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Program death ligand 1/2

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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/28817753/efficacy-and-safety-of-durvalumab-in-locally-advanced-or-metastatic-urothelial-carcinoma-updated-results-from-a-phase-1-2-open-label-study
#2
Thomas Powles, Peter H O'Donnell, Christophe Massard, Hendrik-Tobias Arkenau, Terence W Friedlander, Christopher J Hoimes, Jae Lyun Lee, Michael Ong, Srikala S Sridhar, Nicholas J Vogelzang, Mayer N Fishman, Jingsong Zhang, Sandy Srinivas, Jigar Parikh, Joyce Antal, Xiaoping Jin, Ashok K Gupta, Yong Ben, Noah M Hahn
Importance: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. Objective: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. Design, Setting, and Participants: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817405/cutaneous-eruptions-in-patients-receiving-immune-checkpoint-blockade-clinicopathologic-analysis-of-the-nonlichenoid-histologic-pattern
#3
Genevieve J Kaunitz, Manisha Loss, Hira Rizvi, Sowmya Ravi, Jonathan D Cuda, Karen B Bleich, Jessica Esandrio, Inbal Sander, Dung T Le, Luis A Diaz, Julie R Brahmer, Charles G Drake, Travis J Hollmann, Mario E Lacouture, Matthew D Hellmann, Evan J Lipson, Janis M Taube
Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-programmed cell death protein 1/programmed cell death ligand 1 therapy, and are often clinically and histologically characterized as lichenoid. Nonlichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of nonlichenoid cutaneous irAEs from patients receiving anti-programmed cell death protein 1/programmed cell death ligand 1 therapies for a variety of underlying advanced malignancies...
August 15, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28815042/predictive-role-of-pd-l1-expression-in-the-response-of-renal-medullary-carcinoma-to-pd-1-inhibition
#4
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/28813164/pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-results-from-the-phase-ib-keynote-028-study
#5
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
#6
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
#7
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
#8
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/28807336/programmed-death-1-pd-1-receptor-pd-1-ligand-pd-l1-expression-in-fumarate-hydratase-deficient-renal-cell-carcinoma
#9
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/28807004/predictive-role-of-pd-l1-expression-in-the-response-of-renal-medullary-carcinoma-to-pd-1-inhibition
#10
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/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#11
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28803798/radiosynthesis-and-preclinical-pet-evaluation-of-89-zr-nivolumab-bms-936558-in-healthy-non-human-primates
#12
Erin L Cole, Joonyoung Kim, David J Donnelly, R Adam Smith, Daniel Cohen, Virginie Lafont, Paul E Morin, Richard Y-C Huang, Patrick L Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28801607/enhancing-nk-cell-mediated-cytotoxicity-to-cisplatin-resistant-lung-cancer-cells-via-mek-erk-signaling-inhibition
#13
Li Yang, MingJing Shen, Li Jun Xu, Xiaodong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791774/n-substituted-hydroxynapthalene-imino-oxindole-derivatives-as-new-class-of-pi3-kinase-inhibitor-and-breast-cancer-drug-molecular-validation-and-structure-activity-relationship-studies
#14
M Rajesh Kumar, Manikandan Alagumuthu, V Violet Dhayabaran
N-substituted hydroxynapthalene imino-oxindole derivatives (5a-g) were emerged as the inhibitors of the phosphoinositide 3-kinase (PI3K) which is a crucial regulator of apoptosis or programmed cell death. Electron donor/acceptor substituted indole-imine (5a-g) were achieved and the structures were elucidated by FTIR, 1H NMR, 13C NMR, and HRMS. PI3Ks inhibition potency was assessed by competitive ELISA. Subsequently, an anticancer activity against breast cancer (MCF-7) cell lines was evaluated. In both activities, compounds 5c, 5d, 5f and were showed most potent activities...
August 9, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28782638/prognostic-value-of-programmed-death-ligand-1-p53-and-ki-67-in-patients-with-advanced-stage-colorectal-cancer
#15
Lisha Wang, Zebing Liu, Kurt W Fisher, Fei Ren, Jiaojie Lv, Darrell D Davidson, Lee A Baldridge, Xiang Du, Liang Cheng
Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients...
August 4, 2017: Human Pathology
https://www.readbyqxmd.com/read/28782050/theranostic-gold-nanoantennas-for-simultaneous-multiplexed-raman-imaging-of-immunomarkers-and-photothermal-therapy
#16
Joseph A Webb, Yu-Chuan Ou, Shannon Faley, Eden P Paul, Joseph P Hittinger, Camden C Cutright, Eugene C Lin, Leon M Bellan, Rizia Bardhan
In this study, we demonstrate the theranostic capability of actively targeted, site-specific multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. By utilizing multiplexed surface-enhanced Raman scattering (SERS) imaging, enabled by the narrow peak widths of Raman signatures, we simultaneously targeted immune checkpoint receptor programmed death ligand 1 (PDL1) and the epidermal growth factor receptor (EGFR) overexpressed in TNBC cells. A 1:1 mixture of MGNs functionalized with anti-PDL1 antibodies and Raman tag 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and MGNs functionalized with anti-EGFR antibodies and Raman tag para-mercaptobenzoic acid (pMBA) were incubated with the cells...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28780933/%C3%AE-%C3%AE-t-cells-unexpected-regulators-of-cancer-development-and-progression
#17
REVIEW
Christopher Fleming, Samantha Morrissey, Yihua Cai, Jun Yan
Accumulating evidence suggests a role for gamma delta (γδ) T cells as unexpected drivers of tumor development and progression. These protumoral γδ T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by: (i) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; (ii) functioning as regulatory T (Treg)/T helper 2 (Th2)-like cells; (iii) interfering with dendritic cell (DC) effector function; and (iv) inhibiting antitumor adaptive T cell immunity via the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28778098/pd-1-pd-l1-antibodies-efficacy-and-safety-versus-docetaxel-monotherapy-in-advanced-nsclc-patients-after-first-line-treatment-option-systems-assessment
#18
Qiang Su, Zhigang Sun, Chenguang Zhang, Yanli Hou, Bangwei Cao
Meta-analysis was conducted to systematically assess the effectiveness and safety of programmed cell death protein-1 or ligand-1 (PD-1 or PD-L1) antibodies versus docetaxel alone in advanced non small cell lung cancer (NSCLC). In addition, the prognostic significance of PD-L1 expression in advanced NSCLC was also investigated. 5 eligible studies including 3579 patients were identified through comprehensive search of multiple databases. The results showed that pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were 0...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777458/increased-expression-of-pd-l1-and-pd-l2-in-dermal-fibroblasts-from-alopecia-areata-mice
#19
Yunyuan Li, Ruhi T Kilani, Mohammadreza Pakyari, Gigi Leung, Layla Nabai, Aziz Ghahary
Alopecia areata (AA) is a common autoimmune disorder affecting millions of people worldwide, which manifests as a sudden, non-scarring hair loss. The expression of a pro-inflammatory cytokine, interferon-gamma (INF-γ), has been well established to be involved in the development of AA. As IFN-γ and other cytokines are also known to up-regulate programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), which both negatively control immune responses, we asked whether or not a high number of infiltrated T cells, seen in AA lesions, can modulate the expression of PD-L1 and PD-L2 in skin cells...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#20
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Yet, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Whereas numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment by engaging in several cross-talk mechanisms...
August 3, 2017: Haematologica
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