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PD-L1 Cancer

Yue Xing, Chunliu Mi, Zhe Wang, Zhi Hong Zhang, Ming Yue Li, Hong Xiang Zuo, Jing Ying Wang, Xuejun Jin, Juan Ma
Dictamnus dasycarpus is a traditional Chinese medicine that has been commonly used in the treatment of cancer. Fraxinellone is a natural product isolated from the D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti-inflammatory activities. However, whether fraxinellone exerts anticancer effects and the mechanisms by which it may inhibit tumor growth remain unknown. Here, we found that fraxinellone, in a dose-dependented manner, inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis...
August 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Mohammad Askandar Iqbal, Shweta Arora, Gopinath Prakasam, George A Calin, Mansoor Ali Syed
Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene expression via post-transcriptional regulation of mRNA...
August 10, 2018: Molecular Aspects of Medicine
Samanta Salvi, Valentina Casadio, Filippo Martignano, Giorgia Gurioli, Maria Maddalena Tumedei, Daniele Calistri, Roberta Gunelli, Matteo Costantini
BACKGROUND: We report a case of prostatic carcinosarcoma, a rare variant of prostatic cancer, which is composed of a mixture of epithelial and mesenchymal components with a generally poor outcome. AIMS AND METHODS: We aim to identify molecular alterations, in particular copy number variations of AR and c -MYC genes, methylation and expression of glutathione S-transferase P1 (GSTP1), programmed death-ligand 1 (PD-L1), AR, and phosphorylated AR expression. RESULTS: We found a distinct molecular pattern between adenocarcinoma and carcinosarcoma, which was characterized by high AR copy number variation gain; positive expression of PD-L1, AR, and phosphorylated AR; low espression of GSTP1 in epithelial component...
August 12, 2018: International Journal of Biological Markers
Michäel Duruisseaux, Anna Martínez-Cardús, Maria E Calleja-Cervantes, Sebastian Moran, Manuel Castro de Moura, Veronica Davalos, David Piñeyro, Montse Sanchez-Cespedes, Nicolas Girard, Marie Brevet, Etienne Giroux-Leprieur, Coraline Dumenil, Monica Pradotto, Paolo Bironzo, Enrica Capelletto, Silvia Novello, Alexis Cortot, Marie-Christine Copin, Niki Karachaliou, Maria Gonzalez-Cao, Sergio Peralta, Luis M Montuenga, Ignacio Gil-Bazo, Iosune Baraibar, Maria D Lozano, Mar Varela, Jose C Ruffinelli, Ramon Palmero, Ernest Nadal, Teresa Moran, Lidia Perez, Immaculada Ramos, Qingyang Xiao, Agustin F Fernandez, Mario F Fraga, Marta Gut, Ivo Gut, Cristina Teixidó, Noelia Vilariño, Aleix Prat, Noemi Reguart, Amparo Benito, Pilar Garrido, Isabel Barragan, Jean-François Emile, Rafael Rosell, Elisabeth Brambilla, Manel Esteller
BACKGROUND: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. METHODS: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease...
August 9, 2018: Lancet Respiratory Medicine
Changfeng Li, Ying Zhang, Xing Cheng, Hua Yuan, Shan Zhu, Jiao Liu, Qirong Wen, Yangchun Xie, Jinbao Liu, Guido Kroemer, Daniel J Klionsky, Michael T Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
Pancreatic cancer is an aggressive malignancy with changes in the tumor microenvironment. Here, we demonstrate that PINK1 and PARK2 suppressed pancreatic tumorigenesis through control of mitochondrial iron-dependent immunometabolism. Using mouse models of spontaneous pancreatic cancer, we show that depletion of Pink1 and Park2 accelerates mutant Kras-driven pancreatic tumorigenesis. PINK1-PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increases mitochondrial iron accumulation, which leads to the HIF1A-dependent Warburg effect and AIM2-dependent inflammasome activation in tumor cells...
August 3, 2018: Developmental Cell
Aung Myo Hlaing, Bungo Furusato, Emiko Udo, Yuka Kitamura, Masakazu Souda, Mitsuko Masutani, Junya Fukuoka
BACKGROUND: Lung adenosquamous carcinoma (ASC) is a rare variant of non-small cell lung cancer (NSCLC) with poor prognosis. Certain biological differences may exist between these tumors and other common histological types of NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The phosphoinositide 3-kinase (PI3K) pathway, which links oncogenes and multiple receptor classes to essential cellular functions, is activated by phosphatase and tensin homolog (PTEN) loss. The PTEN loss has been suggested to induce programmed cell death ligand 1 (PD-L1) expression in various cancer types...
August 9, 2018: Biochemical and Biophysical Research Communications
Jean-Louis Pujol, Benoît Roch, Camille N Pujol, Catherine Goze
Small cell lung cancer accounts for 14% of all lung cancers. It remains a major challenge for oncology as the progresses made in the past three decades are modest. After a rapid overview of current knowledge regarding somatic genomic alterations, this state-of-art addresses pathways to improve small-cell lung cancer outcome such as the targeting of DNA damage repair mechanisms firstly anti-PARPs, inhibitory molecules of EZH2, derepression of the NOTCH pathway, rovalbituzumab-tesirine, inhibition of serine/threonine Aurora A kinase, temozolomide and its dependence on methylation of the MGMT promoter...
August 9, 2018: Bulletin du Cancer
Consuelo Buttigliero, Simona Allis, Marcello Tucci, Clizia Zichi, Gianmarco Leone, Rosario Francesco Di Stefano, Maria Grazia Ruo Redda, Umberto Ricardi, Giorgio Vittorio Scagliotti, Massimo Di Maio, Andrea Riccardo Filippi
In the last few years, immune checkpoint inhibitors have been extensively investigated in renal cell carcinoma and led to remarkable results. Radiation therapy may increase the activity of immune modulating agents through different mechanisms, priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. Preclinical studies reported increased loco-regional control when radiation is combined with immune-checkpoint blockade...
July 20, 2018: Cancer Treatment Reviews
Katharina Maisel, Mervyn J Merrilees, Elena N Atochina-Vasserman, Lurong Lian, Kseniya Obraztsova, Ryan Rue, Alexander N Vasserman, Ning Zuo, Luis F Angel, Andrew J Gow, Inkyung Kang, Thomas N Wight, Evgeniy Eruslanov, Melody A Swartz, Vera P Krymskaya
Pulmonary Iymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that is driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved treatment, yet it can only stabilize the disease but not cause regression of existing lesions. However, in other cancers, immunotherapies such as checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in causing tumor regression and even curing some patients...
August 10, 2018: American Journal of Respiratory Cell and Molecular Biology
Gilbert Bigras, Simon Mairs, Paul E Swanson, Didier Morel, Raymond Lai, Iyare Izevbaye
Pembrolizumab is an FDA-approved immune-checkpoint (IC) inhibitor that targets programmed cell death protein PD-1, and recent phase III trials have demonstrated its superiority over chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with Pembrolizumab is based on demonstration of PD-L1 expression on tumoral cells using the approved companion test 22C3 PharmDx (Dako). Access to the drug depends on a tumor proportion score (TPS) expressing the PD-L1 protein above predetermined cutoffs...
August 8, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Lin-Lin Sun, Ri-Yao Yang, Chia-Wei Li, Mei-Kuang Chen, Bin Shao, Jung-Mao Hsu, Li-Chuan Chan, Yi Yang, Jennifer L Hsu, Yun-Ju Lai, Mien-Chie Hung
The ataxia telangiectasia and Rad3-related (ATR) kinase plays a crucial role in maintaining genome stability in response to DNA damage. Once activated, ATR acts via its downstream target to arrest the cell cycle, promote DNA repair, and enhance cell survival. Therefore, ATR has become an attractive therapeutic target in cancer therapy. Multiple clinical studies have demonstrated that ATR inhibitors can sensitize cancer cells to conventional DNA damaging agents. However, the potential effects of ATR inhibitors on immune response in the tumor microenvironment, especially on the expression of immune checkpoint-related proteins, remain elusive...
2018: American Journal of Cancer Research
Shin Hye Yoo, Bhumsuk Keam, Miso Kim, Se Hyun Kim, Yu Jung Kim, Tae Min Kim, Dong-Wan Kim, Jong Seok Lee, Dae Seog Heo
Objectives: Nivolumab is used at 3 mg/kg or fixed doses of 240 mg every 2 weeks. There was no dose-response/toxicity relationship of nivolumab. This study evaluated the efficacy of low-dose nivolumab as an alternative to the financial toxicity of standard-dose nivolumab in treatment of non-small cell lung cancer (NSCLC). Methods: Outcomes of patients with NSCLC treated with nivolumab as a routine practice at two tertiary hospitals in Korea were retrospectively analysed...
2018: ESMO Open
Rajiv Raja, Michael Kuziora, Philip Brohawn, Brandon W Higgs, Ashok Gupta, Phillip A Dennis, Koustubh Ranade
PURPOSE: Immunotherapy has transformed the treatment of many solid tumors, with some patients deriving long-term benefit, but how to identify such patients remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from plasma can be an indicator of disease progression, response to therapy and clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a valuable noninvasive and tumor-specific marker for longitudinal monitoring of tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an anti-PD-L1 therapy...
August 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rebecca A Luchtel, Surendra Dasari, Naoki Oishi, Martin Bjerregård Pedersen, Guangzhen Hu, Karen L Rech, Rhett P Ketterling, Jagmohan Sidhu, Xueju Wang, Ryohei Katoh, Ahmet Dogan, N Sertac Kip, Julie M Cunningham, Zhifu Sun, Saurabh Baheti, Julie C Porcher, Jonathan W Said, Liuyan Jiang, Stephen Jacques Hamilton-Dutoit, Michael Boe Møller, Peter Nørgaard, N Nora Bennani, Wee-Joo Chng, Gaofeng Huang, Brian K Link, Fabio Facchetti, James R Cerhan, Francesco d'Amore, Stephen M Ansell, Andrew L Feldman
Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. While ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling...
August 9, 2018: Blood
Sebastian Kobold, Stanislav Pantelyushin, Felicitas Rataj, Johannes Vom Berg
T cells have been established as core effectors for cancer therapy; this has moved the focus of therapeutic endeavors to effectively enhance or restore T cell tumoricidal activity rather than directly target cancer cells. Both antibodies targeting the checkpoint inhibitory molecules programmed death receptor 1 (PD1), PD-ligand 1 (PD-L1) and cytotoxic lymphocyte activated antigen 4 (CTLA4), as well as bispecific antibodies targeting CD3 and CD19 are now part of the standard of care. In particular, antibodies to checkpoint molecules have gained broad approval in a number of solid tumor indications, such as melanoma or non-small cell lung cancer based on their unparalleled efficacy...
2018: Frontiers in Oncology
Mehdi Touat, Thierry Maisonobe, Samuel Knauss, Omar Ben Hadj Salem, Baptiste Hervier, Karine Auré, Tali-Anne Szwebel, Nora Kramkimel, Claire Lethrosne, Jean-Frédéric Bruch, Pauline Laly, Jacques Cadranel, Nicolas Weiss, Anthony Béhin, Yves Allenbach, Olivier Benveniste, Timothée Lenglet, Dimitri Psimaras, Werner Stenzel, Sarah Léonard-Louis
OBJECTIVE: To report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis). METHODS: We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. Main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed death-1 receptor (PD-1), programmed death ligand (PD-L) 1, and PD-L2 immunohistochemical stains...
August 8, 2018: Neurology
Katherine A Scilla, Dan P Zandberg, Søren M Bentzen, Candace Mainor, Jonathon Heath, Olga B Ioffe, Ashley L Cellini, Martin J Edelman, David J Riedel, Josephine L Feliciano
OBJECTIVE: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients. MATERIALS AND METHODS: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1...
September 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Xiaohan Hu, Joel W Hay
BACKGROUND: Pembrolizumab has shown significant survival benefits in treating chemotherapy-naïve non-small-cell lung cancer patients (NSCLC) with increased level of PD-L1 expression. This analysis aimed to evaluate the cost-effectiveness of pembrolizumab as a first-line treatment for patients with PD-L1 positive NSCLC from the UK health care perspective. METHODS: A Markov model with progression-free, progressive disease and death states was developed. Clinical parameters were informed by the KEYNOTE-024 trial...
September 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Qingrong Sun, Mengyuan Li, Xiaosheng Wang
BACKGROUND: The Cancer Genome Atlas (TCGA) is an important data resource for cancer biologists and oncologists. However, a lack of bioinformatics expertise often hinders experimental cancer biologists and oncologists from exploring the TCGA resource. Although a number of tools have been developed for facilitating cancer researchers to utilize the TCGA data, these existing tools cannot fully satisfy the large community of experimental cancer biologists and oncologists without bioinformatics expertise...
August 8, 2018: BMC Medical Genomics
Jibin Li, Jian Xu, Xiaofei Yan, Keer Jin, Wenya Li, Rui Zhang
BACKGROUND Limited efficacy of immune checkpoint blockades was observed in clinical trials in colorectal (CRC) patients, especially in the microsatellite-stable patients. Interleukin-6 (IL-6) is critical in modeling immune responses in cancers. However, the effects of targeting IL-6 in combination with immune checkpoint blockades is unknown in CRC. MATERIAL AND METHODS In the present study, we investigated the profile of IL-6 expression in tumor tissues of CRC patient and we established CRC mouse models with various IL-6 expression levels using CT26 cells and MC38 cells...
August 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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