Public Health, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Shinichi Yamauchi
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Masanori Tokunaga
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Takeo Fujiwara
- Department of Public Health, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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7
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Simonsen MR, Maksten EF, Jakobsen LH, Severinsen MT, Dann EJ, Frederiksen H, Niemann CU, Jørgensen JM, Clausen MR, Starklint J, Johnsen SP, El-Galaly TC, Baech J. Similar Survival Between Non-Western Immigrant Patients and Danish-Born Patients with Lymphoma: A Danish Population-Based Study. Clin Epidemiol 2025; 17:19-25. [PMID: 39872603 PMCID: PMC11771513 DOI: 10.2147/clep.s484797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 12/30/2024] [Indexed: 01/30/2025] Open
Abstract
Purpose This nationwide Danish cohort study compared overall survival (OS) between non-Western immigrant patients and Danish-born patients with lymphoma in Denmark. Furthermore, differences in clinical and socioeconomic variables were compared, and mediators of OS differences were explored to explain possible outcome differences. Patients and Methods The study included a total of 540 non-Western patients and 16,294 Danish-born patients diagnosed with lymphoma in the period 2000-2020. Inverse probability weighting and mediation analysis using a natural effects Cox model were used to investigate the causal relationship between immigration status and OS. Results Indirect effects mediated through differences in performance status and income indicated a trend towards inferior OS for non-Western immigrant patients with HRs of 1.06 (0.99-1.14) and 1.06 (0.99-1.14). However, no total causal effect of immigration status on OS was observed overall (HR: 0.94 [0.79-1.12]) and within subtype-specific analyses, except for classical Hodgkin lymphoma. Conclusion No significant differences in OS between non-Western immigrant patients and Danish-born patients were discovered.
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Affiliation(s)
- Mikkel Runason Simonsen
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark
| | - Eva Futtrup Maksten
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Lasse Hjort Jakobsen
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
| | - Marianne Tang Severinsen
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Eldad J Dann
- Department of Haematology, Rambam Medical Center, and Bruce Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa, Israel
| | - Henrik Frederiksen
- Department of Hematology, Odense University Hospital, Odense, Denmark
- Academy of Geriatric Cancer Research (Agecare), Odense University Hospital, Odense, Denmark
| | - Carsten Utoft Niemann
- Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | | | | | - Jørn Starklint
- Department of Medicine: Hematology, Goedstrup Hospital, Goedstrup, Denmark
| | - Søren Paaske Johnsen
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University and Aalborg University Hospital, Aalborg, Denmark
| | - Tarec Christoffer El-Galaly
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Hematology, Odense University Hospital, Odense, Denmark
- Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
| | - Joachim Baech
- Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
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Anderson DE, Keko M, James J, Allaire BT, Kozono D, Doyle PF, Kang H, Caplan S, Balboni T, Spektor A, Huynh MA, Hackney DB, Alkalay RN. Metastatic spine disease alters spinal load-to-strength ratios in patients compared to healthy individuals. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.01.06.25320075. [PMID: 39830276 PMCID: PMC11741471 DOI: 10.1101/2025.01.06.25320075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Pathologic vertebral fractures (PVF) are common and serious complications in patients with metastatic lesions affecting the spine. Accurate assessment of cancer patients' PVF risk is an unmet clinical need. Load-to-strength ratios (LSRs) evaluated in vivo by estimating vertebral loading from biomechanical modeling and strength from computed tomography imaging (CT) have been associated with osteoporotic vertebral fractures in older adults. Here, for the first time, we investigate LSRs of thoracic and lumbar vertebrae of 135 spine metastases patients compared to LSRs of 246 healthy adults, comparable by age and sex, from the Framingham Heart Study under four loading tasks. Findings include: (1) Osteolytic vertebrae have higher LSRs than osteosclerotic and mixed vertebrae; (2). In patients' vertebrae without CT observed metastases, LSRs were greater than healthy controls. (3) LSRs depend on the spinal region (Thoracic, Thoracolumbar, Lumbar). These findings suggest that LSRs may contribute to identifying patients at risk of incident PVF in metastatic spine disease patients. The lesion-mediated difference suggests that risk thresholds should be established based on spinal region, simulated task, and metastatic lesion type.
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Affiliation(s)
- Dennis E. Anderson
- Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
- Harvard Medical School, Boston, MA, USA
| | - Mario Keko
- Department of Orthopedics, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Joanna James
- Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
| | - Brett T. Allaire
- Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
| | - David Kozono
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Patrick F Doyle
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
| | - Heejoo Kang
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
| | - Sarah Caplan
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
| | - Tracy Balboni
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Alexander Spektor
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Mai Anh Huynh
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - David B. Hackney
- Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Ron N. Alkalay
- Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
- Harvard Medical School, Boston, MA, USA
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Win T, Kharofa J, Frankart AJ. Evaluation of clinical trials addressing supportive care measures for management of acute and chronic radiation toxicities. Support Care Cancer 2024; 33:11. [PMID: 39653822 DOI: 10.1007/s00520-024-09070-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024]
Abstract
PURPOSE Radiation therapy can cause acute and long-term side effects despite advances in treatment delivery techniques. While significant research has been conducted to prevent the occurrence of toxicity, there is a need for evidence-based supportive care measures to manage radiation side effects. This analysis aims to examine the current state of supportive care trials in radiation oncology and identify areas that require further study. METHODS A Clinicaltrials.gov search was conducted using the term "radiation toxicity" to identify registered trials with a primary endpoint of toxicity management. These studies were further classified as supportive care interventions or toxicity prevention. Study details were evaluated for all supportive care trials. RESULTS Of the thirty-eight supportive care trials identified, most were observational/uncategorized (50%), in phase III (28.9%), or phase II (13.2%). Head and neck (42.1%), genitourinary (18.4%), and breast (13.2%) were the most studied disease sites. Xerostomia (23.7%), mucositis (18.4%), and dermatitis (18.4%) were the most evaluated toxicities. Medication-based (28.9%), procedures (28.9%), and topical agents (21.1%) were the most common interventions. Thirty-two studies included patient-reported outcomes (PROs; 84.2%), of which seventeen trials (53.1%) had PROs as a primary endpoint. CONCLUSIONS Only a small portion of supportive care trials generate high-level evidence to evaluate interventions with patient-reported endpoints. More supportive care trials are needed to effectively manage radiation toxicities and promote compliance and long-term quality of life during and after radiation therapy. Increased funding from government and industry sponsors is required to support this research.
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Affiliation(s)
- Tiffany Win
- Albany Medical College, 50 New Scotland Avenue, MC-41, Albany, NY, 12208, USA.
| | - Jordan Kharofa
- Department of Radiation Oncology, University of Cincinnati, 3151 Bellevue Ave., ML 0757, Cincinnati, OH, 45267, USA
| | - Andrew J Frankart
- Department of Radiation Oncology, University of Cincinnati, 3151 Bellevue Ave., ML 0757, Cincinnati, OH, 45267, USA.
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10
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Shimomura T, Mori K, Ito K, Yasue K, Matsukawa A, Fukuokaya W, Yanagisawa T, Hata K, Murakami M, Koike Y, Miki J, Yamada H, Kimura T. Docetaxel versus androgen receptor signaling inhibitor (ARSI) against chemo-naïve castration-resistant prostate cancer (CRPC): propensity score matched analysis in real world. Int Urol Nephrol 2024; 56:3719-3725. [PMID: 38913290 DOI: 10.1007/s11255-024-04116-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/07/2024] [Indexed: 06/25/2024]
Abstract
PURPOSE Although docetaxel and ARSI are picked up as treatment options against chemo-naïve metastatic CRPC in clinical guidelines for prostate cancer, there is no clear evidence which agent should be introduced as first line treatment. Therefore, we investigated our CRPC cohort treated with docetaxel or ARSI as first-line agent against chemo-naïve CRPC to solve these clinical questions. PATIENTS AND METHODS A total of 345 chemotherapy-naïve CRPC patients introduced to first-line docetaxel or ARSI (abiraterone or enzalutamide) between March 2006 and April 2017 at Jikei University Hospital and its affiliated institutions were included in this study. Propensity score matching method was used to minimize the patients' background. The outcome measures were PSA response rate, PSA decline ≥ 90%, cancer specific survival (CSS) and overall survival (OS). RESULTS PSA decline correlated OS and CSS (p = 0.027, < 0.001, respectively) and median PSA decline rate was 60.4% in docetaxel group and 85.7% in ARSI group (p = 0.0311). Median OS was 33 m (95%CI: 27-53) in docetaxel group and 61 m (95%CI: 47-NA) in ARSI group (p = 0.0246). Median CSS was 34 m (95%CI: 27-53) in docetaxel group and NR (not reached) (95%CI: 61-NA) in ARSI group (p = 0.000133) in propensity score matching cohort. In multivariate analysis, ARSI induction first showed significantly better for OS and CSS (p = 0.0033 and < 0.001, respectively). CONCLUSION In this study, better survival outcome with ARSI induction first than docetaxel against chemo-naïve CRPC. And the candidates who had survival benefit by induction docetaxel first could not be found in this study.
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Affiliation(s)
- Tatsuya Shimomura
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
| | - Keiichiro Mori
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Kagenori Ito
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Keiji Yasue
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Akihiro Matsukawa
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Wataru Fukuokaya
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | | | - Kenichi Hata
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, Atsugi City General Hospital, Atsugi, Japan
| | - Masaya Murakami
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, Fuji City General Hospital, Fuji, Japan
| | - Yusuke Koike
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, JR Tokyo General Hospital, Tokyo, Japan
| | - Jun Miki
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Yamada
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Kimura
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
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11
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Cogua LM, Tupper CJ, Silberstein PT, Coan KE. Intermediate-sized follicular thyroid cancer surgical trends before and after the 2015 American thyroid association guideline changes. Am J Surg 2024; 238:115830. [PMID: 39029373 DOI: 10.1016/j.amjsurg.2024.115830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 06/12/2024] [Accepted: 07/03/2024] [Indexed: 07/21/2024]
Abstract
In 2015, the ATA updated the guidelines to advocate for a lobectomy for tumors <1.0 cm and total thyroidectomy for tumors >4.0 cm. Treatment for tumors of intermediate size 1.0-4.0 cm is dependent on high-risk characteristics. There is limited research comparing the impact of the updated ATA guidelines on clinical practice on intermediate-sized tumors. In this study, the impact of the 2015 ATA guidelines on the surgical treatment of intermediated-sized FTC will be evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. A total of 9983 patients were included; 7769 patients (74.1 %) were diagnosed pre-ATA guidelines and 2709 patients (25.9 %) post-ATA guidelines. The mean rate of lobectomy for intermediate-sized tumors was 22.1 % which increased to 33.4 % post-ATA updates. The results of the logistic regression showed the rate of lobectomy increased significantly in the post-ATA changes period (p < 0.001). Future research could benefit from evaluating how these trends impact patient outcome measures.
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Affiliation(s)
- Laura M Cogua
- Creighton University School of Medicine - Phoenix Regional Campus, Phoenix, AZ, USA.
| | - Connor J Tupper
- Creighton University School of Medicine - Phoenix Regional Campus, Phoenix, AZ, USA
| | - Peter T Silberstein
- Department of Internal Medicine, Division of Hematology/Oncology, Creighton University Medical Center, Omaha, NE, USA
| | - Kathryn E Coan
- Creighton University School of Medicine - Phoenix Regional Campus, Phoenix, AZ, USA; Department of Surgery, Division of Endocrine Surgery, Creighton University School of Medicine - Phoenix Regional Campus, Phoenix, AZ, USA
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12
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Ma J, Wang Y. Myeloid neoplasms post cytotoxic therapy: epidemiology, pathogenesis outcomes, prognostic factors, and treatment options. Ann Med 2024; 56:2329132. [PMID: 38608646 PMCID: PMC11018000 DOI: 10.1080/07853890.2024.2329132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/23/2024] [Indexed: 04/14/2024] Open
Abstract
Myeloid neoplasms post cytotoxic therapy (MN-pCT) are a category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition in 2022 version World Health Organization (WHO) classification. With improved survival of patients with tumors, the incidence of MN-pCT after chemotherapy and/or radiation therapy among patients with tumors has gradually risen. However, the outcome of MN-pCT is poorer than that of primary myeloid neoplasms. This review summarizes the current understanding based on existing research, as a foundation for further research on MN-pCT.
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Affiliation(s)
- Jing Ma
- Department of Hematology and Blood and Marrow Transplantation, Tianjin Cancer Hospital Airport Branch, Tianjin, China
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yafei Wang
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
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13
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Li L, Zhao J, Li F, Pan Z. Comparison of MRI and Ultrasound for Evaluation of Axillary Lymph Node Status in Early Breast Cancer. Cancer Manag Res 2024; 16:1685-1692. [PMID: 39628632 PMCID: PMC11613698 DOI: 10.2147/cmar.s482484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 11/12/2024] [Indexed: 12/06/2024] Open
Abstract
Introduction This study aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in evaluating axillary lymph nodes (ALNs) status in breast cancer patients. Methods We retrospectively analyzed 590 female breast cancer patients who had undergone both ultrasound and MRI to assess ALNs prior to any invasive procedures. Using pathological results as the standard, we compared the diagnostic performance of the two imaging modalities. Results For differentiating between malignancy and benign ALNs, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound were 68.98%, 38.14%, 86.67%, 62.12% and 70.96%, respectively. MRI demonstrated corresponding values of 72.03%, 38.60%, 91.20%, 71.55% and 72.15%. In assessing the burden status of ALNs (high vs low), ultrasound yielded values of 78.47%, 52.75%, 83.17%, 36.36% and 90.61%, while MRI showed corresponding values of 81.19%, 52.75%, 86.37%, 41.38% and 90.93%. There were no statistically significant differences between the two imaging modalities in their ability to evaluate ALN malignancy or burden status. Conclusion Both ultrasound and MRI offer comparable value in assessing ALN status. Whether evaluating for metastatic involvement or determining ALN burden, it may not be necessary for patients to undergo both imaging tests.
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Affiliation(s)
- Ling Li
- Department of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
| | - Jing Zhao
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of China
| | - Fangxuan Li
- Department of Cancer prevention, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of China
| | - Zhanyu Pan
- Department of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
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14
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Tsai KW, Liao JB, Tseng HW. Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis. Cancer Cell Int 2024; 24:384. [PMID: 39563323 PMCID: PMC11575040 DOI: 10.1186/s12935-024-03545-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 10/22/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear. METHODS We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays. RESULTS We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher expression of LINC00094 in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissues (P < 0.001). In nondiabetic patients with melanoma, the overall survival of high LINC00094 expression group was shorter than the low LINC00094 expression group with borderline statistical significance (log-rank test, P = 0.057). Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that silencing-LINC00094 inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis following LINC00094 knockdown revealed G1 phase arrest with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Finally, through in silico analysis, we identified two miR-1270 target genes, CD276 and centromere protein M (CENPM), which may be involved in the biological functions of LINC00094. CONCLUSIONS Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment.
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Affiliation(s)
- Kuo-Wang Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, New Taipei City, Taiwan
| | - Jia-Bin Liao
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Shu Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Hui-Wen Tseng
- Department of Dermatology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.
- Institute of Biomedical Sciences, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan.
- Department of Nursing, College of Nursing, Meiho University, Neipu, Pingtung, Taiwan.
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15
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Qian X, Yao M, Xu J, Dong N, Chen S. From cancer therapy to cardiac safety: the role of proteostasis in drug-induced cardiotoxicity. Front Pharmacol 2024; 15:1472387. [PMID: 39611175 PMCID: PMC11602306 DOI: 10.3389/fphar.2024.1472387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/04/2024] [Indexed: 11/30/2024] Open
Abstract
Drug-induced cardiotoxicity (DICT) poses a significant challenge in the prognosis of cancer patients, particularly with the use of antineoplastic agents like anthracyclines and targeted therapies such as trastuzumab. This review delves into the intricate interplay between drugs and proteins within cardiac cells, focusing on the role of proteostasis as a therapeutic target for mitigating cardiotoxicity. We explore the in vivo modeling of proteostasis, highlighting the complex intracellular environment and the emerging techniques for monitoring proteostasis. Additionally, we discuss how cardiotoxic drugs disrupt protein homeostasis through direct chemical denaturation, endoplasmic reticulum stress, unfolded protein response, chaperone dysfunction, impairment of the proteasome system, and dysregulation of autophagy. Finally, we provide insights into the applications of cardioprotective drugs targeting proteostasis to prevent cardiotoxicity and the adoption of structural proteomics to evaluate potential cardiotoxicity. By gaining a deeper understanding of the role of proteostasis underlying DICT, we can pave the way for the development of targeted therapeutic strategies to safeguard cardiac function while maximizing the therapeutic potential of antineoplastic drugs.
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Affiliation(s)
- Xingyu Qian
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mengdong Yao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jingyu Xu
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Nianguo Dong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Si Chen
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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16
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Haouchine N, Hackney DB, Pieper SD, Wells WM, Sanhinova M, Balboni TA, Spektor A, Huynh MA, Kozono DE, Doyle P, Alkalay RN. An open annotated dataset and baseline machine learning model for segmentation of vertebrae with metastatic bone lesions from CT. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.10.14.24314447. [PMID: 39484265 PMCID: PMC11527073 DOI: 10.1101/2024.10.14.24314447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Automatic analysis of pathologic vertebrae from computed tomography (CT) scans could significantly improve the diagnostic management of patients with metastatic spine disease. We provide the first publicly available annotated imaging dataset of cancerous CT spines to help develop artificial intelligence frameworks for automatic vertebrae segmentation and classification. This collection contains a dataset of 55 CT scans collected on patients with various types of primary cancers at two different institutions. In addition to raw images, data include manual segmentations and contours, vertebral level labeling, vertebral lesion-type classifications, and patient demographic details. Our automated segmentation model uses nnU-Net, a freely available open-source framework for deep learning in healthcare imaging, and is made publicly available. This data will facilitate the development and validation of models for predicting the mechanical response to loading and the resulting risk of fractures and spinal deformity.
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Affiliation(s)
- Nazim Haouchine
- Brigham & Women's Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - David B Hackney
- Beth Israel Deaconess Medical Center, Boston, MA
- Harvard Medical School, Boston, MA
| | | | - William M Wells
- Brigham & Women's Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Malika Sanhinova
- Beth Israel Deaconess Medical Center, Boston, MA
- Harvard Medical School, Boston, MA
| | | | | | | | | | | | - Ron N Alkalay
- Beth Israel Deaconess Medical Center, Boston, MA
- Harvard Medical School, Boston, MA
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17
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Ibrahim AO, Omonijo A, Agbesanwa TA, Alabi AK, Elegbede OT, Olusuyi KM, Yusuf M, Afolabi-Obe EA, Erinomo O, Babalola OF, Abiyere H, Orewole OT, Aremu SK. A 14-Year Analysis of Breast Cancer Risk Factors and Its Determinants of Mortality in Rural Southwestern Nigeria. Clin Med Insights Oncol 2024; 18:11795549241288197. [PMID: 39497926 PMCID: PMC11533210 DOI: 10.1177/11795549241288197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 09/13/2024] [Indexed: 11/07/2024] Open
Abstract
Background Research on breast cancer risk factors and mortality is gaining recognition and attention globally; there is need to add more information on its determinants among patients admitted in hospital. Some studies on risk factors and mortality of breast cancer in Nigeria hospitals conducted in the urban and suburban areas have been documented. Therefore, an addition of a study conducted in the setting of a rural health institution is necessary. This study assessed the risk factors and determinants of mortality among patients admitted for breast cancer in rural Southwestern Nigeria. Methods A retrospective observational study was conducted on 260 patients who were admitted for breast cancer between January 2010 and December 2023 using a data form and a standardized information form. The data were analyzed using SPSS version 22.0. The risk factors and the determinants of mortality of patients with breast cancer were identified using multivariate regression model. Results The breast cancer risk factors were old age, family history, tobacco smoking, combined oral contraceptives, and hormonal therapy use. The case fatality rate was 38.1%, and its determinants of mortality were patients who were older (adjusted odds ratio [AOR], 1.956; 95% confidence interval [CI]:1.341-4.333), obese (AOR, 2.635; 95% CI: 1.485-6.778), stage IV (AOR, 1.895; 95% CI: 1.146-8.9742), mastectomy (AOR, 2.512; 95% CI: 1.003-6.569), discontinued adjuvant chemotherapy (AOR, 1.785; 95% CI: 1.092-4.6311), and yet to commence adjuvant chemotherapy (AOR, 2.568; 95% CI: 1.367-5.002). Conclusion The study revealed that patients with breast cancer were associated with high mortality. Sustained health education to promote early diagnosis, managed co-morbidities, and access to treatment may contribute to reduction in breast cancer mortality in rural Nigeria.
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Affiliation(s)
| | - Adetunji Omonijo
- Department of Family Medicine, Federal Teaching Hospital Ido-Ekiti, Ido-Ekiti, Nigeria
| | | | - Ayodele Kamal Alabi
- Department of Community Medicine, Federal Teaching Hospital Ido-Ekiti, Ido-Ekiti, Nigeria
| | | | | | - Musah Yusuf
- Department of Medicine, Afe Babalola University, Ado-Ekiti, Nigeria
| | | | - Olagoke Erinomo
- Department of Pathology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - Olakunle Fatai Babalola
- Department of Surgery, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - Henry Abiyere
- Department of Surgery, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - Olayinka Tesleem Orewole
- Department of Anaesthesia, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - Shuaib Kayode Aremu
- Department of Otorhinolaryngology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
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18
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Kawachi H, Tamiya M, Oya Y, Saito G, Taniguchi Y, Matsumoto H, Sato Y, Otsuki T, Suzuki H, Fukuda Y, Tanaka S, Tsukita Y, Uchida J, Sakata Y, Nakatani Y, Shibaki R, Arai D, Okada A, Hara S, Takayama K, Nishino K. Real-World Outcomes of Subsequent Chemotherapy after Progression Following Chemoradiation and Consolidative Durvalumab Therapy in Locally Advanced Non-small Cell Lung Cancer: An Exploratory Analysis from the CRIMSON Study (HOPE-005). Clin Lung Cancer 2024; 25:643-652.e4. [PMID: 39138106 DOI: 10.1016/j.cllc.2024.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/11/2024] [Accepted: 07/21/2024] [Indexed: 08/15/2024]
Abstract
BACKGROUND The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population. MATERIALS AND METHODS We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded. RESULTS Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy. CONCLUSION In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.
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Affiliation(s)
- Hayato Kawachi
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan; Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
| | - Motohiro Tamiya
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan
| | - Yuko Oya
- Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; Department of Respiratory Medicine, Fujita Health University, Toyoake, Aichi, Japan
| | - Go Saito
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Chiba, Japan
| | - Yoshihiko Taniguchi
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Sakai, Osaka, Japan
| | - Hirotaka Matsumoto
- Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan
| | - Yuki Sato
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Taiichiro Otsuki
- Department of Respiratory Medicine and Hematology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo, Japan
| | - Hidekazu Suzuki
- Department of Thoracic Oncology, Osaka Habikino Medical Center, Habikino, Osaka, Japan
| | - Yasushi Fukuda
- Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
| | - Satoshi Tanaka
- Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Osaka, Japan
| | - Yoko Tsukita
- Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Junji Uchida
- Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan
| | - Yoshihiko Sakata
- Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Kumamoto, Japan
| | - Yuki Nakatani
- Department of Medical Oncology, Osaka City General Hospital, Osaka, Osaka, Japan
| | - Ryota Shibaki
- Internal Medicine III, Wakayama Medical University, Wakayama, Wakayama, Japan
| | - Daisuke Arai
- Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan
| | - Asuka Okada
- Department of Respiratory Medicine, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Satoshi Hara
- Department of Respiratory Medicine, Itami City Hospital, Itami, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan
| | - Kazumi Nishino
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan
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Dilbaz ZG, Denker S, Ankermann C, Bittenbring JT, Kaddu-Mulindwa D, Kunte AS, Hünecke S, Poeschel V, Stilgenbauer S, Thurner L, Na IK, Bewarder M, Christofyllakis K. Comparison of R-CHOP-14 and R-mini-CHOP in older adults with diffuse large B-cell lymphoma-A retrospective multicenter cohort study. Eur J Haematol 2024; 113:675-684. [PMID: 39086181 DOI: 10.1111/ejh.14268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/22/2024] [Accepted: 06/25/2024] [Indexed: 08/02/2024]
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years.
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Affiliation(s)
- Zelal Guel Dilbaz
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Sophy Denker
- Medical Department, Division of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Carla Ankermann
- Medical Department, Division of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Joerg-Thomas Bittenbring
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Dominic Kaddu-Mulindwa
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Ameya S Kunte
- Department of Stem Cell Transplantation, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Sascha Hünecke
- Helios Universitätsklinikum Wuppertal, Wuppertal, Germany
| | - Viola Poeschel
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Stephan Stilgenbauer
- Ulm Comprehensive Cancer Center, Ulm, Germany
- Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany
| | - Lorenz Thurner
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Il-Kang Na
- Medical Department, Division of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
- ECRC Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner site Berlin, Berlin, Germany
| | - Moritz Bewarder
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
| | - Konstantinos Christofyllakis
- Department of Oncology, Hematology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
- Medical Faculty, Saarland University, Homburg, Germany
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20
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Shan J, Liu Z, Yu J, Zhang Q, Shi H, Ma L. Comparative Cardiovascular Risks of Radical Prostatectomy and External Beam Radiation Therapy in Early-Stage Prostate Cancer: A Comprehensive Retrospective Analysis. Ann Surg Oncol 2024; 31:8427-8437. [PMID: 39164605 DOI: 10.1245/s10434-024-15982-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 08/22/2024]
Abstract
BACKGROUND The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. METHODS Data from patients aged 45-74 years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. RESULTS Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). CONCLUSIONS T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.
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Affiliation(s)
- Jiahao Shan
- The First Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Ziyang Liu
- The First Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Jin Yu
- The First Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Qiang Zhang
- Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hongbin Shi
- Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China.
| | - Lianghong Ma
- Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China.
- Institute of Medical Sciences, Ningxia Human Sperm Bank, General Hospital of Ningxia Medical University, Yinchuan, China.
- Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China.
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21
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Karami F, Osanloo M, Alipanah H, Zarenezhad E, Moghimi F, Ghanbariasad A. Comparison of the efficacy of alginate nanoparticles containing Cymbopogon citratus essential oil and citral on melanoma and breast cancer cell lines under normoxic and hypoxic conditions. BMC Complement Med Ther 2024; 24:372. [PMID: 39427126 PMCID: PMC11490153 DOI: 10.1186/s12906-024-04673-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/01/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Solid tumors often develop hypoxic regions, leading to aggressive behavior and increased drug resistance. METHODS The chemical composition of Cymbopogon citratus essential oil (EO) was analyzed using GC-MS. Alginate nanoparticles containing the EO and its primary component, citral, were synthesized via the ionic gelation method. Encapsulation was confirmed using ATR-FTIR analysis. The anticancer efficacy of C. citratus EO, citral, and their respective alginate nanoparticles was evaluated under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions on breast cancer (MDA-MB-231) and melanoma (A-375) cell lines. Additionally, qPCR and flow cytometry were used to assess apoptosis gene expression ratios (Bax/Bcl-2) and levels of apoptosis. RESULTS Citral (80.98%) was identified as the major component of the EO. Alginate nanoparticles containing C. citratus EO and citral (C. citratus-AlgNPs and citral-AlgNPs) were synthesized with particle sizes of 195 ± 4 nm and 222 ± 9 nm, and zeta potentials of -22 ± 3 mV and - 17 ± 1 mV, respectively. Both samples demonstrated significantly greater efficacy under hypoxic conditions. Citral and C. citratus-AlgNPs had IC50 values of 27 (19-39) µg/mL and 25 (4-147) µg/mL, respectively, against MDA-MB-231 and A-375 cells. Flow cytometry showed increased apoptosis under hypoxic conditions, with the highest rates observed for citral-AlgNPs and C. citratus-AlgNPs (84 ± 5 and 92 ± 5% in MDA-MB-231 and A-375 cells, respectively). CONCLUSION This study demonstrates that alginate nanoparticles enhance the anticancer activity of C. citratus-AlgNPs and citral, particularly under hypoxic conditions, highlighting their potential for hypoxia-targeted cancer therapies.
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Affiliation(s)
- Farnaz Karami
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran
| | - Mahmoud Osanloo
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
| | - Hiva Alipanah
- Department of Physiology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Elham Zarenezhad
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Fatemeh Moghimi
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran
| | - Ali Ghanbariasad
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
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22
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Niu Z, Rivera YM, Baskar J, Shanmugavel A, Manne SL, Hudson SV, Penedo FJ, Heckman CJ. Barriers and facilitators to skin cancer prevention among Hispanics: a qualitative study. BMC Public Health 2024; 24:2690. [PMID: 39358786 PMCID: PMC11445849 DOI: 10.1186/s12889-024-20000-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 09/05/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND In the past two decades, melanoma incidence among Hispanic people has risen greatly. This qualitative study explored Hispanic people's perceived barriers and facilitators to skin cancer-related preventive behaviors. METHODS Five focus groups among Hispanic people (2 in Spanish and 3 in English; n = 34; 11 Spanish-preferring and 23 English-preferring) were conducted, where participants discussed their perceptions and behaviors relating to skin cancer, sun protection, and skin self-examination. Additionally, healthcare providers (n = 9) and Hispanic community leaders (n = 6) were recruited for individual interviews to complement the results of focus groups. A thematic analysis was conducted on all transcripts. RESULTS Perceived barriers to sun protection included: 1) Low levels of knowledge and awareness/misperception; 2) low perceived importance or not a priority, 3) economic issues or limited access, 4) downsides/concerns about engaging in sun protection behaviors, and 5) Hispanic cultural norms (e.g., machismo). Facilitators to sun protection included: 1) relevance/care for family, 2) negative consequences of sun exposure, and 3) Hispanic cultural norms (e.g., familismo). Barriers to skin examination included: 1) low levels of knowledge and awareness, 2) lack of insurance coverage or access, and 3) difficulty or discomfort associated with practicing skin self-examination. Facilitators to skin examination included: 1) relevance/previous experience and 2) having insurance coverage or access. CONCLUSIONS Future interventions should focus on individual, community, and system-level strategies to address misperceptions in the Hispanic community, increase knowledge and awareness, address perceptions of cultures regarding skin cancer preventive activities, and emphasize the importance or priority of health issues related to skin cancer.
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Affiliation(s)
- Zhaomeng Niu
- Department of Health Informatics, Rutgers School of Health Professions, Piscataway, NJ, USA.
| | - Yonaira M Rivera
- Rutgers School of Communication and Information, Rutgers University, New Brunswick, NJ, USA
| | - Jemima Baskar
- Department of Health Informatics, Rutgers School of Health Professions, Piscataway, NJ, USA
| | - Aarthi Shanmugavel
- Department of Health Informatics, Rutgers School of Health Professions, Piscataway, NJ, USA
| | | | - Shawna V Hudson
- Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Frank J Penedo
- University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Carolyn J Heckman
- Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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23
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Niu Z, Rivera YM, Lozada C, Hudson SV, Penedo FJ, Manne SL, Heckman CJ. Designing a Culturally Relevant Digital Skin Cancer Prevention Intervention for Hispanic Individuals: Qualitative Exploration. JMIR Form Res 2024; 8:e56939. [PMID: 39265165 PMCID: PMC11444121 DOI: 10.2196/56939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/22/2024] [Accepted: 05/10/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND In the past 2 decades, melanoma incidence among Hispanic individuals has risen by 20%. The mortality rate of Hispanic individuals is higher than that for non-Hispanic White individuals. Skin cancer can largely be prevented with regular sun protection, and skin cancer outcomes can be improved through early detection, for example, by skin self-examination. Alarmingly, Hispanic individuals are less aware of the symptoms and harms of skin cancers, tend to have misperceptions regarding the risks and benefits of skin cancer prevention behaviors, and engage in less sun protection behaviors than non-Hispanic White individuals. OBJECTIVE This study aimed to use a community-engaged approach and conduct both group and individual interviews among Hispanic individuals and relevant key stakeholders to explore the potential design of a mobile-based skin cancer prevention intervention for Hispanic individuals. METHODS This study used a qualitative design (focus groups and individual interviews). Participants were recruited from local community organizations' social media, local events, and contact lists (eg, email). Zoom interviews were conducted to examine whether Hispanic individuals would be interested in a mobile-based skin cancer intervention and to explore their preferences and suggestions to inform skin cancer prevention intervention design. RESULTS Five focus groups (2 in Spanish and 3 in English) among self-identified Hispanic individuals (n=34) and 15 semistructured, in-depth individual interviews among key stakeholders (health care providers and community leaders; eg, dermatologist, nurse practitioner, licensed social worker, and church leader) were conducted. The main themes and subthemes emerging from the group discussions and individual interviews were organized into the following categories: intervention platform, delivery frequency and format, message design, engagement plan, and activities. WhatsApp and Facebook were identified as suitable platforms for the intervention. Messages including short videos, visuals (eg, images and photographs), and simple texts messages were preferred. Recommendations for message design included personalized messages, personal stories and narratives, culturally relevant design (eg, incorporating family values), and community-trusted sources. Potential engagement and retention recommendations were also discussed. Additional details and exemplar quotes of each theme and subtheme are described. CONCLUSIONS This study provides important insights and directions for the design of a mobile, digital skin cancer intervention to modify Hispanic individuals' sun protection and skin self-examination behaviors to help improve skin cancer outcomes. Insights gathered from community leaders and health care providers provided valuable additions to the community-derived data. Leveraging popular digital platforms among Hispanic individuals such as WhatsApp or Facebook could be a promising approach to skin cancer prevention. Recommendations from the community included the use of concise videos, illustrative images, clear text messages, tailored communications, narratives featuring personal experiences, designs that reflect cultural significance, and information from sources that are trusted by the community, which provided useful strategies for future intervention design among Hispanic individuals.
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Affiliation(s)
- Zhaomeng Niu
- Department of Health Informatics, Rutgers School of Health Professions, Piscataway, NJ, United States
| | - Yonaira M Rivera
- School of Communication and Information, Rutgers University, New Brunswick, NJ, United States
| | - Carolina Lozada
- Cancer Prevention and Outcomes Data Support, Rutgers Cancer Institute, New Brunswick, NJ, United States
| | - Shawna V Hudson
- Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
| | - Frank J Penedo
- University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, United States
| | - Sharon L Manne
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute, New Brunswick, NJ, United States
| | - Carolyn J Heckman
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute, New Brunswick, NJ, United States
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24
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Qiu Y, Yu J, Guo Q, Xu J. Safety and Efficacy of Neoadjuvant Chemoimmunotherapy versus Chemotherapy for Non-Small Cell Lung Cancer Undergoing Sleeve Resection. Cancer Manag Res 2024; 16:1221-1230. [PMID: 39282610 PMCID: PMC11402360 DOI: 10.2147/cmar.s453924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 08/08/2024] [Indexed: 09/19/2024] Open
Abstract
The prognosis of locally advanced non-small cell lung cancer (NSCLC) remains poor despite the addition of neoadjuvant chemotherapy, as it has been shown to improve 5-year absolute benefit survival by only 5%. Recently, neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs), combined with chemotherapy has shown promise in the treatment of locally advanced NSCLC. For NSCLC invading the main bronchus, sleeve resection has become the preferred modality to avoid pneumonectomy and reserve more cardiac or pulmonary function and to reduce postoperative morbidity and mortality. However, there has been a paucity of evidence to evaluate the safety and efficacy of neoadjuvant chemoimmunotherapy on bronchial-vascular reconstruction owing to the limited number of patients treated by sleeve lobectomy. Despite promising initial results, key knowledge gaps remain, including the impact on bronchial-vascular reconstruction, biomarkers predictive of ICI response, and the potential for specific perioperative complications associated with neoadjuvant chemoimmunotherapy in the context of sleeve resection. This review summarizes the latest literature evidence on the efficacy and safety of neoadjuvant chemoimmunotherapy approaches to address the unmet needs of sleeve resection of NSCLC treatment, describes the biomarkers predictive of ICI responses, and perioperative outcomes of sleeve resection after neoadjuvant chemoimmunotherapy.
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Affiliation(s)
- Yanjun Qiu
- Department of Cardiothoracic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou City, Zhejiang Province, People's Republic of China
| | - Jinjiang Yu
- Department of Cardiothoracic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou City, Zhejiang Province, People's Republic of China
| | - Quanmin Guo
- Department of Cardiothoracic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou City, Zhejiang Province, People's Republic of China
| | - Jingyan Xu
- Department of Cardiothoracic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou City, Zhejiang Province, People's Republic of China
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25
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Bhimani F, Feldman S, Cavalli A, Chen Y, Obaid L, Rachofsky C, Gupta A, Pastoriza J, Johnson K, McEvoy M. Axillary Reverse Mapping Aids in Reducing the Rates of Breast Cancer-Related Lymphedema in Underserved Ethnically Diverse Population. Ann Surg Oncol 2024; 31:5937-5946. [PMID: 38844631 DOI: 10.1245/s10434-024-15577-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/22/2024] [Indexed: 08/09/2024]
Abstract
BACKGROUND Breast cancer-related lymphedema (BCRL) poses a significant risk following sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND), particularly affecting ethnic minorities, with a twofold increased risk. Axillary reverse mapping (ARM), a novel technique, shows potential in reducing BCRL rates, yet its utility in ethnic minorities lacks sufficient exploration. Therefore, our study aims to investigate the utility and outcomes of ARM on BCRL in an ethnic diverse group. METHODS A retrospective chart review of ARM patients from January 2019 to July 2022 was conducted, monitoring patients over 24 months at 3-month intervals using SOZO® scores, with comparisons with preoperative baselines. RESULTS Of the 212 patients, 83% belonged to ethnic minorities. SLNB was performed in 83%, ALND in 17%, and 62.3% underwent radiation therapy. Positive lymph nodes were found in 31.6%, with 22.2% exhibiting blue nodes and 25.9% exhibiting blue lymphatics. Of identified blue nodes, 70.2% were excised, including 51.5% crossover nodes. Lymphedema occurred in 3 patients, resulting in a BCRL rate of 1.4%. Compared with an historical BCRL incidence of 40.4% following ALND in ethnic minorities, our study reported a significantly lower rate of 8% (p < 0.001). CONCLUSION The ARM procedure can significantly lower BCRL in ethnic minority groups. The combination of ARM and bioimpedance spectroscopy led to a remarkably low BCRL rate of 1.4%. Notably, none of the patients in our study developed an axillary recurrence at 24-month follow-up. Nevertheless, future studies with larger sample sizes are warranted to better understand the utility of the ARM technique in this population.
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Affiliation(s)
- Fardeen Bhimani
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
| | - Sheldon Feldman
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
- Albert Einstein College of Medicine, Bronx, NY, USA
| | | | - Yu Chen
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
| | - Liane Obaid
- Albert Einstein College of Medicine, Bronx, NY, USA
| | | | - Anjuli Gupta
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
- Albert Einstein College of Medicine, Bronx, NY, USA
| | - Jessica Pastoriza
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
- Albert Einstein College of Medicine, Bronx, NY, USA
| | - Kelly Johnson
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA
| | - Maureen McEvoy
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Care, Bronx, NY, USA.
- Albert Einstein College of Medicine, Bronx, NY, USA.
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Back K, Kim JS, Choe JH, Kim JH. Comparison of actual prognosis between unilateral and bilateral central neck dissection in modified radical neck dissection patients with no clinical central lymph node metastasis: a retrospective cohort study. Ann Surg Treat Res 2024; 107:144-150. [PMID: 39282105 PMCID: PMC11390279 DOI: 10.4174/astr.2024.107.3.144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 06/16/2024] [Accepted: 06/27/2024] [Indexed: 09/18/2024] Open
Abstract
Purpose This study aimed to evaluate the long-term prognosis of contralateral central neck dissection (CND) in papillary thyroid cancer (PTC) patients with ipsilateral lateral neck metastasis. We compared the actual recurrence rate according to the extent of CND-ipsilateral and contralateral sides. Methods A total of 708 PTC patients who underwent total thyroidectomy and concomitant ipsilateral or bilateral CND with ipsilateral lateral neck dissection between January 1997 and December 2022 at Samsung Medical Center were retrospectively analyzed. Results The median follow-up time was 118 months. Locoregional recurrence was observed in 26 patients (7.9%) and 30 patients (7.9%) in the ipsilateral and bilateral CND groups, respectively. There were 6 contralateral recurrence cases (1.8%) in the ipsilateral CND group and 6 cases (1.6%) in the bilateral CND group. There was only 1 contralateral central neck recurrence in the ipsilateral CND group. The incidence of hypocalcemia (P = 0.007) was higher in the bilateral CND group compared to the ipsilateral CND group. Conclusion Surgeons may consider performing only unilateral CND-the side where tumor is for therapeutic purposes to reduce surgical complications.
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Affiliation(s)
- Kyorim Back
- Division of Endocrine Surgery, Department of Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University School of Medicine, Seoul, Korea
| | - Jee Soo Kim
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun-Ho Choe
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung-Han Kim
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Chung SR, Baek JH, Choi YJ, Lee JH. Ten-Year Outcomes of Radiofrequency Ablation for Locally Recurrent Papillary Thyroid Cancer. Korean J Radiol 2024; 25:851-858. [PMID: 39197830 PMCID: PMC11361795 DOI: 10.3348/kjr.2024.0208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 06/18/2024] [Accepted: 06/26/2024] [Indexed: 09/01/2024] Open
Abstract
OBJECTIVE This study investigates the long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC). MATERIALS AND METHODS We retrospectively analyzed 39 consecutive patients with 61 locally recurrent PTCs (14 males, 25 females; mean ± standard deviation age, 52.8 ± 16.7 years; range 21-92 years) who underwent US-guided RFA with curative intent between September 2008 and April 2012. A subgroup of 24 patients with 37 recurrent PTCs who had a follow-up of at least 10 years were analyzed separately. All patients were followed for changes in lesion size on US and thyroglobulin (Tg) levels at 1, 3, 6, and 12 months after RFA, with follow-up every 6-12 months thereafter. Any complications were documented during the follow-up period. Recurrence-free survival (RFS) rates were assessed using Kaplan-Meier estimates. Long-term outcomes were evaluated in patients with follow-up of at least 10 years. RESULTS The follow-up period ranged from 7 to 180 months (median 133 months). The RFS rates for the 39 patients at 3, 5, and 10 years were 86.8%, 75.5%, and 60.6%, respectively. Among the 24 patients with 37 recurrent PTCs followed for more than 10 years, the volume reduction rate was 99.9% (range 96%-100%), and the complete tumor disappearance rate was 91.9%. The mean serum Tg level also decreased significantly, from 2.66 ± 86.5 mIU/L before ablation to 0.43 ± 0.73 mIU/L (P < 0.001) at the final follow-up. In 14 (58.3%) of the 24 patients, Tg levels were undetectable (below 0.08 mIU/L) at the last follow-up. No life-threatening or delayed complications were observed during the 10-year follow-up period. CONCLUSION The high RFS throughout the follow-up period, with efficacy and safety lasting beyond 10 years, supports US-guided RFA as a valuable option for local control of recurrent PTCs.
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Affiliation(s)
- Sae Rom Chung
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jung Hwan Baek
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Young Jun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jeong Hyun Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Li X, Lin Y, Lin S, Huang J, Ruan Z. Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond. Front Pharmacol 2024; 15:1404692. [PMID: 39211774 PMCID: PMC11357958 DOI: 10.3389/fphar.2024.1404692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 08/05/2024] [Indexed: 09/04/2024] Open
Abstract
Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are a class of oral targeted anticancer drugs that have been demonstrated to significantly inhibit tumor progression and improve clinical prognosis in patients diagnosed with EGFR-mutated tumors, particularly in those with non-small cell lung cancer. However, the sustained usage of EGFR-TKIs may cause potential cardiotoxicity, thus limiting their applicability. The primary objective of this review is to systematically analyze the evolving landscape of research pertaining to EGFR-TKI-induced cardiotoxicity and elucidate its underlying mechanisms, such as PI3K signaling pathway inhibition, ion channel blockade, oxidative stress, inflammatory responses, and apoptosis. Additionally, the review includes an exploration of risk assessment for cardiotoxicity induced by EGFR-TKIs, along with management and response strategies. Prospective research directions are outlined, emphasizing the need for more accurate predictors of cardiotoxicity and the development of innovative intervention strategies. In summation, this review consolidates recent research advances, illuminates the risks associated with EGFR-TKI-induced cardiac toxicity and presents crucial insights for refining clinical dosage protocols, optimizing patient management strategies, and unraveling the intricate mechanisms governing EGFR-TKI-induced cardiotoxicity.
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Affiliation(s)
| | | | | | | | - Zhongbao Ruan
- Department of Cardiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, China
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Zhao J, Zhang K, Sui D, Wang S, Li Y, Tang X, Liu X, Song Y, Deng Y. Recent advances in sialic acid-based active targeting chemoimmunotherapy promoting tumor shedding: a systematic review. NANOSCALE 2024; 16:14621-14639. [PMID: 39023195 DOI: 10.1039/d4nr01740d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.
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Affiliation(s)
- Jingyi Zhao
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Kunfeng Zhang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Dezhi Sui
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Shuo Wang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yantong Li
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Xueying Tang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Xinrong Liu
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yanzhi Song
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yihui Deng
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
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Zeng S, Jin N, Yu B, Ren Q, Yan Z, Fu S. Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are effective in the treatment of colorectal cancer. BMC Gastroenterol 2024; 24:249. [PMID: 39107717 PMCID: PMC11302356 DOI: 10.1186/s12876-024-03286-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/07/2024] [Indexed: 08/10/2024] Open
Abstract
OBJECTIVE To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T). METHODS A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts. RESULTS It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P < 0.05). The secretion of killer cytokines TNF-α and IFN-γ in the EpCAM expression positive cell group was higher than that in the negative group (P < 0.05). In the experimental group treated with EpCAM-CAR-T cells, the survival rate of nude mice was higher (P < 0.05), and the tumour was smaller than that in the blank and control groups (P < 0.05). The secretion of serum killer cytokines TNF-α and IFN-γ in tumour-bearing nude mice in the experimental group treated with EpCAM-CAR-T cells was higher than that in the blank and control groups (P < 0.05). CONCLUSION This study successfully constructed EpCAM-CAR cells and found that they can target and recognise EpCAM-positive tumour cells, secrete killer cytokines TNF-α and IFN-γ and better inhibit the growth and metastasis of colorectal cancer in vitro and in vivo than unmodified T cells.
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Affiliation(s)
- Siheng Zeng
- Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, China
- Birth Defects and Regenerative Medicine Laboratory, Department of Biochemistry & Molecular Biology, Biomedicine and Health Graduate Education Innovation Center, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, Shanxi, 030001, China
| | - Ning Jin
- Birth Defects and Regenerative Medicine Laboratory, Department of Biochemistry & Molecular Biology, Biomedicine and Health Graduate Education Innovation Center, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, Shanxi, 030001, China
| | - Baofeng Yu
- Birth Defects and Regenerative Medicine Laboratory, Department of Biochemistry & Molecular Biology, Biomedicine and Health Graduate Education Innovation Center, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, Shanxi, 030001, China
| | - Qing Ren
- Department of Gynecology, Hainan West Central Hospital, Danzhou, Hainan, 571700, China
| | - Zhiqiang Yan
- Department of Gynecology, Hainan West Central Hospital, Danzhou, Hainan, 571700, China
| | - Songtao Fu
- Birth Defects and Regenerative Medicine Laboratory, Department of Biochemistry & Molecular Biology, Biomedicine and Health Graduate Education Innovation Center, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, Shanxi, 030001, China.
- Biomedicine and Health Graduate Education Innovation Center, Taiyuan, Shanxi, 030001, China.
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Hushmandi K, Saadat SH, Mirilavasani S, Daneshi S, Aref AR, Nabavi N, Raesi R, Taheriazam A, Hashemi M. The multifaceted role of SOX2 in breast and lung cancer dynamics. Pathol Res Pract 2024; 260:155386. [PMID: 38861919 DOI: 10.1016/j.prp.2024.155386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 05/09/2024] [Accepted: 05/31/2024] [Indexed: 06/13/2024]
Abstract
Breast and lung cancers are leading causes of death among patients, with their global mortality and morbidity rates increasing. Conventional treatments often prove inadequate due to resistance development. The alteration of molecular interactions may accelerate cancer progression and treatment resistance. SOX2, known for its abnormal expression in various human cancers, can either accelerate or impede cancer progression. This review focuses on examining the role of SOX2 in breast and lung cancer development. An imbalance in SOX2 expression can promote the growth and dissemination of these cancers. SOX2 can also block programmed cell death, affecting autophagy and other cell death mechanisms. It plays a significant role in cancer metastasis, mainly by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, an imbalanced SOX2 expression can cause resistance to chemotherapy and radiation therapy in these cancers. Genetic and epigenetic factors may affect SOX2 levels. Pharmacologically targeting SOX2 could improve the effectiveness of breast and lung cancer treatments.
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Affiliation(s)
- Kiavash Hushmandi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, the Islamic Republic of Iran.
| | - Seyed Hassan Saadat
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, the Islamic Republic of Iran
| | - Seyedalireza Mirilavasani
- Campus Venlo, Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, The Netherlands
| | - Salman Daneshi
- Department of Public Health,School of Health,Jiroft University of Medical Sciences,Jiroft, the Islamic Republic of Iran
| | - Amir Reza Aref
- Department of Translational Sciences, Xsphera Biosciences Inc. Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, V6H3Z6 Canada
| | - Rasoul Raesi
- Department of Health Services Management, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Nursing, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.
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Abdullah, Abid A, Saeed H, Zabeehullah, Iftikhar U, Arshad MK, Shahid MU, Rasool T, Fazal F, Goyal A, Akbar A. A comprehensive study of adverse effects of chemotherapy on female breast cancer patients in NORI Cancer Hospital, Islamabad in a developing country. J Oncol Pharm Pract 2024:10781552241266254. [PMID: 39090979 DOI: 10.1177/10781552241266254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
INTRODUCTION Breast cancer is one of the top three malignancies worldwide. While radiotherapy, hormone replacement therapys, and chemotherapy are treatments, chemotherapy causes adverse effects that hinder daily life activities. OBJECTIVES To assess the prevalence, severity, and association of symptomatic toxicities in female breast cancer patients affecting various organ systems post systemic chemotherapy (adjuvant and neoadjuvant), and their impact on daily activities. Additionally, to determine the severity of adverse effects in specific age groups and their association with family history and disease stage. METHODOLOGY An observational study was conducted on 253 female breast cancer patients receiving chemotherapy at NORI Cancer Hospital from May to October 2023. Data collection tools included the NCI-PRO-CTCAE standardized questionnaire and patient medical records. Analysis was performed using descriptive statistics, T-tests, and Chi-square tests. RESULTS Among the 253 patients, 41.4% were aged 41-50. Significant weight changes (p = 0.034) were observed with more than three chemotherapy cycles. Notable associations included increased chemotherapy cycles with gastrointestinal (mouth/throat sores p = 0.031, vomiting p = 0.021), respiratory (cough p = 0.04), cardiovascular (arm/leg swelling p = 0.007, palpitations p = 0.052), integumentary (hair loss p = 0.000, skin dryness p = 0.054), and musculoskeletal (fatigue p = 0.002) adverse effects. Positive family history and the 18-30 age group also showed significant associations with adverse effect severity. Disease stage significantly influenced the nervous system (stage 2 p = 0.007, stage 3 p = 0.01). CONCLUSION The severity of adverse effects varies among age groups, depending on disease stage, genetics, and treatment duration. These patient-reported outcomes highlight the need for better management strategies considering prognostic factors and treatment adverse effects.
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Affiliation(s)
- Abdullah
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Areesha Abid
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Humza Saeed
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Zabeehullah
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Uswa Iftikhar
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | | | | | - Tayyab Rasool
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Faizan Fazal
- Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Aman Goyal
- Department of Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Anum Akbar
- Department of Pediatrics, University of Nebraska Medical Centre, Omaha, NE, USA
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Bhimani F, McEvoy M, Chen Y, Gupta A, Pastoriza J, Cavalli A, Obaid L, Rachofsky C, Fruchter S, Feldman S. Comprehensive strategies in breast cancer-related lymphedema prevention: insights from a multifaceted program. Front Oncol 2024; 14:1418610. [PMID: 39081716 PMCID: PMC11286467 DOI: 10.3389/fonc.2024.1418610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/24/2024] [Indexed: 08/02/2024] Open
Abstract
Background Breast cancer-related lymphedema (BCRL) profoundly impacts patients' quality of life, causing heightened depression, anxiety, and physical limitations. Surgical removal of the axillary nodes, combined with radiation therapy, is a significant risk factor for BCRL. Smarter axillary surgery, coupled with early detection and fostering lymphedema education, significantly improves BCRL management, promoting timely diagnosis and treatment. A lymphedema prevention program encompassing all these factors can significantly aid in preventing, treating, and reducing the severity of BCRL cases. Therefore, our study aims to share our insights and experiences gained from implementing a lymphedema prevention program at our institution. Methods & Results At our institution, axillary reverse mapping (ARM) is performed on all patients undergoing axillary surgery. We surveil these patients with pre- and postoperative SOZO® measurements using bioimpedance spectroscopy to detect sub-clinical lymphedema. Concerning education, we use a 3-pronged approach with surgeons, nurse practitioners, and video representation for patients. We have had 212 patients undergo the ARM procedure since 2019, with three (1.41%) developing persistent lymphedema. Conclusion Our study underscores the significance of a comprehensive lymphedema prevention program, integrating smarter axillary surgery, early detection, and patient education. The lymphedema rate of 1.41% not only validates the success rate of these interventions but also advocates for their widespread adoption to enhance the holistic care of breast cancer survivors. As we continue to refine and expand our program, further research, and long-term follow-up are crucial to improve prevention strategies continually and enhance the overall well-being of individuals at risk of BCRL.
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Affiliation(s)
- Fardeen Bhimani
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Maureen McEvoy
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Yu Chen
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Anjuli Gupta
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Jessica Pastoriza
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Arianna Cavalli
- Albert Einstein College of Medicine, Bronx, NY, United States
| | - Liane Obaid
- Albert Einstein College of Medicine, Bronx, NY, United States
| | | | - Shani Fruchter
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
| | - Sheldon Feldman
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, United States
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Shimomura T, Mori K, Matsukawa A, Fukuokaya W, Yanagisawa T, Urabe F, Murakami M, Miki J, Yamada H, Kimura T. Abiraterone Acetate Versus Enzalutamide Against Chemo-Naïve Castration-Resistant Prostate Cancer With Full-Dose Induction. Cureus 2024; 16:e64217. [PMID: 39130842 PMCID: PMC11310824 DOI: 10.7759/cureus.64217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2024] [Indexed: 08/13/2024] Open
Abstract
Purpose We recently released the multi-institutional real-world analysis about the difference in survival outcomes between abiraterone acetate and enzalutamide against chemo-naïve castration-resistant prostate cancer (CRPC) in a first-line setting. Although reduced dose induction cases were included in that analysis, induction dose reduction might correlate with reduced efficacy. In this study, we analyzed full-dose induction subgroups from our overall cohort and investigated the true difference in efficacy between these agents. Methods A total of 220 chemotherapy-naïve CRPC cases treated with full-dose induction of first-line androgen receptor signaling inhibitor (ARSI) were analyzed. Outcome measures were prostate-specific antigen (PSA) response, PSA progression-free survival (PSA-PFS), treatment failure-free survival (TFF), cancer-specific survival (CSS), and overall survival (OS). Results Abiraterone acetate and enzalutamide were administered to 58 and 162 patients, respectively. The median PSA response rate (-65.4% (A) and -81.5% (E), p = 0.0252), PSA decline ≥ 90% (22.4% (A) and 37.0% (E), p = 0.0478), PSA-PFS (median four months (A) and seven months (E), p = 0.00833), TFF (median six months (A) and 15 months (E), p<0.0001), CSS (median 45 months (A) and not reached (E), p < 0.0001), and OS (median 34 months (A) and 80 months (E), p<0.001) were significantly better in the E group. Conclusion This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes in the full-dose induction cohort.
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Affiliation(s)
| | - Keiichiro Mori
- Urology, Jikei University School of Medicine, Tokyo, JPN
| | | | | | | | - Fumihiko Urabe
- Urology, Jikei University School of Medicine, Tokyo, JPN
| | | | - Jun Miki
- Urology, Jikei University School of Medicine, Tokyo, JPN
| | - Hiroki Yamada
- Urology, Jikei University School of Medicine, Tokyo, JPN
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Zhu DH, Su KK, Ou-Yang XX, Zhang YH, Yu XP, Li ZH, Ahmadi-Nishaboori SS, Li LJ. Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers. Mol Cell Biochem 2024; 479:1553-1570. [PMID: 38856795 PMCID: PMC11254988 DOI: 10.1007/s11010-024-05040-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 05/18/2024] [Indexed: 06/11/2024]
Abstract
Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.
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Affiliation(s)
- Dan-Hua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Kun-Kai Su
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xiao-Xi Ou-Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yan-Hong Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xiao-Peng Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Zu-Hong Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | | | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Zhang H, Li M, Zhou X, Tang L, Chen G, Zhang Y. Design, synthesis of combretastatin A-4 piperazine derivatives as potential antitumor agents by inhibiting tubulin polymerization and inducing autophagy in HCT116 cells. Eur J Med Chem 2024; 272:116497. [PMID: 38759453 DOI: 10.1016/j.ejmech.2024.116497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/30/2024] [Accepted: 05/11/2024] [Indexed: 05/19/2024]
Abstract
A series of combretastatin A-4 (CA-4) derivatives were designed and synthesized, which contain stilbene core structure with different linker, predominantly piperazine derivatives. These compounds were evaluated for their cytotoxic activities against four cancer cell lines, HCT116, A549, AGS, and SK-MES-1. Among them, compound 13 displayed the best effectiveness with IC50 values of 0.227 μM and 0.253 μM against HCT116 and A549 cells, respectively, showing low toxicity to normal cells. Mechanistic studies showed that 13 inhibited HCT116 proliferation via arresting cell cycle at the G2/M phase through disrupting the microtubule network and inducing autophagy in HCT116 cells by regulating the expression levels of autophagy-related proteins. In addition, 13 displayed antiproliferative activities against A549 cells through blocking the cell cycle and inducing A549 cells apoptosis. Because of the poor water solubility of 13, four carbohydrate conjugates were synthesized which exhibited better water solubility. Further investigations revealed that 13 showed positive effects in vivo anticancer study with HCT116 xenograft models. These data suggest that 13 could be served as a promising lead compound for further development of anti-colon carcinoma agent.
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Affiliation(s)
- Hangqi Zhang
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China
| | - Ming Li
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China
| | - Xueming Zhou
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China
| | - Li Tang
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China
| | - Guangying Chen
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China.
| | - Yongmin Zhang
- Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China; Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France.
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Liu YM, Yang TC, Fang XC, Yang LJ, Shi LW, Wang HQ, Dou TT, Shu L, Chen TL, Hu J, Yu XM, Li XF. Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer: Integrating Bioinformatics Analysis with Experimental Confirmation. Curr Med Sci 2024; 44:529-544. [PMID: 38809379 DOI: 10.1007/s11596-024-2871-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/14/2024] [Indexed: 05/30/2024]
Abstract
OBJECTIVE To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.
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Affiliation(s)
- Yan-Min Liu
- Department of Gastroenterology, the Central Hospital of Wuhan, Key Laboratory for Molecular Diagnosis of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China
| | - Tie-Cheng Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Xiao-Chang Fang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Li-Jie Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Li-Wen Shi
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Hua-Qiao Wang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Ting-Ting Dou
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Lin Shu
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Tian-Liang Chen
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China
| | - Jun Hu
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Xiao-Ming Yu
- Department of Gastrointestinal Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Wuhan, 435001, China.
| | - Xuan-Fei Li
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China.
- Hubei Provincial Clinical Research Center for Cancer, Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, 430071, China.
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Singh J, Iqbal SA, Gajula S, Raghavan P, Rajpal S, Khan A. Assessment of Chemotherapy-Induced Cardiac Dysfunction in Breast Cancer Patients: A Prospective Study. Cureus 2024; 16:e59461. [PMID: 38826896 PMCID: PMC11141790 DOI: 10.7759/cureus.59461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2024] [Indexed: 06/04/2024] Open
Abstract
Background Advances in cancer treatment have markedly improved survival rates but have also heightened morbidity due to treatment-related side effects. Despite this, the literature remains scarce on predicting the incidence of acute cardiac toxicity resulting from chemotherapy. We conducted a prospective evaluation to assess the incidence, timing, clinical correlates, global longitudinal strain (GLS), and response to heart failure (HF) therapy in patients experiencing cardiotoxicity. Aims and objectives Our study aimed to assess the cardiovascular complications of cancer therapy in breast cancer patients, with particular emphasis on therapy-related cardiac dysfunction. Materials and methods We conducted a prospective observational study to detect chemotherapy-related cardiac dysfunction (CTRCD) in breast cancer patients attending the outpatient department (OPD) or admitted to Dayanand Medical College and Hospital (DMCH), Ludhiana, Punjab, between March 1, 2020, and October 31, 2021. We assessed left ventricular ejection fraction (LVEF) at baseline, mid-chemotherapy, and post-chemotherapy. Patients who developed left ventricular dysfunction (LVD) had their chemotherapy regimen modified and were initiated on HF therapy. Results Ninety-seven patients (mean age: 50.74±10.30 years) were enrolled and categorized into the LVD group (n=13) and non-LVD group (n=84). CTRCD developed in 13 patients (13.4%). Patients with estrogen receptor (ER) positive, progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2) positive status, as well as those in cancer stages III and IV, are at higher risk of developing LV dysfunction. Among the 13 patients, 10 (77%) experienced complete recovery, while three (23%) had partial recovery. Markers for partial recovery included cancer stages III-IV, younger age, lower body mass index (BMI), lower radiotherapy dosage, lower mean chemotherapy dosage, and left breast involvement. Conclusion Our findings suggest that acute cardiotoxicity is not linked to the cumulative dose of anthracyclines. Early detection, modification of chemotherapy regimens, and prompt initiation of CTRCD therapy can lead to substantial recovery of cardiac dysfunction.
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Affiliation(s)
- Jasvinder Singh
- Cardiology and Electrophysiology, Asian Institute of Gastroenterology (AIG) Hospital, Hyderabad, IND
| | - Syed Abid Iqbal
- Internal Medicine, Asian Institute of Gastroenterology (AIG) Hospital, Hyderabad, IND
| | - Sahini Gajula
- Internal Medicine, Gandhi Medical College and Hospital, Secunderabad, IND
| | | | - Shreyaa Rajpal
- Internal Medicine, Osmania Medical College, Hyderabad, IND
| | - Aadil Khan
- Trauma Surgery, OSF St Francis Medical Centre, University of Illinois College of Medicine, Peoria, USA
- Cardiology, University of Illinois Chicago, Chicago, USA
- Internal Medicine, Lala Lajpat Rai (LLR) Hospital, Kanpur, IND
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Balachandran L, Haw TJ, Leong AJW, Croft AJ, Chen D, Kelly C, Sverdlov AL, Ngo DTM. Cancer Therapies and Cardiomyocyte Viability: Which Drugs are Directly Cardiotoxic? Heart Lung Circ 2024; 33:747-752. [PMID: 38365500 DOI: 10.1016/j.hlc.2024.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 12/23/2023] [Accepted: 01/01/2024] [Indexed: 02/18/2024]
Abstract
BACKGROUND Increased cancer survivorship represents a remarkable achievement for modern medicine. Unfortunately, cancer treatments have inadvertently contributed to cardiovascular (CV) damage, significantly threatening the health and quality of life of patients living with, through and beyond cancer. Without understanding the mechanisms, including whether the cardiotoxicity is due to the direct or indirect effects on cardiomyocytes, prevention and management of cardiotoxicity can pose challenges in many patients. To date, the cardiotoxicity profiles of most of the chemotherapy drugs are still poorly understood. AIM To conduct a pilot study to investigate the direct effects of a range of cancer therapies on cardiomyocyte viability. METHODS Primary human cardiomyocytes (HCM) were cultured and seeded into 96-well culture plates. A total of 35 different Food and Drug Administration-approved anti-cancer drugs were added to the HCM cells with a concentration of 1uM for 72 hours. The viability of HCMs was determined using CellTitre-Glo. The experiments were repeated at least three times for each drug with HCMs of different passages. RESULTS We identified 15 anti-cancer agents that significantly reduced HCM viability. These drugs were: (1) anthracyclines (daunorubicin [HCM viability, mean %±standard error, 13.7±3.2%], epirubicin [47.6±5.3%]), (2) antimetabolite (azacitidine [67.1±2.4%]), (3) taxanes (paclitaxel [60.2±3.0%]), (4) protein kinase inhibitors (lapatinib [49.8±7.0%], ponatinib [42.4±9.0%], pemigatinib [68.1±2.3%], sorafenib [52.9±10.6%], nilotinib [64.4±4.5%], dasatinib [38.5±3.6%]), (5) proteasome inhibitors (ixazomib citrate [65.4±7.2%]), (6) non-selective histone-deacetylase inhibitor (panobinostat [19.1±4.1%]), poly adenosine diphosphate-ribose polymerase inhibitor (olaparib [68.2±1.7%]) and (7) vinca alkaloids (vincristine [44.6±7.4%], vinblastine [31.2±3.9%]). CONCLUSIONS In total, 15 of the 35 commercially available anti-cancer drugs have direct cardiotoxic effects on HCM. Some of those, have not been associated with clinical cardiotoxicity, while others, known to be cardiotoxic do not appear to mediate it via direct effects on cardiomyocytes. More detailed investigations of the effects of cancer therapies on various cardiovascular cells should be performed to comprehensively determine the mechanisms of cardiotoxicity.
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Affiliation(s)
- Lohis Balachandran
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Tatt Jhong Haw
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Angeline Jia Wen Leong
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Amanda J Croft
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Dongqing Chen
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Conagh Kelly
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Aaron L Sverdlov
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia.
| | - Doan T M Ngo
- Newcastle Centre of Excellence in Cardio-Oncology, Hunter Medical Research Institute, Hunter New England Local Health District, The University of Newcastle and Calvary Mater Newcastle, Newcastle, NSW, Australia.
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Boyev A, Tzeng CWD, Maki H, Arvide EM, Mrema DE, Jain AJ, Haddad A, Lendoire M, Malik N, Odisio BC, Chun YS, Tran Cao HS, Vauthey JN, Newhook TE. Local Therapy Improves Survival for Early Recurrence After Resection of Colorectal Liver Metastases. Ann Surg Oncol 2024; 31:2547-2556. [PMID: 38148351 DOI: 10.1245/s10434-023-14806-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 12/07/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM. METHODS Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6 months), intermediate (RFS 6-12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation. RESULTS Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04). CONCLUSIONS While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.
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Affiliation(s)
- Artem Boyev
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Harufumi Maki
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elsa M Arvide
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Deborah E Mrema
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Anish J Jain
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Antony Haddad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mateo Lendoire
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Neha Malik
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hop S Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Carvalho A, Gonçalves N, Teixeira P, Goulart A, Leão P. The impact of methylene blue in colorectal cancer: Systematic review and meta-analysis study. Surg Oncol 2024; 53:102046. [PMID: 38377643 DOI: 10.1016/j.suronc.2024.102046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/01/2024] [Accepted: 02/04/2024] [Indexed: 02/22/2024]
Abstract
PURPOSE In patients with colorectal cancer (CRC), the most important factor to decide the need of adjuvant chemotherapy is the histological lymph node (LN) evaluation. Our work aimed to give a broad view over the use of methylene blue and its consequences in the number of lymph node harvest. METHODS PUBMED, WEB OF SCIENCE and EMBASE databases were consulted, retrieving clinical trials, which mentioned the used of intra-arterial methylene blue in patients with colorectal cancer. RESULTS Eighteen clinical trials analyzing the use of intra-arterial methylene blue in specimens of colorectal cancer were selected. The articles show a statistical difference between the use of methylene blue and the classical dissection in both variable at study. The results of the statistical analysis of the lymph node harvest variable demonstrate a significant statistical difference between the group that received methylene blue injection and the group that underwent conventional dissection. There is a significant statistical difference between the experimental and control groups for the ideal lymph node harvest (lymph node harvest count greater than 12). CONCLUSION The use of intra-arterial methylene blue revealed a high potential for the quantification of lymph nodes, considering the increase of lymph node harvest and the higher percentage of cases with more than 12 lymph nodes count, albeit the high heterogeneity between the studies in terms of reported results. Future investigations with controlled double blinded studies obtaining better categorized results should be conducted in order to better evaluate this technique and compare it to the current paradigm.
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Affiliation(s)
- Alexandre Carvalho
- Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal.
| | | | - Pedro Teixeira
- Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal
| | - André Goulart
- General Surgery Department, Grupo Trofa Saúde, Braga, Portugal
| | - Pedro Leão
- Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal; General Surgery Department, Grupo Trofa Saúde, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal
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Alzahrani AY, Gomha SM, Zaki ME, Farag B, Abdelgawad FE, Mohamed MA. Chitosan-sulfonic acid-catalyzed green synthesis of naphthalene-based azines as potential anticancer agents. Future Med Chem 2024; 16:647-663. [PMID: 38385167 DOI: 10.4155/fmc-2023-0351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 02/05/2024] [Indexed: 02/23/2024] Open
Abstract
Aim: This study focuses on advancing green chemistry in anticancer drug discovery, particularly through the synthesis of azine derivatives with a naphthalene core using CS-SO3H as a catalyst. Methods: Novel benzaldazine and ketazine derivatives were synthesized using (E)-(naphthalen-1-ylmethylene)hydrazine and various carbonyl compounds. The methods employed included thermal and grinding techniques, utilizing CS-SO3H as an eco-friendly and cost-effective catalyst. Results: The approach resulted in high yields, short reaction times and demonstrated catalyst reusability. Cytotoxicity tests highlighted compounds 3b, 11 and 13 as potent against the HEPG2-1. Conclusion: This study successfully aligns with the objectives of eco-conscious drug development in organic chemistry. Molecular docking and in silico studies further indicate the potential of these ligands as antitumor medicines, with favorable oral bioavailability properties.
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Affiliation(s)
- Abdullah Ya Alzahrani
- Department of Chemistry, Faculty of Science & Arts, King Khalid University, Mohail Assir, Saudi Arabia
| | - Sobhi M Gomha
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia
- Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Magdi Ea Zaki
- Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia
| | - Basant Farag
- Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt
| | - Fathy E Abdelgawad
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia
| | - Mahmoud A Mohamed
- Technology of Textile Department, Faculty of Technology & Education, Beni-Suef University, Beni-Suef, 62521, Egypt
- Chemistry Department, Faculty of Science & Humanity study-Afif, Shaqra University, 11911, Saudi Arabia
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Murnaghan S, Scruton S, Urquhart R. Psychosocial interventions that target adult cancer survivors' reintegration into daily life after active cancer treatment: a scoping review. JBI Evid Synth 2024; 22:607-656. [PMID: 38015073 PMCID: PMC10986786 DOI: 10.11124/jbies-23-00044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
OBJECTIVE This review explored psychosocial interventions targeting adult cancer survivors' reintegration following active cancer treatment. This included the types of interventions tested and the tools used to measure reintegration. INTRODUCTION Cancer survivors face lingering health issues following the completion of cancer treatment. Many cancer survivors still experience unmet psychosocial care needs despite receiving follow-up care. Further, many survivorship interventions do not specifically address outcomes important to survivors. A number of primary studies have identified reintegration as an outcome important to cancer survivors. Reintegration is a concept that focuses on returning to normal activities, routines, and social roles after cancer treatment; however, it is emerging and abstract. INCLUSION CRITERIA Studies involving adult cancer survivors (18 years or older at diagnosis) of any cancer type or stage were included in this review. Studies with psychosocial interventions targeted at reintegrating the person into daily life after cancer treatment were included. Interventions addressing clinical depression or anxiety, and interventions treating solely physical needs that were largely medically focused were excluded. METHODS A literature search was conducted in MEDLINE (Ovid), CINAHL (EBSCOhost), and Embase. Gray literature was searched using ProQuest Dissertations and Theses (ProQuest). Reference lists of included studies were searched. Studies were screened at the title/abstract and full-text levels, and 2 independent reviewers extracted data. Manuscripts in languages other than English were excluded due to feasibility (eg, cost, time of translations). Findings were summarized narratively and reported in tabular and diagrammatic format. RESULTS The 3-step search strategy yielded 5617 citations. After duplicates were removed, the remaining 4378 citations were screened at the title and abstract level, then the remaining 306 citations were evaluated at the full-text level by 2 independent reviewers. Forty studies were included that evaluated psychosocial interventions among adult cancer survivors trying to reintegrate after active cancer treatment (qualitative n=23, mixed methods n=8, quantitative n=8, systematic review n=1). Included articles spanned 10 different countries/regions. Over half of all included articles (n=25) focused primarily on breast cancer survivors. Many studies (n=17) were conducted in primary care or community-based settings. The most common types of interventions were peer-support groups (n=14), follow-up education and support (n=14), exercise programs (n=6), and multidisciplinary/multicomponent programs (n=6). While the majority of included studies characterized the outcome qualitatively, 9 quantitative tools were also employed. CONCLUSIONS This review identified 6 types of interventions to reintegrate survivors back into their daily lives following cancer treatment. An important thread across intervention types was a focus on personalization in the form of problem/goal identification. Given the number of qualitative studies, future research could include a qualitative systematic review and meta-aggregation. Quantitative tools may not be as effective for evaluating reintegration. More primary studies, including mixed methods studies, utilizing consistent measurement tools are required. Furthermore, this work provides a basis for future research to continue examining the complexity of implementing such interventions to successfully achieve reintegration. To do so, primary studies evaluating interventions from an implementation science and complex systems perspective would be useful. REVIEW REGISTRATION Open Science Framework https://osf.io/r6bmx.
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Affiliation(s)
- Sarah Murnaghan
- Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Sarah Scruton
- Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Robin Urquhart
- Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
- Department of Surgery, Nova Scotia Health, Halifax, NS, Canada
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Wang G, Jin Y, Xiong K, Jin X, Wang L, Li C. Utility of auto fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. Photodiagnosis Photodyn Ther 2024; 46:104057. [PMID: 38508439 DOI: 10.1016/j.pdpdt.2024.104057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/15/2024] [Accepted: 03/18/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Bronchoscopy is currently the most common technique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. METHODS We conducted a retrospective study in a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions. RESULTS A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3 % (95 % confidence interval [CI]: 53.1 %-67.1 %), which was higher than that of patients with WLB alone (45.2 %, 95 % CI: 38.2-52.4 %) (P = 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100 %, 95 % CI: 95.5-100 % versus 69.6 %, 95 % CI: 59.6-78.1 %), positive predictive value (100 %, 95 % CI: 96.1-100 % versus 74.3 %, 95 % CI: 65.5-81.7 %) and negative predictive value (56.3 %, 95 % CI: 48.8-63.6 % versus 39.4 %, 95 % CI: 32.3-47.0 %). CONCLUSION Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.
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Affiliation(s)
- Gaozhe Wang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China; School of Medicine, Ningbo University, Ningbo, Zhejiang, China
| | - Yan Jin
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Kunlong Xiong
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Xiaoyan Jin
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Linfeng Wang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China.
| | - Chenwei Li
- Department of Cerebral Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.
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Abrahams B, Gerber A, Hiss DC. Combination Treatment with EGFR Inhibitor and Doxorubicin Synergistically Inhibits Proliferation of MCF-7 Cells and MDA-MB-231 Triple-Negative Breast Cancer Cells In Vitro. Int J Mol Sci 2024; 25:3066. [PMID: 38474312 DOI: 10.3390/ijms25053066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/03/2024] [Accepted: 03/04/2024] [Indexed: 03/14/2024] Open
Abstract
The role of the epidermal growth factor receptor (EGFR) in tumor progression and survival is often underplayed. Its expression and/or dysregulation is associated with disease advancement and poor patient outcome as well as drug resistance in breast cancer. EGFR is often overexpressed in breast cancer and particularly triple-negative breast cancer (TNBC), which currently lacks molecular targets. We examined the synergistic potential of an EGFR inhibitor (EGFRi) in combination with doxorubicin (Dox) in estrogen-positive (ER+) MCF-7 and MDA-MB-231 TNBC cell lines. The exposure of MDA-MB-231 and MCF-7 to EGFRi produced an IC50s of 6.03 µM and 3.96 µM, respectively. Dox induced MDA-MB-231 (IC50 9.67 µM) and MCF-7 (IC50 1.4 µM) cytotoxicity. Combinations of EGFRi-Dox significantly reduced the IC50 in MCF-7 (0.46 µM) and MBA-MB 231 (0.01 µM). Synergistic drug interactions in both cell lines were confirmed using the Bliss independence model. Pro-apoptotic Caspase-3/7 activation occurred in MCF-7 at 0.1-10 µM of EGFRi and Dox single treatments, whilst 1 μM Dox yielded a more potent effect on MDA-MB-231. EGFRi and Dox individually and in combination downregulated the EGFR gene expression in MCF-7 and MDA-MB-231 (p < 0.001). This study demonstrates EGFRi's potential for eliciting synergistic interactions with Dox, causing enhanced growth inhibition, apoptosis induction, and downregulation of EGFR in both cell lines.
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Affiliation(s)
- Beynon Abrahams
- Department of Basic Medical Sciences, Faculty of Health Sciences, University of the Free State, Bloemfontein 9301, South Africa
| | - Anthonie Gerber
- Department of Basic Medical Sciences, Faculty of Health Sciences, University of the Free State, Bloemfontein 9301, South Africa
| | - Donavon Charles Hiss
- Department of Medical Biosciences, Faculty of Natural Sciences, University of the Western Cape, Bellville 7535, South Africa
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Shimomura T, Mori K, Yasue K, Matsukawa A, Fukuokaya W, Yanagisawa T, Hata K, Murakami M, Koike Y, Miki J, Yamada H, Kimura T. Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis. Int J Clin Oncol 2024; 29:213-221. [PMID: 38103156 DOI: 10.1007/s10147-023-02441-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023]
Abstract
PURPOSE The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. CONCLUSION This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.
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Affiliation(s)
- Tatsuya Shimomura
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
| | - Keiichiro Mori
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Keiji Yasue
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Akihiro Matsukawa
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Wataru Fukuokaya
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | | | - Kenichi Hata
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, Atsugi City General Hospital, Atsugi, Japan
| | - Masaya Murakami
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, Fuji City General Hospital, Fuji, Japan
| | - Yusuke Koike
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
- Department of Urology, JR Tokyo General Hospital, Tokyo, Japan
| | - Jun Miki
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Yamada
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Kimura
- Department of Urology, Jikei University School of Medicine, Tokyo, Japan
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Lipton JH. Maximizing the Value of Chronic Myeloid Leukemia Management Using Tyrosine Kinase Inhibitors in the USA: Potential Determinants and Consequences of Healthcare Resource Utilization and Costs, with Proposed Optimization Approaches. Clin Drug Investig 2024; 44:91-108. [PMID: 38182963 DOI: 10.1007/s40261-023-01329-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2023] [Indexed: 01/07/2024]
Abstract
BACKGROUND AND OBJECTIVES The introduction and widespread use of effective and well-tolerated tyrosine kinase inhibitors for chronic myeloid leukemia have been associated with marked increments in life expectancy and disease prevalence. These changes have been accompanied by elevations in costs of tyrosine kinase inhibitors, which typically must be taken ad vitam after diagnosis and tend to be more expensive than medical therapies for many other hematologic malignancies. The aims of this review included evaluating the potential associations and consequences of healthcare resource utilization and costs of tyrosine kinase inhibitors and possible clinical management approaches to mitigate them. METHODS A PubMed search of English-language US study reports was conducted that covered the interval of 2001 (US approval of imatinib) through 17 April, 2023 augmented by manual reviews of published bibliographies from the referenced articles and searches of other databases: Google Scholar and Scopus. RESULTS On the basis of this analysis of chiefly real-world evidence (administrative claims database studies), healthcare resource utilization and costs can be considered indicators of ineffective chronic myeloid leukemia management, including potentially mutation-driven treatment resistance and costly tyrosine kinase inhibitor switches, non-adherence, and suboptimal tolerability, which may culminate in the progression of disease from the chronic to an accelerated or blast phase, with additional excess costs. Costs of tyrosine kinase inhibitors are also associated with reduced treatment adherence. At a willingness-to-pay threshold of $50,000-$200,000 per quality-adjusted life-year, tyrosine kinase inhibitors can be considered cost effective from a US payer perspective. Potential clinical approaches to mitigate costs include regular molecular monitoring with proactive assessments of BCR::ABL1 gene mutations to avoid costly treatment switches, as well as interventions to enhance treatment adherence and tyrosine kinase inhibitor tolerability. CONCLUSIONS Healthcare resource utilization and costs of chronic myeloid leukemia care may be considered barometers of ineffective management, including mutation-driven tyrosine kinase inhibitor resistance and switching as well as non-adherence and intolerance. Future prospective research is warranted to help determine whether costs can be reduced and other treatment outcomes optimized via more proactive and effective diagnostic interventions (i.e., regular molecular monitoring and proactive mutational testing) and treatment approaches. The strengths and limitations of this review include its emphasis on observational research, which, on one hand, offers a naturalistic "real-world" perspective on current chronic myeloid leukemia management, but, on the other hand, is associational in nature and cannot be used to determine causality and/or its direction.
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Affiliation(s)
- Jeffrey H Lipton
- Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.
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Chen X, Mu X, Ding L, Wang X, Mao F, Wei J, Liu Q, Xu Y, Ni S, Jia L, Li J. Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent. Acta Pharm Sin B 2024; 14:729-750. [PMID: 38322326 PMCID: PMC10840436 DOI: 10.1016/j.apsb.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 10/05/2023] [Accepted: 10/26/2023] [Indexed: 02/08/2024] Open
Abstract
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
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Affiliation(s)
- Xin Chen
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
- College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Xianggang Mu
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Lele Ding
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Xi Wang
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Fei Mao
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Jinlian Wei
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Qian Liu
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yixiang Xu
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Shuaishuai Ni
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Lijun Jia
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jian Li
- State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
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Meng X, Zhao X, Zhou B, Song W, Liang Y, Liang M, Du M, Shi J, Gao Y. FSTL3 is associated with prognosis and immune cell infiltration in lung adenocarcinoma. J Cancer Res Clin Oncol 2024; 150:17. [PMID: 38240936 PMCID: PMC10799152 DOI: 10.1007/s00432-023-05553-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 11/15/2023] [Indexed: 01/22/2024]
Abstract
PURPOSE FSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital. METHODS Data on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics. RESULTS FSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3. CONCLUSION FSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.
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Affiliation(s)
- Xiangzhi Meng
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Xiaojian Zhao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Boxuan Zhou
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Weijian Song
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Yicheng Liang
- Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China
| | - Mei Liang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Minjun Du
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Jianwei Shi
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China
| | - Yushun Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan, Nanli 17, Beijing, 100021, People's Republic of China.
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Lu S, Sun X, Tang H, Yu J, Wang B, Xiao R, Qu J, Sun F, Deng Z, Li C, Yang P, Yang Z, Rao B. Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis. Sci Rep 2024; 14:329. [PMID: 38172565 PMCID: PMC10764849 DOI: 10.1038/s41598-023-51028-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 12/29/2023] [Indexed: 01/05/2024] Open
Abstract
The expression level of SLC35A3 is associated with the prognosis of many cancers, but its role in colorectal cancer (CRC) is unclear. The purpose of our study was to elucidate the role of SLC35A3 in CRC. The expression levels of SLC35A3 in CRC were evaluated through tumor immune resource assessment (TIMER), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Human Protein Atlas (HPA), qRT-PCR, and immunohistochemical evaluation. TCGA, GEO, and ICGC databases were used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. A overall survival (OS) model was constructed and validated based on the expression level of SLC35A3 and multivariable analysis results. The cBioPortal tool was used to analyze SLC35A3 mutation in CRC. The UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in colorectal cancer. In addition, the role of SLC35A3 in CRC was determined through GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and immune checkpoint correlation analysis. In vitro experiments validated the function of SLC35A3 in colorectal cancer cells. Compared with adjacent normal tissues and colonic epithelial cells, the expression of SLC35A3 was decreased in CRC tissues and CRC cell lines. Low expression of SLC35A3 was associated with N stage, pathological stage, and lymphatic infiltration, and it was unfavorable for OS, disease-specific survival (DSS), recurrence-free survival (RFS), and post-progression survival (PPS). According to the Receiver Operating Characteristic (ROC) analysis, SLC35A3 is a potential important diagnostic biomarker for CRC patients. The nomograph based on the expression level of SLC35A3 showed a better predictive model for OS than single prognostic factors and TNM staging. SLC35A3 has multiple types of mutations in CRC, and its promoter methylation level is significantly decreased. GO and KEGG analysis indicated that SLC35A3 may be involved in transmembrane transport protein activity, cell communication, and interaction with neurotransmitter receptors. GSEA revealed that SLC35A3 may be involved in energy metabolism, DNA repair, and cancer pathways. In addition, SLC35A3 was closely related to immune cell infiltration and immune checkpoint expression. Immunohistochemistry confirmed the positive correlation between SLC35A3 and helper T cell infiltration. In vitro experiments showed that overexpression of SLC35A3 inhibited the proliferation and invasion capability of colorectal cancer cells and promoted apoptosis. The results of this study indicate that decreased expression of SLC35A3 is closely associated with poor prognosis and immune cell infiltration in colorectal cancer, and it can serve as a promising independent prognostic biomarker and potential therapeutic target.
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Affiliation(s)
- Shuai Lu
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Cancer Foods for Special Medical Purpose (FSMP) for State Market Regulation, Beijing, 100038, China
| | - Xibo Sun
- Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Shandong, 271000, China
| | - Huazhen Tang
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Cancer Foods for Special Medical Purpose (FSMP) for State Market Regulation, Beijing, 100038, China
| | - Jinxuan Yu
- Zibo Central Hospital Affiliated to Binzhou Medical College, Zibo, 255020, China
| | - Bing Wang
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Cancer Foods for Special Medical Purpose (FSMP) for State Market Regulation, Beijing, 100038, China
| | - Ruixue Xiao
- Inner Mongolia Medical University, Hohhot, 010100, China
| | - Jinxiu Qu
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Cancer Foods for Special Medical Purpose (FSMP) for State Market Regulation, Beijing, 100038, China
| | - Fang Sun
- The Fifth Medical Center of the General Hospital of the People's Liberation Army of China, Beijing, 100000, China
| | - Zhuoya Deng
- The First Medical Center of Chinese, PLA General Hospital, Beijing, 100000, China
| | - Cong Li
- The First Medical Center of Chinese, PLA General Hospital, Beijing, 100000, China
| | - Penghui Yang
- The First Medical Center of Chinese, PLA General Hospital, Beijing, 100000, China.
| | - Zhenpeng Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.
| | - Benqiang Rao
- Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Cancer Foods for Special Medical Purpose (FSMP) for State Market Regulation, Beijing, 100038, China.
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