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https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#1
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#2
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156708/a-preclinical-evaluation-of-the-mek-inhibitor-refametinib-in-her2-positive-breast-cancer-cell-lines-including-those-with-acquired-resistance-to-trastuzumab-or-lapatinib
#3
John O'Shea, Mattia Cremona, Clare Morgan, Malgorzata Milewska, Frankie Holmes, Virginia Espina, Lance Liotta, Joyce O'Shaughnessy, Sinead Toomey, Stephen F Madden, Aoife Carr, Naomi Elster, Bryan T Hennessy, Alex J Eustace
Purpose: The MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an in vitro preclinical evaluation of refametinib, an allosteric MEK1/2 inhibitor, in HER2-positive breast cancer cell lines including models of acquired resistance to trastuzumab or lapatinib. Methods: A panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#4
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#5
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156318/how-host-metabolism-impacts-on-virus-pathogenesis
#6
REVIEW
Siva Karthik Varanasi, Barry T Rouse
The outcome of virus infections depends on multiple factors. This review deals with the role of host metabolism as one such factor. We describe how different cells in the immune system employ differential metabolic pathways and how this relates to the outcome of virus infections. We also discuss how nutritional and metabolic diseases can influence the nature of viral pathogenesis as well as how targeted therapies against metabolic processes can impact on the outcome of virus infections. The case is also made for metabolic profiling as a potential tool to predict the outcome of a virus infection and to guide therapies that enhance host resistance...
November 16, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29156206/cytokine-release-syndrome-who-is-at-risk-and-how-to-treat
#7
REVIEW
Noelle Frey
T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell activation and elevated cytokine levels...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156048/unmet-needs-in-clinical-and-basic-hepatitis-b-virus-research
#8
Tung-Hung Su, Jia-Horng Kao
Chronic hepatitis B (CHB) has become a treatable and controllable disease. The current nucleos(t)ide analogue (NUC) and pegylated interferon therapies effectively help slow disease progression and reduce the risk of cirrhosis, hepatocellular carcinoma (HCC), and CHB-associated mortality. Long-term viral suppression is easily achievable by NUC therapy, with limited adverse reactions. However, several unmet requirements still exist, including safety and risk-stratified HCC surveillance among patients who received long-term NUC therapy...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29156047/immunopathogenesis-of-hepatitis-b-virus
#9
Tai-Chung Tseng, Li-Rung Huang
Chronic hepatitis B virus (HBV) infection is a global public health issue. There are >250 million people chronically infected with HBV, and these chronic carriers are at high risk of developing end-stage liver diseases and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) usually acquire the virus perinatally, while most patients infected during adulthood develop acute hepatitis B (AHB), which usually results in viral clearance. HBV infection is noncytopathic, and liver injury is mostly contributed by host immune responses...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29155585/allosteric-inhibitors-of-shp2-with-therapeutic-potential-for-cancer-treatment
#10
Jingjing Xie, Xiaojia Si, Shoulai Gu, Mingliang Wang, Jian Shen, Haoyan Li, Jian Shen, Dan Li, Yanjia Fang, Cong Liu, Jidong Zhu
SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, is involved in multiple cell signaling processes including Ras/MAPK and Hippo/YAP pathways. SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric and breast cancer. It also regulates T-cell activation by interacting with inhibitory immune checkpoint receptors such as the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). Thus, SHP2 inhibitors have drawn great attention by both inhibiting tumor cell proliferation and activating T cell immune responses toward cancer cells...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#11
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29155319/impact-of-human-leukocyte-antigen-hla-alleles-on-outcomes-of-allogeneic-transplantation-for-b-cell-non-hodgkin-lymphomas-a-center-for-international-blood-and-marrow-transplant-research-analysis
#12
Basem M William, Tao Wang, Michael D Haagenson, Katharina Fleischhauer, Michael Verneris, Katharine C Hsu, Marcos J de Lima, Marcelo Fernandez-Viña, Stephen R Spellman, Stephanie J Lee, Brian T Hill
Even in the modern era of targeted therapies, allogeneic hematopoietic stem cell transplantation (allo-HCT) can offer a chance of extended survival in B-cell non-Hodgkin lymphoma (B-NHL) patients who relapse after, or are deemed ineligible for, autologous transplantation. A better understanding of the factors influencing the graft vs lymphoma (GVL) response would be useful in identifying B-NHL patients who may benefit from allo-HCT. Based on prior single-center reports, we hypothesized that certain HLA alleles, or haplotypes, may be associated with superior GVL, compared to others, after allo-HCT...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29155127/mdr1-gene-c3435t-polymorphism-in-chronic-hepatitis-c-patients
#13
Mehdi Parsanahad, Manoochehr Makvandi, Ali Teimoori, Shahram Jalilian, Gholamabas Kayedani, Sara Mahmoodi
BACKGROUND: MDR1 is a highly polymorphic gene that encodes P-glycoprotein (P-gp). This protein anchor to the cell membrane and transports toxins, xenobiotic, chemicals, and drugs from the intracellular to extracellular and thus protect cells. Polymorphism of the MDR1 gene seems to be effective in gene expression and response to treatment. Since one of the main mechanisms of drug resistance is the removal of the drug from the cell by ATP-dependent efflux proteins, thus MDR1, single nucleotide polymorphism (SNP) C3435T can be used as a predictor for treatment outcomes...
November 15, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29154977/polymer-nitric-oxide-donors-potentiate-the-treatment-of-experimental-solid-tumours-by-increasing-drug-accumulation-in-the-tumour-tissue
#14
M Studenovsky, L Sivak, O Sedlacek, R Konefal, V Horkova, T Etrych, M Kovar, B Rihova, M Sirova
The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized...
November 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29154465/the-role-of-immunological-testing-and-intervention-in-reproductive-medicine-a-fertile-collaboration
#15
REVIEW
Syed B Ali, Yogesh Jeelall, Craig E Pennell, Roger Hart, Andrew McLean-Tooke, Michaela Lucas
Advances in reproductive medicine have significantly increased the success of fertility treatments. Nevertheless, some women experience recurrent implantation failure (RIF) after in-vitro fertilization (IVF) or recurrent pregnancy loss (RPL). Imbalances in the immune system and failure to achieve immune tolerance to the foetus have been implicated as potentially modifiable causes of idiopathic RIF and RPL. As such, women are increasingly being treated with immunomodulatory agents in an attempt to achieve a successful pregnancy...
November 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29154370/prr11-immunoreactivity-is-a-weak-prognostic-factor-in-non-mucinous-invasive-adenocarcinoma-of-the-lung
#16
Y Sakai, C Ohbayashi, E Yanagita, N Jimbo, K Kajimoto, T Sakuma, T Hirose, M Yoshimura, Y Maniwa, T Itoh
INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity...
September 2017: Pathologica
https://www.readbyqxmd.com/read/29154044/modulating-host-immune-responses-to-fight-invasive-fungal-infections
#17
REVIEW
James E Scriven, Mark W Tenforde, Stuart M Levitz, Joseph N Jarvis
Modulation of host immunity in invasive fungal infection is an appealing but as yet mostly elusive treatment strategy. Animal studies in invasive candidiasis and aspergillosis have demonstrated beneficial effects of colony stimulating factors, interferon-gamma and monoclonal antibodies. More recent studies transfusing leukocytes pre-loaded with lipophilic anti-fungal drugs, or modulated T-cells, along with novel vaccination strategies show great promise. The translation of immune therapies into clinical studies has been limited to date but this is changing and the results of new Candida vaccine trials are eagerly awaited...
November 15, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29153988/isolation-and-comparative-transcriptome-analysis-of-human-fetal-and-ipsc-derived-cone-photoreceptor-cells
#18
Emily Welby, Jorn Lakowski, Valentina Di Foggia, Dimitri Budinger, Anai Gonzalez-Cordero, Aaron T L Lun, Michael Epstein, Aara Patel, Elisa Cuevas, Kamil Kruczek, Arifa Naeem, Federico Minneci, Mike Hubank, David T Jones, John C Marioni, Robin R Ali, Jane C Sowden
Loss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation of stem cell-derived L/M-opsin cones, which form 90% of the human cone population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and stem cell-derived cones remain to be defined, in addition to development of cone cell purification strategies. Here, we report an analysis of the human L/M-opsin cone photoreceptor transcriptome using an AAV2/9...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29152725/regressed-melanocytic-nevi-secondary-to-pembrolizumab-therapy-an-emerging-melanocytic-dermatologic-effect-from-immune-checkpoint-antibody-blockade
#19
Shakuntala H Mauzo, Michael T Tetzlaff, Kelly Nelson, Rodabe Amaria, Sapna Patel, Phyu P Aung, Priyadharsini Nagarajan, Carlos A Torres-Cabala, Adi Diab, Victor G Prieto, Jonathan L Curry
BACKGROUND: Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy. CASE REPORTS: We report two patients with melanocytic nevi that regressed with pembrolizumab therapy. The first patient had stage IV BRAF K601E/L584F mutant melanoma that developed a regressed melanocytic nevus while being treated with pembrolizumab...
November 20, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/29152681/trichothecenes-immunomodulatory-effects-mechanisms-and-anti-cancer-potential
#20
REVIEW
Qinghua Wu, Xu Wang, Eugenie Nepovimova, Anca Miron, Qianying Liu, Yun Wang, Dongxiao Su, Hualin Yang, Li Li, Kamil Kuca
Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated...
November 20, 2017: Archives of Toxicology
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