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Cancer and immune

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https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#1
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28538671/engineering-exosomes-for-cancer-therapy
#2
REVIEW
Katie E Gilligan, Róisín M Dwyer
There remains an urgent need for novel therapeutic strategies to treat metastatic cancer, which results in over 8 million deaths annually worldwide. Following secretion, exosomes are naturally taken up by cells, and capable of the stable transfer of drugs, therapeutic microRNAs and proteins. As knowledge of the biogenesis, release and uptake of exosomes continues to evolve, and thus also has interest in these extracellular vesicles as potential tumor-targeted vehicles for cancer therapy. The ability to engineer exosome content and migratory itinerary holds tremendous promise...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538494/committee-opinion-no-704-summary-human-papillomavirus-vaccination
#3
(no author information available yet)
Human papillomavirus (HPV) is associated with anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. The HPV vaccination significantly reduces the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only 41.9% of girls in the recommended age group, and only 28.1% of males in the recommended age group have received all recom-mended doses. Compared with many other countries, HPV vaccination rates in the United States are unacceptably low...
June 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28538392/maculopapular-rash-after-intravitreal-injection-of-an-antivascular-endothelial-growth-factor-aflibercept-for-treating-age-related-macular-degeneration-a-case-report
#4
Norihiro Nagai, Mari Ibuki, Hajime Shinoda, Kaori Kameyama, Kazuo Tsubota, Yoko Ozawa
RATIONALE: Aflibercept, an anti-vascular endothelial growth factor (VEGF) drug, is used for treatment of colon cancer as well as retinal diseases, including wet age-related macular degeneration (AMD). It is injected into the vitreous cavity of eyes for treatment of AMD. Although vascular suppression-including cardiovascular events-and local infection related to the injection procedure are well-known potential adverse events, pathological immune responses after intravitreal aflibercept (IVA) injection have not been described...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#5
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#6
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537918/cryoablation-combined-with-allogenic-natural-killer-cell-immunotherapy-improves-the-curative-effect-in-patients-with-advanced-hepatocellular-cancer
#7
Mao Lin, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu, Kecheng Xu
In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537911/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#8
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew Wb Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#9
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537894/intratumoral-depletion-of-regulatory-t-cells-using-cd25-targeted-photodynamic-therapy-in-a-mouse-melanoma-model-induces-antitumoral-immune-responses
#10
Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park, Heung Kyu Lee
Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#11
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537887/dietary-factors-and-microrna-binding-site-polymorphisms-in-the-il13-gene-risk-and-prognosis-analysis-of-colorectal-cancer
#12
Yanming Yu, Junde Zhou, Chen Gong, Zhiping Long, Jingshen Tian, Lin Zhu, Jing Li, Hongyuan Yu, Fan Wang, Yashuang Zhao
Long-term dietary intake influences the structure and activity of microorganisms residing in the human gut. The immune response and gut microbiota have a mutual influence on the risk of colorectal cancer (CRC). This study examines the association of gut microbiota-related dietary factors and polymorphisms in the microRNA-binding site of the interleukin 13 gene (IL13) with the risk and prognosis of CRC. Three polymorphisms (rs847, rs848, and rs1295685) were selected for genotyping in a case-control study (513 cases, 572 controls), and 386 CRC patients were followed up...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537884/a-cancer-vaccine-based-on-fluorine-modified-sialyl-tn-induces-robust-immune-responses-in-a-murine-model
#13
Chengcheng Song, Xiu-Jing Zheng, Chang-Cheng Liu, Yifa Zhou, Xin-Shan Ye
Development of an effective vaccine to target tumor associated carbohydrate antigens, aberrantly expressed on the cell surface of various carcinomas, is an appealing approach toward cancer immunotherapy. However, a major problem of carbohydrate antigens is their poor immunogenicity. Immunization with modified-carbohydrate antigens could improve the immunogenicity and induce cross reaction with the native carbohydrate antigens. In this study, we investigated the antitumor ability of three fluoro-substituted sialyl-Tn (STn) analogues (2, 3, 4) coupled to KLH (keyhole limpet hemocyanin) and studied the mechanism of tumor immunotherapy of the vaccines in a murine model of colon cancer...
May 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537793/in-this-issue-role-of-immune-cells-immune-modulating-factors-and-immunotoxins-in-cancer-immunotherapy
#14
Himanshu Kumar, Adrian Bot
No abstract text is available yet for this article.
May 24, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28537730/discovery-of-small-molecules-as-multi-toll-like-receptor-agonists-with-proinflammatory-and-anticancer-activities
#15
Lei Zhang, Varun Dewan, Hang Hubert Yin
Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Subsequent structural optimization and counter screening of other TLRs produced the first small molecule (CU-CPT24e) capable of simultaneously activating TLRs 3, 8, and 9. Biochemical studies demonstrated that CU-CPT24e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535011/tumor-growth-limited-to-subcutaneous-site-vs-tumor-growth-in-pulmonary-site-exhibit-differential-effects-on-systemic-immunities
#16
Junko Masuda, Eiji Takayama, Warren Strober, Ayano Satoh, Yuji Morimoto, Yasuko Honjo, Tatsuo Ichinohe, Shin-Ichi Tokuno, Toshiaki Ishizuka, Takahiro Nakata, Akifumi Mizutani, Naoki Umemura, Atsushi Kitani, Ivan J Fuss, Tsukasa Shigehiro, Harumi Kawaki, Masako Mizuno-Kamiya, Nobuo Kondoh, Masaharu Seno
To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4+ and CD8+ T cells as well as CD4+ Foxp3+ T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model...
May 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#17
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534338/-application-and-development-of-patient-derived-tumor-xenograft-model-in-translational-medicine-of-tumor
#18
Zhenqiang Wang, Zhenggang Zhu
Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534292/development-and-characterization-of-a-neutralizing-anti-idiotype-antibody-against-mirvetuximab-for-analysis-of-clinical-samples
#19
Sven Loebrich, Mingfang Shen, Erika Cohen, Gillian Payne, Ying Chen, Megan Bogalhas, Yiwei Zhao
Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Taking advantage of the immune system's ability to generate highly specific antibodies, the field has turned to anti-idiotype antibodies as powerful tools for the development of sensitive and specific bioassays...
May 22, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28534250/advancing-immunotherapy-in-metastatic-breast-cancer
#20
REVIEW
Mariam Mansour, Zhi Ling Teo, Stephen J Luen, Sherene Loi
Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms...
June 2017: Current Treatment Options in Oncology
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