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Immune therapy cancer

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https://www.readbyqxmd.com/read/29055015/small-molecule%C3%A2-inhibition-of-pd-1-transcription-is-an-effective-alternative-to-antibody-blockade-in-cancer-therapy
#1
Alison Taylor, David Rothstein, Christopher Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#2
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29054858/mirna-directed-cancer-therapies-implications-in-melanoma-intervention
#3
Anita Thyagarajan, Ahmed Shaban, Ravi P Sahu
Acquired tumor resistance to cancer therapies pose major challenges in the treatment of cancers including melanoma. Among several signaling pathways or factors that affect neocarcinogenesis, cancer progression and therapies, altered microRNAs (miRNAs) expression has been identified as crucial players in modulating the key pathways governing these events. While studies on miRNA field has grown exponentially in the last decade, much remains to be discovered, particularly with respect to their roles in cancer therapies...
October 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29054784/developing-a-xenograft-human-tumor-model-in-immunocompetent-mice
#4
Matthew T Basel, Sanjeev Narayanan, Chanran Ganta, Tej B Shreshta, Alejandro Marquez, Marla Pyle, Jennifer Hill, Stefan H Bossmann, Deryl L Troyer
Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR...
October 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29054421/selenocompounds-in-cancer-therapy-an-overview
#5
Desirée Bartolini, Luca Sancineto, Andreza Fabro de Bem, Kenneth D Tew, Claudio Santi, Rafael Radi, Pierangelo Toquato, Francesco Galli
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29054417/the-regulation-of-pathways-of-inflammation-and-resolution-in-immune-cells-and-cancer-stem-cells-by-selenium
#6
Bastihalli T Diwakar, Arvind M Korwar, Robert F Paulson, K Sandeep Prabhu
Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29052780/immunotherapy-for-hepatocellular-carcinoma-patients-is-it-ready-for-prime-time
#7
REVIEW
Joseph M Obeid, Paul R Kunk, Victor M Zaydfudim, Timothy N Bullock, Craig L Slingluff, Osama E Rahma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver's inherent immunosuppressive function...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052609/neuro-ophthalmic-side-effects-of-molecularly-targeted-cancer-drugs
#8
REVIEW
M T Bhatti, A K S Salama
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity...
October 20, 2017: Eye
https://www.readbyqxmd.com/read/29052129/hepatitis-b-virus-associated-hepatocellular-carcinoma
#9
Youhua Xie
Liver cancer is the fifth most common cancer worldwide in men and the ninth in women. It is also the second most common cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. About 350 million people globally are chronically infected with HBV. Chronic hepatitis B virus (HBV) infection accounts for at least 50% cases of HCC worldwide. Other non-HBV factors may increase HCC risk among persons with chronic HBV infection. Both indirect and direct mechanisms are involved in HCC oncogenesis by HBV...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29051851/biomimetically-engineered-demi-bacteria-potentiate-vaccination-against-cancer
#10
Dezhi Ni, Shuang Qing, Hui Ding, Hua Yue, Di Yu, Shuang Wang, Nana Luo, Zhiguo Su, Wei Wei, Guanghui Ma
Failure in enhancing antigen immunogenicity has limited the development of cancer vaccine. Inspired by effective immune responses toward microorganisms, demi-bacteria (DB) from Bacillus are engineered as carriers for cancer vaccines. The explored hydrothermal treatment enables the Bacillus to preserve optimal pathogen morphology with intrinsic mannose receptor agonist. Meanwhile, the treated Bacillus can be further endowed with ideal hollow/porous structure for efficient accommodation of antigen and adjuvant, such as CpG...
October 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29051161/prostate-cancer-cells-express-more-androgen-receptor-ar-following-androgen-deprivation-improving-recognition-by-ar-specific-t-cells
#11
Brian M Olson, Melissa Gamat, Joseph Seliski, Thomas Sawicki, Justin Jeffery, Leigh Ellis, Charles G Drake, Jamey Weichert, Douglas G McNeel
Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anti-cancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR...
October 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29051029/recent-advances-in-localized-rcc-a-focus-on-vegf-and-immuno-oncology-therapies
#12
REVIEW
Pearl Subramanian, Naomi B Haas Md
Recent advances in advanced renal cell cancer (RCC) research have produced new drugs and therapies for patients with metastatic disease leading to higher response rates, improvements in progression-free survival, and longer overall survival. These advances have yet to be realized in patients with early-stage kidney cancer, and to date, no drug has been approved for the adjuvant treatment of localized kidney cancer. The current standard of care for localized high-risk kidney cancers is resection of the primary tumor...
October 16, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#13
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050127/-immune-related-pneumonitis-caused-by-programmed-death-1-inhibitor-pembrolizumab-a-case-report-and-literature-review
#14
Y L Chen, J Zhao, R Jia, H Y Wang, J Zheng, C Q Bai, M Z Wang, J M Xu
Objective: To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017...
October 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29049843/metabolic-strategies-of-melanoma-cells-mechanisms-interactions-with-the-tumor-microenvironment-and-therapeutic-implications
#15
REVIEW
Grant M Fischer, Y N Vashisht Gopal, Jennifer L McQuade, Weiyi Peng, Ralph J DeBerardinis, Michael A Davies
Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There is also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies...
October 19, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#16
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29046826/incorporation-of-functional-elements-enhances-the-antitumor-capacity-of-car-t-cells
#17
REVIEW
Le Qin, Ruocong Zhao, Peng Li
As chimeric antigen receptor (CAR) T cells have displayed an unprecedented efficacy in the treatment of CD19-positive malignances, it is believed that this cell therapy will be a milestone in the history of mankind's conquering of cancer. However, there are some issues that restrict CAR T cells from reaching their optimal anti-tumor capacity, especially in the treatment of solid tumors. Inhibitory cytokines, immune checkpoint molecules, hypoxia and other adverse factors have been reported to be involved in this process...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29046803/antitumor-activity-of-yulangsan-polysacchrides-in-mice-bearing-s180-sarcoma-tumors
#18
Wen'E Cai, Xiaoyu Chen, Qingdong Pan, Shijun Zhang, Luojiao Tan, Xuyong Sun, Renbin Huang, Aijun Xia
Sarcoma is one of the most prevalent pediatric tumors and the therapeutic role of chemotherapy has yet to be elucidated. It has been reported that extracts of Longyanshen (Yulangsan) may enhance the sensitivity of drug-resistant cancer cell lines, and improve the immune dysfunction induced by cyclophosphamide (CTX) in mice. The present in vivo study investigated the antitumor effects of Yulangsan polysaccharides (YLSPS) and their interaction with CTX in murine sarcoma 180 (S180)-bearing mice. Immunohistochemistry was used to detect the expression of apoptosis-related proteins...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29046677/defining-genome-wide-expression-and-phenotypic-contextual-cues-in-macrophages-generated-by-granulocyte-macrophage-colony-stimulating-factor-macrophage-colony-stimulating-factor-and-heat-killed-mycobacteria
#19
Samer Bazzi, Emale El-Darzi, Tina McDowell, Helmout Modjtahedi, Satvinder Mudan, Marcel Achkar, Charles Akle, Humam Kadara, Georges M Bahr
Heat-killed (HK) Mycobacterium obuense (NCTC13365) is currently being evaluated in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the molecular underpinnings underlying immunomodulatory properties of HK M. obuense are still largely undefined. To fill this void, we sought to perform immunophenotyping, chemokine/cytokine release analysis and genome-wide characterization of monocyte-derived macrophages (MDM) in which monocytes were originally isolated from healthy donors and differentiated by HK M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29046675/interpreting-t-cell-cross-reactivity-through-structure-implications-for-tcr-based-cancer-immunotherapy
#20
Dinler A Antunes, Maurício M Rigo, Martiela V Freitas, Marcus F A Mendes, Marialva Sinigaglia, Gregory Lizée, Lydia E Kavraki, Liisa K Selin, Markus Cornberg, Gustavo F Vieira
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system...
2017: Frontiers in Immunology
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