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Pseudo-or real progression?An ovarian cancer patient under nivolumab:A case report 预览
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作者 Mona Passler Eliane T Taube +1 位作者 Jalid Sehouli Klaus Pietzner 《世界临床肿瘤学杂志(英文版)》 2019年第7期247-255,共9页
BACKGROUND Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma.The first encouraging experience in ovarian cancer was reported for nivolumab,a fully hu... BACKGROUND Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma.The first encouraging experience in ovarian cancer was reported for nivolumab,a fully humanized anti-programmed death-1 antibody.Pseudoprogression is a new phenomenon associated with these novel immuno-oncologic agents.It can be explained by infiltrating leucocytes and edema that result in a temporary increase in tumor size and delayed subsequent shrinkage due to tumor cell destruction.CASE SUMMARY We report on a 47-year old patient with platinum-resistant ovarian cancer that was treated off-label with nivolumab 3mg/kg iv d1q14d.She first experienced classic pseudoprogression with inguinal lymph node swelling after cycle two and subsequent shrinkage.After 6 cycles she presented with rectal bleeding and progressive disease was diagnosed due to new tumor infiltration into the rectum.CONCLUSION Clinicians should be aware of pseudoprogression,its underlying mechanisms and strategies to discriminate pseudo-from real progression in ovarian cancer. 展开更多
关键词 Case report Nivolumab Clinical ONCOLOGY CHECKPOINT inhibition GYNECOLOGIC ONCOLOGY PSEUDOPROGRESSION Immunooncology
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Immunotherapy of hepatocellular carcinoma:strategies for combinatorial intervention
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作者 Mengxin Tian Yinghong Shi +1 位作者 Weiren Liu Jia Fan 《中国科学:生命科学英文版》 SCIE CAS CSCD 2019年第9期1138-1143,共6页
Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients wit... Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients with early-stage HCC develop recurrence by the time of follow-up.Immunotherapeutic intervention has emerged as a novel,effective treatment to delay the progression of aggressive tumors and suppress tumor recurrence and metastasis.However,few clinical immunotherapy trials have been conducted in HCC patients,and there is an unmet need for novel therapeutic strategies.The combination of conventional treatments with specific immunotherapeutic approaches may dramatically improve the efficacy of HCC treatment and the clinical outcome of HCC patients.In this review,we briefly summarize immunotherapy strategies and discuss new advances in combined immunotherapeutic approaches for the treatment of patients with liver cancer. 展开更多
关键词 HEPATOCELLULAR carcinoma IMMUNOTHERAPY IMMUNE CHECKPOINT INHIBITOR strategy combination therapy
NUMA架构下数据热度的内存数据库日志恢复技术 预览
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作者 吴刚 阿卜杜热西提·热合曼 +2 位作者 李梁 乔百友 韩东红 《计算机科学与探索》 CSCD 北大核心 2019年第6期941-949,共9页
在内存数据库故障恢复技术中,命令日志是针对内存数据库设计的粗粒度的、轻量级的日志记录方式。但在非统一内存访问(non-uniform memory access,NUMA)体系架构下面向数据的数据库设计中利用命令日志进行故障恢复时,由于数据访问频率不... 在内存数据库故障恢复技术中,命令日志是针对内存数据库设计的粗粒度的、轻量级的日志记录方式。但在非统一内存访问(non-uniform memory access,NUMA)体系架构下面向数据的数据库设计中利用命令日志进行故障恢复时,由于数据访问频率不均衡,导致负责高频数据恢复的CPU线程负载加重,而其他CPU相对空闲。针对这种工作负载不均衡所导致的恢复时间开销增大的情况,提出了NUMA体系架构下基于热度记录的内存数据库日志恢复算法。该算法中,每一条数据的访问次数作为该数据的热度记录下来。在并行恢复时,根据数据热度,将数据比较均衡地划分到各个节点的CPU线程执行恢复操作,以此来提高数据库的恢复速度。实验结果表明,该方案比NUMA架构下的常规恢复方案快,而且数据的热度越高,恢复速度的提升越明显,最高提升了19%。 展开更多
关键词 内存数据库 日志 检查点 故障恢复 非统一内存访问(NUMA)架构
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Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma 预览
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作者 Elena De Mattia Erika Cecchin +5 位作者 Michela Guardascione Luisa Foltran Tania Di Raimo Francesco Angelini Mario D’Andrea Giuseppe Toffoli 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第29期3870-3896,共27页
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., re... Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literatu 展开更多
关键词 Hepatocellular carcinoma PHARMACOGENETICS Genetic MARKERS SORAFENIB REGORAFENIB Immune CHECKPOINT inhibitors Cytochromes UDP GLUCURONOSYLTRANSFERASE 1A
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Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases
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作者 Zhen Xiang Yingyan Yu 《医学前沿:英文版》 CAS CSCD 2019年第1期24-31,共8页
Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the i... Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various open access databases, including The Cancer Genome Atlas and Gene Expression Omnibus, provide large volumes of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors? In this review, we introduced some methodologies on database selection, biomarker screening, current progress of immune checkpoint blockade in solid tumor treatment, possible mechanisms of drug resistance, strategies of overcoming resistance, and indications for immune checkpoint inhibitor therapy. 展开更多
关键词 IMMUNE CHECKPOINT BLOCKADE sensitivity resistance data MINING
Monitoring checkpoint inhibitors:predictive biomarkers in immunotherapy
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作者 Min Zhang Jingwen Yang +3 位作者 Wenjing Hua Zhong Li Zenghui Xu Qijun Qian 《医学前沿:英文版》 CAS CSCD 2019年第1期32-44,共13页
Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates o... Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors. 展开更多
关键词 IMMUNE CHECKPOINT COMPANION diagnosis PD-L1 tumor mutation BURDEN IMMUNE SCORE
Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma 预览
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作者 Changhoon Choi Gyu Sang Yoo +1 位作者 Won Kyung Cho Hee Chul Park 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第20期2416-2429,共14页
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor o... Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes;therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyteassociated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment. 展开更多
关键词 HEPATOCELLULAR carcinoma Radiation therapy IMMUNE CHECKPOINT INHIBITORS Abscopal effect
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Hepatocellular carcinoma:Therapeutic advances in signaling,epigenetic and immune targets 预览
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作者 Daniel Neureiter Sebastian Stintzing +1 位作者 Tobias Kiesslich Matthias Ocker 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第25期3136-3150,共15页
Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besid... Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here. 展开更多
关键词 Liver cancer IMMUNOTHERAPY CHECKPOINT inhibitors Targeted therapy Mouse model Biomarker Next-generation sequencing Non-alcoholic STEATOHEPATITIS Fibrosis Clinical trial
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基于检验点的移动云资源调度策略研究 预览
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作者 何利 曹启彦 《重庆邮电大学学报:自然科学版》 CSCD 北大核心 2019年第1期103-112,共10页
移动云以按需付费的方式交付给用户,其服务可靠性成为了用户最为关心的性能指标之一。容错资源调度策略常用于云平台中提供服务的可靠性,其中检验点技术是云平台中容错资源调度的一种主要手段。对Web云中检验点技术的原理进行了深入分析... 移动云以按需付费的方式交付给用户,其服务可靠性成为了用户最为关心的性能指标之一。容错资源调度策略常用于云平台中提供服务的可靠性,其中检验点技术是云平台中容错资源调度的一种主要手段。对Web云中检验点技术的原理进行了深入分析,重点讨论了基于检验点策略的容错资源调度方法,分别对预设故障概率服从泊松分布的固定间隔周期检验点容错策略及无预设故障概率的动态间隔周期检验点容错策略进行了深入的分析,比较了不同检验点技术的特点和问题。结合移动云的工作特点,提出了移动云环境下检验点技术未来的研究点。 展开更多
关键词 云计算 容错技术 检验点 资源调度
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Prospects for immunotherapy as a novel therapeutic strategy against hepatocellular carcinoma 预览
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作者 Yu Akazawa Toshihiro Suzuki +3 位作者 Toshiaki Yoshikawa Shoichi Mizuno Yasunari Nakamoto Tetsuya Nakatsura 《世界荟萃分析杂志》 2019年第3期80-95,共16页
Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, with a poor clinical prognosis. Many standard therapies are often considered for HCC treatment today;however, these conventional therapies often... Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, with a poor clinical prognosis. Many standard therapies are often considered for HCC treatment today;however, these conventional therapies often fail to achieve sufficiently effective clinical results. Today, HCC therapy is set to undergo a major revolution, owing to rapid developments in cancer immunotherapy, particularly immune checkpoint inhibitor therapy. Cancer immunotherapy is a novel and promising treatment strategy that differs significantly from conventional therapies in its approach to achieve antitumor effects. In fact, many cancer immunotherapies have been tested worldwide and shown to be effective against various types of cancer;HCC is no exception to this trend. For example, we identified a specific cancer antigen called glypican-3 (GPC3) and performed clinical trials of GPC3-targeted peptide vaccine immunotherapy in patients with HCC. Here, we present an overview of the immune mechanisms for development and progression of HCC, our GPC3-based immunotherapy, and immune checkpoint inhibitor therapy against HCC. Finally, we discuss the future prospects of cancer immunotherapy against HCC. We believe that this review and discussion of cancer immunotherapy against HCC could stimulate more interest in this promising strategy for cancer therapy and help in its further development. 展开更多
关键词 Hepatocellular carcinoma CANCER IMMUNOTHERAPY Immune CHECKPOINT inhibitor GLYPICAN-3 CANCER vaccine Clinical trials CYTOTOXIC T-LYMPHOCYTES
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Antibiotics and immunotherapy in gastrointestinal tumors: Friend or foe? 预览
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作者 Cong Yan Xiao-Xuan Tu +7 位作者 Wei Wu Zhou Tong Lu-Lu Liu Yi Zheng Wei-Qin Jiang Peng Zhao Wei-Jia Fang Hang-Yu Zhang 《世界临床病例杂志》 2019年第11期1253-1261,共9页
The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer pa... The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer patients with low immunity are vulnerable to all sorts of infections, such as respiratory tract infections and urinary tract infections. Moreover, cancer patients easily run into fever and neutropenia induced by myelosuppression. Therefore, antibiotics are used extensively and even overused in many conditions. However, because of the special anatomical location of the gastrointestinal tract, the antibiotic usage will bring changes to the intestinal flora. Besides, with the expanding popularity of immunotherapy, various factors affecting the efficacy of immune checkpoint inhibitors (ICIs) have been extensively explored, including cancer-associated inflammation and the local and systemic factors that lead to immunosuppression. Some biomarkers for ICIs, including the expression of PD-L1, tumor mutation load, and microbiota, also have been investigated, and many studies have confirmed that gut microbiota can affect the efficacy of immunotherapy. But further studies on the influence of antibiotics directly on immunotherapy are rare. In this review, we discuss the relationship between GI tumors and antibiotics, the current status of immunotherapy in GI tumors, and the influence of antibiotics on immunotherapy. 展开更多
关键词 ANTIBIOTICS IMMUNOTHERAPY Gastrointestinal tumor MICROBIOTA Immune CHECKPOINT inhibitors
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Immunotherapy for hepatocellular carcinoma:Current and future 预览
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作者 Michael P Johnston Salim I Khakoo 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第24期2977-2989,共13页
Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fat... Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fatty liver disease.Many patients present with advanced disease out with the criteria for transplant,resection or even locoregional therapy.Currently available therapeutics for HCC are effective in a small minority of individuals.However,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers,great opportunities now exist for treating HCC with newer and more sophisticated agents.Whilst checkpoint inhibitors are at the forefront of this revolution,other therapeutics such as inhibitory cytokine blockade,oncolytic viruses,adoptive cellular therapies and vaccines are emerging.Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response.Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional therapy.Together these agents are likely to generate new and exciting opportunities for treating HCC,which are summarized in this review. 展开更多
关键词 ADOPTIVE cell therapy CANCER VACCINE CHECKPOINT inhibitor Hepatocellular carcinoma IMMUNOTHERAPY Liver CANCER ONCOLYTIC virus
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Targeted and immune therapies for hepatocellular carcinoma:Predictions for 2019 and beyond 预览
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作者 Masatoshi Kudo 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第7期789-807,共19页
Systemic therapy for hepatocellular carcinoma(HCC)has markedly advanced since the survival benefit of a molecular targeted agent,sorafenib,were demonstrated in the SHARP and Asia Pacific trials in 2007.Treatment optio... Systemic therapy for hepatocellular carcinoma(HCC)has markedly advanced since the survival benefit of a molecular targeted agent,sorafenib,were demonstrated in the SHARP and Asia Pacific trials in 2007.Treatment options for patients with advanced HCC increased by sorafenib,and long-term survival for patients with advanced stage HCC has become possible to some extent.However,development of a more potent first-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction.Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016,but all of these clinical trials failed.On the other hand,clinical trials of 4 agents(regorafenib,lenvatinib,cabozantinib,and ramucirumab)succeeded in succession in 2017 and 2018,and their use in clinical practice is possible(regorafenib and lenvatinib)or underway(cabozantinib and ramucirumab).Furthermore,all of 5 clinical trials of combination therapy with transcatheter chemoembolization(TACE)plus a molecular targeted agent failed to date,however,the combination of TACE and sorafenib(TACTICS trials)was reported to be successful and presented at ASCO in 2018.Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing,which suggests treatment paradigm of HCC in all stages from early,intermediate and advanced stage,is expected to be changed drastically in the very near future. 展开更多
关键词 Hepatocellular carcinoma Molecular TARGETED agent IMMUNE CHECKPOINT INHIBITOR SORAFENIB Lenvatinib
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Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer
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作者 Jiaojie Wei Yang Long +7 位作者 Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He 《药学学报:英文版》 CSCD 2019年第4期819-831,共13页
Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod... Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer. 展开更多
关键词 CHECKPOINT BLOCKADE Immunotherapy IMMUNOGENIC cell death ANTI-METASTASIS Nanoparticle
Managing cardiotoxicity associated with immune checkpoint inhibitors
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作者 Sireesha Upadhrasta Hadi Elias +1 位作者 Keval Patel Lei Zheng 《慢性疾病与转化医学:英文版》 CSCD 2019年第1期6-14,共9页
Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied... Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology. 展开更多
关键词 IMMUNE CHECKPOINT inhibitor CARDIOTOXICITY IPILIMUMAB Nivolumab Pembrolizumab
Immunotherapy-based combination strategies for treatment of gastrointestinal cancers:current status and future prospects
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作者 Chenfei Zhou Jun Zhang 《医学前沿:英文版》 CAS CSCD 2019年第1期12-23,共12页
Strategies in comprehensive therapy for gastrointestinal (GI) cancer have been optimized in the last decades to improve patients, outcomes. However, treatment options remain limited for late-stage or refractory diseas... Strategies in comprehensive therapy for gastrointestinal (GI) cancer have been optimized in the last decades to improve patients, outcomes. However, treatment options remain limited for late-stage or refractory diseases. The efficacy of immune checkpoint inhibitors (ICIs) for treatment of refractory GI cancer has been confirmed by randomized clinical trials. In 2017, pembrolizumab was approved by the US Food and Drug Administration as the first agent for treatment of metastatic solid tumors with mismatch repair deficiency, especially for colorectal cancer. Given the different mechanisms, oncologists have focused on determining whether ICIs-based combination strategies could achieve higher efficacy than conventional therapy alone in late-stage or even front-line treatment of GI cancer. This review discusses the current status of combining immune checkpoint inhibitors with molecular targeted therapy, chemotherapy, or radiotherapy in GI cancer in terms of mechanisms, safety, and efficacy to provide basis for future research. 展开更多
关键词 GASTROINTESTINAL cancer IMMUNE CHECKPOINT INHIBITOR combi NATION therapy
PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives
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作者 Yumeng Wang Guiling Li 《医学前沿:英文版》 CAS CSCD 2019年第4期438-450,共13页
Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and pre... Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-l/PD-Ll-related therapeutic strategies for CC. 展开更多
关键词 PD-1 PD-L1 immune CHECKPOINT BLOCKADE antibody IMMUNOTHERAPY CERVICAL cancer
1∶10 000 DOM制作常见问题探讨 预览
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作者 吕海龙 周红梅 +1 位作者 李杰瑞 孟丽颖 《测绘与空间地理信息》 2019年第8期189-190,195,共3页
1∶10 000 DOM在基础测绘和地理国情普查中有着广泛的应用,本文以吉林省部分地区生产DOM数据为例,对生产过程和发现的问题进行总结与讨论,其结果有助于提高影像成果质量和作业效率,同时为后续的动态监测提供参考和借鉴。
关键词 DOM 作业流程 检查点 精度
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Immune checkpoint inhibitor-induced diarrhea/colitis:Endoscopic and pathologic findings 预览
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作者 Tsutomu Nishida Hideki Iijima Shiro Adachi 《世界胃肠病理生理学杂志:英文版(电子版)》 2019年第2期17-28,共12页
The indications of immune checkpoint inhibitors(ICPIs)for cancer treatment have rapidly expanded,and their use is increasing in clinical settings worldwide.Despite the considerable clinical benefits of ICPIs,frequent ... The indications of immune checkpoint inhibitors(ICPIs)for cancer treatment have rapidly expanded,and their use is increasing in clinical settings worldwide.Despite the considerable clinical benefits of ICPIs,frequent immune-related adverse events(ir AEs)have become nonnegligible concerns.Among ir AEs,ICPIinduced colitis/diarrhea is frequent and recognized not only by oncologists but also by gastroenterologists or endoscopists.The endoscopic findings show similarity to those of inflammatory bowel disease to a certain extent,particularly ulcerative colitis,but do not seem to be identical.The pathological findings of ICPI-induced colitis may vary among drug classes.They show acute or chronic inflammation,but it may depend on the time of colitis suggested by colonoscopy,including biopsy or treatment intervention.In the case of chronic inflammation determined by biopsy,the endoscopy findings may overlap with those of inflammatory bowel disease.Here,we provide a comprehensive review of ICPIinduced colitis based on clinical,endoscopic and pathologic findings. 展开更多
关键词 IMMUNE CHECKPOINT INHIBITOR COLITIS DIARRHEA Endoscopic PATHOLOGIC
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Immune checkpoint inhibitor-induced colitis: A comprehensive review 预览
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作者 Aniruddh Som Rohan Mandaliya +4 位作者 Mark C Mattar Dana Alsaadi Maham Farshidpour Aline Charabaty Nidhi Malhotra 《世界临床病例杂志》 2019年第4期405-418,共14页
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen- 4, programmed cell death protein-1, and its ligand programme... Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen- 4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis. 展开更多
关键词 IMMUNE CHECKPOINT inhibitors Immune-related ADVERSE events CYTOTOXIC Tlymphocyte-associated antigen 4 Programmed cell death protein 1 Programmed deathligand 1 IMMUNE-MEDIATED COLITIS
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