检索结果-南通市图书馆

Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng Department of Hepatobiliary-Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China sidney Kimmel comprehensive cancer center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic targets.cancer-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and metabolism.Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been defined.However,the precise functions of these subtypes need to be studied and validated.Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets.Some clinical trials,including phase III trials targeting CAFs,have been performed recently.However,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be performed.This review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving CAFs.Additionally,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

Drug repurposing for cancer therapy

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

Genetic and epigenetic dependencies in colorectal cancer development

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Gastroenterology Report 2022年第1期10卷 115-131页

作者： Sehej Parmar Hariharan Easwaran cancer Genetics and Epigenetics OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMDUSA

Recent studies have mapped key genetic changes in colorectal cancer(CRC)that impact important pathways contributing to the multistep models for CRC initiation and development.In parallel with genetic changes,normal and cancer tissues harbor epigenetic alterations impacting regulation of critical genes that have been shown to play profound roles in the tumor initiation.Cumulatively,these molecular changes are only loosely associated with heterogenous transcriptional programs,reflecting the heterogeneity in the various CRC molecular subtypes and the paths to CRC development.Studies from mapping molecular alterations in early CRC lesions and use of experimental models suggest that the intricate dependencies of various genetic and epigenetic hits shape the early development of CRC via different pathways and its manifestation into various CRC subtypes.We highlight the dependency of epigenetic and genetic changes in driving CRC development and discuss factors affecting epigenetic alterations over time and,by extension,risk for cancer.

关键词： colorectal cancer epigenetics aging classification subtyping DNA methylation consensus molecular subtypes

Chemotherapy and its evolving role in the management of advanced prostate cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2014年第3期16卷 334-340页

作者： Michael T Schweizer Emmanuel S Antonarakis Prostate cancer Research Program Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland USA

Advanced prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins first described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer （CRPC）. Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing ＇level-1 evidence＇ that docetaxel-based chemotherapy led to prolongation in overall survival （OS）. This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efficacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents （e.g. abiraterone and enzalutamide） have also been shown to lead to a survival benefit in men with CRPC. With so many new treatment options available, a number of questions remain. These include： how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may benefit most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era.

关键词： cabazitaxel chemotherapy cyclophosphamide docetaxel mitoxantrone prostate cancer taxanes

Combining active immunotherapy with immune checkpoint blockade for the treatment of advanced prostate cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2012年第4期14卷 520-521页

作者： Emmanuel S Antonarakis Johns Hopkins sidney Kimmel comprehensive cancer center Baltimore MD 21231 USA

Combination immunotherapy is emerging as a promising approach for the treatment of advanced prostate cancer. This research highlight discusses the combination of a PSA-directed pox-viral vaccine and a monoclonal antibody blocking an important immune checkpoint molecule to treat men with metastatic castration- resistant prostate cancer. The results demonstrate feasibility and safety, as well as intriguing clinical responses to this combination therapy.

关键词： DOSE-ESCALATION TRIAL IPILIMUMAB

Prostate cancer epigenetics and its clinicalmplications

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2016年第4期18卷 549-558页

作者： Srinivasan Yegnasubramanian sidney Kimmel comprehensive cancer center Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA

Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

关键词： biomarkers DNA methylation epigenetics epigenomics prostatic neoplasms tumor

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2012年第2期14卷 177-186页

作者： Roisin M Connolly Michael A Carducci Emmanuel S Antonarakis Prostate cancer Research Program Department of Medical Oncology Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD 21231-1000 USA

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

关键词： androgen deprivation therapy androgen synthesis anti-androgen prostate cancer

Targeting glutamine metabolism enhances responses to platinum-based chemotherapy in triple-negative breast cancers(TNBC)

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genes & Diseases 2022年第6期9卷 1408-1411页

作者： Jiaxin Hong Yao-An Shen Chih-Yi Hsu Peng Huang Alicja Tomaszewski Edward Gabrielson Ie-Ming Shih Stephanie Gaillard Tian-Li Wang sidney Kimmel comprehensive cancer center and Department of Oncology BaltimoreMD 21231USA Department of Pathology Johns Hopkins University School of MedicineBaltimoreMD 21231USA cancer center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022PR China Department of Gynecology and Obstetrics Johns Hopkins University School of MedicineBaltimoreMD 21231USA

Reprogramming of metabolic pathways,a hallmark of human cancer,results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and survival.Previous studies have demonstrated that triplenegative breast cancers(TNBC)may use glutamine as an extracellular nutrient source to generate lipids,proteins,and nucleic acids.1 Glutamine catabolism in cancer cells also contributes to the production of the antioxidant,glutathione(GSH),which is critical for redox homeostasis and for protection of cells from oxidative stress elicited by reactive oxygen species(ROS).2 Considering TNBC cell lines are often dependent on glutamine for growth and survival,we sought to determine whether targeting glutaminolysis with a small molecule inhibitor,CB-839,in combination with platinum-based chemotherapy drug,would elicit significant anti-tumor activity.

关键词： metabolism TNBC chemotherapy

The role of nuclear receptors in regulation of Th 17/Treg biology and its implications for diseases

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2015年第5期12卷 533-542页

作者： Benjamin V. Park Fan Pan Immunology and Hematopoiesis Division Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School ofMedicine Baltimore MD 21287 USA

Nuclear receptors in the cell play essential roles in environmental sensing, differentiation, development, homeostasis, and metabolism and are thus highly conserved across multiple species. The anti-inflammatory role of nuclear receptors in immune cells has recently gained recognition. Nuclear receptors play critical roles in both myeloid and lymphoid cells, particularly in helper CD4＋ T-cell type 17 （Th17） and regulatory T cells （Treg）. Th17 and Treg are closely related cell fates that are determined by orchestrated cytokine signaling. Recent studies have emphasized the interactions between nuclear receptors and the known cytokine signals and how such interaction affects Th 17/Treg development and function. This review will focus on the most recent discoveries concerning the roles of nuclear receptors in the context of therapeutic applications in autoimmune diseases.

关键词： nuclear receptors regulation