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immune check point inhibitor

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https://www.readbyqxmd.com/read/29755779/immune-checkpoint-inhibitors-in-gastrointestinal-malignancies
#1
REVIEW
Vishal Jindal
Gastrointestinal (GIT) tumors are extremely fatal and lethal tumors with limited therapeutic options. Antitumor immunity is new line of research in management of solid tumors. Immune check points are negative regulators of immune system and control the immune response. These checkpoints are exploited by cancer cells. Cancer cells causes early activation of checkpoints and suppress the immune response, and therefore have unchecked growth and metastasis of malignant cells. Immune checkpoint inhibitors (ICIs), downregulates these checkpoints and activate the proliferation of cytotoxic T cells which helps in lysis of tumor cells...
April 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29728867/check-point-inhibitors-a-new-era-in-renal-cell-carcinoma-treatment
#2
REVIEW
Mohamed Alsharedi, Heather Katz
In the United States, the estimated number of new cases of renal cell carcinoma (RCC) is approximately 65,000 case with about 15,000 deaths in the year of 2018 (Siegel et al. in CA Cancer J Clin 68(1):7, 2018). RCC as an immunogenic malignancy is supported by many theories and facts which include tumor richness of lymphocytes infiltrate, the occurrence of spontaneous tumor regression, and the proved effect of traditional immunotherapy (Finke et al. in J Immunother 11(1):1-11, 1992), all these factors support the potential therapeutic effect of the novel immunotherapeutic agents in RCC...
May 4, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29723688/braf-mutant-lung-cancer-pd-l1-expression-tumor-mutational-burden-microsatellite-instability-status-and-response-to-immune-check-point-inhibitors
#3
Elizabeth Dudnik, Nir Peled, Hovav Nechushtan, Mira Wollner, Amir Onn, Abed Agbarya, Mor Moskovitz, Shoshana Keren, Noa Popovits-Hadari, Damien Urban, Moshe Mishaeli, Alona Zer, Aaron M Allen, Natalie Maimon Rabinovich, Ofer Rotem, Teodor Kuznetsov, Tzippy Shochat, Laila C Roisman, Jair Bar
INTRODUCTION: The efficacy of immune check-point inhibitors (ICPi) in BRAF mutant NSCLC is unknown. METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (Group A, n=21) and non-V600E (Group B, n=18). PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability status (MSI) were assessed in 29 (74%), 11 (28%) and 12 (31%) patients, respectively. ORR, PFS with ICPi and OS were analyzed...
April 30, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29706000/ipilimumab-more-and-more-discussed-urgent-need-for-predictive-markers-of-response
#4
B Dréno
Immune checkpoint blockade with anti-CTLA-4 and anti-PD-11 has improved clinical responses and long-term survival benefit for patients with advanced melanoma. These 2 papers1, 2 focus on 2 check point inhibitors. However, the practical interest is different taking in count the quickness of the evolution in the management of metastatic melanoma. This article is protected by copyright. All rights reserved.
April 28, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29691476/lymphomas-driven-by-epstein-barr-virus-nuclear-antigen-1-ebna1-are-dependant-upon-mdm2
#5
Sana AlQarni, Yazeed Al-Sheikh, Donald Campbell, Mark Drotar, Adele Hannigan, Shelagh Boyle, Pawel Herzyk, Andrew Kossenkov, Kate Armfield, Lauren Jamieson, Mariarca Bailo, Paul M Lieberman, Penelope Tsimbouri, Joanna B Wilson
Epstein-Barr virus (EBV)-associated Burkitt's lymphoma is characterised by the deregulation of c-Myc expression and a restricted viral gene expression pattern in which the EBV nuclear antigen-1 (EBNA1) is the only viral protein to be consistently expressed. EBNA1 is required for viral genome propagation and segregation during latency. However, it has been much debated whether the protein plays a role in viral-associated tumourigenesis. We show that the lymphomas which arise in EµEBNA1 transgenic mice are unequivocally linked to EBNA1 expression and that both C-Myc and Mdm2 deregulation are central to this process...
April 25, 2018: Oncogene
https://www.readbyqxmd.com/read/29683761/circulating-micrornas-associated-with-prolonged-overall-survival-in-lung-cancer-patients-treated-with-nivolumab
#6
Ann Rita Halvorsen, Vandana Sandhu, Mette Sprauten, Vidar G Flote, Elin H Kure, Odd Terje Brustugun, Åslaug Helland
BACKGROUND: The introduction of immune check-point inhibition in non-small cell lung cancer (NSCLC) therapy represents improved prospects for the patients. The response rates to check-point inhibitors are approximately 20% in unselected NSCLC patients. Increasing levels of tumor PD-L1 expression are associated with higher response rates. However, patients with low PD-L1 levels may also have durable responses, and improved strategies for patient stratification are needed. MATERIAL AND METHODS: In this study, we investigated circulating microRNAs aiming to identify circulating predictive biomarkers associated with increased overall survival after immune check-point treatment...
April 23, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29679556/a-novel-smac-mimetic-apg-1387-exhibited-dual-antitumor-effect-on-hbv-positive-hepatocellular-carcinoma-with-high-expression-of-ciap2-by-inducing-apoptosis-and-enhancing-innate-anti-tumor-immunity
#7
Wentao Pan, Qiuyun Luo, Xianglei Yan, Luping Yuan, Hanjie Yi, Lin Zhang, Baoxia Li, Yuxin Zhang, Jian Sun, Miao-Zhen Qiu, Da-Jun Yang
Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, SMAC mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs)...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29661720/pd-l1-immuno-expression-assay-in-thymomas-study-of-84-cases-and-review-of-literature
#8
Prerna Guleria, Nuzhat Husain, Saumya Shukla, Sunil Kumar, Rajinder Parshad, Deepali Jain
BACKGROUND AND AIMS: Programmed death ligand 1 (PD-L1), an immune check point inhibitor, is known to be expressed in several malignancies and is being considered as a prognostic factor and a potential immunotherapeutic target. The aim of this study was to characterize PD-L1 expression in thymomas and to determine correlation with clinicopathological features and previously published studies in the literature. METHODS: Tissue microarrays were prepared from selected blocks of thymomas and immunohistochemistry (IHC) for PD-L1 was performed...
April 4, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29656755/the-burden-of-lung-cancer-in-latin-america-and-challenges-in-the-access-to-genomic-profiling-immunotherapy-and-targeted-treatments
#9
REVIEW
Luis E Raez, Andrés F Cardona, Edgardo S Santos, Heath Catoe, Christian Rolfo, Gilberto Lopes, Carlos Barrios, Luis A Mas, Carlos Vallejos, Zyanya Lucia Zatarain-Barrón, Christian Caglevic, Oscar Arrieta
Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot escape this reality. This malignant disease has not only a high prevalence in the region, but is also the main cause of cancer related deaths, and in other emerging countries, the incidence rates are still on the rise. Interestingly in most LATAM countries, lung cancer mortality has been decreasing in men but not in women, reflecting smoking patterns in countries such as Chile, Bolivia, and Brazil. Despite the fact that these issues are well known to government agencies, physicians and patients in the region, current efforts still fall behind those needed in order to face this problem of epidemic proportions...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29593888/immunotherapy-in-previously-treated-non-small-cell-lung-cancer-nsclc
#10
REVIEW
Ticiana A Leal, Suresh S Ramalingam
Treatment with immunotherapy has made a significant impact in the outcomes for those individuals diagnosed with metastatic non-small cell lung cancer (NSCLC) and its use is currently an established treatment modality. In light of recent advances in immunotherapy, improved survival, particularly for patients with stage IV NSCLC, has been reported with durable and prolonged responses in a subset of patients. Immune check point inhibitors, which include nivolumab, pembrolizumab, and atezolizumab, are standard treatment options in the salvage setting...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29571945/trophoblast-cd200-expression-in-successful-human-pregancies-and-missed-abortions
#11
David A Clark, M Elizabeth McCready, Kate Harris, Leslie Malloy, Jorge L Arredondo
Presence of the CD200 immune check-point inhibitor at the feto-maternal interface is linked to prevention of spontaneous abortion in mice and humans. In human missed abortions (MA), absence of Th17-driven inflammation has been attributed to expression of villus trophoblast CD200 quantified using immunohistochemistry. While rapid aneuploidy (QF-PCR) testing linked low CD200 to pregnancy failure, data showing normal VT CD200 in first trimester normal pregnancy and in abortion of chromosomally abnormal embryos has not been demonstrated...
March 16, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29535979/immunotherapy-in-merkel-cell-carcinoma-role-of-avelumab
#12
REVIEW
Amruth R Palla, Donald Doll
Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29530393/chemotherapy-and-targeted-therapy-in-the-management-of-cervical-cancer
#13
REVIEW
Lalit Kumar, P Harish, Prabhat S Malik, S Khurana
Management of cervical cancer has undergone refinement in the past two decades; concurrent chemo-radiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach for patients with locally advanced disease (FIGO stage IIB-IVA). About 30%-40% of such patients fail to achieve complete response; alternative approaches are needed to improve outcome for them. Treatment with bevacizumab (an inhibitor of vascular endothelial growth factor) along with chemotherapy is associated with improved survival in patients with recurrent or metastatic cervical cancer...
February 3, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29526974/adjuvant-immunotherapy-for-cancer-both-dendritic-cell-priming-and-check-point-inhibitor-blockade-are-required-for-immunotherapy
#14
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29525401/targeting-immune-checkpoints-in-non-small-cell-lung-cancer
#15
REVIEW
Andrea Bianco, Umberto Malapelle, Danilo Rocco, Fabio Perrotta, Gennaro Mazzarella
Cancers have the ability to disrupt immune response by interfering with adaptive immunity. Blocking checkpoint pathways has become a target for pharmacological research in lung cancer with particular focus on peptides PD-1 and CTLA-4. A number of immune check-point inhibitors (ICIs) targeting both PD-1 and CTLA-4 pathways are under investigation within clinical trials, of which Nivolumab, Pembrolizumab and Atezolizumab have already been approved for lung cancer treatment by both FDA and EMA. Employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC) ICIs have exhibited advantages in terms of overall survival and response rate with some responses being durable...
March 8, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29520474/cancer-immunotherapy-in-patients-with-brain-metastases
#16
REVIEW
Salvatore Caponnetto, Arianna Draghi, Troels Holz Borch, Marianna Nuti, Enrico Cortesi, Inge Marie Svane, Marco Donia
The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain...
May 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29463302/the-impact-of-pd-l1-on-survival-and-value-of-the-immune-check-point-inhibitors-in-non-small-cell-lung-cancer-proposal-policies-and-perspective
#17
Helmy M Guirgis
BACKGROUND: The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. OBJECTIVES: 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). METHODS: Previously reported median overall survival (OS) and prices posted by parent company were utilized...
February 20, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29441072/fatal-necrotizing-encephalopathy-after-treatment-with-nivolumab-for-squamous-non-small-cell-lung-cancer-case-report-and-review-of-the-literature
#18
Markus Leitinger, Mihael V Varosanec, Slaven Pikija, Romana E Wass, Dave Bandke, Serge Weis, Michael Studnicka, Susanne Grinzinger, Mark R McCoy, Larissa Hauer, Johann Sellner
Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29438373/anlotinib-as-a-third-line-therapy-in-patients-with-refractory-advanced-non-small-cell-lung-cancer-a-multicentre-randomised-phase-ii-trial-alter0302
#19
Baohui Han, Kai Li, Yizhuo Zhao, Baolan Li, Ying Cheng, Jianying Zhou, You Lu, Yuankai Shi, Zhehai Wang, Liyan Jiang, Yi Luo, Yiping Zhang, Cheng Huang, Qiang Li, Guoming Wu
BACKGROUND: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer (RA-NSCLC). METHODS: Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per day, per os; days 1-14; 21 days per cycle) or a placebo. The primary end point was progression-free survival (PFS)...
March 6, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29433584/ipilimumab-induced-digital-vasculitis
#20
Amrita Padda, Elena Schiopu, Justin Sovich, Vincent Ma, Ajjai Alva, Leslie Fecher
BACKGROUND: Immune check point inhibitors (ICIs) have emerged as a new therapeutic paradigm for a variety of malignancies including metastatic melanoma. As the use of ICIs expand, immune-mediated adverse events are becoming a common occurrence. CASE PRESENTATION: We describe the first reported patient with small vessel vasculitis, manifested by digital ischemia, following treatment with high dose Ipilimumab for resected stage IIIB/C melanoma. This patient received high dose steroids, five-day intravenous (IV) Epoprostenol protocol, botulinum toxin injections, and Rituximab 375 mg/m2 weekly for four cycles...
February 12, 2018: Journal for Immunotherapy of Cancer
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