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Program death ligand 1/2

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https://www.readbyqxmd.com/read/28532535/-tumor-associated-fibroblasts-promote-pd-l1-expression-in-lung-cancer-cells
#1
Haiyang He, Luyu Qi, Yongsheng Xiao, Yiling Hou
BACKGROUND: Tumor-associated fibroblasts (TAF) is an important part of TME, which inhibits the function of immune cells. CD8+ T cells play a significant role in tumor immunity. T-cell membrane possesses a distinct type of molecule with a negative regulatory function. Upon interaction with its corresponding ligand [programmed death factor ligand 1 (PD-L1)], programmed death factor 1 (PD-1) is activated and thus inhibits the kinase activity of T cells. This study aims to explore the possible effects of TAF on PD-L1 expression in lung cancer cells...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#2
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28522811/pd-l1-expression-in-xp11-2-translocation-renal-cell-carcinoma-indicator-of-tumor-aggressiveness
#3
Kun Chang, Yuanyuan Qu, Bo Dai, Jian-Yuan Zhao, Hualei Gan, Guohai Shi, Yiping Zhu, Yijun Shen, Yao Zhu, Hailiang Zhang, Dingwei Ye
Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28501128/immunochemotherapy-benefits-in-gastric-cancer-patients-stratified-by-programmed-death-1-ligand-1
#4
Jun-Te Hsu, Chih-Sin Hsu, Puo-Hsien Le, Tse-Ching Chen, Wen-Chi Chou, Chun-Yen Lin, Ta-Sen Yeh
BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1 (PD-L1) has not been investigated. Investigating this might help in triaging candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918 patients with stages II and III gastric cancer, undergoing curative gastrectomy, and receiving adjuvant chemotherapy were enrolled in a prospective database, and the patients were retrospectively reviewed...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28500617/post-chemotherapy-pd-l1-expression-correlates-with-clinical-outcomes-in-japanese-bladder-cancer-patients-treated-with-total-cystectomy
#5
Daisuke Noro, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Toshiaki Kawaguchi, Chikara Ohyama
Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in bladder cancer. In the present study, we examined whether PD-L1 expression is associated with clinical outcomes in bladder cancer patients. We enrolled 102 bladder cancer patients treated with cystectomy at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2)...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28496333/immune-checkpoint-blockade-the-role-of-pd-1-pd-l-axis-in-lymphoid-malignancies
#6
REVIEW
Cristina Ilcus, Cristina Bagacean, Adrian Tempescul, Cristian Popescu, Andrada Parvu, Mihai Cenariu, Corina Bocsan, Mihnea Zdrenghea
The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune effector cells, is credited with a protective role for normal tissue during immune responses, by limiting the extent of effector activation. Its presently known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a variety of cells including cancer cells, suggesting a role for these molecules as an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has recently been shown to be effective and was clinically approved in relapsed/refractory tumors such as malignant melanoma and lung cancer, but also classical Hodgkin's lymphoma...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28496056/stat3-inhibitor-abrogates-the-expression-of-pd-1-ligands-on-lymphoma-cell-lines
#7
Chaoya Ma, Hasita Horlad, Cheng Pan, Hiromu Yano, Koji Ohnishi, Yukio Fujiwara, Masao Matsuoka, Aeju Lee, Takuro Niidome, Ryuya Yamanaka, Motohiro Takeya, Yoshihiro Komohara
Recent studies have indicated the significance of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3 for anti-tumor immune responses. We previously investigated PD-1 ligand 1/2 (PD-L1/2) expression in lymphoma cell lines, and found that PD-L1/2 is expressed on the adult T-cell leukemia/lymphoma (ATL-T) and B-cell lymphoma (SLVL) cell lines. In the present study, we investigated whether the Stat3 inhibitor WP1066 abrogated PD-L1/2 expression in lymphoma cell lines...
May 10, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28489510/safety-and-antitumor-activity-of-pembrolizumab-in-advanced-programmed-death-ligand-1-positive-endometrial-cancer-results-from-the-keynote-028-study
#8
Patrick A Ott, Yung-Jue Bang, Dominique Berton-Rigaud, Elena Elez, Michael J Pishvaian, Hope S Rugo, Igor Puzanov, Janice M Mehnert, Kyaw L Aung, Juanita Lopez, Marion Carrigan, Sanatan Saraf, Mei Chen, Jean-Charles Soria
Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28488345/patterns-of-pd-1-pd-l1-and-pd-l2-expression-in-pediatric-solid-tumors
#9
Navin Pinto, Julie R Park, Erin Murphy, Jennifer Yearley, Terri McClanahan, Lakshmanan Annamalai, Douglas S Hawkins, Erin R Rudzinski
BACKGROUND: Significant antitumor effects have been observed in a variety of malignancies via blockade of immune checkpoints. Interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 suppresses T-cell function and restricts immune-mediated tumor killing. We examined expression of these proteins in children with solid tumors, as expression may serve as biomarkers of response to this class of drugs. METHODS: Sections cut from formalin-fixed paraffin-embedded (FFPE) tissue blocks were processed and evaluated for PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC) as well as by mRNA expression...
May 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28488168/the-therapeutic-candidate-for-immune-checkpoint-inhibitors-elucidated-by-the-status-of-tumor-infiltrating-lymphocytes-tils-and-programmed-death-ligand-1-pd-l1-expression-in-triple-negative-breast-cancer-tnbc
#10
Nobumoto Tomioka, Manabu Azuma, Mayuko Ikarashi, Mitsugu Yamamoto, Masako Sato, Ken-Ichi Watanabe, Katsushige Yamashiro, Masato Takahashi
BACKGROUND: The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression...
May 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28475775/autocrine-activation-of-the-ifn-signaling-pathway-may-promote-immune-escape-in-glioblastoma
#11
Manuela Silginer, Sara Nagy, Caroline Happold, Hannah Schneider, Michael Weller, Patrick Roth
Background.: Interferons (IFNs) are cytokines typically induced upon viral infection but are constitutively expressed also in the absence of acute infection. The physiological role of autocrine and paracrine IFN signaling, however, remains poorly understood, and its function in glioblastoma has not been explored in depth. Methods.: Using RNA interference-mediated gene silencing, we characterized constitutive type I IFN signaling and its role in human glioma cells...
May 5, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28471952/prognostic-significance-of-pd-l1-in-solid-tumor-an-updated-meta-analysis
#12
Qianqian Wang, Fang Liu, Lei Liu
BACKGROUND: An increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies. METHODS: The studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28471727/safety-and-clinical-activity-of-the-programmed-death-ligand-1-inhibitor-durvalumab-in-combination-with-poly-adp-ribose-polymerase-inhibitor-olaparib-or-vascular-endothelial-growth-factor-receptor-1-3-inhibitor-cediranib-in-women-s-cancers-a-dose-escalation
#13
Jung-Min Lee, Ashley Cimino-Mathews, Cody J Peer, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Liang Cao, Maria I Harrell, Elizabeth M Swisher, Nicole Houston, Dana-Adriana Botesteanu, Janis M Taube, Elizabeth Thompson, Aleksandra Ogurtsova, Haiying Xu, Jeffers Nguyen, Tony W Ho, William D Figg, Elise C Kohn
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations...
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#14
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28462836/iodine-catalyzed-three-component-synthesis-of-1-2-hydroxy-naphthalen-1-yl-phenyl-methyl-pyrrolidin-2-one-derivatives-rationale-as-potent-pi3k-inhibitors-and-anticancer-agents
#15
Vivek Panyam Muralidharan, Manikandan Alagumuthu, Sathiyanarayanan Kulathu Iyer
A series of 1-((2-hydroxynaphthalen-1-yl)(phenyl)(methyl))pyrrolidin-2-one derivatives by an efficient iodine catalyzed domino reaction involving various aromatic aldehydes, 2-pyrrolidinone and β-naphthol was achieved and the structures were elucidated by FTIR (1)H NMR, (13)C NMR, and HRMS. Subsequently they were evaluated for cytotoxicity against breast cancer (MCF-7), colon cancer (HCT116) cell lines. In the cytotoxicity, the relative inhibition activity was remarkably found to be high in MCF-7 cell lines as 79% (4c), 83% (4f) and the IC50values were 1...
April 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28461396/pembrolizumab-pomalidomide-and-low-dose-dexamethasone-for-relapsed-refractory-multiple-myeloma
#16
Ashraf Badros, Elizabeth Hyjek, Ning Ma, Alexander Lesokhin, Ahmet Dogan, Aaron P Rapoport, Mehmet Kocoglu, Emily Lederer, Sunita Philip, Todd Milliron, Cameron Dell, Olga Goloubeva, Zeba Singh
Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics...
May 1, 2017: Blood
https://www.readbyqxmd.com/read/28461179/immune-characterization-of-the-programmed-death-receptor-pathway-in-high-risk-prostate%C3%A2-cancer
#17
Wesley Baas, Svetlana Gershburg, Danuta Dynda, Kristin Delfino, Kathy Robinson, Daotai Nie, Jennifer Holmes Yearley, Shaheen Alanee
BACKGROUND: Programmed cell death-1 (PD-1), a T-cell inhibitory receptor, and its ligand, PD-L1, have been reported to be expressed in many tumor types, and this expression has led to the development of many drugs targeting the PD-1 pathway. The objective of this study was to determine the expression of PD-1 and PD-L1 in high-grade prostate cancer tissues, and correlate the expression with disease and patient characteristics. MATERIALS AND METHODS: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed and scored from 0 to 5 on prostatectomy/biopsy tissue samples taken from 25 men with high-grade prostate cancer...
April 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28460462/the-prognostic-role-of-immune-checkpoint-markers-programmed-cell-death-protein-1-pd-1-and-programmed-death-ligand-1-pd-l1-in-a-large-multicenter-prostate-cancer-cohort
#18
Nora Ness, Sigve Andersen, Mehrdad Rakaee Khanehkenari, Cecilie V Nordbakken, Andrej Valkov, Erna-Elise Paulsen, Yngve Nordby, Roy M Bremnes, Tom Donnem, Lill-Tove Busund, Elin Richardsen
Programmed cell death protein 1 (PD-1) and its ligand Programmed death ligand 1 (PD-L1) have gained massive attention in cancer research due to recent availability and their targeted antitumor effects. Their role in prostate cancer is still undetermined. We constructed tissue microarrays from prostatectomy specimens from 535 prostate cancer patients. Following validation of antibodies, immunohistochemistry was used to evaluate the expression of PD-1 in lymphocytes and PD-L1 in epithelial and stromal cells of primary tumors...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28458101/role-of-programmed-death-ligand-1-and-kupffer-cell-in-immune-regulation-after-orthotopic-liver-transplantation-in-rats
#19
Junhua Gong, Ding Cao, Yong Chen, Jinzheng Li, Jianping Gong, Zhong Zeng
INTRODUCTION: Role of programmed death ligand 1 (PD-L1) and Kupffer cells (KCs) in liver transplantation immune regulation was unclear. METHODS: Lewis and Brown-Norway (BN) rats were assigned to LEW-BN group (Lewis-to-BN liver transplantation) and BN-BN group (BN-to-BN). Receipts were sacrificed for histology and assessment of cytokines and PD-L1 production. Effect of PD-L1 and KCs on T cells (TCs) was monitored by co-culture of (3)H-Thymidine TCs. KCs transfected with PD-L1-shRNA interference plasmids were co-cultured with TCs, PD-L1 expression and cytokines production were measured respectively...
April 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28453692/safety-and-antitumor-activity-of-the-anti-pd-1-antibody-pembrolizumab-in-patients-with-recurrent-carcinoma-of-the-anal-canal
#20
P A Ott, S A Piha-Paul, P Munster, M J Pishvaian, E M J van Brummelen, R B Cohen, C Gomez-Roca, S Ejadi, M Stein, E Chan, M Simonelli, A Morosky, S Saraf, K Emancipator, M Koshiji, J Bennouna
Background: Safety and efficacy of pembrolizumab, a humanized programmed death 1 monoclonal antibody, was assessed in KEYNOTE-028, a multicohort, phase Ib trial for patients with programmed death ligand 1 (PD-L1)-positive advanced solid tumors. We report results for the cohort of patients with advanced anal carcinoma. Patients and methods: Patients with PD-L1-positive tumors (≥1%) received intravenous pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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