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Immune based cancer therapy

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https://www.readbyqxmd.com/read/28213714/-current-biomarkers-for-gastric-cancer
#1
G B Baretton, D E Aust
Gastric cancer is still a relevant malignant disease with high morbidity and mortality. Current molecular genetic data show that gastric cancer, as other solid tumors as well, is not a single entity but consists of several molecular subtypes of gastric cancer with diverse biology. The increasing understanding of molecular pathways is the basis for innovative therapies. These either directly target altered signaling pathways or genes in tumor cells or as in immune checkpoint inhibitors, indirectly target tumor cells by blocking tumor-induced immune inhibition leading to improvement in the prognosis...
February 17, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28212060/pembrolizumab-as-second-line-therapy-for-advanced-urothelial-carcinoma
#2
Joaquim Bellmunt, Ronald de Wit, David J Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Yabing Mai, Christian H Poehlein, Rodolfo F Perini, Dean F Bajorin
Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine...
February 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28210259/resolution-of-cancer-promoting-inflammation-a-new-approach-for-anticancer-therapy
#3
REVIEW
Qi Zhang, Bo Zhu, Yongsheng Li
Inflammation is a protective response that eliminates harmful stimuli and restores tissue homeostasis, whereas the failure to resolve inflammation leads to the development of malignancies. Immune cells in the tumor inflammatory microenvironment endow cancer cells with their specific hallmarks, including mutations, metabolic reprograming, angiogenesis, invasion, and metastasis. Targeting the inflammatory microenvironment with anti-inflammatory drugs (e.g., aspirin) or by enhancing antitumor immunity (e.g., chimeric antigen receptor T cell therapy) has been extensively investigated and has achieved promising results in many cancers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#4
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#5
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197365/crispr-cas9-mediated-disruption-of-pd-1-on-human-t-cells-for-adoptive-cellular-therapies-of-ebv-positive-gastric-cancer
#6
Shu Su, Zhengyun Zou, Fangjun Chen, Naiqing Ding, Juan Du, Jie Shao, Lin Li, Yao Fu, Bian Hu, Yang Yang, Huizi Sha, Fanyan Meng, Jia Wei, Xingxu Huang, Baorui Liu
The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28186087/baculovirus-directly-activates-murine-nk-cells-via-tlr9
#7
T Moriyama, T Suzuki, M O Chang, M Kitajima, H Takaku
The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and NK cell dependent; however, they were found to be CD4(+) T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28183254/metastatic-colorectal-cancer-role-of-target-therapies-and-future-perspectives
#8
Anna Nappi, Massimiliano Berretta, Carmela Romano, Salvatore Tafuto, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Chiara De Divitiis, Lara Alessandrini, Francesco Fiorica, Alessandro Ottaiano, Guglielmo Nasti
Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that, by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel agents such as aflibercept and regorafenib have recently been approved...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28179283/immune-based-therapies-for-non-small-cell-lung-cancer
#9
REVIEW
Hind Rafei, Ehab El-Bahesh, Antoine Finianos, Samah Nassereddine, Imad Tabbara
Lung cancer is the leading cause of cancer-related death worldwide. Treatment of non-small cell lung cancer has evolved tremendously over the past decade. Specifically, immune checkpoint inhibitors have become an increasingly interesting target of pharmacological blockade. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination with other therapies. Vaccination in non-small cell lung cancer is also an emerging field of research that holds promising results for the future of immunotherapy in non-small cell lung cancer...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178671/pd-1-mrna-expression-in-peripheral-blood-cells-and-its-modulation-characteristics-in-cancer-patients
#10
Wei Wang, Ge Shen, Shikai Wu, Shiping Song, Yanli Ni, Zhuoyao Suo, Xiangying Meng, Dan Li, Lin Zhou, Rimin Hao, Yaowei Zhao, Li Bai, Lili Hou, Bing Liu, Guangxian Liu
Immune checkpoint inhibitors that block the PD-1/PD-L1 signaling pathway have been used to treat a wide variety of cancers. Although results have been promising, significant inter-individual and inter-tumor variability has been observed. It is believed that better clinical outcome could be achieved if the treatment was individually designed based on the functional status of the PD-1/PD-L1 signaling and the cellular immunity. In this study, we analyzed the mRNA expression of PD-1 and other immunomodulatory genes in peripheral blood from cancer patients, and immunomodulatory gene expression during radiotherapy and immunomodulation therapy with cytokines...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174389/-molecular-biology-for-surgical-treatment-of-lung-cancer
#11
Kenichi Suda, Tetsuya Mitsudomi
Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28169355/enhancement-of-5-aminolevulinic-acid-based-fluorescence-detection-of-side-population-defined-glioma-stem-cells-by-iron-chelation
#12
Wenqian Wang, Kouichi Tabu, Yuichiro Hagiya, Yuta Sugiyama, Yasuhiro Kokubu, Yoshitaka Murota, Shun-Ichiro Ogura, Tetsuya Taga
Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169004/immunotherapy-in-ovarian-cancer
#13
Venkatesh Krishnan, Jonathan S Berek, Oliver Dorigo
Immunotherapy aims to develop combination approaches that simultaneously augment immunity while preventing local immune suppression. Despite advances in combinatorial chemotherapy regimens and the advent of intraperitoneal chemotherapy administration, current therapeutic options for patients with ovarian cancer are inadequate. Advances in immunotherapy offer a promising frontier for treating ovarian tumors. Multiple immunotherapeutic modalities are currently developed and tested in clinical trials. Antibody-based therapies, immune checkpoint blockade, cancer vaccines, and chimeric antigen receptor-modified T cells have demonstrated preclinical success and entered clinical testing...
November 15, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28165834/seek-and-destroy-targeted-adeno-associated-viruses-for-gene-delivery-to-hepatocellular-carcinoma
#14
Bijay Dhungel, Aparna Jayachandran, Christopher J Layton, Jason C Steel
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with high incidence globally. Increasing mortality and morbidity rates combined with limited treatment options available for advanced HCC press for novel and effective treatment modalities. Gene therapy represents one of the most promising therapeutic options. With the recent approval of herpes simplex virus for advanced melanoma, the field of gene therapy has received a major boost. Adeno-associated virus (AAV) is among the most widely used and effective viral vectors today with safety and efficacy demonstrated in a number of human clinical trials...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28163164/anti-pd-1-pd-l1-therapy-for-infectious-diseases-learning-from-the-cancer-paradigm
#15
REVIEW
Martin Rao, Davide Valentini, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Immune checkpoint pathways regulate optimal host immune responses against transformed cells; induce immunological memory and limit tissue pathology. Conversely, aberrant immune checkpoint activity signifies poor prognosis in cancer and infectious diseases. Host-directed therapy (HDT) via immune checkpoint blockade has revolutionised cancer treatment with therapeutic implications for chronic infections, thus laying the foundation for this review. METHODS: We performed online literature searches via PubMed, PubMedCentral and Google using the keywords "immune checkpoint inhibition", "host-directed therapy", "T cell exhaustion", "cancer immunotherapy", "anti-PD-1 therapy", "anti-PD-L1 therapy", "chronic infections", "antigen-specific cells", "tuberculosis", "malaria", "viral infections", "human immunodeficiency virus", "hepatitis B virus", "hepatitis C virus", "cytomegalovirus" and "Epstein-Barr virus"...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28152949/improving-screening-and-prophylaxis-of-hepatitis-b-in-immunosuppressed-patients
#16
Violeta Rabrenovich, David M Baer, Joanne E Schottinger
: 139 Background: Kaiser Permanente (KP) is an integrated health care delivery system that provides clinical services to over 10 million members in nine states and the District of Columbia. Since 2007, KP oncology community collaborates at the national level to systematically improve safety and quality of care. Our improvements are accelerated by rapid adoption of evidence based protocols, leveraging of EMR and integration of quality improvement methods into clinical operations. METHODS: KP created a team that included oncologists, hepatologists, rheumatologist, pharmacy, and quality improvement experts to evaluate safety of existing practice...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152514/high-pd-l1-expression-is-associated-with-stage-iv-disease-and-poorer-overall-survival-in-186-cases-of-small-cell-lung-cancers
#17
Yih-Leong Chang, Ching-Yao Yang, Yen-Lin Huang, Chen-Tu Wu, Pan-Chyr Yang
BACKGROUND: Small cell lung cancer (SCLC) is an aggressive malignancy with a distinct natural history and dismal prognosis. SCLC is characterized as a recalcitrant neoplasm with limited therapeutic options and platinum-based chemotherapy is the treatment of choice. Programmed cell death-ligand 1(PD-L1)-mediated immune escape may be a suitable target for specific therapy, but its role in SCLC is unclear. MATERIALS AND METHODS: In total, 186 SCLC cases were investigated...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151713/immune-therapies-in-multiple-myeloma
#18
EDITORIAL
Shaji K Kumar, Kenneth C Anderson
Treatment paradigms have changed rapidly for multiple myeloma, and immune therapies have taken center stage. Advances in therapies for myeloma have led to a dramatic improvement in the survival of patients with this incurable malignancy. The immune system is significantly impaired in patients with myeloma as a result of the disease leading to suppression of normal plasma cells as well the negative effects on cellular immunity. Given this scenario, immune approaches have not been successful until recently. Monoclonal antibodies directed against CD38 (daratumumab) and SLAMF7 (elotuzumab) are already in the clinic, and several other antibodies directed against different plasma cell antigens are under evaluation...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28130601/complementary-and-alternative-medicine-in-radiation-oncology-survey-of-patients-attitudes
#19
Sabrina Lettner, Kerstin A Kessel, Stephanie E Combs
BACKGROUND: Complementary and alternative medicine (CAM) are gaining in importance, but objective data are mostly missing. However, in previous trials, methods such as acupuncture showed significant advantages compared to standard therapies. Thus, the aim was to evaluate most frequently used methods, their significance and the general acceptance amongst cancer patients undergoing radiotherapy (RT). METHODS: A questionnaire of 18 questions based on the categorical classification released by the National Centre for Complementary and Integrative Health was developed...
January 27, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28130276/subgroups-and-prognostication-in-stage-iii-colon-cancer-future-perspectives-for-adjuvant-therapy
#20
E Auclin, A Zaanan, D Vernerey, R Douard, C Gallois, P Laurent-Puig, F Bonnetain, J Taieb
Since the MOSAIC study, oxaliplatin-based adjuvant chemotherapy has been the standard treatment for stage III colon cancer. Combination therapy with fluoropyrimidines and oxaliplatin has improved overall survival (OS) and reduced the risk of recurrence in patients with resected stage III colon cancer. However, only 20% of patients really benefit from adjuvant chemotherapy, exposing 80% of patients to unnecessary toxicity. Recent analyses of large multicenter adjuvant studies have focused on the prognostication of OS and disease free survival (DFS) in stage III colon cancer in order to reduce over-treatment and to find more accurate prognostic tools than those used for adjuvant treatment decision-making in stage II disease...
January 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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