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Qaed E, Liu W, Almoiliqy M, Mohamed R, Tang Z. Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3321-3343. [PMID: 39549063 DOI: 10.1007/s00210-024-03579-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 10/28/2024] [Indexed: 11/18/2024]
Abstract
Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Genistein (Gen), a phytoestrogen soy isoflavone, has emerged as a promising agent in the prevention and treatment of breast cancer due to its ability to function as a natural selective estrogen receptor modulator (SERM). This review explores the multifaceted mechanisms through which Gen and its derivatives exert their anticancer effects, including modulation of the PI3K/Akt signaling pathway, regulation of apoptosis, inhibition of angiogenesis, and impacts on DNA methylation and enzyme functions. We discuss the dual roles of Gen in both enhancing and inhibiting estrogen receptor (ER)-dependent pathways., highlighting its complex interactions with ERα and ERβ. Furthermore, the review examines the synergistic effect of combining Gen with conventional chemotherapeutic agents such as doxorubicin, cisplatin, and selenium, as well as other natural compounds like lycopene. Clinical studies suggest that while isoflavones may not significantly influence breast cancer progression in general, the high consumption of soy isoflavones is associated with reduced recurrence rates in breast cancer survivors. Importantly, Gen's ability to modulate key signaling pathways and enhance the efficacy of existing treatments improves its potential as a valuable adjunct in breast cancer therapy. In conclusion, Gen and its derivatives offer a novel and promising approach for treatment of breast cancer. Continued research into their mechanisms of action and clinical applications will be essential in optimizing their therapeutic potential and translating these findings into effective clinical interventions.
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Affiliation(s)
- Eskandar Qaed
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China.
- State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
| | - Wu Liu
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China
| | - Marwan Almoiliqy
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China
| | - Rawan Mohamed
- College of Clinical Pharmacy, Mansoura University, Mansoura, Egypt
| | - Zeyao Tang
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China.
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Obomanu E, Wattanachayakul P, Jones C, Byfield K, Ratnani A, Mayo R. Impact of Protein Energy Malnutrition on Breast Cancer Patients Hospitalized with Acute Decompensated Heart Failure: Insight from NIS Database 2020. Nutr Cancer 2025; 77:483-489. [PMID: 40070289 DOI: 10.1080/01635581.2025.2474262] [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: 12/03/2024] [Revised: 02/23/2025] [Accepted: 02/25/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Breast cancer patients are at risk of acute decompensated heart failure (ADHF) and protein-energy malnutrition (PEM) due to chemoradiation effects or cancer itself. There are no existing studies on the impact of PEM on breast cancer patients hospitalized for ADHF. This study aims to evaluate the effects of PEM on breast cancer patients admitted for ADHF. METHODS Using the 2020 US National Inpatient Sample (NIS), our study analyzed breast cancer patients aged 18 and older. A multivariate logistic and linear regression analysis determined the odds ratio for various outcomes. The primary outcome was inpatient mortality among patients hospitalized for ADHF based on the presence or absence of PEM, while secondary outcomes included cardiogenic shock, anemia, and total hospital charges. RESULTS Thirty thousand five hundred and fifty-five (30,555) patients were identified, predominantly female (99%) and Caucasian (71.4%). Among them, 6.07% were diagnosed with concurrent PEM. PEM was associated with higher in-hospital mortality risk (aOR 2.61), increased cardiogenic shock (aOR 3.17), anemia (aOR 1.43), more extended hospital stays (b 2.09), and higher hospital charges (average $28,285). CONCLUSIONS The findings indicate that comorbid PEM is associated with increased risks of in-hospital mortality, anemia, cardiogenic shock, prolonged hospital stays and increased overall hospital costs among breast cancer patients admitted for ADHF.
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Affiliation(s)
- Elvis Obomanu
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA
| | | | - Colton Jones
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA
| | - Karecia Byfield
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA
| | - Akshay Ratnani
- Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA
| | - Ryan Mayo
- Department of Hematology/Oncology, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA
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Tolentino-Rodriguez L, Chkeir M, Pofagi V, Ahindu I, Toniolo J, Erazo A, Preux PM, Blanquet V, Vergonjeanne M, Parenté A. Breast cancer characteristics in low- and middle-income countries: An umbrella review. Cancer Epidemiol 2025; 96:102797. [PMID: 40081022 DOI: 10.1016/j.canep.2025.102797] [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: 11/22/2024] [Revised: 02/26/2025] [Accepted: 03/03/2025] [Indexed: 03/15/2025]
Abstract
Breast cancer presents significant challenges in low- and middle-income countries (LMICs) due to disparities in healthcare access and outcomes. This umbrella review synthesizes data on breast cancer characteristics-age at diagnosis, staging, and molecular subtypes-to guide targeted healthcare strategies in LMICs. Our umbrella review was conducted following PRISMA 2020 and JBI guidelines. Systematic reviews from 2009 to 2024 were sourced from PubMed, Google Scholar, and Cochrane. Reviews were assessed with AMSTAR 2, and only those rated moderate or higher were included. Data synthesis and meta-analyses were performed using R. From 1165 records, 35 systematic reviews met initial criteria; nine were included in the final synthesis, representing 305 primary studies (195 relevant to LMICs). Of those, 50 % were hospital-based and 22 % population-based, limiting the generalizability of the data and the importance of promoting more population-based studies. The overall quality of systematic reviews was variable, with only a few meeting high standards. Geographic analysis revealed a significant underrepresentation of high-quality reviews in sub-Saharan Africa and Latin America. Age at diagnosis varied: sub-Saharan Africa (45-52 years), Middle East (36-56 years), and Latin America (∼49-53 years). Advanced-stage diagnoses (stages III and IV) were common, worsening prognostic outcomes. Molecular subtype analysis indicated a predominance of luminal A but highlighted treatment challenges due to limited targeted therapy access. The results emphasize a pressing need to enhance the availability and quality of primary data, including both hospital-based and population-based studies, particularly in underrepresented regions like sub-Saharan Africa and Latin America. Addressing these gaps with rigorous, locally focused studies is essential for improving breast cancer prevention, diagnosis, and treatment. Enhancing methodological standards and expanding research in these areas will be crucial to bridging global breast cancer outcomes disparities.
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Affiliation(s)
- Lisbeth Tolentino-Rodriguez
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France.
| | - Mohamad Chkeir
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Vanina Pofagi
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France; Laboratory of Epidemiology of Chronic and Neurological Diseases, LEMACEN, Champ de foire, Bernadin Gantin, Cotonou, Benin
| | - Irénée Ahindu
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France; Laboratory of Epidemiology of Chronic and Neurological Diseases, LEMACEN, Champ de foire, Bernadin Gantin, Cotonou, Benin
| | - Jean Toniolo
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Andrea Erazo
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Pierre-Marie Preux
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Véronique Blanquet
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Marion Vergonjeanne
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France
| | - Alexis Parenté
- Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, 2 rue du Dr Marcland, Limoges 87000, France; Laboratory of Epidemiology of Chronic and Neurological Diseases, LEMACEN, Champ de foire, Bernadin Gantin, Cotonou, Benin
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Alanazi WN, Mohamed GM, Alosaimi NS, Alosaimi LM. Breast cancer awareness, knowledge and self-screening intention among females in Northern Border of Saudi Arabia, Arar City. BMC Public Health 2025; 25:964. [PMID: 40069709 PMCID: PMC11899163 DOI: 10.1186/s12889-025-22092-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Breast cancer is the most common cancer among females, and early detection plays a crucial role in disease management. This study aimed to assess the knowledge, practices, and barriers related to breast self-examination (BSE) and mammography among Saudi women in Arar City, Saudi Arabia. METHOD A cross-sectional observational study was conducted using an online Google Form distributed to women in Arar City. The survey collected sociodemographic data and assessed knowledge, practices, and barriers related to BSE and mammography. Statistical analyses were performed using IBM SPSS Statistics version 27.0.1, with significance set at p < 0.05. RESULTS The study included 385 females, with women aged 19-25 constituting nearly one-third of the population (n = 118; 30.6%). Most participants were married (n = 217; 56.4%) and held a bachelor's degree (n = 281; 73%). While 84.2% (n = 324) had heard of BSE and 80% (n = 308) demonstrated good knowledge, only 33.5% (n = 129) reported performing BSE. Regarding mammography, only 19.5% (n = 75) reported undergoing screening, despite 65.1% (n = 247) recognizing it as a safe procedure. Educational level (p = 0.018), prior knowledge of BSE (p = 0.009), and history of breast problems (p = 0.027) were significantly associated with higher knowledge scores. CONCLUSION While women demonstrated good awareness and knowledge of BSE, its practice remains low, with many unaware of proper techniques, timing, and frequency. Mammography awareness and utilization were also limited, emphasizing the need for targeted educational campaigns to promote early detection and improve screening behaviours.
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Affiliation(s)
- Waad Nawaf Alanazi
- Department of Plastic & Reconstructive Surgery, North Medical Tower Hospital, Northern Borders Health Cluster, Arar, Saudi Arabia.
| | - Ghofran Mahgoub Mohamed
- General Surgery Specialists, Prince Abdulaziz Bin Musaed Hospital, Northern Borders Health Cluster, Arar, Saudi Arabia
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Shi J, Li J, Gao Y, Chen W, Zhao L, Li N, Tian J, Li Z. The screening value of mammography for breast cancer: an overview of 28 systematic reviews with evidence mapping. J Cancer Res Clin Oncol 2025; 151:102. [PMID: 40047905 PMCID: PMC11885354 DOI: 10.1007/s00432-025-06122-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 01/23/2025] [Indexed: 03/09/2025]
Abstract
BACKGROUND The effectiveness of mammography screening in reducing breast cancer mortality and the accuracy of various mammography techniques have been widely studied. However, the quality and findings of existing systematic reviews and meta-analyses require comprehensive evaluation. METHODS A systematic literature search was conducted in the Cochrane Library, EMBASE, and PubMed for systematic reviews published up until December 20, 2022. A total of 28 systematic reviews with meta-analyses were included. Two reviewers independently extracted data and assessed methodological quality using the Risk Of Bias In Systematic Reviews (ROBIS) tool. RESULTS Of the 28 systematic reviews included, only 17.9% were rated as low risk of bias. The pooled estimates for breast cancer mortality reduction due to mammography screening ranged from 0.51 (95% CI 0.46-0.55) to 1.04 (95% CI 0.84-1.27). The results were influenced by study design, age, and follow-up duration, with an overall trend indicating that mammography screening reduces breast cancer mortality. Sensitivity of mammography techniques ranged from 55 to 91%, and specificity from 84 to 97%. Digital breast tomosynthesis combined with synthetic contrast-enhanced spectral mammography, digital mammography, and film mammography demonstrated relatively high cancer detection rates and low false positives. CONCLUSION Mammography screening appears effective in reducing breast cancer mortality. The accuracy of various mammography techniques is generally reliable, with certain combinations showing high detection rates. However, the methodological quality of most included reviews was at high risk of bias, indicating a need for higher-quality studies in the future.
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Affiliation(s)
- Jiyuan Shi
- School of Nursing, Beijing University of Chinese Medicine, Beijing, 100144, China
| | - Jiang Li
- National Cancer Center, National Clinical Research Center for Cancer; Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ya Gao
- Evidence-Based Medicine Center, Lanzhou University, Lanzhou, 730000, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou, 730000, China
| | - Wanqing Chen
- National Cancer Center, National Clinical Research Center for Cancer; Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Liang Zhao
- Evidence-Based Medicine Center, Lanzhou University, Lanzhou, 730000, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou, 730000, China
| | - Ni Li
- National Cancer Center, National Clinical Research Center for Cancer; Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jinhui Tian
- School of Nursing, Beijing University of Chinese Medicine, Beijing, 100144, China.
- Evidence-Based Medicine Center, Lanzhou University, Lanzhou, 730000, China.
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou, 730000, China.
| | - Zheng Li
- School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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6
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Tan N, Xia C, Yan X, Cao M, Yang F, He S, Zhang S, Cao M, Teng Y, Li Q, Wang J, Chen W. Extending breast cancer screening beyond age 45-64 years in China: A cost-effectiveness analysis. Cancer Lett 2025; 612:217457. [PMID: 39814166 DOI: 10.1016/j.canlet.2025.217457] [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: 02/19/2024] [Revised: 12/03/2024] [Accepted: 01/10/2025] [Indexed: 01/18/2025]
Abstract
The optimal breast cancer (BC) screening age in China remains uncertain. In this study, we evaluated the benefits, harms, and cost-effectiveness of lowering the screening starting age from 45 to 35 years and extending the stopping age from 64 to 79 years in Chinese women at an average risk of progressing BC. Biennial screening showed a lower incremental cost-effectiveness ratio (ICER) compared to annual screening. Extending the screening age beyond 45-64 years in certain scenarios increased the number of false-positive results and each averted breast cancer deaths. Specifically, extending the starting age to 35 years reduced overdiagnosis rate to 10.8 % and had an incremental cost ratio of US$12,746 per quality-adjusted life year (QALY), falling below the cost-effectiveness threshold of US$18,346 per QALY. Regarding the ceasing age, the status quo (age 64 years) was found to be the optimal choice as it was proved to yield the majority of benefits with reduced harm and be the only option under the cost-effectiveness threshold. In summary, biennial screening for average-risk women aged 35-64 years is the most cost-effective approach strategy, aligning with The National Health Commission's screening program for cervical and breast cancer.
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Affiliation(s)
- Nuopei Tan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Changfa Xia
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinxin Yan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Maomao Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Yang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Siyi He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shaoli Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mengdi Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Teng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qianru Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiachen Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Loap P, Uakkas A, Allali S, Bouziane J, Fourquet A, Kirova Y. Long-Term Results of Intensity Modulated Radiotherapy (IMRT) with Helical Tomotherapy in Non-Metastatic Breast Cancer Patients: Final Analysis. Cancers (Basel) 2025; 17:544. [PMID: 39941910 PMCID: PMC11817461 DOI: 10.3390/cancers17030544] [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: 12/30/2024] [Revised: 01/23/2025] [Accepted: 01/30/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) is used in the breast cancer (BC) treatment for years now to obtain homogeneous dose distribution in the treated volumes and reduce the doses to organs at risk. The purpose of this study was to evaluate our experience in terms of local control, overall survival, progression free survival and adverse events in BC patients treated with IMRT-HT with long term follow-up. Methods: This study is a retrospective data analysis of patients irradiated with IMRT-HT. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups of the population. Long-term toxicities including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the independent predictors of the side effects. Results: Between 2009 and 2015, a total of 194 breasts in 179 women with nonmetastatic breast cancer were treated. Most of the tumors were grade III and N+. With a median follow-up of 10 years, we observed 9 local recurrences, 2 loco-regional recurrences, and 29 patients experienced metastatic disease. Only 18 patients are dear, of them 7 cases with breast cancer death. At 10 years, the Local recurrence free survival was 95.3% [95%CI: 92.1-98.5], the loco-regional relapse free survival was 94.5% [91.1-98.1]. The metastases free survival was 82.9% [76.9-89.3]. The progression free survival was 79.9 [73.6-86.7]. The cancer specific survival was 94.3%, and the overall survival 88% [82.8-93.5]. At long term, there were no cardiac, lung, thyroid, digestive radio induced toxicities. A small number of patients experienced grade I or II fibrosis. Conclusions: IMRT-HT could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy. IMRT-HT provides favourable long-term prognosis, while late toxicity is acceptable.
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Affiliation(s)
- Pierre Loap
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
| | - Abdelkarim Uakkas
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
| | - Sofiane Allali
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
| | - Jihane Bouziane
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
| | - Alain Fourquet
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
| | - Youlia Kirova
- Institut Curie, 25 rue d’Ulm, 75005 Paris, France; (P.L.); (A.U.); (S.A.); (J.B.)
- University of Versailles St Quentin, 78 Yvelines, 78000 Versailles, France
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8
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Ren Y, Li P, Xie Y, Xu J, Luo Q, Chen M, Liu R, Feng H, Chen Y, Liu Y, Bao C, Duan J, Li J, Lu W. Dual-responsive nanoparticles for enhanced drug delivery in breast Cancer chemotherapy. J Control Release 2025; 377:146-161. [PMID: 39549730 DOI: 10.1016/j.jconrel.2024.11.026] [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: 08/01/2024] [Revised: 11/09/2024] [Accepted: 11/11/2024] [Indexed: 11/18/2024]
Abstract
Drug delivery efficiency often affects chemotherapy outcome due to dense collagen barrier in tumor environment. Here, we report a nanoparticle capable of pH and glutathione dual-responsive drug delivery to enhance the efficacy of breast cancer chemotherapy. Maleiminated polyethylene glycol and polylactide block copolymer were synthesized as a core material, doxorubicin was encapsulated into the nanoparticle by self-assembly. Thiocollagenase and maleimide were connected on the nanoparticle surface by click chemistry, and further coated with chondroitin sulfate as a protective layer to form dual-responsive doxorubicin nanoparticle. The results showed that the nanoparticle had the ability to penetrate deep tumor tissue, to target on CD44 of cancer cell, and to release doxorubicin in cancer cell in response to pH and glutathione signals, demonstrating superior anticancer efficacy in breast cancer-bearing mice. In conclusion, the dual-responsive nanoparticle could be used as a drug carrier to enhance drug delivery in breast cancer chemotherapy.
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Affiliation(s)
- Yuxin Ren
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Peishan Li
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Ying Xie
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Jiarui Xu
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Qian Luo
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Ming Chen
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Rui Liu
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Hexuan Feng
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Yuling Chen
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Yixuan Liu
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Chunjie Bao
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Jialun Duan
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Jianwei Li
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China; School of Pharmacy, Changzhi Medical College, Changzhi 046000, China; Beijing Zhendong Guangming Pharmaceutical Research Institute Co., Ltd, Beijing 100080, China
| | - Wanliang Lu
- State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, China.
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Manturthi S, El-Sahli S, Bo Y, Durocher E, Kirkby M, Popatia A, Mediratta K, Daniel R, Lee SH, Iqbal U, Côté M, Wang L, Gadde S. Nanoparticles Codelivering mRNA and SiRNA for Simultaneous Restoration and Silencing of Gene/Protein Expression In Vitro and In Vivo. ACS NANOSCIENCE AU 2024; 4:416-425. [PMID: 39713729 PMCID: PMC11659891 DOI: 10.1021/acsnanoscienceau.4c00040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 10/21/2024] [Accepted: 10/22/2024] [Indexed: 12/24/2024]
Abstract
RNA-based agents (siRNA, miRNA, and mRNA) can selectively manipulate gene expression/proteins and are set to revolutionize a variety of disease treatments. Nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside cells to overcome their inherent limitations. Recent studies have focused on siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, cancer needs multitargeted approaches to selectively manipulate multiple gene expressions/proteins. In this proof-of-concept study, we developed NPs containing Luc-mRNA and siRNA-GFP as model agents ((M+S)-NPs) and showed that NPs can simultaneously deliver functional mRNA and siRNA and impact the expression of two genes/proteins in vitro. Additionally, after in vivo administration, (M+S)-NPs successfully knocked down GFP while introducing luciferase into a TNBC mouse model, indicating that our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted approaches for complex diseases like cancer.
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Affiliation(s)
- Shireesha Manturthi
- Department
of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Kidney
Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H
8L6, Canada
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Sara El-Sahli
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Yuxia Bo
- Department
of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Kidney
Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H
8L6, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
| | - Emma Durocher
- Department
of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Kidney
Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H
8L6, Canada
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Melanie Kirkby
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Alyanna Popatia
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Karan Mediratta
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Redaet Daniel
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Seung-Hwan Lee
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Umar Iqbal
- Human Health
Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
| | - Marceline Côté
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Lisheng Wang
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department
of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Suresh Gadde
- Department
of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H
8M5, Canada
- Kidney
Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H
8L6, Canada
- Ottawa
Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Centre
for Infection, Immunity, and Inflammation, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Ottawa-Carleton
Institute for Biomedical Engineering (OCIBME), Ottawa, ON K1S
5B6, Canada
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10
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Zhang X, Li Y, Zhang G, Ma C, Gao M. Trends in hospitalization for female breast and gynecological cancer in China from 2004 to 2020. Sci Rep 2024; 14:27105. [PMID: 39511297 PMCID: PMC11543805 DOI: 10.1038/s41598-024-78490-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 10/31/2024] [Indexed: 11/15/2024] Open
Abstract
Breast and gynecological cancers are common cancers with high mortality and have profound effects on the various physical functions of women. This study assessed trends in the number of hospitalizations, in-hospital mortality, length of stay (LOS), and hospital charges for female breast and gynecological cancer from 2004 to 2020. The data for this study come from the China Health Statistics Yearbook. Time trends of categorical variables were assessed with the Cochran-Armitage Test. The linear model was used to test for the trend of continuous variables. The hospitalizations for breast cancer increased from 15,204 to 276,387 (P for trend < 0.001) and gynecological cancer increased from 12,418 to 214,956 (P for trend < 0.001). The in-hospital mortality rate due to breast cancer decreased from 1.70 to 1.07% (P for trend < 0.001). Hospitalizations for both breast and gynecological cancer increased clearly, whether in urban or rural. The gap between urban and rural has narrowed. The average cost per hospitalization for breast cancer significantly increased. However, the average LOS for breast cancer gradually decreased (from 17.0 to 10.7 days, P for trend < 0.001). The average cost per hospitalization for gynecological cancer increased significantly. However, this steady downward trend was observed in the average LOS for gynecological cancer (from 10.34 to 6.69 days, P for trend = 0.003). The increase in hospitalizations and medical expenses for breast and gynecological cancer should encourage healthcare policymakers and healthcare system stakeholders to develop more cost-effective approaches to women's cancer management.
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Affiliation(s)
- Xinqiang Zhang
- Department of Radiophysical Technology, Shandong Cancer Hospital, Jinan, China
| | - Yuanyuan Li
- Department of Statistics and Programming, Qilu Pharmaceutical Co., Ltd, Jinan, China
| | - Guifang Zhang
- Department of Radiophysical Technology, Shandong Cancer Hospital, Jinan, China
| | - Changsheng Ma
- Department of Radiophysical Technology, Shandong Cancer Hospital, Jinan, China
| | - Min Gao
- Department of Radiophysical Technology, Shandong Cancer Hospital, Jinan, China.
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11
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Ram S, More-Adate P, Tagalpallewar AA, Pawar AT, Nagar S, Baheti AM. An in-silico investigation and network pharmacology based approach to explore the anti-breast-cancer potential of Tecteria coadunata (Wall.) C. Chr. J Biomol Struct Dyn 2024; 42:9650-9661. [PMID: 37655689 DOI: 10.1080/07391102.2023.2252091] [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: 11/03/2022] [Accepted: 08/21/2023] [Indexed: 09/02/2023]
Abstract
Uncontrolled cell proliferation is a common definition of cancer. After lung carcinoma, breast neoplasm is the second-most prevalent kind of cancer. The majority of breast cancer cells and healthy breast cells both have receptors for circulating oestrogen and progesterone. In order to promote the development and division of cancer cells, oestrogen and progesterone bind to the receptors and may collaborate with growth factors (such as oncogenes and mutant tumour suppressor genes). As per the literature, Tecteria coadunata (Wall.) C. Chr. has anticancer, antioxidant and anti-inflammatory potential. After the hydroalcoholic extraction of this rhizome, total of 200 phytochemicals were retrieved from HR-LCMS analysis. In this current study, Network pharmacology was carried out to explore the rationale of Tecteria coadunata (Wall.) C. Chr. by using different database using Cytoscape software. The network depicted the interaction of Bioactives with their targets and their association with several disease, especially breast cancer. Tecteria coadunata (Wall.) C. Chr. has offered new relationship with variety of genes and its applications in different types of breast cancers. Further Gene Ontology was carried out and it showed key targets were TP53, BRCA2, PGR and CHEK 2. Further Signalling pathways were also enriched. Flex-X software was used for molecular docking studies, and it verified that Dopaxanthin, Dantrolene and Orotidin shows the highest binding affinities with key targets. Additionally, Pharmacokinetic analysis revealed that all top three lead compounds which follows the Lipinski Rule (Rule of three) without interrupting the conditions of bioavailability with minimal toxicity.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Shraddha Ram
- School of Health Sciences and Technology, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India
| | - Pallavi More-Adate
- School of Health Sciences and Technology, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India
| | - Amol A Tagalpallewar
- School of Health Sciences and Technology, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India
| | - Anil T Pawar
- School of Health Sciences and Technology, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India
| | - Shuchi Nagar
- Bioinformatics Research Centre, Dr. D.Y. Patil. Biotechnology & Bioinformatics Institute, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Akshay M Baheti
- School of Health Sciences and Technology, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India
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12
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Anvar MT, Rashidan K, Arsam N, Rasouli-Saravani A, Yadegari H, Ahmadi A, Asgari Z, Vanan AG, Ghorbaninezhad F, Tahmasebi S. Th17 cell function in cancers: immunosuppressive agents or anti-tumor allies? Cancer Cell Int 2024; 24:355. [PMID: 39465401 PMCID: PMC11514949 DOI: 10.1186/s12935-024-03525-9] [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] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open
Abstract
T helper (Th) 17 cells, a distinct subset of Th lymphocytes, are known for their prominent interleukin (IL)-17 production and other pro-inflammatory cytokines. These cells exhibit remarkable plasticity, allowing them to exhibit different phenotypes in the cancer microenvironment. This adaptability enables Th17 cells to promote tumor progression by immunosuppressive activities and angiogenesis, but also mediate anti-tumor immune responses through employing immune cells in tumor setting or even by directly converting toward Th1 phenotype and producing interferon-gamma (IFN-γ). This dual role of Th17 cells in cancer makes it a double-edged sword in encountering cancer. In this review, we aim to elucidate the complexities of Th17 cell function in cancer by summarizing recent studies and, ultimately, to design novel therapeutic strategies, especially targeting Th17 cells in the tumor milieu, which could pave the way for more effective cancer treatments.
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Affiliation(s)
- Milad Taghizadeh Anvar
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kimiya Rashidan
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nima Arsam
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ashkan Rasouli-Saravani
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Yadegari
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Ahmadi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeynab Asgari
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Ghorbani Vanan
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Farid Ghorbaninezhad
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Safa Tahmasebi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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13
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Bojarska J, Breza M, Borowiecki P, Madura ID, Kaczmarek K, Ziora ZM, Wolf WM. An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions. ROYAL SOCIETY OPEN SCIENCE 2024; 11:40962. [PMID: 39386982 PMCID: PMC11462612 DOI: 10.1098/rsos.240962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 10/12/2024]
Abstract
Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular 'chameleonicity' related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the (R)-(2-tert-butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene (1), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C-H…O and C-O…π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of 'atoms-in-molecules' (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand-protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood-brain barrier permeation was also revealed.
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Affiliation(s)
- Joanna Bojarska
- Chemistry Department, Institute of Ecological and Inorganic Chemistry, Technical University of Lodz, 116 Zeromskiego St., Lodz90-924, Poland
| | - Martin Breza
- Department of Physical Chemistry, Slovak Technical University, Radlinskeho 9, BratislavaSK-81237, Slovakia
| | - Paweł Borowiecki
- Laboratory of Biocatalysis and Biotransformation, Department of Drugs Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, 75 Koszykowa St., Warsaw00-662, Poland
| | - Izabela D. Madura
- Faculty of Chemistry, Warsaw University of Technology, 3 Noakowskiego St., Warsaw00-664, Poland
| | - Krzysztof Kaczmarek
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Zeromskiego St., Lodz90-924, Poland
| | - Zyta M. Ziora
- Institute for Molecular Bioscience, The University of Queensland, St LuciaQLD 4072, Australia
| | - Wojciech M. Wolf
- Chemistry Department, Institute of Ecological and Inorganic Chemistry, Technical University of Lodz, 116 Zeromskiego St., Lodz90-924, Poland
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14
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Xu W, Li A, Yackel HD, Sarta ML, Salner A, Judge MP. Dietary consumption patterns in breast cancer survivors: Pilot evaluation of diet, supplements and clinical factors. Eur J Oncol Nurs 2024; 72:102678. [PMID: 39159551 DOI: 10.1016/j.ejon.2024.102678] [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: 04/24/2024] [Revised: 07/13/2024] [Accepted: 07/16/2024] [Indexed: 08/21/2024]
Abstract
PURPOSE Adherence to dietary intake guidelines is recommended for optimal nutrition and outcomes in breast cancer survivors. The purpose of this study was to examine dietary quality in a cohort of breast cancer survivors related to current guidelines, guiding further education-based research. METHODS This exploratory evaluation examined compliance with current dietary guidelines. Data collected included demographics, medical histories and repeated, three-day 24-h dietary recalls. Women with early-stage breast cancer (n = 97) who completed breast cancer treatment between 6 and 24 months were recruited. Descriptive statistics and frequencies were calculated for demographic and lifestyle characteristics, reported fish consumption, body mass index categories, supplement consumption, and adequacy of macronutrient and micronutrient consumption (classified as below, meeting, or exceeding needs). RESULTS In this cohort, 28.9% were classified as overweight and 35% were obese. The mean dietary macronutrient consumption was 44.3% (±8.9%) carbohydrates, 36.6% (±7.3%) fat, and 17.3% (±4.7%) protein. Additionally, 32.3% participants consumed >45 g sugar/d. The mean n-6 to n-3 ratio was 8.0 (±3.3):1. Further, 38% of survivors reported consuming less than 1 serving of fish per week. Participants consumed between 0 and 1.03 servings of fish per day, with an average consumption of 0.16 (±0.26) servings per day and 61.5% (n = 59) consuming 0 servings per day. The mean daily combined dietary and supplement consumption of multiple micronutrients was below the Recommended Daily Allowance for Vitamin D (30%), Calcium (52.6%), Magnesium (42.1%), and Vitamin E (80%). CONCLUSION Breast cancer survivors 0.5-2 years post-treatment are not meeting recommended nutrition consumption guidelines for a number of nutrients. Findings suggested that nutrition therapy targeting weight loss through reduced sugar, total and saturated fat, while increasing foods rich in omega-3, and ensuring adequate micronutrient consumption would promote better nutritional consumption patterns and improve overall health during survivorship.
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Affiliation(s)
- Wanli Xu
- University of Connecticut School of Nursing, Storrs, CT, 06269, United States
| | - Aolan Li
- University of Connecticut Department of Statistics, CT, 06269, United States
| | - Hayley D Yackel
- Hartford Healthcare Cancer Institute at Hartford Hospital, CT, 06106, United States
| | - Michelle L Sarta
- Charlotte Hungerford Hospital, Hartford Healthcare, Torrington, CT, 06790, United States
| | - Andrew Salner
- Hartford Healthcare Cancer Institute at Hartford Hospital, CT, 06106, United States
| | - Michelle P Judge
- University of Connecticut School of Nursing, Storrs, CT, 06269, United States.
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15
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Deng J, Shi M, Wang M, Liao N, Jia Y, Lu W, Yao F, Sun S, Zhang Y. Age‑integrated breast imaging reporting and data system assessment model to improve the accuracy of breast cancer diagnosis. Mol Clin Oncol 2024; 21:60. [PMID: 39071974 PMCID: PMC11273246 DOI: 10.3892/mco.2024.2758] [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: 11/03/2023] [Accepted: 04/30/2024] [Indexed: 07/30/2024] Open
Abstract
Early diagnosis is an effective strategy for decreasing breast cancer mortality. Ultrasonography is one of the most predominant imaging modalities for breast cancer owing to its convenience and non-invasiveness. The present study aimed to develop a model that integrates age with Breast Imaging Reporting and Data System (BI-RADS) lexicon to improve diagnostic accuracy of ultrasonography in breast cancer. This retrospective study comprised two cohorts: A training cohort with 975 female patients from Renmin Hospital of Wuhan University (Wuhan, China) and a validation cohort with 500 female patients from Maternal and Child Health Hospital of Hubei Province (Wuhan, China). Logistic regression was used to construct a model combining BI-RADS score with age and to determine the age-based prevalence of breast cancer to predict a cut-off age. The model that integrated age with BI-RADS scores demonstrated the best performance compared with models based solely on age or BI-RADS scores, with an area under the curve (AUC) of 0.872 (95% CI: 0.850-0.894, P<0.001). Furthermore, among participants aged <30 years, the prevalence of breast cancer was lower than the lower limit of the reference range (2%) for BI-RADS subcategory 4A lesions but within the reference range for BI-RADS category 3 lesions, as indicated by linear regression analysis. Therefore, it is recommended that management for this subset of participants are categorized as BI-RADS category 3, meaning that biopsies typically indicated could be replaced with short-term follow-up. In conclusion, the integrated assessment model based on age and BI-RADS may enhance accuracy of ultrasonography in diagnosing breast lesions and young patients with BI-RADS subcategory 4A lesions may be exempted from biopsy.
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Affiliation(s)
- Jingwen Deng
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Manman Shi
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Min Wang
- Department of Thyroid and Breast Surgery, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430070, P.R. China
| | - Ni Liao
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yan Jia
- Department of Medical Ultrasonography, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Wenliang Lu
- Department of Thyroid and Breast Surgery, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430070, P.R. China
| | - Feng Yao
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Shengrong Sun
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yimin Zhang
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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16
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Xi Y, Zhou S, Long J, Zhou L, Tang P, Qian H, Jiang J, Hu Y. Construction of polypyrrole nanoparticles with a rough surface for enhanced chemo-photothermal therapy against triple negative breast cancer. NANOSCALE ADVANCES 2024; 6:d4na00434e. [PMID: 39247870 PMCID: PMC11378020 DOI: 10.1039/d4na00434e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 08/17/2024] [Indexed: 09/10/2024]
Abstract
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.
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Affiliation(s)
- Yuanyin Xi
- Breast Disease Center, Southwest Hospital, Army Medical University Chongqing 400038 China
| | - Shiqi Zhou
- Department of Plastic, Reconstructive and Cosmetic Surgery, Xinqiao Hospital, Army Medical University Chongqing 400037 China
| | - Junhui Long
- Department of Dermatology, The 958th Army Hospital of the Chinese People's Liberation Army China
| | - Linxi Zhou
- Breast Disease Center, Southwest Hospital, Army Medical University Chongqing 400038 China
| | - Peng Tang
- Breast Disease Center, Southwest Hospital, Army Medical University Chongqing 400038 China
| | - Hang Qian
- Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Army Medical University Chongqing 400037 China
| | - Jun Jiang
- Breast Disease Center, Southwest Hospital, Army Medical University Chongqing 400038 China
| | - Ying Hu
- Breast Disease Center, Southwest Hospital, Army Medical University Chongqing 400038 China
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17
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Lai Y, Lin Y. Biological functions and therapeutic potential of CKS2 in human cancer. Front Oncol 2024; 14:1424569. [PMID: 39188686 PMCID: PMC11345170 DOI: 10.3389/fonc.2024.1424569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 07/23/2024] [Indexed: 08/28/2024] Open
Abstract
The incidence of cancer is increasing worldwide and is the most common cause of death. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Cyclin-dependent kinase subunit 2 (CKS2) is involved in cell cycle and proliferation processes, and based on these processes, CKS2 was identified as a cancer gene. CKS2 is expressed in a variety of tissues in the human body, but its abnormal expression is associated with cancer in a variety of systems. CKS2 is generally elevated in cancer, plays a role in almost all aspects of cancer biology (such as cell proliferation, invasion, metastasis, and drug resistance) through multiple mechanisms regulating certain important genes, and is associated with clinicopathological features of patients. In addition, CKS2 expression patterns are closely related to cancer type, stage and other clinical variables. Therefore, CKS2 is considered as a tool for cancer diagnosis and prognosis and may be a promising tumor biomarker and therapeutic target. This article reviews the biological function, mechanism of action and potential clinical significance of CKS2 in cancer, in order to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy and scientific research of cancer.
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Affiliation(s)
- Yueliang Lai
- Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China
- The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China
| | - Ye Lin
- Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China
- The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China
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18
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Andra O, Manea A, Nirestean A, Niculescu R, Elena-Gabriela S. Breast Cancer and Its Impact on Individual Personality Through a Dimensional Perspective: A Literature Review. Cureus 2024; 16:e64348. [PMID: 38993624 PMCID: PMC11239186 DOI: 10.7759/cureus.64348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2024] [Indexed: 07/13/2024] Open
Abstract
Psychiatric pathology stands out in contemporary society not only as independent but also through its association with other medical comorbidities such as neoplastic diseases. Specialized literature confirms over time the coexistence of these diseases. There is a tendency to develop various psychiatric manifestations such as mood disorders and somatoform disorders, as well as decompensation of underlying existing psychiatric pathologies (anxiety disorders and psychotic disorders) or personality disorders (a good example is the exacerbation of anxiety in obsessive-compulsive personality disorder). Breast cancer, like any disabling disease, affects the person's psyche and behaviors as a whole. It is scientifically proven that mental balance influences the quality of life of patients and also the evolution and prognosis of the disease, psychological processes being able to modulate the activity of the tumor process. It is necessary to expand clinical practice and research beyond the simple evaluation of symptoms, and the goal of treatment should not only be to reduce symptoms but also to improve in terms of both physically and mentally the quality of life of cancer patients.
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Affiliation(s)
- Oltean Andra
- Department of Psychiatry, Emergency Clinical County Hospital of Targu Mures, Targu Mures, ROU
| | - Andrei Manea
- Department of Radiology, Emergency Clinical County Hospital of Targu Mures, Targu Mures, ROU
| | - Aurel Nirestean
- Department of Psychiatry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, ROU
| | - Raluca Niculescu
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, ROU
| | - Strete Elena-Gabriela
- Department of Psychiatry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, ROU
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19
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Badu-Peprah A, Otoo OK, Amamoo M, Quarshie F, Adomako B. Breast imaging reporting and data system for sonography: Positive and negative predictive values of sonographic features in Kumasi, Ghana. Transl Oncol 2024; 45:101976. [PMID: 38697004 PMCID: PMC11070917 DOI: 10.1016/j.tranon.2024.101976] [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: 12/22/2023] [Revised: 04/15/2024] [Accepted: 04/27/2024] [Indexed: 05/04/2024] Open
Abstract
BACKGROUND Breast cancer is the most common female cancer globally. The method of choice for screening and diagnosing breast cancer is mammography, which is not widely available in Ghana as compared to ultrasonography. This study aimed to evaluate the sonographic features of solid breast lesions using the new sonographic Breast Imaging- Reporting and Data System (BI-RADS-US) lexicon for malignancy with histopathology as the gold standard. METHODS This was a prospective quantitative study that sonographically scanned female patients with breast masses and consecutively selected cases recommended for core biopsy from May 2018 to May 2021. Sixty (60) solid breast masses were described using the sonographic BI-RADS lexicon features. Lesion description and biopsy results from histopathology were compared and analyzed using Pearson's Chi-square test. Odds ratios, sensitivity, specificity, and predictive values were also calculated. Statistical significance level was set at p ≤ 0.05. RESULTS Irregular shape (p < 0.0001), spiculated mass margins (p < 0.0001), and not parallel mass orientation (p= 0.0007) were more commonly associated with malignant masses. The sensitivity of breast ultrasound for malignancy was 93.9 % and the specificity was 55.6 % with an overall accuracy rate of 76.6 %. The negative predictive value was 88.7 % and the positive predictive value was 72.1 %. Descriptors like irregular shape, non-parallel orientation, angular and spiculated margins, echogenic halo, and markedly hypoechoic internal content, demonstrated higher odds ratios for malignancy. CONCLUSIONS This study adds valuable insights to the diagnosis of breast cancer using the sonographic BI-RADS lexicon features. The results demonstrate that specific sonographic descriptors can effectively differentiate between benign and malignant breast masses.
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Affiliation(s)
- Augustina Badu-Peprah
- Radiology Directorate, Komfo Anokye Teaching Hospital, Kumasi, Ghana; Radiology Department, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Obed Kojo Otoo
- Radiology Directorate, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Mansa Amamoo
- Radiology Directorate, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Frank Quarshie
- Research Directorate, Klintaps College of Health and Allied Sciences, Klagon-Tema,Ghana
| | - Benjamin Adomako
- Research and Development Unit, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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Liu Y, Wen HK, Xu RX, Liu C, Li XH, Qin XD, Zhao YX, Jia YX, Luo DQ. Semisynthesis and antitumor activity of endertiin B and related triterpenoids from Ganoderma lucidum. Org Biomol Chem 2024; 22:4978-4986. [PMID: 38832762 DOI: 10.1039/d4ob00641k] [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: 06/05/2024]
Abstract
Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 μM and 12.12 ± 0.95 μM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.
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Affiliation(s)
- Yu Liu
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - Hong-Kai Wen
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - Rui-Xuan Xu
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - Chang Liu
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - Xiao-Han Li
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - Xiang-Dong Qin
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
| | - You-Xing Zhao
- Hainan Institute for Tropical Agricultural Resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, People's Republic of China
| | - Yan-Xing Jia
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, and Chemical Biology Center, Peking University, Beijing, China
| | - Dou-Qiang Luo
- College of Life Science, Hebei University, Baoding, China.
- Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, China
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21
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Bellavita R, Piccolo M, Leone L, Ferraro MG, Dardano P, De Stefano L, Nastri F, Irace C, Falanga A, Galdiero S. Tuning Peptide-Based Nanofibers for Achieving Selective Doxorubicin Delivery in Triple-Negative Breast Cancer. Int J Nanomedicine 2024; 19:6057-6084. [PMID: 38911501 PMCID: PMC11193445 DOI: 10.2147/ijn.s453958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 04/10/2024] [Indexed: 06/25/2024] Open
Abstract
Introduction The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options. Purpose In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy. Methods Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed. Results The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox. Discussion We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
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Affiliation(s)
- Rosa Bellavita
- Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Napoli, Italy
| | - Marialuisa Piccolo
- Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Napoli, Italy
| | - Linda Leone
- Department of Chemical Sciences, University of Napoli “Federico II”, Naples, Italy
| | - Maria Grazia Ferraro
- Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Napoli, Italy
- School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Principia Dardano
- Institute of Applied Sciences and Intelligent Systems, Consiglio Nazionale delle Ricerche, Naples, Italy
| | - Luca De Stefano
- Institute of Applied Sciences and Intelligent Systems, Consiglio Nazionale delle Ricerche, Naples, Italy
| | - Flavia Nastri
- Department of Chemical Sciences, University of Napoli “Federico II”, Naples, Italy
| | - Carlo Irace
- Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Napoli, Italy
| | - Annarita Falanga
- Department of Agricultural Science, University of Naples “Federico II”, Portici, Italy
| | - Stefania Galdiero
- Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Napoli, Italy
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Raikwar S, Yadav V, Jain S, Jain SK. Antibody-conjugated pH-sensitive liposomes for HER-2 positive breast cancer: development, characterization, in vitro and in vivo assessment. J Liposome Res 2024; 34:239-263. [PMID: 37594466 DOI: 10.1080/08982104.2023.2248505] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/27/2023] [Accepted: 08/04/2023] [Indexed: 08/19/2023]
Abstract
The object of the current study was to develop and evaluate trastuzumab-conjugated Paclitaxel (PTX) and Elacridar (ELA)-loaded PEGylated pH-sensitive liposomes (TPPLs) for site-specific delivery of an anticancer drug. In this study, paclitaxel is used as an anticancer drug which promotes microtubules polymerization and arrest cell cycle progression at mitosis and subsequently leading to cell death. The single use of PTX causes multiple drug resistance (MDR) and results failure of the therapy. Hence, the combination of PTX and P-glycoprotein inhibitor (ELA) are used to achieve maximum therapeutic effects of PTX. Moreover, monoclonal antibody (trastuzumab) is used as ligand for the targeting the drug bearing carriers to BC. Thus, trastuzumab anchored pH-sensitive liposomes bearing PTX and ELA were developed using thin film hydration method and Box-Behnken Design (BBD) for optimizing various formulation variables. The optimized liposomes undergo characterization such as vesicle size, PDI, and zeta potential, which were observed to be 122 ± 2.14 nm, 0.224, and -15.5 mV for PEGylated pH-sensitive liposomes (PEG-Ls) and 134 ± 1.88 nm, 0.238, and -13.98 mV for TPPLs, respectively. The results of the in vitro drug release study of both formulations (PEG-Ls and TPPLs) showed enhanced percentage drug release at an acidic pH 5 as compared to drug release at a physiological pH 7.4. Further, the in vitro cytotoxicity studies were performed in the SK-BR-3 and MDA-MB-231 cell lines. The cellular uptake study of FITC-loaded TPPLs in SK-BR-3 cells showed greater uptake than FITC-loaded PEG-Ls, while in MDA-MB-231 cells there was no significant difference in cell uptake between FITC-loaded TPPLs and FITC-loaded PEG-Ls. Hence, it can be concluded that the HER-2 overexpressing cancer cell line (SK-BR-3) was showed better cytotoxicity and cell uptake of TPPLs than the cells that expressed low levels of HER2 (MDA-MB-231). The in vivo tumor regression study, TPPLs showed significantly more tumor burden reduction i.e. up ∼74% as compared to other liposomes after 28 days. Furthermore, the in vivo studies of TPPLs showed a minimal toxicity profile, minimal hemolysis, higher tumor tissue distribution, and superior antitumor efficacy as compared to other formulations. These studies confirmed that TPPLs are a safe and efficacious treatment for breast cancer.
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Affiliation(s)
- Sarjana Raikwar
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.), India
| | - Vivek Yadav
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India
| | - Sanyog Jain
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India
| | - Sanjay K Jain
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.), India
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Xue JD, Xiang WF, Cai MQ, Lv XY. Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer. Front Oncol 2024; 14:1332148. [PMID: 38835366 PMCID: PMC11148273 DOI: 10.3389/fonc.2024.1332148] [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: 11/02/2023] [Accepted: 04/26/2024] [Indexed: 06/06/2024] Open
Abstract
Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.
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Affiliation(s)
- Juan-di Xue
- The School of Basic Medicine Sciences of Lanzhou University, Lanzhou, China
| | - Wan-Fang Xiang
- School/Hospital of Stomatology of Lanzhou University, Lanzhou, China
| | - Ming-Qin Cai
- School/Hospital of Stomatology of Lanzhou University, Lanzhou, China
| | - Xiao-Yun Lv
- The School of Basic Medicine Sciences of Lanzhou University, Lanzhou, China
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24
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Farghadani M, Sanei P. MRI Evaluation of Mass-Like and None-Mass-Like-Proven Breast Cancer from Moderate-to-High Background Enhancement. Adv Biomed Res 2024; 13:36. [PMID: 39234434 PMCID: PMC11373728 DOI: 10.4103/abr.abr_221_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 01/29/2022] [Accepted: 02/05/2022] [Indexed: 09/06/2024] Open
Abstract
Background Breast cancer is considered one of the most prevalent cancers among females worldwide. The aim of this study was to assess the magnetic resonance imaging (MRI) patterns of female breast cancer, and also the prevalence of mass-like and nonmass-like lesions among these patients. Materials and Methods 32 patients with proven breast cancer (based on their pathologic findings and background parenchymal enhancement [BPE] of their magnetic resonance [MR] images) were included in this cross-sectional study which was performed from 2017 to 2019 in Isfahan, Iran, using a1.5 Tesla (Achieva Philips, Netherland) MRI scanner system. The MR sequences (noncontrast image and at least two contrast-enhanced images) were done in the prone position for studied patients. Results It was found that 68.8% (n = 44) and 31.2% (n = 20) of breast cancers were suffered from moderate and severe BPE, respectively. Furthermore, the prevalence of mass-like nonmass-like and both tumors were 43.8%, 43.8%, and 12.4%, respectively. Pathological studies indicated that 50%, 37.5%, and 12.5% of cancers were ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and DCIS, respectively. In addition, a significant relationship between MRI characteristics and pathologic findings was found for IDC and DCIS (P = 0.03). Conclusion Based on the results of this study, the relationship between BPE level and MRI finding including mass-like or nonmass-like lesions in biopsy-proven breast cancers was not significant.
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Affiliation(s)
- Maryam Farghadani
- Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parinaz Sanei
- Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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25
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Wang Y, Bai Z, Liu Q, Yu H, Tang Z, Liu X, Liu Q. Analysis on status quo and related factors of delays in diagnosis and treatment of breast cancer in Ningxia Hui Autonomous Region. Medicine (Baltimore) 2024; 103:e37826. [PMID: 38669416 PMCID: PMC11049709 DOI: 10.1097/md.0000000000037826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 03/15/2024] [Indexed: 04/28/2024] Open
Abstract
This study aimed to explore factors contributing to the delays in the diagnosis and treatment of breast cancer (BC) in Ningxia Hui Autonomous Region. We conducted a cohort analysis of 1012 patients with BC diagnosed at the General Hospital of Ningxia Medical University between January 2018 and December 2019. Sociodemographic data were collected through questionnaires, and clinical data were gathered and analyzed from relevant databases. Furthermore, observations were made regarding delays in the diagnosis and treatment of BC, followed by an analysis of the correlations between patient delay and both sociological factors within the population and clinical factors specific to patients with BC. Subsequently, the factors associated with patient delay and system delay were examined using Cox regression analysis, along with the inclusion of neoadjuvant therapy. In the prevention and treatment of BC in Ningxia, the patient delay rate was 33.20%, the diagnosis delay rate was 17.89%, the treatment delay rate was 0.0099% and the system delay rate was 41.60%. There was a higher proportion of patient delay and system delay in aged patients (age ≥ 61 years) with rural registered permanent residence (RPR), multiple clinical symptoms (such as nipple spillage, axillary abnormalities, etc), a T4 tumor size classification, and the initial use of neoadjuvant therapy. Besides, significant positive correlations were observed between patient delay and system delay time with BC stage. Patients aged 51 to 60 and those with molecular types (Limanal1B: ki-67 > 14%, Limanal1B: HER-2 positive) were prone to patient delay, whereas molecular characteristics influenced system delay, unrelated to sociodemographic factors. The study identifies significant age, residency, and tumor molecular subtype correlations with diagnostic and treatment delays in Ningxia's patients with BC, predominantly affecting women aged 41 to 60, especially urban dwellers. These findings underscore the need for targeted interventions to reduce delays and improve BC care in this region.
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Affiliation(s)
- Yuchen Wang
- Department of Third Oncology Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Zhoulan Bai
- Department of Radiotherapy, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Qingyuan Liu
- Department of Third Oncology Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hui Yu
- Department of Third Oncology Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Zhenning Tang
- Department of Third Oncology Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Xiang Liu
- Ningxia Medical University, Yinchuan, China
| | - Qilun Liu
- Department of Third Oncology Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
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Huang Q, Zheng S, Gu H, Yang Z, Lu Y, Yu X, Guo G. The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells. Acta Biochim Biophys Sin (Shanghai) 2024; 56:564-575. [PMID: 38449391 DOI: 10.3724/abbs.2024005] [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: 03/08/2024] Open
Abstract
Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and ZEB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo. In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy.
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Affiliation(s)
- Qidi Huang
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Shurong Zheng
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Huayan Gu
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Zhi Yang
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yiqiao Lu
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xia Yu
- Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Guilong Guo
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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Cirocchi R, Matteucci M, Randolph J, Duro F, Properzi L, Avenia S, Amato B, Iandoli R, Tebala G, Boselli C, Covarelli P, Sapienza P. Anatomical variants of the intercostobrachial nerve and its preservation during surgery, a systematic review and meta-analysis. World J Surg Oncol 2024; 22:92. [PMID: 38605346 PMCID: PMC11007944 DOI: 10.1186/s12957-024-03374-w] [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: 11/16/2023] [Accepted: 03/28/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND The anatomic variants of the intercostobrachial nerve (ICBN) represent a potential risk of injuries during surgical procedure such as axillary lymph node dissection and sentinel lymph node biopsy in breast cancer and melanoma patients. The aim of this systematic review and meta-analysis was to investigate the different origins and branching patterns of the intercostobrachial nerve also providing an analysis of the prevalence, through the analysis of the literature available up to September 2023. MATERIALS AND METHODS The protocol for this study was registered on PROSPERO (ID: CRD42023447932), an international prospective database for reviews. The PRISMA guideline was respected throughout the meta-analysis. A systematic literature search was performed using PubMed, Scopus and Web of Science. A search was performed in grey literature through google. RESULTS We included a total of 23 articles (1,883 patients). The prevalence of the ICBN in the axillae was 98.94%. No significant differences in prevalence were observed during the analysis of geographic subgroups or by study type (cadaveric dissections and in intraoperative dissections). Only five studies of the 23 studies reported prevalence of less than 100%. Overall, the PPE was 99.2% with 95% Cis of 98.5% and 99.7%. As expected from the near constant variance estimates, the heterogeneity was low, I2 = 44.3% (95% CI 8.9%-65.9%), Q = 39.48, p = .012. When disaggregated by evaluation type, the difference in PPEs between evaluation types was negligible. For cadaveric dissection, the PPE was 99.7% (95% CI 99.1%-100.0%) compared to 99.0% (95% CI 98.1%-99.7%). CONCLUSIONS The prevalence of ICBN variants was very high. The dissection of the ICBN during axillary lymph-node harvesting, increases the risk of sensory disturbance. The preservation of the ICBN does not modify the oncological radicality in axillary dissection for patients with cutaneous metastatic melanoma or breast cancer. Therefore, we recommend to operate on these patients in high volume center to reduce post-procedural pain and paresthesia associated with a lack of ICBN variants recognition.
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Affiliation(s)
- Roberto Cirocchi
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy.
| | - Matteo Matteucci
- Department of Medicine and Surgery, University of Milan, Milan, 20122, Italy
| | - Justus Randolph
- Georgia Baptist College of Nursing, Mercer University, Atlanta, GA, 30341, USA
| | - Francesca Duro
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy
| | - Luca Properzi
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy
| | - Stefano Avenia
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy
| | - Bruno Amato
- Department of Public Health, University of Naples "Federico II", Naples, 80131, Italy
| | - Ruggiero Iandoli
- Department of General Surgery, P.O Frangipane Ariano Irpino, Avellino, 83031, Italy
| | - Giovanni Tebala
- Department of Digestive and Emergency Surgery, AOSP of Terni, Terni, 05100, Italy
| | - Carlo Boselli
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy
| | - Piero Covarelli
- Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy
| | - Paolo Sapienza
- Department of Surgery, "Sapienza" University of Rome, Roma, 00161, Italy
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Kirkpatrick DR, Kobayashi H, Walker HM, Tuttle RM. Initiation of Breast Cancer Screening at a Later Age May Disproportionately Impact Minority Groups: Review of Ohio Data (1996-2022). Am Surg 2024; 90:897-901. [PMID: 37993112 DOI: 10.1177/00031348231216487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2023]
Abstract
Among women with breast cancer, delays in diagnosis and earlier presentation have been documented among minority women. Consequently, initiation of breast cancer screening at a later age may disproportionately harm minority groups. This study seeks to determine whether minority women face a higher proportional risk of younger age breast cancer than their White peers. Using publicly available data from the Ohio Department of Public Health Data Warehouse, we constructed a database allowing for retrospective evaluation of all breast cancer patients in the state of Ohio from 1996 to 2020. White women represented the bulk of total breast cancer cases in each age group and overall; however, the proportion of cancers attributable to White women increased in each successively older cohort group: 80.7% of cases under age 40 up to 91.3% of the 80 or older group. By a significant margin, the opposite is true in minority groups with African American women accounting for 15% of cases under the age of 40, trending down to 7.8% of the 80 and older group. Comparison of the proportions of these groups demonstrates statistically significant proportional decreases among minority groups and statistically significant increases among White women. Our findings suggest that women of color in the Ohio population face a disproportionately high risk of being diagnosed with younger age breast cancer and support the findings of other authors who recommend tailoring breast cancer screening by racial cohort. Efforts should be made to promote younger-age screening for minority women to prevent disproportionate harm.
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Affiliation(s)
| | | | - Hannah M Walker
- Department of Surgery, Wright State University Boonschoft School of Medicine, Dayton, OH, USA
| | - Rebecca M Tuttle
- Department of Surgery, Wright State University Boonschoft School of Medicine, Dayton, OH, USA
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Mitchell SM, Heise RM, Murray ME, Lambo DJ, Daso RE, Banerjee IA. An investigation of binding interactions of tumor-targeted peptide conjugated polyphenols with the kinase domain of ephrin B4 and B2 receptors. Mol Divers 2024; 28:817-849. [PMID: 36847923 PMCID: PMC9969393 DOI: 10.1007/s11030-023-10621-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 02/02/2023] [Indexed: 03/01/2023]
Abstract
Recent studies have shown that Ephrin receptors may be upregulated in several types of cancers including breast, ovarian and endometrial cancers, making them a target for drug design. In this work, we have utilized a target-hopping approach to design new natural product-peptide conjugates and examined their interactions with the kinase-binding domain of EphB4 and EphB2 receptors. The peptide sequences were generated through point mutations of the known EphB4 antagonist peptide TNYLFSPNGPIA. Their anticancer properties and secondary structures were analyzed computationally. Conjugates of most optimum of peptides were then designed by binding the N-terminal of the peptides with the free carboxyl group of the polyphenols sinapate, gallate and coumarate, which are known for their inherent anticancer properties. To investigate if these conjugates have a potential to bind to the kinase domain, we carried out docking studies and MMGBSA free energy calculations of the trajectories based on the molecular dynamics simulations, with both the apo and the ATP bound kinase domains of both receptors. In most cases binding interactions occurred within the catalytic loop region, while in some cases the conjugates were found to spread out across the N-lobe and the DFG motif region. The conjugates were further tested for prediction of pharmacokinetic properties using ADME studies. Our results indicated that the conjugates were lipophilic and MDCK permeable with no CYP interactions. These findings provide an insight into the molecular interactions of these peptides and conjugates with the kinase domain of the EphB4 and EphB2 receptor. As a proof of concept, we synthesized and carried out SPR analysis with two of the conjugates (gallate-TNYLFSPNGPIA and sinapate-TNYLFSPNGPIA). Results indicated that the conjugates showed higher binding with the EphB4 receptor and minimal binding to EphB2 receptor. Sinapate-TNYLFSPNGPIA showed inhibitory activity against EphB4. These studies reveal that some of the conjugates may be developed for further investigation into in vitro and in vivo studies and potential development as therapeutics.
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Affiliation(s)
- Saige M Mitchell
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA
| | - Ryan M Heise
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA
| | - Molly E Murray
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA
| | - Dominic J Lambo
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA
| | - Rachel E Daso
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA
| | - Ipsita A Banerjee
- Department of Chemistry, Fordham University, 441 E. Fordham Rd, Bronx, NY, 10458, USA.
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Lin Y, Zheng X, Chen Y, Nian Q, Lin L, Chen M. A real-world disproportionality analysis of FDA adverse event reporting system (FAERS) events for alpelisib. Heliyon 2024; 10:e27529. [PMID: 38496864 PMCID: PMC10944239 DOI: 10.1016/j.heliyon.2024.e27529] [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: 10/09/2023] [Revised: 02/29/2024] [Accepted: 03/01/2024] [Indexed: 03/19/2024] Open
Abstract
In this study, we delved into the safety profile of alpelisib, an FDA-approved treatment for hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer, and PIK3CA-Related Overgrowth Spectrum (PROS). Despite its approval, real-world, long-term safety data is lacking. Our research scrutinizes the FDA database to assess alpelisib 's safety. We retrospectively analyzed data from April 2019 to June 2023 using four algorithms. Among 7,609,450 reports, 6692 implicated alpelisib as the primary suspected drug, uncovering adverse events (AEs) across 26 organ systems. Notably, we identified 21 previously unlisted AEs. Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.
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Affiliation(s)
- Yu Lin
- Department of Orthopedics, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, 350400, PR China
- Department of Orthopedics, Fujian Medical University Union Hospital, NO.29 Xinquan road, Fuzhou, 350001, PR China
| | - Xinlei Zheng
- Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, 350400, PR China
| | - Yan Chen
- Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, 350400, PR China
| | - Qichun Nian
- Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, 350400, PR China
| | - Li Lin
- Department of Medical Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, NO.134 Dongjie Street, Fuzhou, 350001, Fujian, PR China
| | - Maohua Chen
- Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, 350400, PR China
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Esmat E, Haidary AM, Saadaat R, Rizvi SN, Aleena S, Haidari M, Hofiani SMS, Hussaini N, Hakimi A, Khairy A, Abdul-Ghafar J. Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan. BMC Cancer 2024; 24:388. [PMID: 38539179 PMCID: PMC10967195 DOI: 10.1186/s12885-024-12129-5] [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: 05/02/2023] [Accepted: 03/15/2024] [Indexed: 04/02/2024] Open
Abstract
BACKGROUND Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation. METHODOLOGY A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years. RESULTS One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases. CONCLUSION In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.
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Affiliation(s)
- Esmatullah Esmat
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Ahmed Maseh Haidary
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Ramin Saadaat
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Syeda Naghma Rizvi
- Aga Khan University School of Nursing and Midwifery (AKU-SoNaM), Karachi, Pakistan
| | - Syeda Aleena
- Aga Khan University School of Nursing and Midwifery (AKU-SoNaM), Karachi, Pakistan
| | - Mujtaba Haidari
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Sayed Murtaza Sadat Hofiani
- Department of Academic and Research, Postgraduate Medical Education (PGME), French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan
| | - Nasrin Hussaini
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Ahmadullah Hakimi
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Abdullatif Khairy
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan
| | - Jamshid Abdul-Ghafar
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mother and Children (FMIC), Kabul, Afghanistan.
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Dave S, Choudhury A, Alurkar SS, Shah AM. Is Ki-67 Really Useful as a Predictor for Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer? Indian J Surg Oncol 2024; 15:44-52. [PMID: 38511030 PMCID: PMC10948718 DOI: 10.1007/s13193-023-01822-9] [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: 05/24/2023] [Accepted: 09/21/2023] [Indexed: 03/22/2024] Open
Abstract
Neoadjuvant chemotherapy (NACT) is routinely offered to operable locally advanced breast cancer (LABC) patients desirous of breast conservation surgery and inoperable LABC patients. Pathological complete response (pCR) following chemotherapy is recognized as a surrogate for survival outcomes in high grade tumour subtypes. Many biological and tumor characters have been shown to predict pCR. The current study was performed with the aim of investigating the ability of Ki-67 in predicting pCR with NACT in breast cancer patients. A total of 105 patients with locally advanced breast cancer who completed NACT followed by surgery were included in this study from January 2020 till December 2022. Patients with advanced metastatic breast carcinoma, who did not give consent for NACT, who did not complete NACT and who did not undergo surgery were excluded. All patients were assessed for Ki-67 score on core-needle biopsy samples and response rate was assessed clinically and by histopathological examination of resected specimen. Quantitative variables were compared using unpaired t-test or Mann-Whitney 'U' test and for categorical variables Chi-square or Fisher's exact test were used. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive potential of Ki-67 expression levels in predicting pCR. To identify the predictive factors associated with pCR, univariate analysis was performed. The P value < 0.05 was considered as statistically significant. Mean age was 51.57 ± 10.8 years. 51 patients achieved clinical complete response (cCR) and 33 achieved pCR after NACT. Mean Ki-67 index in overall study population, in pCR group and no pCR group was 46.44 ± 22.92%, 51.60 ± 22.3% and 44.06 ± 22.7%, respectively. On univariate analysis, ER negativity, PR negativity and Her 2neu positivity were found predictive of pCR. On subgroup analysis, TNBC and Her 2neu positive sub groups were associated with higher cCR and pCR rate. We found no significant association between Ki-67 and pCR. This result may be confounded by the fact that a significant duration of the study was in the COVID-19 pandemic. Validation of this data is required in a large prospective study.
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Affiliation(s)
- Sukruti Dave
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Arpan Choudhury
- Department of Surgical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Shirish S. Alurkar
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Akash M. Shah
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
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Bruno E, Borea G, Valeriani R, De Luca A, Lo Torto F, Loreti A, Ribuffo D. Evaluating the Quality of Online Patient Information for Prepectoral Breast Reconstruction Using Polyurethane-Coated Breast Implants. JPRAS Open 2024; 39:11-17. [PMID: 38107035 PMCID: PMC10724489 DOI: 10.1016/j.jpra.2023.10.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/29/2023] [Indexed: 12/19/2023] Open
Abstract
Background An increasing number of patients are using online information regarding medical issues; however, the Internet is not subject to content ratings or filters. Unreliable information found on the web can heavily influence patients to the extent that it can lead to wrong decisions in the choice of treatment. In our daily experience we meet more informed patients and given the increasing use of polyurethane-coated implants in breast reconstruction in Europe, we wondered about the level of information available online. Our study aims to assess the quality of information available online on breast reconstruction with polyurethane-coated implants. Materials and Methods Assuming that the most used search engines are Google and Yahoo, we used a search strategy to identify online information regarding prepectoral breast reconstruction with polyurethane-coated implants. The selected websites were divided into 5 groups (practitioners, hospitals, healthcare portals, professional societies, and encyclopedias), and the quality of information was assessed by using an expanded version of the Ensuring Quality Information for Patients (EQIP) tool, which is a checklist applicable to all existing types of information. Results Fifty-six websites were selected and were categorized into 5 groups: 17 practitioners, 9 hospitals, 13 healthcare portals, 7 professional societies, 10 encyclopedias. The average score was 17 points (range: 12 - 25). We found 13 reliable websites with a score higher than 20 using the expanded version of the EQIP tool, whereas 43 were deemed unreliable, as they scored lower. Conclusion Proper communication between surgeon and patient is crucial in the therapeutic choice, as the available online information presently is scarce and can lead to wrong decisions if not properly verified.
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Affiliation(s)
- Edoardo Bruno
- Department of Plastic and Reconstructive Surgery, Sapienza Università di Roma, 00161, Rome, Italy
| | - Gianluca Borea
- Department of Plastic and Reconstructive Surgery, Sapienza Università di Roma, 00161, Rome, Italy
| | - Roberto Valeriani
- Department of Plastic and Reconstructive Surgery, Sapienza Università di Roma, 00161, Rome, Italy
- School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, via Montpellier 1, 00133, Rome, Italy
| | - Alessandro De Luca
- Department of Surgical Sciences, Sapienza Università di Roma, 00161, Rome, Italy
| | - Federico Lo Torto
- Department of Plastic and Reconstructive Surgery, Sapienza Università di Roma, 00161, Rome, Italy
| | - Andrea Loreti
- Department of Plastic and Reconstructive Surgery, Azienda Ospedaliera San Giovanni-Addolorata, Via Dell'Amba Aradam 8, 00161, Rome, Italy
| | - Diego Ribuffo
- Department of Plastic and Reconstructive Surgery, Sapienza Università di Roma, 00161, Rome, Italy
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Oladipupo AR, Alaribe SCA, Ogunlaja AS, Beniddir MA, Gordon AT, Ogah CO, Okpuzor J, Coker HAB. Structure-based molecular networking, molecular docking, dynamics simulation and pharmacokinetic studies of Olax subscorpioidea for identification of potential inhibitors against selected cancer targets. J Biomol Struct Dyn 2024; 42:1110-1125. [PMID: 37029762 DOI: 10.1080/07391102.2023.2198032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 03/28/2023] [Indexed: 04/09/2023]
Abstract
The rationale at the basis of targeted approach in oncology is radically shifting-from development of highly specific agents aiming at a single target towards molecules interfering with multiple targets. This study was performed to isolate and characterize bioactive molecules from Olax subscorpioidea stem and investigate their potentials as multi-targeted inhibitors against selected non-small cell lung cancer, breast cancer and chronic myelogenous leukemia oncogenic targets. Three compounds: β-sitosterol (1), α-amyrin (2) and stigmasterol (3) were isolated. The structures of 1 - 3 were elucidated by analysis of their spectroscopic data (NMR, MS and IR). To the best of our knowledge, this is the first time these compounds were isolated from O. subscorpioidea stems. Furthermore, integrated analysis of MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) workflow enabled dereplication and identification of 26 compounds, including alkaloids (remerine, boldine), terpenoids (3-hydroxy-11-ursen-28,13-olide, oleanolic acid), flavonoids (kaempferitrin, olax chalcone A) and saponins in O. subscorpioidea stem. Molecular docking studies revealed that some of the compounds, including olax chalcone A (-9.2 to -10.9 kcal/mol), 3-Hydroxy-11-ursen-28,13-olide (-6.6 to -10.2 kcal/mol), α-amyrin (-6.6 to -10.2 kcal/mol), stigmasterol (-7.7 to -10.1 kcal/mol), β-Sitosterol (-7 to -9.9 kcal/mol) and kaempferitrin (-7.7 to -9 kcal/mol) possessed good inhibitory potentials against selected cancer targets, when compared with reference inhibitors (-8.4 to -13.7 kcal/mol). A few of these compounds were shown to have considerable to favorable pharmacokinetic and drug-likeness properties. This study provides some rationale for the use of O. subscorpioidea in ethnomedicinal management of cancer and identifies some potential anticancer agents.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Akolade R Oladipupo
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, CMUL Campus, Lagos, Nigeria
| | - Stephenie C A Alaribe
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, CMUL Campus, Lagos, Nigeria
| | - Adeniyi S Ogunlaja
- Department of Chemistry, Nelson Mandela University, Port-Elizabeth, South Africa
| | - Mehdi A Beniddir
- Equipe Chimie des Substances Naturelles, BioCIS, Université Paris-Saclay, CNRS, Châtenay-Malabry, France
| | - Allen T Gordon
- Department of Chemistry, Nelson Mandela University, Port-Elizabeth, South Africa
| | - Celina O Ogah
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, CMUL Campus, Lagos, Nigeria
| | - Joy Okpuzor
- Department of Cell Biology & Genetics, Faculty of Science, University of Lagos, Yaba, Lagos, Nigeria
| | - Herbert A B Coker
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, CMUL Campus, Lagos, Nigeria
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Alahwal AM, Aljaaly H. The Top 100 Most-Cited Articles on the Treatment of Lymphedema. Cureus 2023; 15:e50887. [PMID: 38130906 PMCID: PMC10734209 DOI: 10.7759/cureus.50887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2023] [Indexed: 12/23/2023] Open
Abstract
A multitude of articles have been published on lymphedema management. We aim to identify the 100 most-cited articles on the management of lymphedema and perform a bibliometric analysis. In July 2023, a title-specific search was made on the Scopus database using "lymphedema" as the primary search term. The top 100 most-cited articles were reviewed. The top 100 most-cited articles on lymphedema received a mean citation of 81.7 ± 71.9 per article (range of 11.0 to 420.0). The publication dates ranged from 1977 to 2015. Most of the articles were original (63.0%), interventional studies (35.0%), randomized controlled trials (RCTs) (31.0%), and systematic reviews (32.0%). The largest number of articles (31) were found between 2007 and 2011. The top 10 articles' citation counts ranged from 164 to 420 (mean of 244.7 ± 83.9 citations). Five of these 10 articles were published between the years 1990 and 2000. Twenty-five countries contributed to the 100 most-cited articles. The United States produced the most number of articles (n = 32), followed by Italy (n = 11), Sweden, and Turkey, with seven articles each. Four of the top 10 articles were RCTs; the remaining six were systematic, retrospective, and prospective studies. The New England Journal of Medicine published two of these top 10 articles. Retrospective studies had the highest mean citation with 196.5, followed by RCTs with 100.9. We identified the 100 most-cited articles that depict the advancement in treatment methods for lymphedema. This extensive information directory can be an excellent source for further research.
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Affiliation(s)
- Abdullah M Alahwal
- Department of Otorhinolaryngology, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
| | - Hattan Aljaaly
- Department of Plastic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
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Mallepogu V, Sankaran KR, Pasala C, Bandi LR, Maram R, Amineni UM, Meriga B. Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA-MB-231 and MCF-7 breast cancer cells, an in-vitro and in silico studies. J Cell Biochem 2023; 124:1900-1918. [PMID: 37992132 DOI: 10.1002/jcb.30496] [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: 08/05/2023] [Revised: 10/10/2023] [Accepted: 10/30/2023] [Indexed: 11/24/2023]
Abstract
Epithelial-mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA-MB-231 and MCF-7 breast cancer cells. The apparent anticancer activity of UA on MDA-MB-231 and MCF-7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA-MB-231 and MCF-7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G0 /G1 phase, S phase, G2 /M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum-polarized-ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with -53.865, -48.971 and -40.617 MMGBSA (ΔGbind ) scores, respectively. The long-range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent.
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Affiliation(s)
- Venkataswamy Mallepogu
- Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
| | | | - Chiranjeevi Pasala
- Department of Bioinformatics, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - Lokesh Reddy Bandi
- Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
| | - Rajasekhar Maram
- Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
| | - Uma Maheswari Amineni
- Department of Bioinformatics, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - Balaji Meriga
- Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
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Tang LH, Dai M, Wang DH. ANO6 is a reliable prognostic biomarker and correlates to macrophage polarization in breast cancer. Medicine (Baltimore) 2023; 102:e36049. [PMID: 37960776 PMCID: PMC10637410 DOI: 10.1097/md.0000000000036049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 10/19/2023] [Indexed: 11/15/2023] Open
Abstract
To investigate the value of Anoctamin 6 (ANO6) in breast cancer (BC) by analyzing its expression, prognostic impact, biological function, and its association with immune characteristics. We initially performed the expression and survival analyses, followed by adopting restricted cubic spline to analyze the nonlinear relationship between ANO6 and overall survival (OS). Stratified and interaction analyses were conducted to further evaluate its prognostic value in BC. Next, we performed enrichment analyses to explore the possible pathways regulated by ANO6. Finally, the correlations between ANO6 and immune characteristics were analyzed to reveal its role in immunotherapy. Lower ANO6 expression was observed in BC than that in the normal breast group, but its overexpression independently predicted poor OS among BC patients (P < .05). Restricted cubic spline analysis revealed a linear relationship between ANO6 and OS (P-Nonlinear > 0.05). Interestingly, menopause status was an interactive factor in the correlation between ANO6 and OS (P for interaction = 0.016). Additionally, ANO6 was involved in stroma-associated pathways, and its elevation was significantly linked to high stroma scores and macrophage polarization (P < .05). Moreover, ANO6 was notably correlated with immune checkpoint expression levels, and scores of tumor mutation burden and microsatellite instability (all P < .05). ANO6 was an independent prognostic factor for BC, and might be a potential target for the BC treatment. Besides, ANO6 might affect BC progression via the regulation of stroma-related pathways and macrophage polarization.
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Affiliation(s)
- Long-Huan Tang
- General Surgical Department One, FengHua People's Hospital, Ningbo, China
| | - Min Dai
- Department of General Surgery, Hai'an Hospital Affiliated to Nantong University, Hai'an, China
| | - Dong-Hai Wang
- General Surgical Department One, FengHua People's Hospital, Ningbo, China
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Beverly Hery CM, Janse SA, Van Zee KJ, Naftalis EZ, Paskett ED, Naughton MJ. Factors associated with insomnia symptoms over three years among premenopausal women with breast cancer. Breast Cancer Res Treat 2023; 202:155-165. [PMID: 37542630 PMCID: PMC10504151 DOI: 10.1007/s10549-023-07058-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 07/16/2023] [Indexed: 08/07/2023]
Abstract
PURPOSE We examined longitudinal trends and factors associated with insomnia over 3 years in a cohort of young breast cancer patients. METHODS Women with stage I-III breast cancer at ≤ 45 years were recruited at five institutions from New York, Texas, and North Carolina, within 8 months of diagnosis (n = 836). Participants completed questionnaires every 6 months for 3 years. Linear mixed-effects models were used to examine insomnia over time, using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). We evaluated the relations of insomnia with demographic (age, race, education, income, employment, marital status), clinical (cancer stage, histologic grade, chemotherapy, radiation, hormone therapy, surgery, tumor size, body mass index, hot flashes), and social/behavioral variables (smoking status, social support, physical activity, depressive symptoms). RESULTS At baseline, 57% of participants met or exceeded the cut-off for clinical insomnia (WHIIRS score ≥ 9). Insomnia symptoms were most prevalent at baseline (p < 0.0001), but decreased significantly throughout follow-up (p < 0.001). However, 42% of participants still experienced insomnia symptoms 3 years after diagnosis. In multivariable models, older age (p = 0.02), hot flashes (p < 0.0001), and depressive symptoms (p < 0.0001) remained significantly associated with insomnia over time. CONCLUSIONS Insomnia symptoms were most frequent closer to breast cancer diagnosis and treatment, but persisted for some women who were older and those reporting higher hot flashes and depressive symptoms. Survivorship care should include assessing insomnia symptoms, particularly during and immediately after primary treatment. Implementing early interventions for sleep problems may benefit young breast cancer survivors and improve their quality of life.
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Affiliation(s)
- Chloe M Beverly Hery
- Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH, 43210, USA.
- Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
| | - Sarah A Janse
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Kimberly J Van Zee
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Elizabeth Z Naftalis
- Director of Breast Services, Health Texas Community Health Services Corporate, Dallas, TX, 75001, USA
| | - Electra D Paskett
- Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA
| | - Michelle J Naughton
- Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA
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Sullu Y, Tomak L, Demirag G, Kuru B, Ozen N, Karagoz F. Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system. Discov Oncol 2023; 14:190. [PMID: 37875716 PMCID: PMC10597910 DOI: 10.1007/s12672-023-00809-w] [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: 05/13/2023] [Accepted: 10/20/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels. METHODS A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system. RESULTS Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response. CONCLUSION Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.
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Affiliation(s)
- Yurdanur Sullu
- Department of Pathology, Faculty of Medicine, Ondokuz Mayis University, 55139, Samsun, Turkey.
| | - Leman Tomak
- Department of Biostatistics and Informatics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Guzin Demirag
- Department of Medical Oncology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Bekir Kuru
- Department of Surgery, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Necati Ozen
- Department of Surgery, Medical Park Hospital, Samsun, Turkey
| | - Filiz Karagoz
- Department of Pathology, Faculty of Medicine, Ondokuz Mayis University, 55139, Samsun, Turkey
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Roheel A, Khan A, Anwar F, Akbar Z, Akhtar MF, Imran Khan M, Sohail MF, Ahmad R. Global epidemiology of breast cancer based on risk factors: a systematic review. Front Oncol 2023; 13:1240098. [PMID: 37886170 PMCID: PMC10598331 DOI: 10.3389/fonc.2023.1240098] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/11/2023] [Indexed: 10/28/2023] Open
Abstract
Background Numerous reviews of the epidemiology and risk factors for breast cancer have been published previously which heighted different directions of breast cancer. Aim The present review examined the likelihood that incidence, prevalence, and particular risk factors might vary by geographic region and possibly by food and cultural practices as well. Methods A systematic review (2017-2022) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, reporting on epidemiological and risk factor reports from different world regions. Medical Subject Heading (MeSH) terms: "Breast neoplasm" "AND" country terms such as "Pakistan/epidemiology", "India/epidemiology", "North America/epidemiology", "South Africa/epidemiology" were used to retrieve 2068 articles from PubMed. After applying inclusion and exclusion terms, 49 papers were selected for systematic review. Results Results of selected articles were summarized based on risk factors, world regions and study type. Risk factors were classified into five categories: demographic, genetic and lifestyle risk factors varied among countries. This review article covers a variety of topics, including regions, main findings, and associated risk factors such as genetic factors, and lifestyle. Several studies revealed that lifestyle choices including diet and exercise could affect a person's chance of developing breast cancer. Breast cancer risk has also been linked to genetic variables, including DNA repair gene polymorphisms and mutations in the breast cancer gene (BRCA). It has been found that most of the genetic variability links to the population of Asia while the cause of breast cancer due to lifestyle modifications has been found in American and British people, indicating that demographic, genetic, and, lifestyle risk factors varied among countries. Conclusion There are many risk factors for breast cancer, which vary in their importance depending on the world region. However, further investigation is required to better comprehend the particular causes of breast cancer in these areas as well as to create efficient prevention and treatment plans that cater to the local population.
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Affiliation(s)
- Amna Roheel
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Aslam Khan
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Fareeha Anwar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Zunaira Akbar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Mohammad Imran Khan
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Mohammad Farhan Sohail
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Islamabad, Pakistan
| | - Rizwan Ahmad
- Department of Natural Products, College of Clinical Pharmacy, Imam Andulrahman Bin Faisal University, Rakah, Dammam, Saudi Arabia
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Chen Q, Hu Q, Chen Y, Shen N, Zhang N, Li A, Li L, Li J. PRMT6 methylation of STAT3 regulates tumor metastasis in breast cancer. Cell Death Dis 2023; 14:655. [PMID: 37813837 PMCID: PMC10562413 DOI: 10.1038/s41419-023-06148-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 10/11/2023]
Abstract
Overcoming distant metastasis stands as a paramount challenge in enhancing the outcomes of breast cancer treatments. Thus, delving deeper into comprehending the intricate mechanisms underlying breast cancer metastasis becomes imperative, offering potential avenues for pioneering therapeutic approaches. PRMT6, an arginine N-methyltransferase, possesses the ability to methylate both histone and non-histone proteins. It has been reported that methylation of non-histone proteins impacts their cellular localization, stability, and activation, consequently influencing tumor progression. However, the extent to which PRMT6-mediated non-histone protein methylation influences cancer cell metastasis, particularly in the context of breast cancer, remains elusive. In this study, we established that PRMT6 exerted a positive regulatory influence on breast cancer metastasis through both in vivo and in vitro experiments. Mechanistically, we innovatively revealed that PRMT6 asymmetrically di-methylated STAT3 at arginine 729 (STAT3 R729me2a). This modification proved indispensable for STAT3's membrane localization, its interaction with JAK2, STAT3 Y705 phosphorylation, and PRMT6-driven cancer cell metastasis. From a clinical perspective, we unearthed the promising potential of STAT3 R729me2a as a robust prognostic marker for predicting the overall survival time of breast cancer patients. In terms of therapeutic intervention, we demonstrated the significant capability of the PRMT6 inhibitor, EPZ020411, to curtail breast cancer metastasis both in vivo and in vitro. In sum, our study unveils the pivotal biological role of PRMT6-mediated STAT3 R729me2a in breast cancer metastasis and underscores the prospective utility of PRMT6 inhibitors as effective therapeutic strategies against STAT3-driven metastatic breast cancer.
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Affiliation(s)
- Qianzhi Chen
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qingyi Hu
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yan Chen
- Department of Hematology, Wuhan No. 1 Hospital, 430022, Wuhan, China
- Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Shen
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ning Zhang
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Anshu Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China
| | - Lei Li
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Junjun Li
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Pandurangappa V, Paruthy SB, Jamwal R, Singh A, Tanwar S, Kumar D, Pal S, Mohan SK, Das A, Trs PR. Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma Using Image-Guided Clip Placement. Cureus 2023; 15:e47763. [PMID: 38021852 PMCID: PMC10679795 DOI: 10.7759/cureus.47763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2023] [Indexed: 12/01/2023] Open
Abstract
Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington) to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor.
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Affiliation(s)
- Vikas Pandurangappa
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Shivani B Paruthy
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Rupi Jamwal
- Radiodiagnosis, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Arun Singh
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Sushant Tanwar
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Deepak Kumar
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Soni Pal
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Sajith K Mohan
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Anirban Das
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Prudhvi Raju Trs
- Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
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Chowdhry DN, Miles RC, Escamilla Guevara A, Flores EJ, Narayan AK. Prevalence of Modifiable Breast Cancer Risk Factors and Potential Opportunities for Primary Prevention Among Women Engaged in Screening Mammography: National Health Interview Survey Results. JOURNAL OF BREAST IMAGING 2023; 5:538-545. [PMID: 38416916 DOI: 10.1093/jbi/wbad054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Indexed: 03/01/2024]
Abstract
OBJECTIVE To determine the prevalence of modifiable breast cancer risk factors among women engaged in screening mammography using nationally representative cross-sectional survey data and to inform potential opportunities for breast facilities to contribute to primary prevention. METHODS 2018 National Health Interview Survey respondents who were women ages 40-74 years without history of breast cancer were included and then categorized based on whether they reported screening mammography within the prior two years. Proportions of these women reporting evidence-based modifiable breast cancer risk factors, including elevated body mass index (BMI), lack of physical activity, or moderate or heavy alcohol consumption were calculated and stratified by demographics. Multivariable logistic regression was used to estimate the association between these risk factors and sociodemographic characteristics. RESULTS Among 4989 women meeting inclusion criteria and reporting screening mammography, 79% reported at least one modifiable risk factor. Elevated BMI was the most reported risk factor (67%), followed by lack of physical activity (24%) and alcohol consumption (16%). The majority of each race/ethnicity category reported at least one modifiable risk factor, with the highest proportion reported by Black respondents (90%). Asian, college educated, and higher-income participants were less likely to have at least one modifiable risk factor. CONCLUSION Modifiable breast cancer risk factors are prevalent among women engaged in screening mammography. This provides potential opportunities for breast imaging facilities to contribute to the primary prevention of breast cancer by providing resources for lifestyle modification at the time of screening mammography.
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Affiliation(s)
- Divya N Chowdhry
- University of Rochester Medical Center, Division of Breast Imaging, Rochester, NY, USA
| | - Randy C Miles
- Denver Health Medical Center, Department of Radiology, Denver, CO, USA
| | | | - Efren J Flores
- Massachusetts General Hospital, Department of Radiology, Boston, MA, USA
| | - Anand K Narayan
- University of Wisconsin-Madison, Department of Radiology, Madison, WI, USA
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Taghehchian N, Lotfi M, Zangouei AS, Akhlaghipour I, Moghbeli M. MicroRNAs as the critical regulators of Forkhead box protein family during gynecological and breast tumor progression and metastasis. Eur J Med Res 2023; 28:330. [PMID: 37689738 PMCID: PMC10492305 DOI: 10.1186/s40001-023-01329-7] [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: 02/07/2023] [Accepted: 08/29/2023] [Indexed: 09/11/2023] Open
Abstract
Gynecological and breast tumors are one of the main causes of cancer-related mortalities among women. Despite recent advances in diagnostic and therapeutic methods, tumor relapse is observed in a high percentage of these patients due to the treatment failure. Late diagnosis in advanced tumor stages is one of the main reasons for the treatment failure and recurrence in these tumors. Therefore, it is necessary to assess the molecular mechanisms involved in progression of these tumors to introduce the efficient early diagnostic markers. Fokhead Box (FOX) is a family of transcription factors with a key role in regulation of a wide variety of cellular mechanisms. Deregulation of FOX proteins has been observed in different cancers. MicroRNAs (miRNAs) as a group of non-coding RNAs have important roles in post-transcriptional regulation of the genes involved in cellular mechanisms. They are also the non-invasive diagnostic markers due to their high stability in body fluids. Considering the importance of FOX proteins in the progression of breast and gynecological tumors, we investigated the role of miRNAs in regulation of the FOX proteins in these tumors. MicroRNAs were mainly involved in progression of these tumors through FOXM, FOXP, and FOXO. The present review paves the way to suggest a non-invasive diagnostic panel marker based on the miRNAs/FOX axis in breast and gynecological cancers.
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Affiliation(s)
- Negin Taghehchian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Lotfi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Zhang M, Wang M, Jiang Z, Fu Z, Ma J, Gao S. Candidate Oligo Therapeutic Target, miR-330-3p, Induces Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Cells via HDAC4. Breast J 2023; 2023:2875972. [PMID: 37711168 PMCID: PMC10499526 DOI: 10.1155/2023/2875972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 08/04/2023] [Accepted: 08/19/2023] [Indexed: 09/16/2023]
Abstract
Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p's link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant.
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Affiliation(s)
- Meng Zhang
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Mei Wang
- Department of Pathology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, China
| | - Zhiming Jiang
- Department of Ultrasound Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Ziyi Fu
- Department of Breast Disease Research Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Jingjing Ma
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Sheng Gao
- Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China
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Abstract
Breast cancer is the most commonly diagnosed cancer in women. Associated psychological symptoms include stress, adjustment difficulties, anxiety, depression, impaired cognitive function, sleep disturbances, altered body image, sexual dysfunction, and diminished overall well-being. Distress screening and assessment identifies women who will benefit from therapeutic interventions. Addressing these symptoms improves compliance with treatment and outcomes including disease-related outcomes, psychological symptoms, and quality of life. The most effective treatments include teaching coping skills such as expressing emotion, along with other structured cognitive behavioral, interpersonal, and mindfulness approaches. Patients should be provided these psychosocial supports throughout their cancer journey.
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Affiliation(s)
- Jennifer Kim Penberthy
- Department of Psychiatry & Neurobehavioral Sciences, UVA Cancer Center, University of Virginia School of Medicine & Health System, PO Box 800623, Charlottesville, VA 22908, USA.
| | - Anne Louise Stewart
- Department of Psychiatry & Neurobehavioral Sciences, UVA Cancer Center, University of Virginia School of Medicine & Health System, PO Box 800623, Charlottesville, VA 22908, USA
| | - Caroline F Centeno
- Department of Psychiatry & Neurobehavioral Sciences, UVA Cancer Center, University of Virginia School of Medicine & Health System, PO Box 800623, Charlottesville, VA 22908, USA
| | - David R Penberthy
- Department of Radiation Oncology, Penn State Cancer Institute, Penn State Health Milton S. Hershey College of Medicine, Hershey, PA, USA
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Yin M, Gu K, Cai H, Shu XO. Association between chronic pain and quality of life in long-term breast cancer survivors: a prospective analysis. Breast Cancer 2023; 30:785-795. [PMID: 37329439 DOI: 10.1007/s12282-023-01472-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/25/2023] [Indexed: 06/19/2023]
Abstract
PURPOSE Pain is a leading cause of disability worldwide and is highly prevalent among breast cancer survivors. Pain and quality of life (QOL) are associated in breast cancer patients undergoing active treatment, but little is known about the relationship between the two in long-term survivors. METHODS We evaluated associations between pain information collected during a 5-year post-diagnosis follow-up survey and QOL assessed by the SF-36 during a 10-year post-diagnosis survey for 2828 participants in the Shanghai Breast Cancer Survival Study. RESULTS The mean overall QOL score was 78.7 for the entire study population and decreased as pain severity and frequency measured at the 5-year timepoint increased (none: 81.9, mild: 75.9, moderate/severe: 70.4, infrequent: 76.7, frequent: 72.3; P < 0.001). Significant inverse associations were found between pain and all QOL domains, including pain at 10-years post-diagnosis after multivariate adjustments. Concurrent pain was significantly and strongly associated with QOL. Most of the associations between 5-years post-diagnosis pain and QOL at 10-years post-diagnosis persisted after further adjustment for concurrent pain. CONCLUSIONS Pain is associated prospectively and concurrently with poor QOL among long-term breast cancer survivors. Programs to manage pain are needed to improve QOL among breast cancer survivors.
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Affiliation(s)
- Michelle Yin
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University Institute of Medicine and Public Health, 2525 West End Avenue, Suite 600, Nashville, TN, 37203-1738, USA
| | - Kai Gu
- Department of Cancer Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People's Republic of China
| | - Hui Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University Institute of Medicine and Public Health, 2525 West End Avenue, Suite 600, Nashville, TN, 37203-1738, USA
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University Institute of Medicine and Public Health, 2525 West End Avenue, Suite 600, Nashville, TN, 37203-1738, USA.
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Wei W, Yi XL, Yang J, Liao H, Su D. CT values of contrast-enhanced CBBCT: A useful diagnostic tool for benign and malignant breast lesions. Acta Radiol 2023; 64:2379-2386. [PMID: 37287251 DOI: 10.1177/02841851231177379] [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: 06/09/2023]
Abstract
BACKGROUND Computed tomography (CT) value studies of cone-beam breast CT (CBBCT) mainly focus on the enhancement value or enhancement rate, and there has been no study on the CT value (Hounsfield units [HU]) of the lesion itself. PURPOSE To investigate the CT values under contrast-enhanced CBBCT (CE-CBBCT) and non-contrast-enhanced CBBCT (NC-CBBCT) in scanning for the differential diagnosis of benign and malignant breast lesions. MATERIAL AND METHODS A retrospective analysis was performed on 189 cases of mammary glandular tissues that underwent NC-CBBCT and CE-CBBCT examination. The qualitative CT values of the lesions, standardized Δ(L-A), standardized Δ*(L - G), standardized Δ(L-A) (Post 1st-Pre), and standardized Δ*(L-G) (Post 2nd-Post 1st) between the benign and malignant groups were compared. Prediction performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS In total, 58 cases were included in the benign group, 79 cases were included in the malignant group, and 52 cases were included in the normal group. The best diagnostic thresholds of CT values for L (Post 1st-Pre), Δ(L-A) (Post 1st-Pre), and Δ*(L-G) (Post 1st-Pre) were 49.5, 44, and 64.8 HU, respectively. The Δ(L-A) Post-1st rate values of CBBCT had medium diagnostic efficacy (AUC = 0.74, sensitivity = 76.6%, specificity = 69.4%). CONCLUSION CE-CBBCT can improve the diagnostic efficiency of breast lesions compared with NC-CBBCT. The CT values (HU) of lesions do not need to be standardized with fat and can be directly used in clinical differential diagnosis. The first contrast phase (60 s) is recommended to reduce the radiation exposure.
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Affiliation(s)
- Wei Wei
- Medical imaging Department, Guangxi Medical University Cancer Hospital and Guangxi Cancer Research Institute, Nanning, PR China
- Guangxi Key Clinical Specialty (Medical imaging Department), Nanning, PR China
- Dominant Cultivation Discipline of Guangxi Medical University Cancer Hospital (Medical imaging Department), PR China
| | - Xian Lin Yi
- Department of urology, WuMing Hospital of Guangxi Medical University, Nanning, PR China
| | - Jun Yang
- Medical imaging Department, Guangxi Medical University Cancer Hospital and Guangxi Cancer Research Institute, Nanning, PR China
- Guangxi Key Clinical Specialty (Medical imaging Department), Nanning, PR China
- Dominant Cultivation Discipline of Guangxi Medical University Cancer Hospital (Medical imaging Department), PR China
| | - Hai Liao
- Medical imaging Department, Guangxi Medical University Cancer Hospital and Guangxi Cancer Research Institute, Nanning, PR China
- Guangxi Key Clinical Specialty (Medical imaging Department), Nanning, PR China
- Dominant Cultivation Discipline of Guangxi Medical University Cancer Hospital (Medical imaging Department), PR China
| | - DanKe Su
- Medical imaging Department, Guangxi Medical University Cancer Hospital and Guangxi Cancer Research Institute, Nanning, PR China
- Guangxi Key Clinical Specialty (Medical imaging Department), Nanning, PR China
- Dominant Cultivation Discipline of Guangxi Medical University Cancer Hospital (Medical imaging Department), PR China
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Zhao Y, Xie X, Xie J, Zhang L, Li B, Liu J, Jiang H. Evaluation of Serum Fructosamine as Diagnostic Marker of Postoperative Recurrence in the Patients with Breast Cancer. BIOMED RESEARCH INTERNATIONAL 2023; 2023:6435776. [PMID: 37475819 PMCID: PMC10356523 DOI: 10.1155/2023/6435776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/11/2023] [Accepted: 06/17/2023] [Indexed: 07/22/2023]
Abstract
Objectives A series of laboratory parameters were screened to identify the proper serum markers that could be used to predict breast cancer recurrence at an early stage. Methods A case-control retrospective study on 224 patients without postoperative recurrence and 43 patients with postoperative recurrence of breast cancer was performed. The edgeR software package was used to identify the test indicators expressed differently between the two groups. Univariate analysis was used to screen for diagnostic marker that could predict postoperative recurrence of breast cancer. In addition, the differential test indicators at different time points from surgery to recurrence were collected in patients with postoperative recurrence of breast cancer as a verification database. Results We screened out three test indicators (TBA, GSP, and URBC) for differential expression, which were all expressed downregulated in the postoperative recurrence group of breast cancer. Univariate analysis suggested that only the difference in GSP levels between the two groups was statistically significant (P = 0.001). ROC curve analysis showed that the area under the curve of GSP was 0.662, while the area under the curve of GSP+AFP+CEA+CA125+CA153+age was increased to 0.828. In addition, serum GSP levels were significantly reduced after recurrence compared with before recurrence in breast cancer patients (P < 0.01). Conclusions In summary, GSP could be used for early diagnosis of breast cancer recurrence after surgery, and the predicted value of combining GSP, tumor markers, and age was better than that of individual indicators.
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Affiliation(s)
- Yuanqing Zhao
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
| | - Xuelong Xie
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
- Department of Laboratory Medicine, The Second People's Hospital of Yibin, Sichuan 644000, China
| | - Jingling Xie
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
| | - Limei Zhang
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
| | - Baolin Li
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
| | - Jinbo Liu
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
| | - Hui Jiang
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Sichuan 646000, China
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Sun J, Li L, Chen X, Yang C, Wang L. The circRNA-0001361/miR-491/FGFR4 axis is associated with axillary response evaluated by ultrasound following NAC in subjects with breast cancer. Biochem Biophys Rep 2023; 34:101481. [PMID: 37250983 PMCID: PMC10209698 DOI: 10.1016/j.bbrep.2023.101481] [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: 01/20/2023] [Revised: 04/21/2023] [Accepted: 04/27/2023] [Indexed: 05/31/2023] Open
Abstract
Background miR-491-5p has been reported to regulate the expression of FGFR4 and promote gastric cancer metastasis. Hsa_circ_0001361 was demonstrated to play an oncogenic role in bladder cancer invasion and metastasis by sponging the expression of miR-491-5p. This work aimed to study the molecular mechanism of the effect of hsa_circ_0001361 on axillary response in the treatment of breast cancer. Methods Ultrasound examinations was performed to evaluate the response of breast cancer patients receiving NAC treatment. Quantitative real-time PCR, IHC assay, luciferase assay and Western blot were performed to analyze the molecular interaction between miR-491, circRNA_0001631 and FGFR4. Results Patients with low circRNA_0001631 expression had a better outcome after NAC treatment. The expression of miR-491 was remarkably higher in the tissue sample and serum collected from patients with lower circRNA_0001631 expression. On the contrary, the FGFR4 expression was notably suppressed in the tissue sample and serum collected from patients with lower circRNA_0001631 expression when compared with patients with high circRNA_0001631 expression. The luciferase activities of circRNA_0001631 and FGFR4 were effectively suppressed by miR-491 in MCF-7 and MDA-MB-231 cells. Moreover, inhibition of circRNA_0001631 expression using circRNA_0001361 shRNA effectively suppressed the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Up-regulation of circRNA_0001631 expression remarkably enhanced the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Conclusion Our study suggested that the up-regulation of hsa_circRNA-0001361 could up-regulate the expression of FGFR4 via sponging the expression of miR-491-5p, resulting in the alleviated axillary response after neoadjuvant chemotherapy (NAC) in breast cancer.
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Affiliation(s)
| | | | | | - Chunfeng Yang
- Department of Ultrasound, Yantai Yuhuangding Hospital, Yantai, 264099, China
| | - Li Wang
- Department of Ultrasound, Yantai Yuhuangding Hospital, Yantai, 264099, China
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