|
1
|
Giovarelli M, Mocciaro E, Carnovale C, Cervia D, Perrotta C, Clementi E. Immunosenescence in skeletal muscle: The role-play in cancer cachexia chessboard. Semin Cancer Biol 2025; 111:48-59. [PMID: 40020976 DOI: 10.1016/j.semcancer.2025.02.012] [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: 12/23/2024] [Revised: 02/20/2025] [Accepted: 02/21/2025] [Indexed: 03/03/2025]
Abstract
With the increase in life expectancy, age-related conditions and diseases have become a widespread and relevant social burden. Among these, immunosenescence and cancer cachexia play a significant often intertwined role. Immunosenescence is the progressive aging decline of both the innate and adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, and malignancies. Cancer cachexia affects elderly patients with cancer causing severe weight loss, muscle wasting, inflammation, and reduced response to therapies. Whereas the connections between immunosenescence and cancer cachexia have been raising attention, the molecular mechanisms still need to be completely elucidated. This review aims at providing the current knowledge about the interplay between immunosenescence, skeletal muscle, and cancer cachexia, analyzing the molecular pathways known so far to be involved. Finally, we highlight potential therapeutic strategies suited for elderly population aimed to block immunosenescence and to preserve muscle mass in cachexia, also presenting the analysis of the current state-of-the-art of related clinical trials.
Collapse
Affiliation(s)
- Matteo Giovarelli
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy.
| | - Emanuele Mocciaro
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy
| | - Carla Carnovale
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy
| | - Davide Cervia
- Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, Viterbo 01100, Italy
| | - Cristiana Perrotta
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy
| | - Emilio Clementi
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy.
| |
Collapse
|
|
2
|
Wu Y, Zhao J, Zhao S, Li J, Luo J, Wang Y. PFKFB4 promotes endometrial cancer by regulating glycolysis through SRC‑3 phosphorylation. Oncol Rep 2025; 53:53. [PMID: 40116122 PMCID: PMC11948970 DOI: 10.3892/or.2025.8886] [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: 12/04/2024] [Accepted: 03/06/2025] [Indexed: 03/23/2025] Open
Abstract
The present study aimed to investigate the role of 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 4 (PFKFB4) in endometrial cancer cells and to explore its potential molecular mechanisms. PFKFB4 expression in endometrial cancer tissues was detected by immunohistochemistry. Cell Counting Kit‑8, Transwell assays and flow cytometry were used to detect cell proliferation, invasion and apoptosis in endometrial cancer cells after PFKFB4 knockdown. An enzyme‑linked immunosorbent assay was used to detect the glucose and lactic acid contents. Western blotting was performed to detect the levels of glycolysis‑related enzymes, steroid receptor coactivator‑3 (SRC‑3), and phosphorylated SRC‑3. In vivo experiments were performed to investigate the tumorigenic potential of PFKFB4. PFKFB4 expression was upregulated in endometrial cancer tissues compared with that in normal controls, and its upregulation was positively correlated with the depth of myometrial invasion, lymph node metastasis, surgical pathological stage and vascular invasion. PFKFB4 knockdown significantly inhibited proliferation and invasion, increased apoptosis, and decreased oxygen consumption and lactic acid production in endometrial cancer cells. PFKFB4 knockdown decreased SRC‑3 phosphorylation. After simultaneous PFKFB4 knockdown and SRC‑3 overexpression in cancer cells, oxygen consumption, lactic acid production, and glycolysis‑related protein expression were increased compared with those in control cells. PFKFB4 knockdown inhibited tumor proliferation, apoptosis and the expression of Ki‑67. PFKFB4 may regulate glycolysis in endometrial cancer cells by targeting SRC‑3, thus promoting endometrial cancer progression.
Collapse
Affiliation(s)
- Yaling Wu
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
- Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
- Department of Gynecology and Obstetrics, People's Hospital of Shanxi, Taiyuan, Shanxi 030012, P.R. China
| | - Jianzhen Zhao
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
- Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
| | - Shuangshuang Zhao
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
- Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
| | - Jianfang Li
- Department of Gynecology and Obstetrics, People's Hospital of Shanxi, Taiyuan, Shanxi 030012, P.R. China
| | - Jin Luo
- Department of Pathology, People's Hospital of Shanxi, Taiyuan, Shanxi 030012, P.R. China
| | - Yingmei Wang
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
- Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
| |
Collapse
|
|
3
|
Lou K, Cheng X. Prognostic value of the neutrophil‑to‑lymphocyte ratio in renal cell carcinoma: A systematic review and meta‑analysis. Oncol Lett 2025; 29:231. [PMID: 40114748 PMCID: PMC11925002 DOI: 10.3892/ol.2025.14977] [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: 11/01/2024] [Accepted: 02/11/2025] [Indexed: 03/22/2025] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) not only indicates the inflammatory response within the tumor microenvironment but may also correlate with tumor biological behavior (such as aggressiveness). The present study aimed to systematically review and conduct a meta-analysis on the impact of the NLR on the prognosis of patients with renal cell carcinoma (RCC). To this aim, a comprehensive search of multiple relevant databases, including PubMed, Embase and the Cochrane Library, was conducted to identify literature related to NLR and RCC prognosis. Following rigorous literature screening and quality assessment, a systematic quantitative analysis was ultimately performed on several studies that met the inclusion criteria. The results indicated a significant association between elevated NLR levels and poor prognosis in patients with RCC, suggesting that high NLR levels may serve as an independent predictor of unfavorable outcomes. Therefore, the present study provides important evidence for clinical decision-making, further demonstrating that NLR can serve as an independent prognostic indicator for patients with RCC, aiding healthcare professionals in making more precise judgments in patient management and treatment strategy formulation.
Collapse
Affiliation(s)
- Kecheng Lou
- Department of Urology, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Xin Cheng
- Department of Urology, Ganzhou Cancer Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
| |
Collapse
|
|
4
|
Rathi K, Kumar S, Bhushan B, Rawat V, Kumar A, Bhardwaj A, Prakash A, Verma VP. Zirconium oxide nano-catalyzed bis(indolyl)methanes: A sustainable route to anticancer therapies. Bioorg Med Chem Lett 2025; 120:130132. [PMID: 39923904 DOI: 10.1016/j.bmcl.2025.130132] [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: 12/02/2024] [Revised: 01/13/2025] [Accepted: 02/06/2025] [Indexed: 02/11/2025]
Abstract
Bis(indolyl)methanes (BIMs) are a class of compounds known for their diverse biological activities, including potential anticancer properties. Modern synthetic chemistry techniques are examined in this work to develop and manufacture novel anticancer medications with increased effectiveness and fewer side effects. The cytotoxic efficacy of a moderate and very effective method for creating pharmacologically active BIMs 3a-j using ZrO2 nanoparticles as a catalyst was assessed against the MCF-7 breast cancer cell line. Remarkably, compounds 3a and 3b exhibited exceptional potency, with IC50 values of 0.17 and 0.13 μM, respectively, surpassing the activity of standard anticancer agents sorafenib (IC50: 1.23 μM). Another compound 3j demonstrated moderate inhibition effect with an IC50 value of 8.6 μM. These results highlight the potential of BIMs as promising anticancer agents and warrant further investigation into their mechanism of action and therapeutic applications.
Collapse
Affiliation(s)
- Komal Rathi
- Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India
| | - Suryakant Kumar
- Department of Bioscience and Biotechnology, Banasthali University, Tonk 304022, Rajasthan, India
| | - Bidya Bhushan
- Department of Pharmaceutical Chemistry, Mallige College of Pharmacy, RGUHS University, Bangalore 560041, Karnataka, India
| | - Varun Rawat
- Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Ashwani Kumar
- Department of Education in Science and Mathematics (DESM), Regional Institute of Education, Bhubaneshwar 751022, India
| | - Aman Bhardwaj
- Department of Education in Science and Mathematics (DESM), Regional Institute of Education, Bhubaneshwar 751022, India
| | - Anand Prakash
- Department of Bioscience and Biotechnology, Banasthali University, Tonk 304022, Rajasthan, India
| | - Ved Prakash Verma
- Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India; Department of Education in Science and Mathematics (DESM), Regional Institute of Education, Bhubaneshwar 751022, India.
| |
Collapse
|
|
5
|
Ding Q, Guo A, Zhang S, Gu C, Wang X, Li X, Gu M, Kim JS. Phototheranostics: An advanced approach for precise diagnosis and treatment of gynecological inflammation and tumors. Biomaterials 2025; 316:123012. [PMID: 39693783 DOI: 10.1016/j.biomaterials.2024.123012] [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: 07/09/2024] [Revised: 11/24/2024] [Accepted: 12/13/2024] [Indexed: 12/20/2024]
Abstract
Gynecological inflammations have a significant impact on the daily lives of women. Meanwhile, cancers such as ovarian, cervical, and endometrial cancers pose severe threats to their physical and mental well-being. While current options such as conventional pharmacotherapy, surgical interventions, and recent advancements in immunotherapy and targeted therapy provide viable solutions, they possess limitations in effectively addressing the intricacies associated with gynecological diseases. These complexities include post-surgical complications, early cancer detection, and drug resistance. The management of these challenges, however, requires the implementation of innovative treatment modalities. Phototheranostics has emerged as a promising approach to effectively address these challenges. It not only treats inflammation and tumors efficiently but also aids in disease imaging and diagnosis. The distinguishing features of phototheranostics lie in their non-invasive nature, minimal risk of drug resistance, and precise targeting capabilities through the use of photosensitizers or photothermal agents. These distinctive features underscore its potential to revolutionize early diagnosis and treatment of gynecological conditions. This review aims to summarize the application of phototheranostics in managing gynecological inflammation and tumors while highlighting its significant potential for early disease detection and treatment.
Collapse
Affiliation(s)
- Qihang Ding
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China; Department of Chemistry, Korea University, Seoul, 02841, South Korea; Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China
| | - Aoxue Guo
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China
| | - Shuai Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road Nangang District, Harbin, Heilongjiang Province, 150040, China
| | - Chuanqi Gu
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China
| | - Xinyu Wang
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China
| | - Xin Li
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China.
| | - Meijia Gu
- Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430072, China; Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China; Hubei International Science and Technology Cooperation Base for Research and Clinical techniques for Brain Glioma Diagnosis and Treatment, Wuhan, 430071, China
| | - Jong Seung Kim
- Department of Chemistry, Korea University, Seoul, 02841, South Korea.
| |
Collapse
|
|
6
|
Hasan R, Zhao Z, Li Y, Liu Y, Zhang Y, Cheng K. Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis. J Control Release 2025; 380:269-282. [PMID: 39889882 PMCID: PMC11908897 DOI: 10.1016/j.jconrel.2025.01.072] [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: 10/16/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 02/03/2025]
Abstract
Pancreatic cancer is one of the most aggressive malignancies with poor prognostic outcomes, necessitating the exploration of novel biomarkers and therapeutic targets for early detection and effective treatment. Small extracellular vesicles (sEVs) secreted by cells, have gained considerable attention in cancer research due to their role in intercellular communication and their potential as non-invasive biomarkers. This review focuses on the role of sEVs in the progression of pancreatic cancer and their application as biomarkers. We delve into the biogenesis, composition, and functional implications of sEVs in pancreatic tumor biology, emphasizing their involvement in processes such as tumor growth, metastasis, immune modulation, and chemotherapy resistance. In addition, we discuss the challenges in isolating and characterizing sEVs. The review also highlights recent advances in the utilization of sEV-derived biomarkers for the early diagnosis, prognosis, and monitoring of pancreatic cancer. By synthesizing the latest findings, we aim to underscore the significance of sEVs in pancreatic cancer and their potential to revolutionize patient management through improved diagnostics and targeted therapies.
Collapse
Affiliation(s)
- Reaid Hasan
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Zhen Zhao
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Yuanke Li
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Yanli Liu
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Yuanyuan Zhang
- Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA
| | - Kun Cheng
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
| |
Collapse
|
|
7
|
Yang Y, Liu L, Cui H, Cheng B, Peng W, Wang R, Wang J, Chen W, Cao M, Li Y, Liang J, Chen S, Bai S, Zhao Y. Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer. Carcinogenesis 2025; 46:bgae072. [PMID: 39526455 DOI: 10.1093/carcin/bgae072] [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: 07/16/2024] [Revised: 10/20/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024] Open
Abstract
New-onset diabetes (NOD) is a common condition among patients with pancreatic adenocarcinoma (PAAD) and is related to poor clinical outcomes. The potential impact of NOD on PAAD progression and the tumor microenvironment remains unclear. Here, we revealed that NOD in PAAD was associated with metabolic disorders. Utilizing three machine-learning algorithms, an NOD-related metabolism signature (NRMS) was established. Validated in three independent cohorts, patients with a high NRMS score exhibited a worse prognosis. Moreover, an elevated NRMS score was associated with an immunosuppressive microenvironment and diminished response to immunotherapy. Further experiments demonstrated that ALDH3A1, a key feature in NRMS, was significantly upregulated in tissues from PAAD patients with NOD and played a crucial role in tumor progression and immune suppression. Our findings highlight the potential of NRMS as a prognostic biomarker and an indicator of immunotherapy response for patients with PAAD.
Collapse
Affiliation(s)
- Yilei Yang
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
| | - Luyao Liu
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Haochen Cui
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Bin Cheng
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Wang Peng
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Ronghua Wang
- Department of Surgery, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburg, PA 15213M, United States
| | - Jinlin Wang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
| | - Wei Chen
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Mengdie Cao
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Yanling Li
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Jingwen Liang
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Shiru Chen
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Shuya Bai
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Yuchong Zhao
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| |
Collapse
|
|
8
|
Sanghvi G, Roopashree R, Kashyap A, Sabarivani A, Ray S, Bhakuni PN. KIFC1 in cancer: Understanding its expression, regulation, and therapeutic potential. Exp Cell Res 2025; 447:114510. [PMID: 40058447 DOI: 10.1016/j.yexcr.2025.114510] [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: 01/10/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/25/2025]
Abstract
Kinesins are a family of motor proteins essential for intracellular transport and cellular dynamics, with kinesin family member C1 (KIFC1) emerging as a key regulator of cancer progression. Recent studies highlight KIFC1's crucial role in mitotic spindle assembly, chromosome segregation, and cell migration-processes frequently dysregulated in cancer. Its involvement in promoting malignant cell proliferation and metastasis underscores its significance in tumor biology. In various cancer types, aberrant KIFC1 expression correlates with poor prognosis and aggressive phenotypes, suggesting its potential as a biomarker for disease severity. Mechanistically, KIFC1 influences signaling pathways linked to cell cycle regulation and programmed cell death, reinforcing its role in oncogenesis. Given its pivotal function in cancer cell dynamics, KIFC1 represents a promising therapeutic target. Strategies aimed at modulating its activity, including small molecules or RNA interference, could disrupt cancer cell viability and proliferation. The current review article highlights KIFC1's importance in cancer biology, advocating for further investigation into its mechanisms and the development of KIFC1-targeted therapies to enhance treatment efficacy and improve patient outcomes across various malignancies.
Collapse
Affiliation(s)
- Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, 360003, Gujarat, India
| | - R Roopashree
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Aditya Kashyap
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
| | - A Sabarivani
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Subhashree Ray
- Department of Biochemistry, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India
| | - Pushpa Negi Bhakuni
- Department of Allied Science, Graphic Era Hill University, Bhimtal, Uttarakhand, 248002, India; Graphic Era Deemed to be University, Dehradun, Uttarakhand, India.
| |
Collapse
|
|
9
|
Devasahayam Arokia Balaya R, Sen P, Grant CW, Zenka R, Sappani M, Lakshmanan J, Athreya AP, Kandasamy RK, Pandey A, Byeon SK. An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum. J Gastroenterol 2025; 60:496-511. [PMID: 39666045 DOI: 10.1007/s00535-024-02197-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 12/01/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC. METHODS We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC. RESULTS We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites. CONCLUSIONS Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.
Collapse
Affiliation(s)
| | - Partho Sen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Caroline W Grant
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA
| | - Roman Zenka
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Marimuthu Sappani
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, 632002, India
| | - Jeyaseelan Lakshmanan
- College of Medicine, Mohammad Bin Rashid University of Medicine and Health Sciences, Dubai, 505055, UAE
| | - Arjun P Athreya
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA
- Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Richard K Kandasamy
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
- Manipal Academy of Higher Education, Manipal, Karnataka, 5761904, India
| | - Akhilesh Pandey
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
- Manipal Academy of Higher Education, Manipal, Karnataka, 5761904, India.
- Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
| | - Seul Kee Byeon
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
| |
Collapse
|
|
10
|
Zambrano-O YT, Mejía-Garcia A, Morales PD, Tsao HM, Rey-Vargas L, Montero-Ovalle W, Huertas-Caro CA, Sanabria-Salas MC, Riaño-Moreno J, Rodriguez JL, Orozco CA, Lopez-Kleine L, Jordan IK, Serrano-G SJ. Inference of genetic ancestry from a multi-gene cancer panel in Colombian women with cancer. Breast Cancer Res Treat 2025; 210:251-259. [PMID: 39643752 PMCID: PMC11930861 DOI: 10.1007/s10549-024-07557-7] [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: 10/15/2024] [Accepted: 11/06/2024] [Indexed: 12/09/2024]
Abstract
INTRODUCTION Cancer health disparities among racial and ethnic populations significantly burden health systems due to unequal access to early detection, treatment, and healthcare resources. These disparities lead to worse outcomes and increased costs from delayed diagnoses, advanced treatments, and prolonged care. Genetic differences can also influence cancer susceptibility and treatment response, thus analyzing genetic ancestry is essential for uncovering genetic factors that may contribute to these disparities. Utilizing data from clinical multigene cancer panels to infer genetic ancestry offers a valuable approach to understand population structure and the impact of individual ancestries in development of complex diseases. AIM To evaluate the accuracy of global ancestry inference using genetic markers from the TruSight™ Hereditary Cancer Panel, which was used to investigate hereditary cancer syndromes in a cohort of 116 female cancer patients at the Colombian National Cancer Institute. Additionally, to compare these results with genetic ancestry estimations from traditional genome-wide markers. RESULTS Our results demonstrate a strong correlation between global genetic ancestry inferred with markers captured from TruSightTM panel (4785 markers) and Whole Genome Sequencing (WGS, 8 million markers in admixed populations. The correlation values were 0.96 (p < 0.0001) for the Native American and European ancestry components, and 0.99 (p < 0.0001) for the African ancestry fraction. Genetic ancestry mean proportions in the Colombian cohort were 45.7%, 46.2%, and 8.11% for the European, the Native American, and the African components, respectively. CONCLUSION This study demonstrates the accuracy of ancestry inference from clinical panel data offering a promising approach for understanding cancer health disparities in admixed populations.
Collapse
Affiliation(s)
- Yina T Zambrano-O
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia.
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia.
| | | | - P Daniela Morales
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Hsuan Megan Tsao
- Department of Human Genetics, McGill University, Montreal, Canada
| | - Laura Rey-Vargas
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
| | - Wendy Montero-Ovalle
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Carlos A Huertas-Caro
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
| | - M C Sanabria-Salas
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2C1, Canada
| | - Julián Riaño-Moreno
- Departamento de Patología y Oncología Molecular, Instituto Nacional de Cancerología, Bogotá, Colombia
- Faculty of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia
| | - Juliana L Rodriguez
- Grupo de Investigación Clínica y Epidemiológica, Instituto Nacional de Cancerología, Bogotá, Colombia
- Departamento de Ginecología y Obstetricia, Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Carlos A Orozco
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Grupo de Apoyo y Seguimiento Para La Investigación, Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Liliana Lopez-Kleine
- Grupo de Investigación en Bioinformática y Biología de Sistemas, Departamento de Estadística, Universidad Nacional de Colombia, Bogotá, Colombia
| | - I King Jordan
- Bioinformatics Department, Georgia Institute of Technology, Atlanta, USA
| | - Silvia J Serrano-G
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia.
| |
Collapse
|
|
11
|
Guo W, Liu H, Zhong M, Qi Q, Li Y. circ_0006528 promotes nonsmall cell lung cancer progression by sponging miR-892a and regulating NRAS expression. Anticancer Drugs 2025; 36:261-270. [PMID: 37982201 DOI: 10.1097/cad.0000000000001439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
Micro-RNAs play essential roles in developing and progressing nonsmall cell lung cancer (NSCLC) and drug resistance. Nevertheless, the functions and mechanisms are partly explored. Therefore, the present study analyzes the effect of circ_0006528 and the mechanism of regulation of NSCLC cell progression by sponging miR-892a to regulate neuroblastoma rat sarcoma viral oncogene (NRAS) expression. Initially, circ_0006528 is identified using divergent primers-based PCR and RNase R exonuclease treatments. After administration of the designed circ_0006528-specific siRNA, the RT-qPCR analysis is used to determine the interference efficiency of siRNA. At the same time, cell growth, invasion, and migration are assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Transwell, and scratch assays in the NSCLC cell lines [secretory pathway Ca2+-ATPase isoform 1 (SPCA-1) and A549] in vitro, respectively. Further, miR-892a inhibitor is added to the cells for functional recovery assay. Finally, the xenograft mouse model is constructed to explore the effect of circ_0006528 on tumor growth in vivo . The RT-qPCR analysis in 66 pairs of NSCLC cancer and noncancerous tissues revealed that circ_0006528 is highly expressed in NSCLC patient tissues. The RNase R experiments revealed that HSA_circ_0006528 is unaffected by RNase R exonuclease. MTT assay showed that knockdown of hsa_circ_0006528 by siRNA significantly decreased cell proliferation and viability in A549 and SPCA-1 cells. The luciferase reporter assay showed direct binding of hsa_circ_0006528 to miR-892a, and miR-892a targets binding NRAS. In addition, the miR-892a inhibitor terminated the hsa_circ_0006528 siRNA, triggering inhibition of proliferation, invasion, and migration of NSCLC cells. In summary, the study revealed that the knockout of hsa_circ_0006528 downregulation of NRAS expression by sponging miR-892a inhibited NSCLC cell growth and invasion.
Collapse
Affiliation(s)
- Weixi Guo
- Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University
| | - Hongming Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University
| | - Ming Zhong
- Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University
| | - Qinghua Qi
- Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University
| | - Yibin Li
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, The First Affiliated Hospital of Xiamen University, Xiamen, China
| |
Collapse
|
|
12
|
Huang T, Ekenga CC. Associations between social capital and screening mammography among older U.S. women. Prev Med Rep 2025; 52:103026. [PMID: 40160970 PMCID: PMC11951863 DOI: 10.1016/j.pmedr.2025.103026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 04/02/2025] Open
Abstract
Objective To investigate the association between county-level social capital and screening mammography rates among older women in the United States. Methods This cross-sectional ecological study included 2765 U.S. counties, using 2018 county-level screening mammography rates among female Medicare enrollees aged 67-69 as the outcome. Social capital data were obtained from the 2018 Social Capital Project, including indices for Family Unity, Institutional Health, Collective Efficacy, and Community Health. Multivariable log-binomial regression analyses were conducted to estimate adjusted prevalence ratios (aPRs) and confidence intervals for "high" mammography rates (top 10 % nationally), controlling for county-level demographic and healthcare covariates. Stratified analyses examined associations among metropolitan and nonmetropolitan counties. Results Mammography screening rates ranged from 17 % to 64 %, with a mean of 41 %. Strong positive associations were observed between social capital and mammography rates (Q4 vs. Q1: aPR = 2.29, 95 % CI: 1.20-4.36), particularly for the dimensions of Community Health (Q4 vs. Q1: aPR = 1.99, 95 % CI = 1.25-3.17) and Institutional Health (Q4 vs. Q1: aPR = 4.31, 95 % CI = 2.40-7.75). These associations were strongest among nonmetropolitan counties. No significant associations were found for Family Unity or Collective Efficacy. Conclusions County-level social capital, specifically community and institutional health, is significantly associated with higher mammography screening rates, particularly in non-metropolitan areas. These findings suggest that enhancing public trust and community engagement may improve screening behaviors. Future research should explore the role of social capital at multiple levels and its influence on various cancer screening behaviors.
Collapse
Affiliation(s)
- Tracy Huang
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Christine C. Ekenga
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| |
Collapse
|
|
13
|
Wei T, Lei M, Jiang H, Cai J, Peng Q, Wei Y, Chen Z, Geng J, Ren F, Chen C, Yang Z, Zhang Y, Chu Z, Jia H, Yin Z, Zhao T. Attenuated Salmonella carrying IL-21 overexpression plasmid enhances radiotherapy efficacy in a preclinical model of melanoma. Int Immunopharmacol 2025; 154:114590. [PMID: 40174337 DOI: 10.1016/j.intimp.2025.114590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 04/04/2025]
Abstract
Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8+ T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8+ T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.
Collapse
Affiliation(s)
- Tian Wei
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan 453000, PR China
| | - Mengyu Lei
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Hanyu Jiang
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Jingjing Cai
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Qi Peng
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Yuqing Wei
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Zhihan Chen
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Jiaxin Geng
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Feng Ren
- Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan 453000, PR China
| | - Caili Chen
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Zishan Yang
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China
| | - Yongxi Zhang
- Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, PR China
| | - Zhili Chu
- Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan 453000, PR China
| | - Huijie Jia
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China.
| | - Zhinan Yin
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan 453000, PR China.
| | - Tiesuo Zhao
- Department of Immunology, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang 453000, Henan, PR China; Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453000, Henan, PR China.
| |
Collapse
|
|
14
|
Zhou M, Peng C, Zhang Q, Tong Y. Hypoxic Cancer Cells-Derived Exosomes Strengthen the Development of Cancer Stem Cell-Like Properties Through Delivering LINC00665 in Thyroid Cancer Cells. Cell Biol Int 2025; 49:384-396. [PMID: 39831459 DOI: 10.1002/cbin.12274] [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: 07/22/2024] [Revised: 12/16/2024] [Accepted: 01/04/2025] [Indexed: 01/22/2025]
Abstract
Hypoxia is a common phenomenon for solid tumors due to a lack of effective vascular system, and has been deemed as an important factor that drives the progression of thyroid cancer (TC) via altering the characteristics of tumor cells. The present study suggested that hypoxic TC cells enhanced cancer stem cell properties and progression of TC by delivering long intergenic non-protein coding RNA 665 (LINC00665)-containing exosomes. Specifically, TPC1 cells were exposed to normoxic or hypoxic environment, and it was found that hypoxic TPC1 cells-secreted exosomes (H-exo) were enriched with LINC00665, compared to normoxic TPC1 cells-derived exosomes (N-exo). In addition, by establishing the in vitro exosomes-TC cells coculture system, we found that in contrast to N-exo, H-exo apparently promoted cell proliferation, epithelial mesenchymal transition (EMT) and cancer stem cell properties via delivering LINC00665. This was supported by the in vivo results that H-exo transferred LINC00665 to promote tumorigenesis and the expression of EMT and stemness-associated markers in xenograft tumor-bearing mice models. Further mechanical experiments validated that LINC00665 combined with EPHB4 mRNA to sustain its stability to enhance cancer aggressiveness of TC. Altogether, our findings verified that hypoxic TC cells-secreted exosomes regulated the LINC00665/EPHB4 axis to enhance cancer stem cell properties of TC, providing novel signatures for TC diagnosis and therapy.
Collapse
Affiliation(s)
- Ming Zhou
- Department of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Chengcheng Peng
- Department of Breast and Thyroid Surgery, Huanggang Central Hospital, Huangzhou District, Huanggang, China
| | - Qiong Zhang
- Department of Dermatology, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Yanchu Tong
- Department of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| |
Collapse
|
|
15
|
Lee D, Lee C, Han K, Goo T, Kim B, Han Y, Kwon W, Lee S, Jang JY, Park T. Machine learning models for pancreatic cancer diagnosis based on microbiome markers from serum extracellular vesicles. Sci Rep 2025; 15:10995. [PMID: 40164714 PMCID: PMC11958759 DOI: 10.1038/s41598-025-94183-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: 12/16/2024] [Accepted: 03/12/2025] [Indexed: 04/02/2025] Open
Abstract
Pancreatic cancer (PC) is a fatal disease with an extremely low 5-year survival rate, mainly because of its poor detection rate in early stages. Given emerging evidence of the relationship between microbiota composition and diseases, this study aims to identify microbiome markers linked to the diagnosis of pancreatic cancer. We utilized extracellular vesicles (EVs) data obtained from blood samples of 38 pancreatic cancer patients and 51 health controls. Least absolute shrinkage and selection operator (LASSO) and stepwise method were used to obtain some candidate markers in genus and phylum levels. These markers were used to develop various machine learning models including logistic regression (LR), random forest (RF), support vector machine (SVM), and Deep Neural Network (DNN) methods. In phylum level, DNN performed best with three markers (Verrucomicrobia, Actinobacteria and Proteobacteria) selected by stepwise method with the test AUC 0.959. In genus level, DNN using 11 markers selected by LASSO (Ruminococcaceae UCG-013, Ruminiclostridium, Propionibacterium, Lachnospiraceae NK4A136 group, Corynebacterium.1, Akkermansia, Mucispirillum, Pseudomonas, Diaphorobacter, Clostridium sensu stricto 1 and Turicibacter) outperformed others with 0.961 test AUCs. These results highlight the potential of microbiome markers and prediction models in clinical studies of PC diagnosis.
Collapse
Affiliation(s)
- Doeun Lee
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea
| | - Chanhee Lee
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea
| | - Kyulhee Han
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea
| | - Taewan Goo
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea
| | - Boram Kim
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Seungyeoun Lee
- Department of Applied Mathematics, Sejong University, Seoul, 03080, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.
| | - Taesung Park
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea.
- Department of Statistics, Seoul National University, Seoul, 08826, Korea.
| |
Collapse
|
|
16
|
Khajetash B, Hajianfar G, Talebi A, Mahdavi SR, Ghavidel B, Kalati FA, Molana SH, Lei Y, Tavakoli M. Impact of harmonization on predicting complications in head and neck cancer after radiotherapy using MRI radiomics and machine learning techniques. Med Phys 2025. [PMID: 40162683 DOI: 10.1002/mp.17793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 01/21/2025] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Variations in medical images specific to individual scanners restrict the use of radiomics in both clinical practice and research. To create reproducible and generalizable radiomics-based models for outcome prediction and assessment, data harmonization is essential. PURPOSE This study aims to investigate the impact of harmonization in performance of machine learning-based radiomics model toward the prediction of radiotherapy-induced toxicity (early and late sticky saliva and xerostomia) in head and neck cancer (HNC) patients after radiation therapy usingT 1 $T_1$ andT 2 $T_2$ -weighted magnetic resonance (MR) images. METHODS A total of 85 HNC patients who underwent radiotherapy was studied. Radiomic features were extracted fromT 1 $T_1$ andT 2 $T_2$ -weighted MR images with standardized protocols. Data harmonization was performed using ComBat algorithm to reduce inter-center variability. Besides imaging features, both dosimetric and demographic features were extracted and used in our model. Recursive feature elimination was employed as feature selection method to identify the most important variables. Ten classification algorithms, including eXtreme Gradient Boosting (XGBoost), multilayer perceptron (MLP), support vector machines (SVM), random forest (RF), k-nearest neighbor (KNN), Naive Bayes (NB), logistic regression (LR), and decision tree (DT), boosted generalized linear model (GLMB), and stack learning (SL) were utilized and compared to develop predictive models. This evaluation comparisons were performed before and after harmonization to demonstrate its significance. RESULTS Our results indicate that harmonization consistently enhances predictive performance across various complications and imaging modalities. In early and late sticky saliva prediction usingT 1 $T_1$ -weighted images, the SVM and RF models achieved an impressive area under the curve (AUC) of 0.88 ± $\pm$ 0.09 and 0.97 ± $\pm$ 0.05 with harmonization versus 0.42 ± $\pm$ 0.12 and 0.83 ± $\pm$ 0.08 without harmonization, respectively. Similarly, in early and late xerostomia prediction, the model attained an AUC of 0.79 ± $\pm$ 0.15 and 0.61 ± $\pm$ 0.14 with harmonization and 0.55 ± $\pm$ 0.17 and 0.46 ± $\pm$ 0.14 without harmonization. CONCLUSION Our study highlights the importance of harmonization techniques in improving the performance of predictive models utilizing magnetic resonance imaging radiomics features. While harmonization consistently enhanced performance for sticky saliva and early xerostomia usingT 1 $T_1$ -weighted features, the prediction of early and late xerostomia usingT 2 $T_2$ -weighted features remains challenging. These findings try to develop accurate and reliable predictive models in medical imaging, that contribute to improve patient care and treatment outcomes.
Collapse
Affiliation(s)
- Benyamin Khajetash
- Department of Medical physics, Iran University of Medical Sciences, Tehran, Iran
| | - Ghasem Hajianfar
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran
| | - Amin Talebi
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seid Rabi Mahdavi
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Beth Ghavidel
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | | | - Seyed Hadi Molana
- Department of Radiation Oncology, Roshana Cancer Institute, Tehran, Iran
| | - Yang Lei
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Meysam Tavakoli
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| |
Collapse
|
|
17
|
Yang Y, Zhao TT, Liu ZH. Network pharmacology and molecular docking analysis of mechanism of action of Weifuchun in treatment of colorectal cancer. Shijie Huaren Xiaohua Zazhi 2025; 33:225-234. [DOI: 10.11569/wcjd.v33.i3.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/19/2025] [Accepted: 03/25/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND This study employed network pharmacology and molecular docking to explore the mechanism of Weifuchun capsules in treating colorectal cancer. We hypothesized that active components in Weifuchun (chrysosplenol D, oleanolic acid, and nobiletin) regulate core targets like SRC, AKT1, and TP53, affecting pathways such as lipid metabolism and neuroactive ligand-receptor interactions, thereby exerting anti-tumor effects.
AIM To analyze the mechanisms of Weifuchun capsules in the treatment of colorectal cancer.
METHODS To identify the key components and their potential targets of Weifuchun capsule, the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction database were utilized, along with the existing academic literature. Targets related to colorectal cancer were collected from databases including GeneCards, DisGeNET, DrugBank, TTD, and PharmGKB. The component-target-disease interaction network was constructed using Cytoscape software. The study also involved the establishment and analysis of protein-protein interaction networks (PPI), as well as Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses conducted via Metascape. Molecular docking of active components and targets was performed using Pymol 2.4.0, and the results were visualized.
RESULTS A total of 38 active components and 647 potential targets were identified, with 545 shared targets between the active components and the disease. PPI networks were constructed at primary, secondary, and tertiary levels, as well as for core targets, identifying key targets such as SRC, AKT1, and TP53. GO functional enrichment analysis covered multiple categories, while KEGG pathway enrichment analysis primarily involved lipid metabolism and atherosclerosis, as well as neuroactive ligand-receptor interactions. Molecular docking results demonstrated high binding affinity between the active components and the core targets.
CONCLUSION Weifuchun capsules exert potential therapeutic effects on colorectal cancer through active components such as chrysosplenol D, oleanolic acid, nobiletin, and ursolic acid. These components target key proteins including SRC, AKT1, and TP53, and modulate processes such as lipid metabolism and atherosclerosis, as well as neuroactive ligand-receptor interactions.
Collapse
Affiliation(s)
- Yi Yang
- Department of Gastroenterology, Deqing County People's Hospital, Huzhou 313299, Zhejiang Province, China
| | - Ting-Ting Zhao
- Department of Gastroenterology, Deqing County People's Hospital, Huzhou 313299, Zhejiang Province, China
| | - Zhi-Hong Liu
- Department of Gastroenterology, Deqing County People's Hospital, Huzhou 313299, Zhejiang Province, China
| |
Collapse
|
|
18
|
Alipour M, Moghanibashi M, Naeimi S, Mohamadynejad P. LINC00894, YEATS2-AS1, and SUGP2 genes as novel biomarkers for N0 status of lung adenocarcinoma. Sci Rep 2025; 15:10628. [PMID: 40148389 PMCID: PMC11950442 DOI: 10.1038/s41598-024-84640-5] [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: 03/07/2024] [Accepted: 12/25/2024] [Indexed: 03/29/2025] Open
Abstract
Research on genes affecting tumors without lymph node metastasis is limited, hence this study employed both bioinformatic and experimental approaches to identify specific genes associated with lung cancer adenocarcinoma (LUAD) before lymph node metastasis occurs. Expression profiles of mRNAs and lncRNAs and LUAD clinical data were downloaded from the Cancer Genome Atlas (TCGA) using R software to identify differentially expressed genes (DEGs) associated with N0 and N + status. TargetScan, miRTarBase, and miRDB databases were used to identify interactions between miRNAs and mRNAs. The DIANA database and lncBase tool were used to find the association between lncRNA and miRNA. After selecting some genes, the expression of candidate genes was confirmed by real-time RT-PCR technique. Following the knockdown LINC00894 gene using the shRNA technique, its effect on invasion, migration, and apoptosis in the calu-3 cell line was investigated. In total, we found 321 specific DEGs not only in N0 vs. normal but also in N0 Vs. N + in LUAD, most of which were lncRNA and we identified a ceRNA network containing nine lncRNAs with the highest degree of connectivity. Among them, in addition to bioinformatic analyses, LINC00894 and YEATS2-AS1 were significantly increased in tumor tissues compared to normal tissues (P = 0.0001). also, SUGP2 that was shared in both lncRNA-related ceRNA subnetworks was significantly upregulated (P = 0.0001). Additionally, following the knockdown of LINC00894 in Calu-3 cell line, a significant decrease in migration and invasion was observed, but early apoptosis was significantly increased in the shLINC00894(48 h) group (P = 0.007). The findings of the present study show that lncRNAs play an important role in the N0 status of LUAD. Moreover, LINC00894, YEATS2-AS1, and SUGP2 can act as biomarkers in patients with N0 LUAD.
Collapse
Affiliation(s)
- Marzyeh Alipour
- Department of Genetics, Colleague of Science, Kazerun Branch, Islamic Azad University, P.O. Code 7319866451, Kazerun, Iran
| | - Mehdi Moghanibashi
- Department of Genetics, Faculty of Basic Sciences, Kazerun Branch, Islamic Azad University, P.O. Code 7319866451, Kazerun, Iran.
| | - Sirous Naeimi
- Department of Biology, Zand Institute of Higher Education, Shiraz, Iran.
| | - Parisa Mohamadynejad
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| |
Collapse
|
|
19
|
Jia Y, Yan L, Fan C, Sun H, Zhou X, Shi Z. Progress of immune senescence in multiple myeloma treatment resistance. Discov Oncol 2025; 16:402. [PMID: 40138127 PMCID: PMC11947401 DOI: 10.1007/s12672-025-02136-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 03/12/2025] [Indexed: 03/29/2025] Open
Abstract
Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment, to provide new research ideas for the in-depth study of the mechanism of immune senescence and the search for new immunotherapeutic targets to overcome the phenomenon of drug resistance in the immunotherapy of MM patients.
Collapse
Affiliation(s)
- Yanan Jia
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Lixiang Yan
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Chenyang Fan
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Hui Sun
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Xinli Zhou
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Zhexin Shi
- Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China.
| |
Collapse
|
|
20
|
Zhao X, Lai H, Li G, Qin Y, Chen R, Labrie M, Stommel JM, Mills GB, Ma D, Gao Q, Fang Y. Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer. Oncogene 2025:10.1038/s41388-025-03351-x. [PMID: 40133477 DOI: 10.1038/s41388-025-03351-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/14/2025] [Accepted: 03/11/2025] [Indexed: 03/27/2025]
Abstract
Rictor/mTORC2 has been demonstrated to have important roles in cancer development and progression in a number of solid and hematologic malignancies. However, little is known about the role of Rictor/mTORC2 in ovarian cancer pathophysiology. Herein, using conditional Rictor knockout mice, we were able to demonstrate that Rictor deletion disrupted glutathione metabolism through AKT/Nrf2 signaling pathway and induced intracellular oxidative stress during the malignant transformation of Kras/Pten-mutant ovarian surface epithelial cells. Elevated reactive oxygen species and activated FOXO3a in Rictor-deleted cells strikingly shifts the functional interaction of β-catenin from TCF to FOXO3a, which strongly inhibits classical Wnt/β-catenin signaling. Our findings emphasize a pivotal role for Rictor in orchestrating crosstalk between the PI3K/AKT and Wnt/β-catenin signaling in the development of ovarian cancer. Illustration of Rictor/mTORC2 in promoting tumor onset by regulating glutathione metabolism and mediating oncogenic signaling.
Collapse
Affiliation(s)
- Xuejiao Zhao
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huiling Lai
- Department of Gynecology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Guannan Li
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Qin
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ruqi Chen
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Marilyne Labrie
- Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Jayne M Stommel
- Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
| | - Gordon B Mills
- Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
- Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA
| | - Ding Ma
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Qinglei Gao
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yong Fang
- National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| |
Collapse
|
|
21
|
Vasilogianni AM, Achour B, Al-Majdoub ZM, Peters SA, Barber J, Rostami-Hodjegan A. The quest to define cancer-specific systems parameters for personalized dosing in oncology. Expert Opin Drug Metab Toxicol 2025:1-17. [PMID: 40042382 DOI: 10.1080/17425255.2025.2476560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 02/11/2025] [Accepted: 03/03/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Clinical trials in oncology initially recruit heterogeneous populations, without catering for all types of variability. The target cohort is often not representative, leading to variability in pharmacokinetics (PK). To address enrollment challenges in clinical trials, physiologically based pharmacokinetic models (PBPK) models can be used as a guide in the absence of large clinical studies. These models require patient-specific systems data relevant to the handling of drugs in the body for each type of cancer, which are scarce. AREAS COVERED This review explores system parameters affecting PK in cancer and highlights important gaps in data. Changes in drug-metabolizing enzymes (DMEs) and transporters have not been fully investigated in cancer. Their impaired expression can significantly affect capacity for drug elimination. Finally, the use of PBPK modeling for precision dosing in oncology is highlighted. Google Scholar and PubMed were mainly used for literature search, without date restriction. EXPERT OPINION Model-informed precision dosing is useful for dosing in sub-groups of cancer patients, which might not have been included in clinical trials. Systems parameters are not fully characterized in cancer cohorts, which are required in PBPK models. Generation of such data and application of cancer models in clinical practice should be encouraged.
Collapse
Affiliation(s)
- Areti-Maria Vasilogianni
- Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK
| | - Brahim Achour
- Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Zubida M Al-Majdoub
- Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK
| | - Sheila Annie Peters
- Translational Quantitative Pharmacology, BioPharma, R&D Global Early Development, Merck KGaA, Darmstadt, Germany
- Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co., Ingelheim am Rhein, Germany
| | - Jill Barber
- Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK
| | - Amin Rostami-Hodjegan
- Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK
- Certara Predictive Technologies (CPT), Simcyp Division, Sheffield, UK
| |
Collapse
|
|
22
|
Chan SPY, Rashid MBMA, Lim JJ, Goh JJN, Wong WY, Hooi L, Ismail NN, Luo B, Chen BJ, Noor NFBM, Phua BXM, Villanueva A, Sam XX, Ong CAJ, Chia CS, Abidin SZ, Yong MH, Kumar K, Ooi LL, Tay TKY, Woo XY, Toh TB, Yang VS, Chow EKH. Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments. NPJ Precis Oncol 2025; 9:83. [PMID: 40121334 PMCID: PMC11929909 DOI: 10.1038/s41698-025-00851-7] [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: 08/20/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
Soft tissue sarcomas (STS) are rare, heterogeneous tumors with poor survival outcomes, primarily due to reliance on cytotoxic chemotherapy and lack of targeted therapies. Given the uniquely individualized nature of STS, we hypothesized that the ex vivo drug sensitivity platform, quadratic phenotypic optimization platform (QPOP), can predict treatment response and enhance combination therapy design for STS. Using QPOP, we screened 45 primary STS patient samples, and showed improved or concordant patient outcomes that are attributable to QPOP predictions. From a panel of approved and investigational agents, QPOP identified AZD5153 (BET inhibitor) and pazopanib (multi-kinase blocker) as the most effective combination with superior efficacy compared to standard regimens. Validation in a panel of established patient lines and in vivo models supported its synergistic interaction, accompanied by repressed oncogenic MYC and related pathways. These findings provide preliminary clinical evidence for QPOP to predict STS treatment outcomes and guide the development of novel therapeutic strategies for STS patients.
Collapse
Affiliation(s)
- Sharon Pei Yi Chan
- Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01 Centre for Translational Medicine, Singapore, 117599, Republic of Singapore
| | | | - Jhin Jieh Lim
- KYAN Technologies, 1 Research Link, #05-45, Singapore, 117604, Republic of Singapore
| | - Janice Jia Ni Goh
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Republic of Singapore
| | - Wai Yee Wong
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Republic of Singapore
| | - Lissa Hooi
- Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01 Centre for Translational Medicine, Singapore, 117599, Republic of Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, #12-01 Centre for Translational Medicine, Singapore, 117599, Republic of Singapore
| | - Nur Nadiah Ismail
- The Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, #05-COR, Singapore, 117456, Republic of Singapore
| | - Baiwen Luo
- The N1 Institute for Health, National University of Singapore, 28 Medical Drive, Singapore, 117456, Republic of Singapore
| | - Benjamin Jieming Chen
- Translational Precision Oncology Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore
| | - Nur Fazlin Bte Mohamed Noor
- Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Republic of Singapore
| | - Brandon Xuan Ming Phua
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Republic of Singapore
| | - Andre Villanueva
- Translational Precision Oncology Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore
| | - Xin Xiu Sam
- Department of Anatomical Pathology, Singapore General Hospital, College Road, Level 7 Academia, Singapore, 169856, Republic of Singapore
| | - Chin-Ann Johnny Ong
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Republic of Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Republic of Singapore
- Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Republic of Singapore
- Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
| | - Suraya Zainul Abidin
- Department of Orthopaedic Surgery, Singapore General Hospital, 10 Hospital Boulevard, Tower Level 4 SingHealth Tower, Singapore, 168582, Republic of Singapore
| | - Ming-Hui Yong
- Department of Neurology, National Neuroscience Institute (Singapore General Hospital Campus), Outram Rd, Singapore, 169608, Republic of Singapore
| | - Krishan Kumar
- Department of Neurosurgery, National Neuroscience Institute (Singapore General Hospital Campus), Outram Rd, Singapore, 169608, Republic of Singapore
| | - London Lucien Ooi
- Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore
- Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169608, Republic of Singapore
| | - Timothy Kwang Yong Tay
- Department of Anatomical Pathology, Singapore General Hospital, College Road, Level 7 Academia, Singapore, 169856, Republic of Singapore
| | - Xing Yi Woo
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Republic of Singapore
| | - Tan Boon Toh
- The Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, #05-COR, Singapore, 117456, Republic of Singapore.
- The N1 Institute for Health, National University of Singapore, 28 Medical Drive, Singapore, 117456, Republic of Singapore.
| | - Valerie Shiwen Yang
- Translational Precision Oncology Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
- Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Republic of Singapore.
- Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Republic of Singapore.
| | - Edward Kai-Hua Chow
- Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01 Centre for Translational Medicine, Singapore, 117599, Republic of Singapore.
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, #12-01 Centre for Translational Medicine, Singapore, 117599, Republic of Singapore.
- The N1 Institute for Health, National University of Singapore, 28 Medical Drive, Singapore, 117456, Republic of Singapore.
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore, 117600, Republic of Singapore.
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, 4 Engineering Drive 3, #04-08, Singapore, 117583, Republic of Singapore.
| |
Collapse
|
|
23
|
Hameed H, Afzal M, Khan MA, Javaid L, Shahzad M, Abrar K. Unraveling the role of withanolides as key modulators in breast cancer mitigation. Mol Biol Rep 2025; 52:331. [PMID: 40117002 DOI: 10.1007/s11033-025-10442-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/14/2025] [Indexed: 03/23/2025]
Abstract
Addressing the elaborated landscape of therapeutics of global health concern i.e. breast cancer, this comprehensive review explores the promising effects of withanolides, bioactive compounds derived from Withania somnifera, for the treatment of breast cancer. In the breast, random mutations can accumulate over time, eventually transforming it into a tumor cell as certain receptors may be overexpressed by BC cells, which elicits downstream signaling and causes the production of genes involved in angiogenesis, survival, growth and migration, and other critical cell cycle practices. Merging insights from recent studies, our exploration delves into the molecular mechanisms that highlight withanolide's potential in the intervention of breast cancer. The study of apoptotic pathways unveils the withanolide's distinctive as well as pro-apoptotic effects, hinting at its effect as a potent modulator of the progression of breast cancer cells. Beyond its independent potential, there is a discussion on its distinctive perspective over the other therapies. Inweaving together these threads of evidence illuminates channels for future research. This review acts as a guide for researchers and clinicians negotiating the challenges of incorporating withanolides into the changing landscape for the treatment of breast cancer by balancing optimism with perceptive interpretation.
Collapse
Affiliation(s)
- Huma Hameed
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan.
| | - Maham Afzal
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Mahtab Ahmad Khan
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Laiba Javaid
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Maria Shahzad
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Kamran Abrar
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| |
Collapse
|
|
24
|
Liu D, Liu X. Polyphenols as microRNA modulator in endometrial cancer: implications for apoptosis induction. Mol Genet Genomics 2025; 300:34. [PMID: 40117011 DOI: 10.1007/s00438-025-02238-6] [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: 11/14/2024] [Accepted: 02/24/2025] [Indexed: 03/23/2025]
Abstract
Endometrial cancer (EC) accounts for approximately 417,336 cases globally, making it the sixth most commonly diagnosed cancer among women. Such factors have led to hesitancy in utilizing aggressive treatments or enrolling older patients in clinical trials. Recent molecular studies have identified unique expression patterns of microRNAs (miRNAs) in endometrial cancer tissue compared to healthy endometrial tissue, highlighting their role in tumorigenesis through pathways that support proliferation, invasion, and metastasis. Polyphenols, bioactive compounds found in a variety of plant-based foods such as fruits, vegetables, tea, and soybeans, have demonstrated diverse physiological benefits, including antioxidant, anti-inflammatory, and anticancer properties. These compounds influence cellular pathways critical to cancer progression, including apoptosis, immune modulation, and inflammation reduction. Emerging evidence suggests that polyphenols may exert anticancer effects in part by modulating miRNAs involved in carcinogenesis. Specifically, compounds like curcumin, quercetin, resveratrol, and genistein have shown potential in targeting oncogenic and tumor-suppressive miRNAs, thereby impacting cellular mechanisms linked to cancer progression. Therefore, this review examines the role of polyphenols in regulating miRNAs within the context of endometrial cancer, focusing on their potential to modulate apoptosis and other cancer hallmarks. By elucidating these mechanisms, this paper aims to contribute to the understanding of polyphenol-mediated miRNA regulation as a promising therapeutic avenue in endometrial cancer management.
Collapse
Affiliation(s)
- Dan Liu
- Affiliated Hospital of Jinggangshan University, Ji'an, 343000, Jiangxi, China
| | - Xiaohua Liu
- Affiliated Hospital of Jinggangshan University, Ji'an, 343000, Jiangxi, China.
| |
Collapse
|
|
25
|
Li X, Cho YS, Han Y, Zhou M, Liu Y, Yang Y, Zhuo S, Jiang J. The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2. J Biol Chem 2025:108430. [PMID: 40120683 DOI: 10.1016/j.jbc.2025.108430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 03/07/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025] Open
Abstract
The prevailing view in the cancer field is that Hippo signaling pathway functions as a tumor suppressor pathway by blocking the oncogenic potential of the pathway effectors Yes1 associated transcriptional regulator (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ). However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCC). We find that, in additional to inhibiting hypoxia-inducible factor 2α (HIF2α), a major oncogenic driver in Von Hippel-Lindau (VHL)-/- ccRCC, YAP also blocks nuclear factor κB (NF-κB) signaling in ccRCC to inhibit cancer cell growth under conditions where HIF2α is dispensable. Mechanistically, YAP inhibits the expression of Zinc fingers and homeoboxes 2 (ZHX2), a VHL substrate and critical co-factor of NF-κB in ccRCC. Furthermore, YAP competes with ZHX2 for binding to the NF-κB subunit p65. Consequently, elevated nuclear YAP blocks the cooperativity between ZHX2 and the NF-κB subunit p65, leading to diminished NF-κB target gene expression. Pharmacological inhibition of Hippo kinase blocked NF-κB transcriptional program and suppressed ccRCC cancer cell growth, which can be rescued by overexpression of ZHX2 or p65. Our study uncovers a crosstalk between the Hippo and NF-κB/ZHX2 pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hippo pathway may provide a therapeutical opportunity for ccRCC treatment.
Collapse
Affiliation(s)
- Xu Li
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
| | - Yong Suk Cho
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Math and Sciences, Tarrant County College-NE Campus, 828 W Harwood Rd, Hurst, TX 76054, USA
| | - Yuhong Han
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Mengmeng Zhou
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Yuchen Liu
- Department of Developmental Biology, Harvard School of Dental Medicine; Harvard Stem Cell Institute; Dana-Farber/Harvard Cancer Center, 188 Longwood Ave. Boston, MA 02215, USA
| | - Yingzi Yang
- Department of Developmental Biology, Harvard School of Dental Medicine; Harvard Stem Cell Institute; Dana-Farber/Harvard Cancer Center, 188 Longwood Ave. Boston, MA 02215, USA
| | - Shu Zhuo
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Jin Jiang
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
| |
Collapse
|
|
26
|
Guyon L, Ladaycia A, Bosio A, Lemaire L, Franconi F, Lelièvre B, Lautram N, Pigeon P, Jaouen G, Passirani C, Lepeltier E. Self-assemblies of cell-penetrating peptides and ferrocifens: design and biological evaluation of an innovative platform for lung cancer treatment. NANOSCALE 2025. [PMID: 40105246 DOI: 10.1039/d5nr00643k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Abstract
Chemotherapy, currently used for lung cancer treatment, often consists in a combination of drugs with a moderate efficacy and severe side effects. A major drawback of the classical inorganic drugs used is their hydrophobicity, leading to a very low blood availability and weak efficacy. To overcome this constraint, a nanoplatform was set up in order to vectorize a ferrocifen drug, an organometallic tamoxifen derivative known for its really potent in vitro activity, but as well for its poor water solubility. Two different ferrocifens were tested: P54 and P819. The covalent conjugation of a cell-penetrating peptide (CPP) to the ferrocifen was performed, leading to an amphiphilic prodrug, potentially able to self-assemble. The CPPs used in this study are polyarginines and RLW. Moreover, in order to bring stealth and mucopenetration properties, polyethylene glycol (PEG) was incorporated into the nanostructure. The co-nanoprecipitation of CPP-ferrocifen and PEG-ferrocifen was investigated to achieve self-assemblies. A comparison of the biological activities of different suspensions was performed in vitro on a healthy cell line and on two different lung cancer cell lines. The biological activity of P54 was increased by a factor of 9 with the Arg9-P54 suspension by increasing the cell internalization. Moreover, the P54-based-self-assemblies were chosen to test their in vivo activity on mice bearing lung tumors. The results showed that the intratracheal nebulization of Arg9-P54/PEG-P54 or Arg9-P54 suspensions slowed up significantly the evolution of lung cancer in mice: the suspension with PEG brought an additional comfort to the animal during the administration.
Collapse
Affiliation(s)
- Léna Guyon
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
| | | | - Agnese Bosio
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
| | - Laurent Lemaire
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
- Univ Angers, Univ Rennes, INRAE, Inserm, CNRS, PRISM, Biogenouest, F-49000 Angers, Rennes, France
| | - Florence Franconi
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
- Univ Angers, Univ Rennes, INRAE, Inserm, CNRS, PRISM, Biogenouest, F-49000 Angers, Rennes, France
| | - Bénédicte Lelièvre
- Centre régional de pharmacovigilance, Laboratoire de pharmacologie-toxicologie, CHU Angers, 4 rue Larrey, F-49100 Angers, France
| | - Nolwenn Lautram
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
| | - Pascal Pigeon
- CNRS, Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, 4 Place Jussieu, 75005 Paris, France
- PSL, Chimie ParisTech, 11 Rue Pierre et Marie Curie, 75005 Paris, France
| | - Gérard Jaouen
- CNRS, Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, 4 Place Jussieu, 75005 Paris, France
- PSL, Chimie ParisTech, 11 Rue Pierre et Marie Curie, 75005 Paris, France
| | | | - Elise Lepeltier
- Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
- Institut Universitaire de France (IUF), France
| |
Collapse
|
|
27
|
Peacock O, Brown K, Waters PS, Jenkins JT, Warrier SK, Heriot AG, Glyn T, Frizelle FA, Solomon MJ, Bednarski BK. Operative Strategies for Beyond Total Mesorectal Excision Surgery for Rectal Cancer. Ann Surg Oncol 2025:10.1245/s10434-025-17151-w. [PMID: 40102284 DOI: 10.1245/s10434-025-17151-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 02/24/2025] [Indexed: 03/20/2025]
Affiliation(s)
- Oliver Peacock
- Department of Colorectal Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
| | - Kilian Brown
- Department of Colorectal Surgery, Surgical Outcomes Research Centre and Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, NSW, Australia
| | | | - John T Jenkins
- Department of Colorectal Surgery, St Mark's Hospital, London, UK
| | - Satish K Warrier
- Department of Colorectal Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Alexander G Heriot
- Department of Colorectal Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Tamara Glyn
- Department of Colorectal Surgery, Christchurch Hospital, Christchurch, New Zealand
| | - Frank A Frizelle
- Department of Colorectal Surgery, Christchurch Hospital, Christchurch, New Zealand
| | - Michael J Solomon
- Department of Colorectal Surgery, Surgical Outcomes Research Centre and Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, NSW, Australia
| | - Brian K Bednarski
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
28
|
Ibrahim S, Yousef EH, El-Dessouki AM, Raslan NA, Alzokaky AA. Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03938-x. [PMID: 40100373 DOI: 10.1007/s00210-025-03938-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 02/16/2025] [Indexed: 03/20/2025]
Abstract
Although gemcitabine is a primary chemotherapy for pancreatic cancer, its effectiveness is limited by chemoresistance and nephrotoxicity, posing significant clinical challenges. Therefore, the development of novel therapeutic approaches to prevent pancreatic malignancy remains crucial. This study aimed to investigate the potential of melatonin in enhancing gemcitabine's anticancer efficacy while mitigating its nephrotoxic effects through modulation of the Keap1/p62 pathway. A pancreatic cancer xenograft model was established in rats, which received either gemcitabine (50 mg/kg, I.P.), melatonin (50 mg/kg, I.P.), or their combination three times per week for 2 weeks. Our findings demonstrate that melatonin potentiates gemcitabine's cancer-suppressing effects via modulation of the Kelch-like-ECH associated protein-1 (Keap1)/p62 pathway, resulting in reduced fibrosis, oxidative stress, and inflammatory markers. Additionally, melatonin significantly mitigated gemcitabine-induced nephrotoxicity. These results suggest that melatonin may serve as an adjuvant therapy in pancreatic cancer treatment, enhancing chemotherapy efficacy while reducing its adverse effects.
Collapse
Affiliation(s)
- Samar Ibrahim
- Pharmacy Practice and Clinical Pharmacy Department, Faculty of Pharmacy, Galala University, Ataka, Egypt
| | - Eman H Yousef
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ahmed M El-Dessouki
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, Giza, 12566, Egypt
| | - Nahed A Raslan
- Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11651, Egypt
- Department of Clinical Pharmacy Program, College of Health Sciences and Nursing, Al-Rayan Colleges, AL-Madina AL-Munawarah, Saudi Arabia
| | - Amany A Alzokaky
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt.
- Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11651, Egypt.
| |
Collapse
|
|
29
|
Imaoka K, Shimomura M, Okuda H, Yano T, Shimizu W, Yoshimitsu M, Ikeda S, Nakahara M, Kohyama M, Kobayashi H, Shimizu Y, Kochi M, Akabane S, Sumitani D, Mukai S, Takakura Y, Ishizaki Y, Kodama S, Fujimori M, Ishikawa S, Adachi T, Hattori M, Ohdan H. Intraoperative Blood Loss Predicts Local Recurrence After Curative Resection for Stage I-III Colorectal Cancer. World J Surg 2025. [PMID: 40088136 DOI: 10.1002/wjs.12533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 01/12/2025] [Accepted: 02/16/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND To identify the predictors of local recurrence and distant metastasis after radical surgery for stage I-III colorectal cancer. MATERIALS AND METHODS Patient and tumor characteristics, clinicopathological stages, perioperative factors, and postoperative outcomes, including local and distant recurrence, of patients who underwent primary colorectal resection were evaluated in this multicenter retrospective analysis. Univariate and multivariate regression analyses were performed to identify the risk factors for local and distant recurrences, with a focus on the intraoperative blood loss (IBL) ratio [IBL (mL)/total blood volume (mL)] and postoperative complications. RESULTS The risk factors for local and distant recurrence pattern differed. The predictors for local recurrence included perioperative factors, such as the IBL ratio and anastomotic leakage, as well as tumor factors, including pT4, rectal cancer, and poorly differentiated histology, in the multivariate analysis. On the other hand, the predictors for distant recurrence included perioperative factors, such as Clavien-Dindo score ≥ 3, and absence of adjuvant chemotherapy as well as tumor factors including pT stage, pN stage, and rectal cancer. The area under the receiver operating characteristic curve (AUC) for local recurrence in the IBL ratio was 0.745, which was higher than the AUCs for other recurrence patterns in the IBL ratio. Patients with a higher IBL ratio had a higher rate of early local recurrence within 2 years postoperatively (Wilcoxon test and p = 0.028). CONCLUSION Reducing IBL and formulating perioperative strategies to prevent anastomotic leakage may help decrease the local recurrence rate and improve prognosis.
Collapse
Affiliation(s)
- Kouki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Okuda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Shimizu
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Masanori Yoshimitsu
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Satoshi Ikeda
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | | | - Mohei Kohyama
- Department of Surgery, Hiroshima General Hospital, Hatsukaichi, Japan
| | | | - Yosuke Shimizu
- Department of Surgery, Kure Medical Center/Chugoku Cancer Center, Institute for Clinical Research, Kure, Japan
| | - Masatoshi Kochi
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | - Shintaro Akabane
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | | | | | - Yuji Takakura
- Department of Surgery, Chuden Hospital, Hiroshima, Japan
| | - Yasuyo Ishizaki
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, Otake, Japan
| | - Shinya Kodama
- Department of Surgery, Yoshida General Hospital, Akitakata, Japan
| | - Masahiko Fujimori
- Department of Surgery, Kure City Medical Association Hospital, Kure, Japan
| | - Sho Ishikawa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomohiro Adachi
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Minoru Hattori
- Advanced Medical Skills Training Center, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
30
|
Szuber N, Guglielmelli P, Gangat N. Topics of Interest in Women With Myeloproliferative Neoplasms. Am J Hematol 2025. [PMID: 40084464 DOI: 10.1002/ajh.27665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 02/19/2025] [Accepted: 02/27/2025] [Indexed: 03/16/2025]
Abstract
OVERVIEW Sex and gender have emerged as central modifiers of disease biology, phenotype, and clinical outcomes in myeloproliferative neoplasms (MPNs). This review will uniquely highlight issues affecting women with MPN and articulate their relevant determinants. EPIDEMIOLOGY AND DIAGNOSIS A higher overall prevalence of MPN has been established in women. The incidence of essential thrombocythemia (ET) predominates, while, conversely, polycythemia vera (PV) and myelofibrosis (MF) are seen in lower frequencies as compared to men. Diagnostic criteria are dictated by sex-driven physiological variances in hemoglobin and hematocrit levels in PV, mandating separate diagnostic thresholds, respectively: > 16.0 g/dL and > 48% in women vs. > 16.5 and > 49% in men. GENETIC FRAMEWORK AND PHENOTYPE Women with MPN harbor fewer acquired somatic mutations and a lower frequency of high-risk mutations than their male counterparts; lower JAK2V617F driver variant allele frequency and attenuated allele burden kinetics have also been reported. Women with MPN are younger at diagnosis than men and, contingent on subtype, display more indolent disease features. Importantly, validated symptom burden assessments consistently disclose higher scores in women vs. men. THROMBOSIS AND OUTCOMES Women with MPN have a unique thrombotic diathesis with respect to men, more frequently involving the splanchnic venous system in those ultimately diagnosed with PV. Outcomes data depict female sex as a variable associated with more favorable clinical trajectories, including lower rates of MF/leukemic transformation and secondary cancers, as well as improved overall survival rates vis-à-vis men. LIFE-CYCLE WINDOWS, PREGNANCY, AND POSTPARTUM Potential challenges at each significant life stage will be addressed: puberty, preconception and fertility, and perimenopause; these include issues surrounding oral contraceptives and hormone use. Prospective studies suggest overall favorable maternal and fetal outcomes with pregnancy in women with MPN. Full details on risks and reported outcomes will be discussed, as well as a risk-adapted approach to management informed by obstetric and thrombosis history. Recommendations include aspirin 81 mg daily in all patients and cytoreduction with interferon-α in those with antecedent thrombosis, as well as in low-risk cases with higher-risk features (e.g., poorly controlled hematocrit and recurrent fetal loss). Antepartum anticoagulation with low molecular weight heparin (LMWH) is recommended in cases with previous venous thromboembolism. CONCLUSIONS AND FUTURE DIRECTIONS This review highlights female sex and gender as critical drivers of MPN incidence, presentation, and natural history. It further outlines the impact and management of MPN as related to unique female reproductive phases. A sex-informed lens will be required in order to recalibrate current prognostic tools, a requisite to refining patient counselling and clinical decision-making in line with precision medicine. Moreover, while several mechanisms underpinning sex-defined discrepancies have been defined, these mandate further prospective study. Finally, sex and gender-based differences must be weighted in clinical trials with systematized procedures to correct participation imbalances in favor of sex and gender equity.
Collapse
Affiliation(s)
- Natasha Szuber
- Division of Hematology, Department of Internal Medicine, Université de Montréal, Montréal, Quebec, Canada
| | - Paola Guglielmelli
- Department of Experimental and Clinical Medicine, CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy
| | - Naseema Gangat
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
31
|
Hosseini SA, Hajianfar G, Hall B, Servaes S, Rosa-Neto P, Ghafarian P, Zaidi H, Ay MR. Robust vs. Non-robust radiomic features: the quest for optimal machine learning models using phantom and clinical studies. Cancer Imaging 2025; 25:33. [PMID: 40075547 PMCID: PMC11905451 DOI: 10.1186/s40644-025-00857-1] [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: 01/02/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025] Open
Abstract
PURPOSE This study aimed to select robust features against lung motion in a phantom study and use them as input to feature selection algorithms and machine learning classifiers in a clinical study to predict the lymphovascular invasion (LVI) of non-small cell lung cancer (NSCLC). The results of robust features were also compared with conventional techniques without considering the robustness of radiomic features. METHODS An in-house developed lung phantom was developed with two 22mm lesion sizes based on a clinical study. A specific motor was built to simulate motion in two orthogonal directions. Lesions of both clinical and phantom studies were segmented using a Fuzzy C-means-based segmentation algorithm. After inducing motion and extracting 105 radiomic features in 4 feature sets, including shape, first-, second-, and higher-order statistics features from each region of interest (ROI) of the phantom image, statistical analyses were performed to select robust features against motion. Subsequently, these robust features and a total of 105 radiomic features were extracted from 126 clinical data. Various feature selection (FS) and multiple machine learning (ML) classifiers were implemented to predict the LVI of NSCLC, followed by comparing the results of predicting LVI using robust features with common conventional techniques not considering the robustness of radiomic features. RESULTS Our results demonstrated that selecting robust features as input to FS algorithms and ML classifiers surges the sensitivity, which has a gentle negative effect on the accuracy and the area under the curve (AUC) of predictions compared with commonly used methods in 12 of 15 outcomes. The top performance of the LVI prediction was achieved by the NB classifier and RFE FS without considering the robustness of radiomic features with 95% area under the curve of AUC, 67% accuracy, and 100% sensitivity. Moreover, the top performance of the LVI prediction using robust features belonged to the NB classifier and Boruta feature selection with 92% AUC, 86% accuracy, and 100% sensitivity. CONCLUSION Robustness over various influential factors is critical and should be considered in a radiomic study. Selecting robust features is a solution to overcome the low reproducibility of radiomic features. Although setting robust features against motion in a phantom study has a minor negative impact on the accuracy and AUC of LVI prediction, it boosts the sensitivity of prediction to a large extent.
Collapse
Affiliation(s)
- Seyyed Ali Hosseini
- Translational Neuroimaging Laboratory, Douglas Hospital, The McGill University Research Centre for Studies in Aging, McGill University, Montréal, Québec, Canada
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montréal, Québec, Canada
| | - Ghasem Hajianfar
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211, Geneva 4, Switzerland
| | - Brandon Hall
- Translational Neuroimaging Laboratory, Douglas Hospital, The McGill University Research Centre for Studies in Aging, McGill University, Montréal, Québec, Canada
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montréal, Québec, Canada
| | - Stijn Servaes
- Translational Neuroimaging Laboratory, Douglas Hospital, The McGill University Research Centre for Studies in Aging, McGill University, Montréal, Québec, Canada
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montréal, Québec, Canada
| | - Pedro Rosa-Neto
- Translational Neuroimaging Laboratory, Douglas Hospital, The McGill University Research Centre for Studies in Aging, McGill University, Montréal, Québec, Canada
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montréal, Québec, Canada
| | - Pardis Ghafarian
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- PET/CT and cyclotron center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Habib Zaidi
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211, Geneva 4, Switzerland.
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, Netherlands.
- Department of Nuclear Medicine, University of Southern Denmark, DK-500, Odense, Denmark.
- University Research and Innovation Center, Óbuda University, Budapest, Hungary.
| | - Mohammad Reza Ay
- Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Molecular and Cellular Imaging (RCMCI), Advanced Medical Technologies and Equipment Institute (AMTEI), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| |
Collapse
|
|
32
|
Imaoka K, Shimomura M, Okuda H, Yano T, Shimizu W, Yoshimitsu M, Ikeda S, Nakahara M, Kohyama M, Kobayashi H, Shimizu Y, Kochi M, Sumitani D, Mukai S, Takakura Y, Ishizaki Y, Kodama S, Fujimori M, Ishikawa S, Adachi T, Ohdan H. Multivisceral Resection Serves as a Key Indicator of Recurrence in Locally Advanced Colorectal Cancers with Pathological T3 Tumors. J Gastrointest Surg 2025:102015. [PMID: 40081790 DOI: 10.1016/j.gassur.2025.102015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/23/2025] [Accepted: 03/07/2025] [Indexed: 03/16/2025]
Abstract
PURPOSE This study aimed to elucidate the clinical outcomes of patients with pathological T3 and T4 tumors undergoing radical resection with multivisceral resection (MVR), and to assess the prognostic significance of MVR in locally advanced colorectal cancers (CRC) in pT3-4 tumors. METHODS This multicenter retrospective analysis evaluated the characteristics, clinicopathological stages, perioperative factors, and clinical outcomes of patients who underwent primary colorectal resection. Patients were divided into four groups: those with a pT3 tumor who did not undergo MVR (pT3-MVR; n=1108), those with a pT3 tumor who did undergo MVR (pT3+MVR; n=56), those with a pT4 tumor who did not undergo MVR (pT4-MVR; n=306), and those with a pT4 tumor who did undergo MVR (pT4+MVR; n=123). Univariate and multivariate regression analyses were performed to identify risk factors for recurrence. RESULTS The pT3+MVR group exhibited a higher 5-year recurrence rate than the pT3-MVR group, with recurrence rates similar to those of the pT4-MVR or pT4+MVR groups (pT3-MVR, 17.4%; pT3+MVR, 31.6%; pT4-MVR, 33.4%; and pT4+MVR, 35.1%). Multivariate analysis identified MVR as an independent risk factor for recurrence, particularly peritoneal dissemination, in pT3 tumors, whereas MVR had less impact on recurrence in pT4 tumors. CONCLUSION pT3 tumors requiring MVR had a high recurrence rate comparable to that of pT4 tumors. The surgeon's clinical assessment of a potential T4 tumors requiring MVR at the time of surgery was an important prognostic indicator in advanced CRC.
Collapse
Affiliation(s)
- Kouki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan.
| | - Hiroshi Okuda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan
| | - Wataru Shimizu
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima Japan
| | - Masanori Yoshimitsu
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima Japan
| | - Satoshi Ikeda
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima Japan
| | | | - Mohei Kohyama
- Department of Surgery, Hiroshima General Hospital, Hatsukaichi, Japan
| | | | - Yosuke Shimizu
- Department of Surgery, Kure Medical Center/ Chugoku Cancer Center, Institute for Clinical Research, Kure, Japan
| | - Masatoshi Kochi
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | | | | | - Yuji Takakura
- Department of Surgery, Chuden Hospital, Hiroshima, Japan
| | - Yasuyo Ishizaki
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, Otake, Japan
| | - Shinya Kodama
- Department of Surgery, Yoshida General Hospital, Akitakata, Japan
| | - Masahiko Fujimori
- Department of Surgery, Kure City Medical Association Hospital, Kure, Japan
| | - Sho Ishikawa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan
| | - Tomohiro Adachi
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima Japan
| |
Collapse
|
|
33
|
Martin D, Billy M, Becce F, Maier D, Schneider M, Dromain C, Hahnloser D, Hübner M, Grass F. Impact of Preoperative CT-Measured Sarcopenia on Clinical, Pathological, and Oncological Outcomes After Elective Rectal Cancer Surgery. Diagnostics (Basel) 2025; 15:629. [PMID: 40075876 PMCID: PMC11899399 DOI: 10.3390/diagnostics15050629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 02/24/2025] [Accepted: 03/03/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Patients with rectal cancer may be exposed to a loss of muscle strength and quality. This study aimed to assess the role of preoperative CT-based sarcopenia on postoperative clinical, pathological, and oncological outcomes after rectal cancer surgery. Methods: This retrospective monocentric study included patients who underwent elective oncologic resection for rectal adenocarcinoma between 01/2014 and 03/2022. The skeletal muscle index (SMI) was measured using CT at the third lumbar vertebral level, and sarcopenia was defined based on pre-established sex-specific cut-offs. Patients with sarcopenia were compared to those without sarcopenia in terms of outcomes. A Cox proportional hazard regression analysis was used to determine the independent prognostic factors of disease-free survival (DFS) and overall survival (OS). Results: A total of 208 patients were included, and 123 (59%) had preoperative sarcopenia. Patients with sarcopenia were significantly older (66 vs. 61 years, p = 0.003), had lower BMI (24 vs. 28 kg/m2, p < 0.001), and were mainly men (76 vs. 48%, p < 0.001). There was no difference in overall and major complication rates between the sarcopenia and non-sarcopenia group (43 vs. 37%, p = 0.389, and 17 vs. 17%, p = 1.000, respectively). Preoperative and postoperative features related to rectal surgery were comparable. The only predictive factor impacting OS was R1/R2 resection (HR 4.915, 95% CI, 1.141-11.282, p < 0.001), while sarcopenia (HR 2.013, 95% CI 0.972-4.173, p = 0.050) and T3/T4 status (HR 2.108, 95% CI 1.058-4.203, p = 0.034) were independently associated with DFS. Conclusions: A majority of patients undergoing rectal cancer surgery had preoperative CT-based sarcopenia. In this cohort, sarcopenia had no impact on postoperative morbidity and OS but was independently associated with DFS.
Collapse
Affiliation(s)
- David Martin
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| | - Mathilde Billy
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| | - Fabio Becce
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (F.B.); (D.M.); (C.D.)
| | - Damien Maier
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (F.B.); (D.M.); (C.D.)
| | - Michael Schneider
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| | - Clarisse Dromain
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (F.B.); (D.M.); (C.D.)
| | - Dieter Hahnloser
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| | - Fabian Grass
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland; (D.M.); (M.B.); (M.S.); (D.H.); (M.H.)
| |
Collapse
|
|
34
|
Song Z, Tao Y, You J. The potential applications of peptide-loading complex in cancer treatment. Front Immunol 2025; 16:1526137. [PMID: 40098955 PMCID: PMC11911339 DOI: 10.3389/fimmu.2025.1526137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/05/2025] [Indexed: 03/19/2025] Open
Abstract
Immunotherapy for cancer has made significant strides in the last several years. The prognosis for cancer patients has significantly improved as a result, particularly in hematological diseases. However, it was discovered that translating these achievements to solid tumors proved challenging. The peptide-loading complex (PLC), a temporary multisubunit membrane assembly in the endoplasmic reticulum (ER), is crucial for initiating a hierarchical immune response. Chaperones calreticulin and tapasin make up the PLC, unique to class I glycoproteins, thiooxido-reductase ERp57, and a transporter associated with antigen processing. The loading and editing of major histocompatibility complex class I (MHC-I) molecules with peptide translocation into the ER are synchronized by the PLC. One of the immune escape strategies revealed for tumors so far is changes in the expression of MHC molecules. This is because MHC antigens are crucial in presenting antigens to T-lymphocytes and controlling NK cell activity. Furthermore, decreased MHC-I expression has been linked to malignancies resistant to T-cell-based cancer immunotherapies (adoptive transfer of antitumor CD8 T-cells or checkpoint inhibition). The PLC is essential for T-cell priming, differentiation, and tumor growth control because it can bind to a wide range of MHC-I allomorphs. In this review, we have looked into PLC's function and effects in all forms of cancer to improve cancer therapy techniques.
Collapse
Affiliation(s)
- Zhidu Song
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
| | - Ying Tao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jiaxin You
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
35
|
Ma X, Ma Z, Qi X, Zhang X, Liu X, Liu X, Zhang A, Yue G, Li G, Li J. Identification of a novel Src inhibitor K882 derived from quinazoline-based stilbenes with anti-NSCLC effect. Bioorg Chem 2025; 156:108185. [PMID: 39947800 DOI: 10.1016/j.bioorg.2025.108185] [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: 11/19/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 03/28/2025]
Abstract
The growing concern about drug resistance to KRAS G12C inhibitors emphasizes the urgent need for effective therapies targeting NSCLC with KRAS G12C mutation. In this research, a series of quinazoline-based stilbene derivatives were designed, synthesized and assayed for cytotoxic activities against human KRAS G12C mutant NSCLC NCI-H358 cells. Among them, K882 (4e) exhibited remarkable inhibitory activities on tumor cell proliferation, migration and invasion, as well as tumor organoids growth in vitro. Subsequent study revealed that K882 arrested NCI-H358 cell cycle in G2/M phase and induced apoptosis. In a NCI-H358 xenograft tumor model, K882 showed potential tumor inhibition effect in vivo without causing obvious organ damage. Mechanistically, K882 bound to ATP binding hydrophobic pocket of Src and inhibited its downstream signaling pathways including Jak/Stat, PI3K/Akt and RAS/MAPK activation, thereby exerting its anti-tumor effect. These findings highlight the promising potential of K882 as a therapeutic targeting agent for the treatment of KRAS mutant NSCLC while also providing novel insights into targeted therapy strategies for this type of malignancy. Furthermore, the information of structure-activity relationship presents valuable molecular design blueprints for the development of novel and highly potent compounds targeting Src.
Collapse
MESH Headings
- Humans
- Quinazolines/pharmacology
- Quinazolines/chemistry
- Quinazolines/chemical synthesis
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/chemical synthesis
- Cell Proliferation/drug effects
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/metabolism
- Structure-Activity Relationship
- Stilbenes/chemistry
- Stilbenes/pharmacology
- Stilbenes/chemical synthesis
- Animals
- Drug Screening Assays, Antitumor
- Lung Neoplasms/drug therapy
- Lung Neoplasms/pathology
- Molecular Structure
- src-Family Kinases/antagonists & inhibitors
- src-Family Kinases/metabolism
- Dose-Response Relationship, Drug
- Protein Kinase Inhibitors/pharmacology
- Protein Kinase Inhibitors/chemistry
- Protein Kinase Inhibitors/chemical synthesis
- Apoptosis/drug effects
- Mice
- Cell Line, Tumor
- Neoplasms, Experimental/drug therapy
- Neoplasms, Experimental/pathology
- Neoplasms, Experimental/metabolism
- Mice, Nude
Collapse
Affiliation(s)
- Xiuwei Ma
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Zongchen Ma
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Xin Qi
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Xiaomin Zhang
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Xiaochun Liu
- Marine Biomedical Research Institute of Qingdao, Qingdao 266071 China
| | - Xiaoyu Liu
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Aotong Zhang
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Gan Yue
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China
| | - Guoqiang Li
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China.
| | - Jing Li
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National, Laboratory for Marine Science and Technology, Qingdao 266003 China.
| |
Collapse
|
|
36
|
Malone CD, Bajaj S, He A, Mody K, Hickey RM, Sarwar A, Krishnan S, Patel TC, Toskich BB. Combining Radioembolization and Immune Checkpoint Inhibitors for the Treatment of Hepatocellular Carcinoma: The Quest for Synergy. J Vasc Interv Radiol 2025; 36:414-424.e2. [PMID: 39586534 DOI: 10.1016/j.jvir.2024.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 11/06/2024] [Accepted: 11/13/2024] [Indexed: 11/27/2024] Open
Abstract
Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (90Y) radioembolization (RE) and systemic therapy in the form of immune checkpoint inhibitors (ICI) have expanded treatment options for patients with an otherwise poor prognosis. Despite these gains, ICIs and 90Y-RE each have key limitations with low objective response rates and persistent hazard of out-of-field recurrence, respectively, and overall survival remains low. However, each therapy's strength may mitigate the other's weakness, making them potentially ideal partners for combination treatment strategies. This review discusses the scientific and clinical rationale for combining 90Y-RE with ICIs, highlights early clinical trial data on its safety and effectiveness, and proposes key issues to be addressed in this emerging field. With optimal strategies, combination therapies can potentially result in increasing likelihood of durable and curative outcomes in later stage patients.
Collapse
Affiliation(s)
- Christopher D Malone
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri.
| | - Suryansh Bajaj
- Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Aiwu He
- Division of Gastroenterology and Medical Oncology, MedStar Health, Washington, DC
| | | | - Ryan M Hickey
- Department of Radiology, NYU Langone Health, New York, New York
| | - Ammar Sarwar
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Sunil Krishnan
- Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center, Houston, Texas
| | - Tushar C Patel
- Department of Transplant, Mayo Clinic, Jacksonville, Florida
| | - Beau B Toskich
- Division of Vascular and Interventional Radiology, Mayo Clinic, Jacksonville, Florida
| |
Collapse
|
|
37
|
Andresen JR, Widhalm HK, Andresen R. Radiofrequency sacroplasty as a pain treatment for symptomatic sacral destruction due to prostate metastasis: a case report and a review of the literature. J Surg Case Rep 2025; 2025:rjae733. [PMID: 40083741 PMCID: PMC11906032 DOI: 10.1093/jscr/rjae733] [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: 10/07/2024] [Accepted: 11/03/2024] [Indexed: 03/16/2025] Open
Abstract
In progressive malignant diseases such as prostate cancer, metastatic bone destruction is a frequent cause of chronic, debilitating pain. Pathological fractures of the sacrum can lead to complete immobility in patients. Cement augmentation of the sacrum has proven effective in treating sacral insufficiency fractures, resulting in significant pain reduction and improved mobility. In recent years, this technique has also been applied to pathological fractures of the sacrum. We present a case of successful treatment of prostate cancer-induced sacral bone infiltration and destruction using advanced radiofrequency sacroplasty. Literature reports describe individual cases of sacral bone destruction, where cement augmentation using various methods has led to substantial pain relief and improved overall outcomes.
Collapse
Affiliation(s)
- Julian Ramin Andresen
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
| | - Harald K Widhalm
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
| | - Reimer Andresen
- Institute of Diagnostic and Interventional Radiology/Neuroradiology, Westkuestenklinikum Heide, Academic Teaching Hospital of the Universities of Kiel, Luebeck and Hamburg, Esmarchstraße 50, 25746 Heide, Germany
| |
Collapse
|
|
38
|
Modesto VC, Galvão ND, Souza RAGD, Alves MR, Bustamante-Teixeira MT, Andrade ACDS. Time trends in the incidence of cancer in the state of Mato Grosso, Brazil, from 2001 to 2016. CIENCIA & SAUDE COLETIVA 2025; 30:e05932023. [PMID: 40136161 DOI: 10.1590/1413-81232025303.05932023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 12/14/2023] [Indexed: 03/27/2025] Open
Abstract
The scope was to analyze the time-series trend in the incidence of cancer in the health macro-regions of the State of Mato Grosso from 2001 to 2016. It involved an ecological time-series study with data from the Mato Grosso Population-Based Cancer Registry. Age-standardized incidence rates, disaggregated by year, sex, macro-region and type of cancer, were calculated. For men, the trend was increasing for prostate cancer in the state and the Central-Northwest, East, West, and South macro-regions, and for colorectal cancer in the North; and decreasing for stomach cancer in the state and the Central-Northwest and North, for lung cancer in the East, and for esophageal cancer in the Central-Northwest. For women, the trend was increasing for breast cancer in the state from 2009 to 2016, for lung cancer in the state (2008 to 2016) and in the Central-North (2001 to 2016) and South (2007 to 2016) macro-regions; and decreasing for cervical cancer in the state and for all macro-regions, and for stomach cancer in the state and in the Central-Northwest. Colorectal cancer revealed a stable trend for the state and all macro-regions. Cancer surveillance, prevention and control actions should consider regional differences and variations in magnitude of the occurrence of the disease.
Collapse
Affiliation(s)
- Viviane Cardozo Modesto
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | - Noemi Dreyer Galvão
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
- Secretaria de Estado de Saúde de Mato Grosso. Cuiabá MT Brasil
| | - Rita Adriana Gomes de Souza
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | - Mário Ribeiro Alves
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | | | - Amanda Cristina de Souza Andrade
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| |
Collapse
|
|
39
|
Liu P, Hao L, Hsu JC, Zhou M, Luo Z, Peng Y, Cai W, Hu S. Biomineralized Nanocomposite-Integrated Microneedle Patch for Combined Brachytherapy and Photothermal Therapy in Postoperative Melanoma Recurrence and Infectious Wound Healing. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2414468. [PMID: 39903769 PMCID: PMC11948049 DOI: 10.1002/advs.202414468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/16/2025] [Indexed: 02/06/2025]
Abstract
In the surgical management of malignant melanoma, incomplete tumor resection and large-area cutaneous defects are major contributors to high locoregional recurrence and uncontrolled wound infections, resulting in poor prognosis and prolonged recovery times for patients. Herein, a versatile nanocomposite microneedle patch (referred to as GM-Ag2S/Ca32P) is designed to simultaneously eliminate residual tumor post-surgery and promote the healing of infectious wounds. This microneedle patch effectively penetrates subcutaneous tissues, delivering therapeutic payloads to infiltrating tumor cells and bacteria. The Ag2S/Ca32P nanocomposites encapsulated within the microneedle patch decompose in the acidic microenvironment of tumors and bacterial biofilms, releasing radioactive 32P and Ag2S nanodots, which enhance tumor eradication and bacteria killing through synergistic brachytherapy and photothermal therapy (PTT). Moreover, the nanocomposite microneedle patch promotes scar-free wound healing by reducing inflammation, and promoting granulation tissue formation, collagen deposition, and angiogenesis, thanks to localized hyperthermia, radiation, and the swelling and biodegradation of the microneedle matrices. This microneedle patch-based postoperative adjuvant therapy offers a comprehensive strategy for addressing melanoma recurrence and infectious wound healing, with promising potential for clinical application in postsurgical management.
Collapse
Affiliation(s)
- Peng Liu
- Department of Nuclear MedicineXiangya HospitalCentral South UniversityNo. 87 Xiangya RoadChangshaHunan410008China
- Key Laboratory of Biological NanotechnologyNHC. No. 87 Xiangya RoadChangshaHunan410008China
- Departments of Radiology and Medical PhysicsUniversity of Wisconsin‐MadisonMadisonWI53705USA
| | - Lu Hao
- Department of Nuclear MedicineXiangya HospitalCentral South UniversityNo. 87 Xiangya RoadChangshaHunan410008China
| | - Jessica C. Hsu
- Departments of Radiology and Medical PhysicsUniversity of Wisconsin‐MadisonMadisonWI53705USA
| | - Ming Zhou
- Department of Nuclear MedicineXiangya HospitalCentral South UniversityNo. 87 Xiangya RoadChangshaHunan410008China
| | - Zhisheng Luo
- Department of Nuclear MedicineXiangya HospitalCentral South UniversityNo. 87 Xiangya RoadChangshaHunan410008China
| | - Ying Peng
- Xiangya School of Pharmaceutical SciencesCentral South UniversityChangshaHunan410013China
| | - Weibo Cai
- Departments of Radiology and Medical PhysicsUniversity of Wisconsin‐MadisonMadisonWI53705USA
| | - Shuo Hu
- Department of Nuclear MedicineXiangya HospitalCentral South UniversityNo. 87 Xiangya RoadChangshaHunan410008China
- Key Laboratory of Biological NanotechnologyNHC. No. 87 Xiangya RoadChangshaHunan410008China
| |
Collapse
|
|
40
|
Vincent L, Decaux O, Perrot A, Royer B, Chalopin T, Bobin A, Macro M, Caillot D, Karlin L, Jacquet C, Sonntag C, Mohty M, Frenzel L, Jaccard A, Manier S, Sanhes L, Chaoui D, Moreau P, Garlantézec R, Texier N, Louni C, Maarouf Z, Loiseau HA, Hulin C, Merzoug KB. Real-World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated Before the Era of Anti-CD38 Antibodies: The EMMY Cohort From 2017 to 2020. Cancer Med 2025; 14:e70619. [PMID: 40087879 PMCID: PMC11909396 DOI: 10.1002/cam4.70619] [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: 10/04/2024] [Revised: 12/16/2024] [Accepted: 12/21/2024] [Indexed: 03/17/2025] Open
Abstract
AIMS/BACKGROUND Recent agents have profoundly reshaped the multiple myeloma (MM) landscape. Their real-world impacts need to be assessed over the long term. METHODS EMMY is a non-interventional, prospective dynamic cohort, conducted in France, since 2017, with 900 patients enrolled each year. Newly diagnosed MM (NDMM) who initiated a treatment from 2017 to 2020 are here described. RESULTS A total of 1036 non-transplant eligible (NTE) patients (median age: 74.9 years) and 561 patients who received autologous stem cell transplantation (ASCT) (median age: 60.6 years) were enrolled. For ASCT patients, a shift in induction treatment from bortezomib-thalidomide-dexamethasone (VTd) (29.1%) to bortezomib-lenalidomide-dexamethasone (VRd) (55.1%) marked the period. Maintenance treatment with R after ASCT became a standard (75% of patients). In NTE patients, R-based regimens were increasingly used from 29.4% in 2017 (of whom Rd.: 17.0%, VRd: 10.6%) to 73.3% in 2020 (of whom Rd.: 21.8%, VRd: 48.5%). Median progression-free survival (mPFS) was 46.5 months (95% CI: 37.8-50.6) and 18.7 months (95% CI: 16.3-20.8) in ASCT and NTE patients, respectively. In the ASCT group, patients treated with and without R maintenance had a mPFS of 51.8 (95% CI: 44.1-NA) and 29.6 months (95% CI: 21.8-40.9), respectively. In the NTE group, the mPFS was 26.3 (95% CI: 21.9-30.9) and 14.6 months (95% CI: 11.9-17.7) in patients who received an R-based and non-R-based regimen, respectively. The estimated 48-month overall survival rates were 89% (95% CI: 84.5-92.2) and 63% (95% CI: 58.5-67.1) for ASCT and NTE patients, respectively. CONCLUSIONS The 2017-2020 period was marked by the expansion of R use in both NDMM ASCT and NTE patients.
Collapse
Affiliation(s)
- Laure Vincent
- Department of Clinical HematologyMontpellier University Hospital CenterMontpellierFrance
| | - Olivier Decaux
- Centre Hospitalier Universitaire de Rennes ‐ Hôpital PontchaillouRennesFrance
| | - Aurore Perrot
- Centre Hospitalier Universitaire de ToulouseIUCT‐Oncopole, Université de Toulouse, UPS, Service d'HématologieToulouseFrance
| | | | - Thomas Chalopin
- Centre hospitalier universitaire de Tours, HospitalToursFrance
| | | | | | - Denis Caillot
- Hématologie CliniqueCentre Hospitalier Universitaire de Dijon BourgogneDijonFrance
| | - Lionel Karlin
- Hôpital Lyon SudHospices Civils de LyonPierre‐BéniteFrance
| | | | | | - Mohamad Mohty
- Department of HaematologySaint Antoine HospitalParisFrance
| | | | - Arnaud Jaccard
- Referral Center for AL AmyloidosisLimogesFrance
- Hematologie cliniqueCentre Hospitalier Universitaire de LimogesLimogesFrance
| | - Salomon Manier
- HématologieCentre Hospitalier Universitaire de LilleLilleFrance
| | | | | | - Philippe Moreau
- Department of HaematologyCentre Hospitalier Universitaire de NantesNantesFrance
| | - Ronan Garlantézec
- Santé publique et épidémiologieCentre Hospitalier Universitaire de RennesRennesFrance
| | | | | | | | | | - Cyrille Hulin
- Centre Hospitalier Universitaire de BordeauxPessac CedexFrance
| | - Karim Belhadj Merzoug
- Unité Hémopathies LymphoïdesCentre Hospitalier Universitaire Henri MondorCréteilFrance
| |
Collapse
|
|
41
|
Pandit K, Puri D, Yuen K, Yodkhunnatham N, Meagher M, Bagrodia A. Optimal imaging techniques across the spectrum of testicular cancer. Urol Oncol 2025; 43:150-155. [PMID: 38960839 DOI: 10.1016/j.urolonc.2024.05.023] [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: 12/21/2023] [Revised: 05/19/2024] [Accepted: 05/21/2024] [Indexed: 07/05/2024]
Abstract
Over the years, several imaging techniques have been used in the diagnosis and management of testicular cancer. We compartmentalize disease stages into preorchiectomy, stage 1, initial stage 2 and 3 and postchemotherapy stage 2 and 3. We then elaborate on various imaging modalities that are relevant to each of these stages. We also describe evolving imaging tools that have shown promise. We attempt to provide a comprehensive review of these techniques over the spectrum of testicular cancer.
Collapse
Affiliation(s)
- Kshitij Pandit
- Department of Urology, UC San Diego School of Medicine, La Jolla, California
| | - Dhruv Puri
- Department of Urology, UC San Diego School of Medicine, La Jolla, California
| | - Kit Yuen
- Department of Urology, UC San Diego School of Medicine, La Jolla, California
| | | | - Margaret Meagher
- Department of Urology, UC San Diego School of Medicine, La Jolla, California
| | - Aditya Bagrodia
- Department of Urology, UC San Diego School of Medicine, La Jolla, California.
| |
Collapse
|
|
42
|
Chang Y, Zhou H, Ren Y, Zhang J, Sun L, Du M, Zhao J, Chu H, Zhao Y. Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis. J Biomol Struct Dyn 2025; 43:2109-2119. [PMID: 38102880 DOI: 10.1080/07391102.2023.2294168] [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: 04/24/2023] [Accepted: 07/30/2023] [Indexed: 12/17/2023]
Abstract
Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- Yibin Chang
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Hongmei Zhou
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Yuxiang Ren
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Jiaqi Zhang
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Lei Sun
- College of Medical Devices, Shenyang Pharmaceutical University, Shenyang, China
| | - Minghui Du
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Jian Zhao
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Huiying Chu
- Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
| | - Yongshan Zhao
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| |
Collapse
|
|
43
|
Zhang X, Hu J, Fan X, Chen Q, Zheng D, Huang M, Xu Y. The effect of Bevacizumab treatment on the incidence of hypertension in patients with ovarian cancer: a systematic review and meta-analysis. J Oncol Pharm Pract 2025; 31:294-304. [PMID: 39930904 DOI: 10.1177/10781552241307868] [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: 03/14/2025]
Abstract
IntroductionThis study aims to evaluate the effect of bevacizumab treatment on the incidence of hypertension in patients with ovarian cancer.MethodsA comprehensive search of PubMed, Scopus, Embase, Cochrane, Web of Science, and Google Scholar databases was conducted until August 2024. We included only randomized clinical trials that compared ovarian cancer patients treated with Bevacizumab to those treated with other therapies. The primary outcome was the relative risk (RR) of developing hypertension, stratified by grade. Statistical analyses were performed using a random-effects model to account for heterogeneity between studies. Subgroup analyses were conducted based on hypertension severity (grade ≥2 and grade ≥3) and disease stage. Sensitivity analyses and publication bias assessments were also performed.ResultsA total of 11 randomized trials were included, comprising 5212 patients. The meta-analysis revealed that patients receiving Bevacizumab had a significantly higher risk of hypertension compared to controls (RR = 2.91, 95% CI: 1.65-5.16, P = 0.0002). Subgroup analysis showed that the risk of grade ≥2 hypertension was 1.68 times higher (95% CI: 0.92-3.07), and grade ≥3 hypertension was 5.10 times higher (95% CI: 2.46-10.55) in the Bevacizumab group. Sensitivity analysis confirmed the robustness of these findings, and no significant publication bias was detected.ConclusionBevacizumab treatment in ovarian cancer significantly increases the risk of hypertension, particularly severe hypertension (grade ≥3). These findings underscore the need for vigilant blood pressure monitoring and management in patients receiving Bevacizumab to mitigate cardiovascular complications and optimize treatment outcomes.
Collapse
Affiliation(s)
- Xiaoyan Zhang
- Pharmaceutical Department, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Jumei Hu
- Department of Gynecology, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Xijing Fan
- Clinical Laboratory, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Qiaoqiao Chen
- Pharmaceutical Department, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Danjun Zheng
- Pharmaceutical Department, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Minjuan Huang
- Pharmaceutical Department, Jinhua Municipal Central Hospital, Jinhua City, China
| | - Yuanqing Xu
- Pharmaceutical Department, Jinhua Municipal Central Hospital, Jinhua City, China
| |
Collapse
|
|
44
|
Cicek N, Cobandede Z, Adiguzel S, Yilmaz H, Culha M. Synergistic anti-cancer effects of piezoelectric hexagonal boron nitride nanocarriers for controlled doxorubicin release. Nanomedicine (Lond) 2025; 20:455-466. [PMID: 39887263 PMCID: PMC11875468 DOI: 10.1080/17435889.2025.2459055] [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: 11/03/2024] [Accepted: 01/23/2025] [Indexed: 02/01/2025] Open
Abstract
AIMS This study aims to develop a piezoelectric drug delivery system based on hexagonal boron nitride nanosheets (hBNs). MATERIALS AND METHODS hBNs were synthesized using the chemical vapor deposition (CVD) method and characterized through imaging and spectroscopic techniques. Their piezoelectric properties were evaluated to confirm their functionality. Subsequently, the potential of hBNs as nanocarriers was assessed through in vitro experiments with doxorubicin (Dox) as a model drug. RESULTS The piezoelectric hBNs were successfully synthesized and exhibited efficient loading and controlled release of Dox. In vitro experiments conducted on PC3 (human prostate cancer) and PNT1A (normal adult prostate epithelial) cell lines demonstrated that ultrasound (US)-induced Dox-loaded hBNs (hBN-Dox) significantly inhibited the proliferation of prostate cancer cells, achieving efficacy at a much lower Dox concentration compared to conventional methods. The system enhanced reactive oxygen species (ROS) generation, impaired cancer cell colony formation, and induced both early and late apoptosis. CONCLUSIONS These findings highlight the potential of piezoelectric hBNs as nanocarriers for efficient drug delivery, leveraging the synergistic effect of piezoelectricity-induced drug release and the degradation products of hBNs in biological media. Their ability to enhance drug efficacy while reducing the required dose holds promise for advanced cancer therapies.
Collapse
Affiliation(s)
- Nilay Cicek
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla Istanbul, Turkey
| | - Zehra Cobandede
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla Istanbul, Turkey
| | - Sevin Adiguzel
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla Istanbul, Turkey
| | - Hulya Yilmaz
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla Istanbul, Turkey
| | - Mustafa Culha
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla Istanbul, Turkey
- Chemistry and Biochemistry Department, College of Science and Mathematics, Augusta University, Augusta, GA, USA
| |
Collapse
|
|
45
|
Chen P, Yang J, Chen L, Liu C, Li Z, Long X, Wu J, Wu B, Wu J. Moscatilin Induces Ferroptosis in Clear Cell Renal Cell Carcinoma via the JAK-STAT Signaling Pathway. Chem Biol Drug Des 2025; 105:e70071. [PMID: 40070232 DOI: 10.1111/cbdd.70071] [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: 08/25/2024] [Accepted: 01/22/2025] [Indexed: 03/25/2025]
Abstract
Moscatilin, a biphenyl compound derived from Dendrobium nobile, exhibits significant anti-tumor activity. However, the specific role of moscatilin in clear cell renal cell carcinoma (ccRCC) and its underlying molecular mechanisms have not been fully studied. This study aims to fill this gap by demonstrating through a series of experiments that moscatilin can effectively inhibit the proliferation and migration of ccRCC and induce its apoptosis process. More importantly, we found that moscatilin can also trigger ferroptosis in ccRCC, a process accompanied by significant increases in Fe2+, MDA (a lipid peroxidation product), and ROS (reactive oxygen species) levels, as well as decreases in mitochondrial membrane potential and GSH (glutathione) levels. These changes strongly suggest a key role for moscatilin in inducing ferroptosis. To further explore its underlying mechanism, we speculate that moscatilin may inhibit the phosphorylation level of the JAK-STAT signaling pathway, thereby blocking the function of the key protein SLC7A11 in the ferroptosis signaling pathway, which promotes the occurrence of ferroptosis. This discovery not only reveals a new mechanism of moscatilin in the treatment of ccRCC but also provides new ideas for the development of related drugs in the future. In summary, based on the important discovery that moscatilin can induce ferroptosis in ccRCC, we have reason to believe that moscatilin has the potential to become a new type of drug for the treatment of ccRCC.
Collapse
Affiliation(s)
- Pei Chen
- Department of Urology, Zunyi Medical University, Zunyi, Guizhou, China
| | - Jin Yang
- Department of Urology, Zunyi Medical University, Zunyi, Guizhou, China
- Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Lin Chen
- Department of Urology, Zunyi Medical University, Zunyi, Guizhou, China
- Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Chenhuan Liu
- Department of Urology, Zunyi Medical University, Zunyi, Guizhou, China
- Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Zhihao Li
- Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Xiaoming Long
- Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Jinbang Wu
- Department of Urology, The Fifth Hospital of DeYang, DeYang, China
| | - Bo Wu
- Department of Urology, the Third Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Jianjun Wu
- Department of Urology, the Third Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| |
Collapse
|
|
46
|
Xia J, Liu W, Ni Y, Shahzad A, Cui K, Xu Z, Zhang J, Wei Z, Teng Z, Yang Z, Zhang Q. Advances in the impact of ASS1 dysregulation on metabolic reprogramming of tumor cells. Cell Signal 2025; 127:111593. [PMID: 39778698 DOI: 10.1016/j.cellsig.2025.111593] [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: 11/13/2024] [Revised: 12/29/2024] [Accepted: 01/04/2025] [Indexed: 01/11/2025]
Abstract
ASS1(argininosuccinate synthase 1) is a rate-limiting enzyme in the urea cycle, catalyzing the synthesis of argininosuccinate from citrulline and aspartate to ultimately produce arginine and support cellular metabolism. Increasing evidence suggests that ASS1 is commonly dysregulated in the tumor microenvironment, promoting tumor cell metastasis and infiltration. With a deeper understanding of tumor metabolic reprogramming in recent years, the impact of ASS1 dysregulation on abnormal tumor metabolism has attracted growing interest among researchers. In tumors with lacked or downregulated expression of ASS1, tumor cells become 'addicted' to exogenous arginine. Several strategies for arginine deprivation have been developed and entered clinical trials for treating such tumors. Therefore, we focus on elucidating the commonalities and characteristics of ASS1 dysregulation in tumors, as well as its implications for diagnosis, treatment, and prognosis. The mechanisms by which ASS1 gene dysregulation leads to metabolic abnormalities in tumor cells vary across different types of tumors. Extensive experimental studies have demonstrated that overexpression or low expression of ASS1 exhibits varying effects-either inhibitory or stimulatory proliferation-on tumor cells across different types. Restoring its expression can inhibit proliferation in some tumors lacking or downregulating ASS1 but can promote metastasis and infiltration in others (e.g., resistance to arginine deprivation therapy). Additionally, the expression level of ASS1 dynamically changes during tumorigenesis and progression. Finally, this review discusses the diagnostic, therapeutic, and prognostic value of ASS1 in future clinical practice.
Collapse
Affiliation(s)
- Jiaojiao Xia
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Wenjing Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Yueli Ni
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Asif Shahzad
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Kun Cui
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Zhe Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China; Qujing Medical College, Qujing 655011, Yunnan Province, China
| | - Jinshan Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China
| | - Zhenyan Wei
- Yunnan Center for Disease Control and Prevention, Kunming 650022, China
| | - Zhuoran Teng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China.
| | - Zhe Yang
- Departments of Pathology, The First Affiliated Hospital of Kunming Medical University, Yunnan, Kunming 650032, PR China.
| | - Qiao Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, PR China.
| |
Collapse
|
|
47
|
Saeed H, Majeed U, Iqbal M, Shahid S, Hussain AT, Iftikhar HA, Siddiqui MR, Ch IA, Khalid S, Tahirkheli NK. Unraveling trends and disparities in acute myocardial infarction-related mortality among adult cancer patients: A nationwide CDC-WONDER analysis (1999-2020). INTERNATIONAL JOURNAL OF CARDIOLOGY. CARDIOVASCULAR RISK AND PREVENTION 2025; 24:200371. [PMID: 39925345 PMCID: PMC11803891 DOI: 10.1016/j.ijcrp.2025.200371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 12/28/2024] [Accepted: 01/21/2025] [Indexed: 02/11/2025]
Abstract
Background Cancer patients are at an increased risk for the incidence and complications of acute myocardial infarction (AMI) due to shared risk factors and treatment-related adverse effects. Mortality trends for AMI-related deaths in adult cancer patients in the U.S. remain unexplored. Methodology This study used CDC WONDER data for death certificates from 1999 to 2020, identifying U.S. adults (≥25 years) with cancer (ICD-10: C00-D49) who died of AMI (ICD-10: I21) as the underlying cause. Age-adjusted mortality rates (AAMRs) and annual percent changes (APCs) were calculated and stratified by gender, age, race, and geographic location. Results Between 1999 and 2020, there were 109,462 AMI-related deaths in adult cancer patients. The AAMR decreased from 4.3 per 100,000 in 1999 to 1.4 in 2020. A significant decline occurred from 1999 to 2015 (APC: 6.65; 95 % CI: 6.95 to -6.40; p < 0.001), followed by a stable trend from 2015 to 2020 (APC: 1.36; 95 % CI: 2.69 to 0.91; p = 0.152). Men had higher AAMRs than women (3.5 vs. 1.5). AAMRs were highest in older adults (10.5) compared to middle-aged (0.7) and young adults (0.1). Racial disparities showed the highest AAMRs in non-Hispanic (NH) Black patients (2.7), followed by NH Whites (2.4), NH American Indian/Alaska Native (1.6), Hispanic/Latino (1.3), and NH Asian/Pacific Islander (1.1). Non-metropolitan areas had higher AAMRs than metropolitan areas (2.8 vs. 2.2). Conclusions This analysis highlights a significant decline in AMI-related mortality among cancer patients in the U.S., with persistent disparities by gender, age, race and geographical location.
Collapse
Affiliation(s)
- Humza Saeed
- Rawalpindi Medical University, Rawalpindi, Pakistan
| | | | | | - Sufyan Shahid
- Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Tsukamoto S, Huaze Y, Weisheng Z, Machinaga A, Kakiuchi N, Ogawa S, Seno H, Higashiyama S, Matsuda M, Hiratsuka T. Quantitative Live Imaging Reveals Phase Dependency of PDAC Patient-Derived Organoids on ERK and AMPK Activity. Cancer Sci 2025; 116:724-735. [PMID: 39731327 PMCID: PMC11875792 DOI: 10.1111/cas.16439] [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: 08/24/2024] [Revised: 12/06/2024] [Accepted: 12/12/2024] [Indexed: 12/29/2024] Open
Abstract
Patient-derived organoids represent a novel platform to recapitulate the cancer cells in the patient tissue. While cancer heterogeneity has been extensively studied by a number of omics approaches, little is known about the spatiotemporal kinase activity dynamics. Here we applied a live imaging approach to organoids derived from 10 pancreatic ductal adenocarcinoma (PDAC) patients to comprehensively understand their heterogeneous growth potential and drug responses. By automated wide-area image acquisitions and analyses, the PDAC cells were non-selectively observed to evaluate their heterogeneous growth patterns. We monitored single-cell ERK and AMPK activities to relate cellular dynamics to molecular dynamics. Furthermore, we evaluated two anti-cancer drugs, a MEK inhibitor, PD0325901, and an autophagy inhibitor, hydroxychloroquine (HCQ), by our analysis platform. Our analyses revealed a phase-dependent regulation of PDAC organoid growth, where ERK activity is necessary for the early phase and AMPK activity is necessary for the late stage of organoid growth. Consistently, we found PD0325901 and HCQ target distinct organoid populations, revealing their combination is widely effective to the heterogeneous cancer cell population in a range of PDAC patient-derived organoid lines. Together, our live imaging quantitatively characterized the growth and drug sensitivity of human PDAC organoids at multiple levels: in single cells, single organoids, and individual patients. This study will pave the way for understanding the cancer heterogeneity and promote the development of new drugs that eradicate intractable cancer.
Collapse
Affiliation(s)
- Shoko Tsukamoto
- Laboratory of Cell Cycle Regulation, Graduate School of BiostudiesKyoto UniversityKyotoJapan
| | - Ye Huaze
- Department of Molecular Oncology, Graduate School of MedicineOsaka UniversityOsakaJapan
| | - Zhang Weisheng
- Department of Molecular Oncology, Graduate School of MedicineOsaka UniversityOsakaJapan
| | - Akihito Machinaga
- Oncology Tsukuba Research Department, Discovery, Medicine CreationOBG, Eisai Co. Ltd.TsukubaJapan
| | - Nobuyuki Kakiuchi
- Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto UniversityKyotoJapan
- The Hakubi Center for Advanced ResearchKyoto UniversityKyotoJapan
| | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hiroshi Seno
- The Hakubi Center for Advanced ResearchKyoto UniversityKyotoJapan
| | - Shigeki Higashiyama
- Department of Oncogenesis and Growth Regulation, Research CenterOsaka International Cancer InstituteOsakaJapan
| | - Michiyuki Matsuda
- Laboratory of Cell Cycle Regulation, Graduate School of BiostudiesKyoto UniversityKyotoJapan
- Affiliated Graduate School, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Toru Hiratsuka
- Department of Molecular Oncology, Graduate School of MedicineOsaka UniversityOsakaJapan
- Department of Oncogenesis and Growth Regulation, Research CenterOsaka International Cancer InstituteOsakaJapan
| |
Collapse
|
|
49
|
Wang F, Yu X, Han Y, Zhang L, Liu S. Prognostic value of upper paratracheal lymph node resection in stage IB right‑sided lung cancer: A retrospective cohort study. Oncol Lett 2025; 29:137. [PMID: 39839609 PMCID: PMC11747950 DOI: 10.3892/ol.2025.14883] [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: 08/21/2024] [Accepted: 12/06/2024] [Indexed: 01/23/2025] Open
Abstract
The aim of the present study was to investigate the impact of upper paratracheal lymph node resection on the prognosis of patients with stage IB non-small cell lung cancer (NSCLC). A retrospective analysis of 339 patients with upper lobe stage IB NSCLC who underwent surgery at Sun Yat-Sen University Cancer Center (Guangzhou, China) between 1999 and 2009 was conducted. The Cox regression model was used to investigate prognostic factors. Variables with P<0.1 in univariate analysis were incorporated into multivariate analysis. A 1-to-1 propensity score matching (PSM) was conducted to decrease potential bias when comparing the impact of upper paratracheal lymph node resection on survival outcomes. Following PSM, 202 cases were identified. Kaplan-Meier analysis and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS). Of the 339 patients identified, 152 did not undergo resection of upper paratracheal lymph node, while 187 did undergo the surgery. Cases were separated into two groups based on the resection of the upper paratracheal lymph node. Cox regression analysis demonstrated that a family history of malignant tumors and smoking were considered significant prognostic variables for OS. Age and family history of malignant tumors were significant independent prognostic variables for RFS. Resection of the upper paratracheal lymph node was not significantly associated with OS and RFS. Additionally, resection of the upper paratracheal lymph node was not significantly associated with OS and RFS. In conclusion, there was no statistical association between upper paratracheal lymph node resection and OS or RFS for patients with stage IB NSCLC. Therefore, upper paratracheal lymph node resection may not be necessary for patients with early stage NSCLC, and application of this knowledge could reduce unnecessary surgical trauma and decrease lymph node-related complications.
Collapse
Affiliation(s)
- Feng Wang
- Department of Minimally Invasive Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Xiangyang Yu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China
| | - Yi Han
- Department of Minimally Invasive Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Lanjun Zhang
- State Key Laboratory of Oncology in South China, Department of Thoracic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Shuku Liu
- Department of Minimally Invasive Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| |
Collapse
|
|
50
|
Babaei Khorzoughi S, Tavakoli M, Mortazavi M, Jafarnejad Z, Malekpour A, Kopaiee Malek T, Kargar F. A review of recombinant HER3 affibodies with an effective diagnostic view of cancer cells. J Drug Target 2025; 33:316-327. [PMID: 39485069 DOI: 10.1080/1061186x.2024.2420202] [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: 07/05/2024] [Revised: 09/10/2024] [Accepted: 10/16/2024] [Indexed: 11/03/2024]
Abstract
Breast cancer is one of the leading causes of cancer-related deaths among women globally. Factors like increased expression of HER family members contribute to its development, with elevated HER3 levels-especially in conjunction with tyrosine kinase receptors like HER2-playing a critical role in activating cancer pathways essential for cell survival and proliferation. Detecting high HER3 levels is vital for effective treatment. Affibody proteins, a class that includes antibodies, are used to identify elevated HER3 expression due to their high binding affinity. These innovative non-immune probes show promise in therapy, diagnostics, and biotechnology because of their exceptional specificity and affinity for target proteins. The design of recombinant affibodies enhances HER3 detection accuracy and supports the development of targeted therapies. Advanced engineering techniques optimize these affibodies for stability and binding efficacy, making them suitable for clinical applications. Additionally, their versatility allows integration with imaging technologies for real-time monitoring of HER3 expression and therapeutic responses. This comprehensive approach could lead to more personalized treatment options for patients with HER3-positive breast cancers, improving patient management and outcomes. This study presents recombinant affibodies designed to bind HER3 for cancer cell identification and introduces novel methods for producing various affibody molecules.
Collapse
Affiliation(s)
- Sahar Babaei Khorzoughi
- Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | - Mehrnoosh Tavakoli
- Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | - Mojtaba Mortazavi
- Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | - Zahra Jafarnejad
- Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | | | - Tara Kopaiee Malek
- Department of Cell and Molecular Biology, Faculty of Science, Azad University of Damghan, Damghan, Iran
| | - Farzane Kargar
- Department of Medical Biotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|