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https://www.readbyqxmd.com/read/28822650/progressive-and-reversible-conduction-disease-with-checkpoint-inhibitors
#1
Neeti Reddy, Rohit Moudgil, Juan C Lopez-Mattei, Kaveh Karimzad, Elie N Mouhayar, Neeta Somaiah, Anthony P Conley, Shreyaskumar Patel, Dana E Giza, Cezar Iliescu
Novel antineoplastic therapies are focused on harnessing our own immune system to fight cancer. To that end, cytotoxic T-lymphocyte-associated antigen 4 and programmed death ligand 1 are 2 coinhibitory signals that play central roles in decreasing T-cell response and represent a class of medications termed "checkpoint inhibitors." We present an unusual case of progressive conduction abnormalities induced by checkpoint inhibitors. Prompt medical intervention resulted in full recovery. Despite the anticancer efficacy, the newer antineoplastic agents pose a significant and often life-threatening risk of cardiotoxicity...
June 8, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#2
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#3
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28820897/persistent-infection-due-to-a-small-colony-variant-of-burkholderia-pseudomallei-leads-to-pd-1-upregulation-on-circulating-immune-cells-and-mononuclear-infiltration-in-viscera-of-experimental-balb-c-mice
#4
Jia-Xiang See, Samudi Chandramathi, Mahmood Ameen Abdulla, Jamuna Vadivelu, Esaki M Shankar
BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28819856/fiber-optic-array-scanning-technology-fast-for-detection-and-molecular-characterization-of-circulating-tumor-cells
#5
Zheng Ao, Xiaohe Liu
Circulating tumor cell (CTC) as an important component in "liquid biopsy" holds crucial clinical relevance in cancer prognosis, treatment efficiency evaluation, prediction and potentially early detection. Here, we present a Fiber-optic Array Scanning Technology (FAST) that enables antigen-agnostic, size-agnostic detection of CTC. By immunofluorescence staining detection of a combination of a panel of markers, FAST technology can be applied to detect rare CTC in non-small cell lung cancer (NSCLC) setting with high sensitivity and specificity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28819402/pd-l1-expression-is-associated-with-foxp3-regulatory-t-cell-infiltration-of-soft-tissue-sarcoma-and-poor-patient-prognosis
#6
Yi Que, Wei Xiao, Yuan-Xiang Guan, Yao Liang, Shu-Mei Yan, Huo-Ying Chen, Qiao-Qiao Li, Bu-Shu Xu, Zhi-Wei Zhou, Xing Zhang
Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#7
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28818019/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-a-review-of-current-evidence
#8
Karim Rihawi, Francesco Gelsomino, Francesca Sperandi, Barbara Melotti, Michelangelo Fiorentino, Laura Casolari, Andrea Ardizzoni
Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors...
August 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28815042/predictive-role-of-pd-l1-expression-in-the-response-of-renal-medullary-carcinoma-to-pd-1-inhibition
#9
Quaovi Sodji, Kandy Klein, Kavuri Sravan, Jigarkumar Parikh
BACKGROUND: Renal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#10
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813164/pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-results-from-the-phase-ib-keynote-028-study
#11
Patrick A Ott, Elena Elez, Sandrine Hiret, Dong-Wan Kim, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Janice M Mehnert
Purpose The safety and efficacy of pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), were assessed in patients with programmed death ligand 1 (PD-L1)-expressing extensive-stage small-cell lung cancer (SCLC) in the multicohort, phase Ib open-label KEYNOTE-028 study ( ClinicalTrials.gov identifier: NCT02054806). Methods Patients with SCLC received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. PD-L1 expression was assessed by immunohistochemistry...
August 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#12
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811971/preclinical-immunopet-ct-imaging-using-zr-89-labeled-anti-pd-l1-monoclonal-antibody-for-assessing-radiation-induced-pd-l1-upregulation-in-head-and-neck-cancer-and-melanoma
#13
Masahiro Kikuchi, David A Clump, Raghvendra M Srivastava, Lingyi Sun, Dexing Zeng, Julio A Diaz-Perez, Carolyn J Anderson, W Barry Edwards, Robert L Ferris
Radiation therapy (RT) can induce upregulation of programmed death ligand 1 (PD-L1) on tumor cells or myeloid cells, which may affect response to PD-1-based immunotherapy. PD-L1 upregulation during RT is a dynamic process that has been difficult to monitor during treatment. The aim of this study was to evaluate the RT-induced PD-L1 upregulation in the tumor and its microenvironment using immunoPET/CT imaging of two syngeneic murine tumor models (HPV+ head and neck squamous cell carcinoma (HNSCC) or B16F10 melanoma)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#14
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810601/comparative-study-of-dendritic-cells-matured-by-using-il-1%C3%AE-il-6-tnf-%C3%AE-and-prostaglandins-e2-for-different-time-span
#15
Xuejie Wu, Feng Xu, Jinliang Liu, Guiqiang Wang
Interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and prostaglandins E2 is considered as the standard cocktail for maturing dendritic cells (DCs). However, the appropriate time span for DC maturation with the standard cocktail remains unclear. The present study aimed to compare the differences between DCs matured with the standard cocktail for 24 and 48 h, respectively, and determine whether 24-h stimulation was sufficient for DC maturation. The findings demonstrated that, compared with DCs matured for 48 h, the levels of cluster of differentiation (CD)80, CD83, CD86 and programmed death-ligand 1 expression in DCs matured for 24 h were relatively lower...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807336/programmed-death-1-pd-1-receptor-pd-1-ligand-pd-l1-expression-in-fumarate-hydratase-deficient-renal-cell-carcinoma
#16
Reza Alaghehbandan, Jan Stehlik, Kiril Trpkov, Cristina Magi-Galluzzi, Enric Condom Mundo, Maria Pane Foix, Daniel Berney, Mathilde Sibony, Saul Suster, Abbas Agaimy, Delia Perez Montiel, Kristyna Pivovarcikova, Kvetoslava Michalova, Ondrej Daum, Ondrej Ondic, Pavla Rotterova, Martin Dusek, Milan Hora, Michal Michal, Ondrej Hes
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and aggressive tumor affecting mostly younger patients. This is the first study to assess the expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) in FH-RCC. Formalin-fixed paraffin-embedded samples from 13 FH-RCCs collected in an international multi-institutional study, were evaluated by immunohistochemistry (IHC) for PD-1/PD-L1 reactivity in tumor cells and tumor infiltrating lymphocytes (TILs). PD-1/PD-L1 expression was further evaluated by qPCR...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28807210/personalized-treatment-in-patients-with-colorectal-liver-metastases
#17
Dimitrios Moris, Timothy M Pawlik
BACKGROUND: Precision Medicine Initiative is a new research effort aiming to offer personalized treatment in many diseases, including cancer. The aim of the present article is to offer novel insights about the role of personalized treatment in patients with colorectal liver metastases (CRLM). METHODS: A review of the literature regarding personalized medicine and colorectal liver metastases was performed mainly in the MEDLINE/PubMed database. RESULTS: Surgical resection remains the only hope for cure of CRLM...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28807004/predictive-role-of-pd-l1-expression-in-the-response-of-renal-medullary-carcinoma-to-pd-1-inhibition
#18
Quaovi Sodji, Kandy Klein, Kavuri Sravan, Jigarkumar Parikh
BACKGROUND: Renal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#19
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#20
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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