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Immune checkpoint inhibitor

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https://www.readbyqxmd.com/read/29145329/new-onset-of-myasthenia-gravis-after-intravesical-bacillus-calmette-guerin-a-case-report-and-literature-review
#1
Tsubasa Takizawa, Marenori Kojima, Shigeaki Suzuki, Takashi Osada, Satoshi Kitagawa, Jin Nakahara, Shinichi Takahashi, Norihiro Suzuki
RATIONALE: Recently, drug-related myasthenia gravis (MG) has received attention, because the number of reported cases involving MG associated with immune checkpoint inhibitors, a new immunotherapy, is increasing. We present a case involving the new onset of MG, in which the symptoms started shortly after intravesical Bacillus Calmette-Guerin (BCG) for bladder cancer. PATIENT CONCERNS: A 69-year-old male with bladder cancer developed ptosis and diplopia 4 days after the completion of a treatment regimen with intravesical BCG weekly for 6 weeks...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29145036/liver-immunotolerance-and-hepatocellular-carcinoma-patho-physiological-mechanisms-and-therapeutic-perspectives
#2
REVIEW
Gaël S Roth, Thomas Decaens
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1...
November 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29144835/modern-systemic-therapy-for-metastatic-renal-cell-carcinoma-of-the-clear-cell-type
#3
Mamta Parikh, Primo N Lara
In the last 30 years, there have been many advances in the treatment of metastatic renal cell carcinoma of the clear cell type. Renal cell carcinoma has long been understood to have a component of immune mediation and has been responsive to immune-based therapies; in addition to early cytokine therapy, newer checkpoint inhibition therapies have also demonstrated activity. Molecular characterization of the genome of clear cell renal cell carcinoma enabled identification of the roles of angiogenesis and hypoxic stress...
November 16, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29144791/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-i-colorectal-cancer-microsatellite-instability-testing-and-clinical-implications
#4
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29143108/immune-checkpoint-inhibitor-colitis-the-flip-side-of-the-wonder-drugs
#5
Naziheh Assarzadegan, Elizabeth Montgomery, Robert A Anders
Immune checkpoint inhibitors block the co-inhibitory receptors on T cells to activate their cytotoxic immune function and are rapidly being explored for the treatment of various advanced-stage malignancies. These novel drugs have already significantly increased survival rates. The first available immune checkpoint inhibitors were cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors (such as ipilimumab), followed by programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors (such as pembrolizumab and nivolumab)...
November 15, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29142605/aviscumine-a-recombinant-ribosomal-inhibitor-increases-the-antitumor-activity-of-natural-killer-cells
#6
Gabriele Gamerith, Arno Amann, Bettina Schenk, Thomas Auer, Hans Lentzen, Dirk O Mügge, Katharina M Cima, Judith Löffler-Ragg, Wolfgang Hilbe, Heinz Zwierzina
Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29140833/immune-checkpoint-inhibitor-therapy-in-a-liver-transplant-recipient-with-a-rare-subtype-of-melanoma-a-case-report-and-literature-review
#7
James C Kuo, Leslie B Lilly, David Hogg
Immunotherapy with immune checkpoint inhibitors (ICIs) may be considered as a treatment option for various types of tumors, but the transplant recipient population as well as patients requiring long-term systemic immunosuppression for other reasons have been systematically excluded from clinical trials involving ICIs. We report a case of successful treatment with ICI in a liver transplant recipient diagnosed with a rare subtype of melanoma. This patient had not required any modification to her antirejection immunosuppression before or during immunotherapy, had not experienced any serious immune-related adverse event, and had a durable objective response for nearly 1...
November 14, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#8
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29139554/immune-checkpoint-inhibitors-new-strategies-to-checkmate-cancer
#9
REVIEW
Ruairi A M Wilson, T R Jeffry Evans, Alasdair R Fraser, Robert J B Nibbs
Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging...
November 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#10
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29138137/the-next-frontier-head-and-neck-cancer-immunoprevention
#11
J Silvio Gutkind, Jack D Bui
Restoring T cell-mediated antitumor immunity by targeting immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) results in immunomodulation and durable remissions. However, the overall response rate to these immunotherapies in HNSCC is only approximately 20%. This raises the possibility that immunologic intervention earlier in the HNSCC continuum, such as in oral premalignant lesions (OPL) could elicit an increased therapeutic response. New experimental studies suggest that immune therapies can be used for HNSCC prevention rather than therapy...
November 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29137370/comparative-efficacy-and-safety-of-immune-checkpoint-inhibitor-related-therapies-for-advanced-melanoma-a-bayesian-network-analysis
#12
Xin Li, Junpeng Wang, Yun Yao, Lei Yang, Zhiqin Li, Cheng Yu, Peiyan Zhao, Yongli Yu, Liying Wang
Objectives: We aimed to compare and rank the effects of 9 immune checkpoint inhibitor-related therapies for treating advanced melanoma. Methods: We searched Pubmed, Cochrane databases, Web of Science, and ClinicalTrials.gov for randomized controlled trials of the immune checkpoint inhibitor-related treatments for advanced melanoma. Analysis was done on a Bayesian framework. Results: Twelve trials including 5413 patients were identified. Ipilimumab plus nivolumab, nivolumab, and pembrolizumab were significantly more efficacious for progression-free survival (PFS) than ipilimumab (hazard ratio [HR], 0...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135922/targeting-immune-cell-checkpoints-during-sepsis
#13
REVIEW
Naeem K Patil, Yin Guo, Liming Luan, Edward R Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135284/atezolizumab-in-urothelial-bladder-carcinoma
#14
Zineb Hamilou, Pernelle Lavaud, Yohann Loriot
Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades. Moreover, many patients are unable to receive cisplatin-based therapy. Recently, immune-checkpoint inhibitors transformed the management and prognosis of many malignancies and will certainly redefine the standard of care for bladder cancer. Atezolizumab, an antiprogrammed cell death ligand-1 antibody, was the first immune-checkpoint inhibitor to be approved by the US FDA in May 2016 for patients with urothelial carcinoma...
November 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#15
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29132694/unrelated-immunodeficiency-states-may-impact-outcomes-and-immune-checkpoint-molecule-expression-in-patients-with-mycosis-fungoides-a-clinicopathologic-case-control-study
#16
Shay Warren, Meenal Kheterpal, Patricia L Myskowski, Alison Moskowitz, Steven M Horwitz, Melissa P Pulitzer
BACKGROUND: Immunodeficiency (ID) correlates with worse outcomes and decreased immune checkpoint molecule expression in melanoma. The impact of ID in mycosis fungoides (MF) is unknown. OBJECTIVE: Our goal was to evaluate the impact of ID in MF. METHODS: We conducted a case-control study of 17 patients with MF and ID versus age-, stage-, and race-matched controls as a subset of a comparative analysis of 23 patients with MF with ID (prior lymphoma, recent/current pregnancy, HIV, hypogammaglobulinemia, and prior chemotherapy) versus without ID...
November 10, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29131763/immune-checkpoint-inhibitor-cancer-therapy-spectrum-of-imaging-findings
#17
Gary X Wang, Vikram Kurra, Justin F Gainor, Ryan J Sullivan, Keith T Flaherty, Susanna I Lee, Florian J Fintelmann
Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden...
November 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29131530/biomarkers-for-immune-checkpoint-inhibitors-the-importance-of-tumor-topography-and-the-challenges-to-cytopathology
#18
REVIEW
Douglas P Clark
The recent emergence of immune checkpoint inhibitors for cancer therapy has created much excitement among cancer patients, drug and diagnostic developers, and health care professionals. This is due largely to the dramatic and sustained responses among some advanced cancers that were previously refractory to therapy. Unfortunately, these responses are difficult to predict, so the goal of the right drug for the right patient at the right time remains elusive. This is in part due to the complexity of the tumor immune microenvironment and its role in drug efficacy...
November 13, 2017: Cancer
https://www.readbyqxmd.com/read/29129093/xxxxx
#19
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) requires the development of newer more effective therapies to further improve the treatment outcomes for this disease. Immunotherapy is a novel treatment strategy that is dramatically changing the treatment landscape for several types of cancers. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death the programmed death (PD)-1/PD-ligand are essential immune checkpoint inhibitors that suppress T cell activation. Targeting of these immune checkpoints with monoclonal antibodies has shown clinical efficacy in several solid tumors which has led to their approval and use in routine clinical practice...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29129088/systemic-therapy-for-esophagogastric-cancer-targeted-therapies
#20
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) has resulted in an increased focus on the use of targeted agents in this disease. Targets include epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Her2, mammalian target of rapamycin (mTOR), MET, poly (ADP-ribose) polymerase (PARP) and claudin 18.2 (CLDN18.2). Trastuzumab, an anti-Her2 antibody, was approved by the U.S. FDA in 2010 as first-line therapy in combination with chemotherapy for Her2-positive disease...
October 2017: Chinese Clinical Oncology
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