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Immunotherapy lung cancer

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https://www.readbyqxmd.com/read/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#1
Radoslav Matěj, Zdeněk Rohan, Kristýna Němejcová, Pavel Dundr
The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29225707/how-to-evaluate-the-immune-status-of-lung-cancer-patients-before-immunotherapy
#2
Joanna Domagala-Kulawik, Agata Raniszewska
Nowadays, cancer immunotherapy is a promising strategy in solid tumour treatment. It has become a breakthrough in achieving long-term survival in many advanced cases. The essence of modern immunotherapy is to improve the host antitumour immune defence. Currently, it is critically important to determine the biomarkers that could be helpful in planning this type of individual therapy. It has turned out that an important prognostic factor is the evaluation of inflammatory infiltration of the tumour mass, including the characteristics of populations of lymphocytes and macrophages, and the expression of suppressive and regulatory molecules...
December 2017: Breathe
https://www.readbyqxmd.com/read/29222126/autoimmune-crmp5-neuropathy-phenotype-and-outcome-defined-from-105-cases
#3
Divyanshu Dubey, Vanda A Lennon, Avi Gadoth, Sean J Pittock, Eoin P Flanagan, John E Schmeling, Andrew McKeon, Christopher J Klein
OBJECTIVE: To establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)-immunoglobulin G (IgG) neuropathy. METHODS: Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed. RESULTS: One hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG...
December 8, 2017: Neurology
https://www.readbyqxmd.com/read/29217732/peptide-blocking-of-pd-1-pd-l1-interaction-for-cancer-immunotherapy
#4
Chunlin Li, Nengpan Zhang, Jundong Zhou, Chen Ding, Yaqing Jin, Xueyuan Cui, Kefeng Pu, Yimin Zhu
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. Monoclonal antibody (mAb) targeting to PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer or merkel cell carcinoma by the Food and Drug Administration (FDA). However, the high cost of the antibody can limit its application. In our study, TPP-1 (targeting PD-L1 peptide), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods...
December 7, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#5
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#6
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29209560/pd-l1-and-epithelial-mesenchymal-transition-in-circulating-tumor-cells-from-non-small-cell-lung-cancer-patients-a-molecular-shield-to-evade-immune-system
#7
Cristina Raimondi, Guido Carpino, Chiara Nicolazzo, Angela Gradilone, Walter Gianni, Alain Gelibter, Eugenio Gaudio, Enrico Cortesi, Paola Gazzaniga
The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understanding the events underlying tumor immune resistance. Although the expression of PD-L1 in tumor tissue has been correlated with clinical response to anti PD-1 inhibitors, the ability of this marker to discriminate the subgroup of patients who derive benefit from immunotherapy is suboptimal...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209070/assessment-of-concordance-between-22c3-and-sp142-immunohistochemistry-assays-regarding-pd-l1-expression-in-non-small-cell-lung-cancer
#8
Haipeng Xu, Gen Lin, Cheng Huang, Weifeng Zhu, Qian Miao, Xirong Fan, Biao Wu, Xiaobing Zheng, Xiandong Lin, Kan Jiang, Dan Hu, Chao Li
Different anti-PD-1 and anti-PD-L1 antibodies bind different epitopes. However, whether the results from the SP142 and 22C3 immunochemistry (IHC) assays can be interchanged to determine patient eligibility for immunotherapy remains largely unknown. Histologic sections from 135 tumor samples were probed with both 22C3 and SP142 antibodies. The concordance of PD-L1 expression determined by the two assays was assessed. Additionally, we evaluated the association of PD-L1 expression detected by different assays with clinicopathological features and prognosis...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207685/excellent-response-to-chemotherapy-post-immunotherapy
#9
Ashish D Dwary, Samip Master, Abhishek Patel, Constance Cole, Richard Mansour, Glenn Mills, Nebu Koshy, Prakash Peddi, Gary Burton, Dalia Hammoud, Kavitha Beedupalli
Introduction: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#10
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29203588/spatially-resolved-and-quantitative-analysis-of-vista-pd-1h-as-a-novel-immunotherapy-target-in-human-non-small-cell-lung-cancer
#11
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel F Sanmamed, Vamsidhar Velcheti, Konstantinos N Syrigos, Maria I Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
PURPOSE: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human NSCLC. EXPERIMENTAL DESIGN: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1 and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells, CD20+ B-lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#12
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29200082/pneumonitis-in-irradiated-lungs-after-nivolumab-a-brief-communication-and-review-of-the-literature
#13
Farkhad Manapov, Olarn Roengvoraphoj, Maurice Dantes, Sebastian Marschner, Minglun Li, Chukwuka Eze
Nivolumab is a feasible therapy option in patients with advanced non-small cell lung cancer (NSCLC) who progress on first-line treatment. However, there is limited information about an overlapping toxicity of PD-1 inhibitors when administered following thoracic radiotherapy (TRT). Three of 25 patients with advanced NSCLC were treated with palliative or curative intent. Nivolumab was initiated as second or third-line therapy after TRT for recurrent or progressive disease. All 3 patients developed grade 3 pneumonitis at some point during nivolumab therapy...
December 1, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29199595/epidermal-growth-factor-receptor-tyrosine-kinase-a-potential-target-in-treatment-of-non-small-cell-lung-carcinoma
#14
REVIEW
Venugopal Vinod Prabhu, Niranjali Devaraj
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29198327/critical-features-and-challenges-associated-with-imaging-in-patients-undergoing-cancer-immunotherapy
#15
REVIEW
Cinzia Solinas, Michele Porcu, Zuzana Hlavata, Pushpamali De Silva, Marco Puzzoni, Karen Willard-Gallo, Mario Scartozzi, Luca Saba
Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29196495/comparative-transcriptome-profiling-reveals-coding-and-noncoding-rna-differences-in-nsclc-from-african-americans-and-european-americans
#16
Khadijah A Mitchell, Adriana Zingone, Leila Toulabi, Jacob Boeckelman, Bríd M Ryan
Purpose: To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs).Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and 19 EAs) and miRNA (n = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29195578/programmed-death-cell-ligand-1-pd-l1-is-associated-with-survival-in-stage-i-non-small-cell-lung-cancer
#17
Boris Sepesi, Edwin Parra Cuentas, Jaime Rodriguez Canales, Carmen Behrens, Arlene M Correa, Ara Vaporciyan, Annikka Weissferdt, Neda Kalhor, Cesar Moran, Stephen Swisher, Ignacio Wistuba
Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis...
2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29195503/recent-development-in-clinical-applications-of-pd-1-and-pd-l1-antibodies-for-cancer-immunotherapy
#18
REVIEW
Bingshan Liu, Yongping Song, Delong Liu
Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials...
December 1, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29194117/non-small-cell-lung-cancer-from-hiv-infected-patients-expressed-pd-l1-with-marked-inflammatory-infiltrates
#19
Charlotte Domblides, Martine Antoine, Cécile Hamard, Nathalie Rabbe, Anita Rodenas, Thibault Vieira, Perrine Crequit, Jacques Cadranel, Armelle Lavolé, Marie Wislez
OBJECTIVE: Immunotherapy techniques targeting the programmed cell death protein 1 (PD-1) to PD ligand 1 (PD-L1) checkpoint have improved prognosis in lung cancer. PD-1/PD-L1 status, however, has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study sought to assess PD-L1 status and tumor immune-cell infiltration in non-small cell lung cancer (NSCLC) in HIV patients. METHODS: All consecutive HIV patients treated for NSCLC between 1996 and 2014 were enrolled...
November 30, 2017: AIDS
https://www.readbyqxmd.com/read/29194007/product-review-on-the-anti-pd-l1-antibody-atezolizumab
#20
Neil J Shah, William J Kelly, Stephen V Liu, Karin Choquette, Alexander Spira
Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more...
December 1, 2017: Human Vaccines & Immunotherapeutics
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