{"title":"Advancement of Traditional Chinese Medicine in Regulation of Intestinal Flora: Mechanism-based Role in Disease Management.","authors":"Zezhen Wu, Yongru Chen, Dan Zhu, Yingmiao Zheng, Khan Barkat Ali, Kaijian Hou","doi":"10.2174/1574892816666210929164930","DOIUrl":"https://doi.org/10.2174/1574892816666210929164930","url":null,"abstract":"<p><p>Intestinal microecology is the largest and most complex human microecology. The intestinal microflora plays an important role in human health. Imbalance of intestinal microflora contributes to the occurrence and development of many diseases. Recently, the treatment of human diseases by regulating intestinal microflora has become a research topic of interest. Traditional Chinese medicine considers the whole human body as the central concept in disease treatment strategies. It advocates maintaining the coordination and balance of the functions of various organs and systems of the human body, including the intestinal microflora. Traditional Chinese medicine improves the metabolism and immune function of the human body by regulating the intestinal microflora. The intestinal microflora could trigger pharmacological activity or reduce toxicity of drugs through regulating metabolism, which enables traditional Chinese medicine formulations to exert their best therapeutic effects. This review summarized the relationship between the intestinal microflora and digestive system, tumors, and other diseases. Furthermore, the role of traditional Chinese medicine in the treatment of tumors, and other diseases is discussed. The relationship among traditional Chinese medicine and the common intestinal microflora, pathogenesis of human diseases, and effective intervention methods were elaborated. In addition, we explored the research progress of traditional Chinese medicine in the treatment of various human diseases by regulating intestinal microflora to provide new treatment concepts. There is a close relationship between traditional Chinese medicine and the intestinal microflora. Traditional Chinese medicine formulations contribute to maintain the natural balance of the intestinal tract and the intestinal microflora to achieve treatment effects. This paper summarizes the mechanism of action of traditional Chinese medicine formulations in regulating the intestinal microflora in the prevention and treatment of various diseases. Furthermore, it summarizes information on the application of the interaction between traditional Chinese medicine preparations and the regulation of intestinal microflora in the treatment of common human diseases. Intestinal microflora plays a key role in traditional Chinese medicine in maintaining the natural balance of physiology and metabolism of human body. It will provide a theoretical basis for the traditional Chinese medicine preparations in the prevention and treatment of common human diseases, and simulate future research on this aspect.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 2","pages":"136-144"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39493380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic and Therapeutic Values of Autophagy-related Genes in Triple-negative Breast Cancer.","authors":"Minling Liu, Lei Li, Shan Huang, Xiaofen Pan, Huiru Dai, Zhe-Sheng Chen, Yihang Pan, Shuo Fang","doi":"10.2174/1574892816666211130170149","DOIUrl":"https://doi.org/10.2174/1574892816666211130170149","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with a poor prognosis. Therefore, it is imperative to develop new prognostic or therapeutic biomarkers for TNBC.</p><p><strong>Objectives: </strong>To explore the prognostic and therapeutic values of autophagy-related genes (ARGs) in TNBC.</p><p><strong>Methods: </strong>Overall, 157 TNBC patients' data were obtained from The Cancer Genome Atlas database, and the ARGs were acquired from the Human Autophagy Database. Differentially expressed ARGs (DEGs) between tumor and normal tissues were identified, and the prognostic ARGs were developed using R software. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were both used to evaluate the accuracy of the signature. Patents about prognostic ARGs were reviewed through Worldwide Espacenet® and Patentscope®.</p><p><strong>Results: </strong>We obtained 28 DEGs and two prognostic ARGs (EIF4EBP1 and PARP1). The Kaplan- Meier survival curves showed that the survival rate of patients with low 2-ARG signature risk score was significantly higher than that of patients with high-risk score (P =0.003). ROC at 5 years indicated that the signature had good prognostic accuracy (AUC =0.929). The signature was independent of T, N, M, and TNM stages (P <0.05). The patent review suggested that many mTOR inhibitors alone or in combination with another anticancer agent have been provided for the treatment of many cancers and shown promising results. No drug patents about PARP1 overexpression were disclosed.</p><p><strong>Conclusion: </strong>We developed a 2-ARG signature (EIF4EBP1 and PARP1), which was an independent prognostic biomarker for TNBC. As EIF4EBP1 was upregulated in TNBC, mTOR inhibitors which blocked the mTOR/4EBP1/eIF4E pathway, may be a promising therapeutic strategy for TNBC.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 4","pages":"380-386"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39946884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Eudragit, a Nifty Polymer for Anticancer Preparations: A Patent Review.","authors":"Priyanka Kriplani, Kumar Guarve","doi":"10.2174/1574892816666211013113841","DOIUrl":"https://doi.org/10.2174/1574892816666211013113841","url":null,"abstract":"<p><strong>Background: </strong>Polymers are the backbone of modern pharmaceutical formulations and drug delivery technologies. Polymers that may be natural, synthetic, or semisynthetic are used to control the release of drugs in a pre-programmed fashion. The drug delivery systems are mainly prepared to enhance the bioavailability, site-specific release, sustained release, controlled release, i.e., to modify the release of drug from dosage form may be a tablet, capsule, etc. Objectives: The objective of the present study is to overview the recent patents concerning the application of eudragit in the prevention of cancer and other ailments. Eudragit polymers are polymethacrylates and may be anionic, cationic, or non-ionic polymers of methacrylic acid, dimethylaminoethyl methacrylates, and methacrylic acid esters in varying ratios. Eudragit is available in various grades with solubilities at different pH, thus helping the formulators design the preparation to have a well-defined release pattern.</p><p><strong>Methods: </strong>In this review, patent applications of eudragit in various drug delivery systems employed to cure mainly cancer are covered.</p><p><strong>Results: </strong>Eudragit has proved its potential as a polymer to control the release of drugs as coating polymer and formation of the matrix in various delivery systems. It can increase the bioavailability of the drug by site-specific drug delivery and can reduce the side effects/toxicity associated with anticancer drugs.</p><p><strong>Conclusion: </strong>The potential of eudragit to carry the drug may unclutter novel ways for therapeutic intercessions in various tumors.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 1","pages":"92-101"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39514519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Downregulation of miRNA-14669 Reverses Vincristine Resistance in Colorectal Cancer Cells through PI3K/AKT Signaling Pathway.","authors":"Weihua Dong, Fang Wang, Qingyu Liu, Tianyun Wang, Yun Yang, Peixia Guo, Xiang Li, Bingdi Wei","doi":"10.2174/1574892816666210806154225","DOIUrl":"https://doi.org/10.2174/1574892816666210806154225","url":null,"abstract":"<p><strong>Background: </strong>Vincristine (VCR) is a chemotherapeutic drug commonly used in the treatment of Colorectal Cancer (CRC). However, VCR drug resistance may result in reduced efficacy and even failure of chemotherapy in CRC treatment. MiRNA has been demonstrated to be associated with the sensitivity of tumor cells to chemotherapy.</p><p><strong>Objectives: </strong>This study aimed to identify a novel miRNA-14669 that can reverse vincristine resistance and sensitize drug-resistant colorectal cancer cells.</p><p><strong>Methods: </strong>High-throughput sequencing was performed to screen miRNAs that are associated with VCR drug resistance, and qRT-PCR was used for further validation. The miRNA mimic and inhibitor were designed and transfected into HCT-8,HCT-116 and HCT-8/VCR cells. Wound healing test examined the effect of the miRNA on the migration of colorectal cancer cells. Flow cytometry was used to evaluate cell apoptosis of HCT-8 cells. Survivin, Bcl-2, GST3, MDR1 and MRP1 expressions were detected by Western blot.</p><p><strong>Results: </strong>The expression of miRNA-14669 in HCT-8/VCR cells was 1.925 times higher than that of the HCT-8 cells. After transfecting with mimic miRNA, HCT-8 and HCT-116 cells showed an increased survival rate. The survival rate of HCT-8/VCR cells decreased by transfection of inhibitor. The inhibitor also sensitized HCT-8 and HCT-116 cells to VCR or 5-Fluorouracil (5-FU). The migratory ability of HCT-8 and HCT-116 cells increased by miRNA mimic while reduced by miRNA inhibitor. Overexpression of miRNA-14669 reduced apoptosis, while downregulation of miRNA- 14669 increased cell apoptosis in HCT-8 cells. The mechanism of the miRNA involved in drug resistance may be attributed to apoptosis of tumor cells, detoxification of GST3 and drug efflux induced by MDR1 and MRP1. PI3K / AKT is the signaling pathway related to drug resistance.</p><p><strong>Conclusion: </strong>We identified a novel miRNA-14669 that may be associated with the chemotherapeutic resistance in CRC cells.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 2","pages":"178-186"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39289591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheng-Xiong Zhang, Wei Liu, Bo Ai, Ling-Ling Sun, Zhe-Sheng Chen, Li-Zhu Lin
{"title":"Current Advances and Outlook in Gastric Cancer Chemoresistance: A Review.","authors":"Sheng-Xiong Zhang, Wei Liu, Bo Ai, Ling-Ling Sun, Zhe-Sheng Chen, Li-Zhu Lin","doi":"10.2174/1574892816666210929165729","DOIUrl":"https://doi.org/10.2174/1574892816666210929165729","url":null,"abstract":"<p><strong>Background: </strong>Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs.</p><p><strong>Objectives: </strong>Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy.</p><p><strong>Conclusion: </strong>The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 1","pages":"26-41"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39493381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of Acetylsalicylic Acid (Asa) on the Mechanical Properties of Breast Cancer Epithelial Cells.","authors":"Dornaz Milani, Siamak Khorramymehr, Behnoush Vasaghi-Gharamaleki","doi":"10.2174/1574892817666220104094846","DOIUrl":"https://doi.org/10.2174/1574892817666220104094846","url":null,"abstract":"<p><strong>Background: </strong>In most communities, the risk of developing breast cancer is increasing. By affecting the cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes and actin filaments, acetylsalicylic acid (Aspirin) has been shown to reduce the risk of breast cancer and prevent cell migration in both laboratory and clinical studies.</p><p><strong>Methods: </strong>The purpose of this study is to determine the mechanical properties of normal and cancerous breast tissue cells, as well as the short-term effect of aspirin on cancer cells. To this end, the mechanical properties and deformation of three cell types were investigated: healthy MCF-10 breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with a 5 μM aspirin solution. Atomic Force Microscopy (AFM) was used to determine the mechanical properties of the cells. Cell deformation was analyzed in all groups, and Young's modulus was calculated using the Hertz model.</p><p><strong>Results: </strong>According to the obtained data, cancer cells deformed at a rate half that of healthy cells. Nonetheless, when aspirin was used, cancer cells deformed similarly to healthy cells. Additionally, healthy cells' Young's modulus was calculated to be approximately three times that of cancer cells, which was placed closer to that of healthy cells by adding aspirin to Young's modulus.</p><p><strong>Conclusion: </strong>Cell strength appears to have increased due to aspirin's intervention on actin filaments and cytoskeletons, and the mechanical properties of breast cancer cells have become more similar to those of normal cells. The likelihood of cell migration and metastasis decreases as cell strength increases.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 4","pages":"410-415"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39873975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MiR-125b Inhibits Cell Proliferation and Induces Apoptosis in Human Colon Cancer SW480 Cells via Targeting STAT3.","authors":"Junhe Zhang, Wenwen Yang, Yunxi Xiao, Linlin Shan","doi":"10.2174/1574892816666210708165037","DOIUrl":"https://doi.org/10.2174/1574892816666210708165037","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer is one of the most common types of cancer worldwide. Multiple studies have unveiled the key role of microRNAs (miRNAs) in the development of various types of cancer. However, the mechanism of action of miR-125b in the development and progression of colon cancer remains unknown.</p><p><strong>Objectives: </strong>In this study, we explored the association of miR-125b and signal transducer and activator of transcription 3 (STAT3) and its role in the proliferation and apoptosis of SW480 colon cancer cells.</p><p><strong>Methods: </strong>The miR-125b expression in NCM460, SW480, HT29, and HCT8 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). SW480 cells were transfected with lentiviruses of GFP-miR-125b and GFP-NC to establish a stable miR-125b overexpression colon cancer cell model and a control model. The targeting relationship between miR-125b and STAT3 was analyzed using bioinformatics and verified by the dual-luciferase reporter gene assay. Cell proliferation and apoptosis were assessed using the Cell Counting Kit-8 assay and TUNEL staining. The expression levels of STAT3, Bcl-2, and Bax were analyzed using Western blot analysis.</p><p><strong>Results: </strong>It was found that the relative mRNA expression of miR-125b was decreased in SW480, HT29, and HCT8 cells compared with that in NCM460 cells (P<0.05). The luciferase reporter gene assay confirmed that miR-125b downregulated the STAT3 gene expression (P<0.05). Overexpression of miR-125b inhibited proliferation and promoted apoptosis in SW480 colon cancer cells and was accompanied by upregulated Bax expression and downregulated Bcl-2 expression (P<0.05). Re-expression of STAT3 promoted cell proliferation and inhibited cell apoptosis, whereas Bcl-2 expression increased, and Bax expression decreased (P<0.05).</p><p><strong>Conclusion: </strong>The miR-125b regulates the expression of Bax and Bcl-2 by downregulating the expression of STAT3, thereby inhibiting proliferation and inducing apoptosis of SW480 colon cancer cells.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 2","pages":"187-194"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39164797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haneen Amawi, Sayer Al-Azzam, Tasnim Alzanati, Neveen Altamimi, Alaa Hammad, Karem H Alzoubi, Charles R Ashby, Amit K Tiwari
{"title":"The Validity of Mobile Applications to Facilitate Patient Care Provided to Cancer Patients: Opportunities and Limitations.","authors":"Haneen Amawi, Sayer Al-Azzam, Tasnim Alzanati, Neveen Altamimi, Alaa Hammad, Karem H Alzoubi, Charles R Ashby, Amit K Tiwari","doi":"10.2174/1574892816666210728122304","DOIUrl":"https://doi.org/10.2174/1574892816666210728122304","url":null,"abstract":"<p><strong>Background: </strong>The use of health-related applications (apps) on smartphones has become widespread. This is especially of value during the ongoing SAR-COV-2 pandemic, where accessibility to health care services has been greatly limited. Patients with free access to apps can obtain information to improve their understanding and management of health issues. Currently, there are cancer-related apps available on iPhones and androids. However, there are no guidelines to control these apps and ensure their quality. Furthermore, these apps may significantly modify the patients' perception and knowledge about drug-related health services.</p><p><strong>Objectives: </strong>The aim of this study was to assess the convenience, quality, safety and efficacy of apps for cancer patient care.</p><p><strong>Methods: </strong>The study was conducted by searching all apps related to cancer care on both Google Play Store and Apple iTunes Store. A detailed assessment was then performed using the mobile application rating scale (MARS) and risk assessment tools.</p><p><strong>Results: </strong>The results indicated that on a scale from 1-5, 47% of the apps were rated ≥ 4. The MARS assessment of the apps yielded an overall quality rating of 3.38 ± 0.9 (mean ± SD). The visual appeal of the app was found to have a significant effect on app functionality and user engagement. The potential benefits of these apps come with challenges and limitations. Patents related to smartphone applications targeting patients were also discussed.</p><p><strong>Conclusion: </strong>We recommend a greater emphasis toward producing evidence-based apps. These apps should be rigorously tested, evaluated and updated by experts, particularly clinical pharmacists. Also, these apps may alter patient attitudes toward services provided by physicians and pharmacists. Finally, these apps should not replace in-person interactive health services.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"17 2","pages":"204-213"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39254900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of Nano Drug Delivery System (NDDS) in Cancer Therapy: A Perspective.","authors":"Junyu Liu, Shuqin Li, Jia Wang, Nannan Li, Jingna Zhou, Haixia Chen","doi":"10.2174/1574892817666220713150521","DOIUrl":"https://doi.org/10.2174/1574892817666220713150521","url":null,"abstract":"<p><strong>Background: </strong>Cancer is the biggest killer that threatens human health. Poor bioavailability and strong drug resistance of cancer drugs are common defects. In recent years, drug delivery therapy based on nanotechnology has become a focused research area, and nano drug delivery system has been widely studied in cancer treatment.</p><p><strong>Objectives: </strong>Based on the articles and patents published on the application of nano drug delivery systems in cancer treatment in the past five years, this paper summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in order to provide a reference for future anticancer research on nano drug delivery systems.</p><p><strong>Methods: </strong>This perspective summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in recent five years, and proposes the development direction of nano drug delivery systems in the future.</p><p><strong>Results: </strong>Based on the review of articles and patents, we found that the nano drug delivery system is mainly divided into encapsulated nano drug delivery system and covalently bound nanoprodrug delivery system. Its advantages in cancer treatment are mainly reflected in enhancing drug stability, improving bioavailability, reducing toxicity and better application in cancer diagnosis. However, nano drug delivery system is a new field of science, some of these drug delivery systems might have high toxicity and low bioavailability; the off-target phenomenon often occurs, and most studies are just focused on the early stage, its mechanism of action, clinical efficacy and patient tolerance, and the toxicity of treatment remains to be further investigated.</p><p><strong>Conclusion: </strong>This perspective systematically summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment based on the published articles and patents obtained in the last five years. Future research on nano drug delivery system should consider the potential risks, and stable and efficient nano drug delivery systems should be designed to treat cancer by changing or functionalizing the nanomaterial.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"18 2","pages":"125-132"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10624680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles L Wiseman, Alexander Kharazi, Vivekananda G Sunkari, Jacqueline L Galeas, Vito Dozio, Hind Hashwah, Eva Macúchová, William V Williams, Markus D Lacher
{"title":"Regression of Breast Cancer Metastases Following Treatment with Irradiated SV-BR-1-GM, a GM-CSF Overexpressing Breast Cancer Cell Line: Intellectual Property and Immune Markers of Response.","authors":"Charles L Wiseman, Alexander Kharazi, Vivekananda G Sunkari, Jacqueline L Galeas, Vito Dozio, Hind Hashwah, Eva Macúchová, William V Williams, Markus D Lacher","doi":"10.2174/1574892817666220518123331","DOIUrl":"10.2174/1574892817666220518123331","url":null,"abstract":"<p><strong>Background: </strong>SV-BR-1-GM, derived from a patient with grade 2 (moderately differentiated) breast cancer, is a GM-CSF-secreting breast cancer cell line with properties of antigen-presenting cells. SV-BR-1-GM and next-generation versions are covered by several pending and granted patents.</p><p><strong>Methods: </strong>We report findings from an open-label phase I, single-arm pilot study with irradiated SV-BR-1-GM cells in 3 breast and 1 ovarian cancer subjects. Inoculations were preceded by lowdose intravenous cyclophosphamide and followed by interferon-alpha2b injections into the SVBR- 1-GM inoculation sites. We assessed both cellular and humoral immune responses, and measured expression levels of SV-BR-1-GM HLA alleles.</p><p><strong>Results: </strong>Treatment was generally safe and well tolerated. Immune responses were elicited universally. Overall survival was more than 33 months for three of the four patients. As previously reported, one patient had prompt regression of metastases in lung, breast, and soft tissue. Following cessation of treatment, the patient relapsed widely, including in the brain. Upon retreatment, rapid tumor response was again seen, including complete regression of brain metastases. Consistent with a role of Class II HLA in contributing to SV-BR-1-GM's mechanism of action, this patient allele-matched SV-BR-1-GM at the HLA-DRB1 and HLA-DRB3 loci. We are in the process of developing next-generation SV-BR-1-GM, expressing patient-specific HLAs. Patent applications were filed in various jurisdictions. Thus far, one is granted, in Japan.</p><p><strong>Conclusion: </strong>A whole-cell immunotherapy regimen with SV-BR-1-GM cells induced regression of metastatic breast cancer. We develop intellectual property based on SV-BR-1-GM's predicted mechanism of action to develop additional whole-cell immunotherapies for cancer patients.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"18 2","pages":"224-240"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10624645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}