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DNA mismatch repair in trinucleotide repeat instability

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Science China(Life Sciences) 2017年第10期60卷 1087-1092页

作者： Jinzhen Guo Luping Chen Guo-Min Li Department of Radiation Oncology University of Texas Southwestern Medical Center Department of Biochemistry and Molecular Medicine Norris Comprehensive Cancer Center University of Southern California Keck School of Medicine

Trinucleotide repeat expansions cause over 30 severe neuromuscular and neurodegenerative disorders, including Huntington's disease, myotonic dystrophy type 1, and fragile X syndrome. Although previous studies have substantially advanced the understanding of the disease biology, many key features remain unknown. DNA mismatch repair(MMR) plays a critical role in genome maintenance by removing DNA mismatches generated during DNA replication. However, MMR components,particularly mismatch recognition protein MutSβ and its interacting factors MutLα and MutLγ, have been implicated in trinucleotide repeat instability. In this review, we will discuss the roles of these key MMR proteins in promoting trinucleotide repeat instability.

关键词： DNA mismatch repair trinucleotide repeat instability neurodegenerative diseases MutSβ

Exportin 1 governs the immunosuppressive functions of myeloid-derived suppressor cells in tumors through ERK1/2 nuclear export

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Cellular & Molecular Immunology 2024年第8期21卷 873-891页

作者： Saeed Daneshmandi Qi Yan Jee Eun Choi Eriko Katsuta Cameron R.MacDonald Mounika Goruganthu Nathan Roberts Elizabeth A.Repasky Prashant K.Singh Kristopher Attwood Jianmin Wang Yosef Landesman Philip L.McCarthy Hemn Mohammadpour Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Cell Stress Biology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Oncology Yokohama City UniversityGraduate School of MedicineYokohamaJapan Department of cancer Genetics&Genomics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Biostatistics&Bioinformatics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Karyopharm Therapeutics NewtonMAUSA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNYUSA

Myeloid-derived suppressor cells(MDSCs)are a main driver of immunosuppression in *** the mechanisms that determine the development and immunosuppressive function of these cells could provide new therapeutic targets to improve antitumor ***,using preclinical murine models,we discovered that exportin 1(XPO1)expression is upregulated in tumor MDSCs and that this upregulation is induced by IL-6-induced STAT3 activation during MDSC ***1 blockade transforms MDSCs into T-cell-activating neutrophil-like cells,enhancing the antitumor immune response and restraining tumor ***,XPO1 inhibition leads to the nuclear entrapment of ERK1/2,resulting in the prevention of ERK1/2 phosphorylation following the IL-6-mediated activation of the MAPK signaling ***,XPO1 blockade in human MDSCs induces the formation of neutrophil-like cells with immunostimulatory ***,our findings revealed a critical role for XPO1 in MDSC differentiation and suppressive functions;exploiting these new discoveries revealed new targets for reprogramming immunosuppressive MDSCs to improve cancer therapeutic responses.

关键词： MDSCs Tumor Exportin 1 MAPK pathway

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

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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

New developments in the treatment of castration resistant prostate cancer

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Asian Journal of Andrology 2014年第4期16卷 555-560页

作者： Roxanne Wadia Daniel P Petrylak Department of Medicine Smilow Cancer Center Yale University School of Medicine Yale Comprehensive Cancer Center New Haven Connecticut USA

In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer （CRPC） have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRPC, as well as the new drugs and targets, which have evolved from this basic research.

关键词： castration resistant prostate cancer abiraterone enzalutamide chemotherapy docetaxel cabazitaxel PSMA antibody

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer

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Asian Journal of Andrology 2018年第3期20卷 215-220页

作者： Tanya B Dorff Neeraj Agarwal USC Keck School of Medicine USC Norris Comprehensive Cancer Center Genitourinary Oncology Los Angeles CA 90033 USA Hunts Man cancer Institute Universityof Utah 2000 Circle of Hope Salt Lake City UT 84112 USA

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

关键词： bisphosphonate bone metastases prostate cancer radiopharmaceutical receptor activator of nuclear factor-kappa B-ligand

MicroRNA-371a-3p as a blood-based biomarker in testis cancer

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Asian Journal of Urology 2021年第4期8卷 400-406页

作者： Hamed Ahmadi Thomas L.Jang Siamak Daneshmand Saum Ghodoussipour Department of Urology University of Southern California/Norris Comprehensive Cancer CenterLos AngelesCAUSA Section of Urologic Oncology Rutgers Cancer Institute of New JerseyNew BrunswickNJUSA

MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor *** almost 31 different miRNA clusters identified in germ cell tumors(GCTs),miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous *** is easily obtainable and correlates well with tumor *** multiinstitutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%e100%sensitivity and 90%e100%*** accuracy may address other unmet needs in the management of patients with *** studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II *** clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I *** its strong association with viable GCT after treatment with chemotherapy,miR-371a-3p does not seem to accurately predict the presence of teratoma in residual ***,standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.

关键词： Biomarker MicroRNA Non Seminoma Seminoma Testis cancer Tumor marker

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

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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： Dementia Nutrition Obesity Weight management

Hepatitis B among Asian Americans:Prevalence, progress, and prospects for control

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World Journal of Gastroenterology 2015年第42期21卷 11924-11930页

作者： Moon S Chen Jr Julie Dang Division of Hematology and Oncology Department of Internal Medicine University of California Davis School of Medicine Sacramento University of California Davis Comprehensive Cancer Center Sacramento National cancer Institute-funded National center for Reducing Asian American cancer Health Disparities University of California Davis Comprehensive Cancer Center Sacramento

After tobacco use, chronic hepatitis B(CHB) viral infections are the most important cause of cancer globally in that 1 out of 3 individuals have been infected with the hepatitis B virus(HBV). Though infection rates are low(< 1%) in the United States, Asian Americans who comprise about 6% of the population experience about 60% of the CHB burden. This paper reviews the magnitude of hepatitis B(HBV) burden among Asian Americans and the progress being made to mitigate this burden, primarily through localized, communitybased efforts to increase screening and vaccination among Asian American children, adolescents, and adults. This review brings to light that despite the numerous community-based screening efforts, a vast majority of Asian Americans have not been screened and that vaccination efforts, particularly for adults, are sub-optimal. Greater efforts to integrate screenings by providers within existing healthcare systems are urged. Evidence-based strategies are offered to implement CDC's three major recommendations to control and prevent hepatitis B through targeted screening and enhanced vaccination efforts.

关键词： Hepatitis B Asian Americans Chronic hepatitis B Va

De novo nucleotide biosynthetic pathway and cancer

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Genes & Diseases 2023年第6期10卷 2331-2338页

作者： Jie Chen Siqi Yang Yingge Li Xu Ziwen Pingfeng Zhang Qibin Song Yi Yao Huadong Pei cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430062China Lombardi comprehensive cancer center Georgetown University Medical CenterWashingtonD.C.20057USA

De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all *** purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and ***,the dysregulation of the de novo nucleotide biosynthetic pathway contributes to the development of many human diseases,such as *** has been shown that many enzymes in this pathway are overactivated in different *** this review,we summarize and update the current knowledge on the de novo nucleotide biosynthetic pathway,regulatory mechanisms,its role in tumorigenesis,and potential targeting opportunities.

关键词： Biosynthetic pathway cancer de novo synthesis Metabolism Nucleotide