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https://www.readbyqxmd.com/read/28944501/synergistic-effects-of-interferon-beta-and-nivolumab-in-oral-mucosal-melanoma
#1
Takayuki Fusumae, Koji Kamiya, Binluen Chiang, Hirofumi Okada, Naomi Nakano, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
Mucosal melanoma is a rare aggressive cancer with a very poor prognosis. Clinical and pathological characteristics of mucosal melanoma differ from those of cutaneous melanoma and there are no established management guidelines for mucosal melanoma. Complete surgical excision is one of the most effective treatments for localized lesions, while targeted therapies and immunotherapies, such as monoclonal antibodies that target cytotoxic T-lymphocyte-associated molecule-4, and the programmed death (PD)-1/PD-ligand 1 pathway inhibitors, are treatment options for unresectable or metastatic lesions...
September 25, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#2
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28943128/patterns-of-care-and-impact-of-brachytherapy-boost-utilization-for-squamous-cell-carcinoma-of-the-base-of-tongue-in-a-large-national-cohort
#3
Anna Lee, Babak Givi, S Peter Wu, Moses M Tam, Naamit K Gerber, Kenneth S Hu, Peter Han, David Schreiber
PURPOSE: The National Cancer Data Base was analyzed to evaluate the patterns of care and impact of brachytherapy (BT) boost on overall survival (OS) for patients with squamous cell carcinoma of the base of tongue. METHODS AND MATERIALS: Patients with nonmetastatic squamous cell carcinoma of the base of tongue between 2004 and 2012 who received concurrent external beam radiation therapy (EBRT) and chemotherapy with or without BT boost in the definitive setting were queried...
September 21, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28942608/early-anthracycline-induced-cardiotoxicity-monitored-by-echocardiographic-doppler-parameters-combined-with-serum-hs-ctnt
#4
Chu-Jie Zhang, Xiao-Li Pei, Fei-Yan Song, Ye Guo, Qun-Ling Zhang, Xian-Hong Shu, David H Hsi, Lei-Lei Cheng
PURPOSE: As growing numbers of long-term cancer survivors faced with the cardiac side effects by anthracycline treatment, it is necessary to explore the optimal monitoring method for the early detection of cardiac toxicity. METHODS: We conducted a retrospective analysis of 82 consecutive patients with diffuse large B-cell lymphoma treated with chemotherapy. Echocardiographic Doppler imaging-derived Tei index and mitral annular peak systolic velocity (Sm) measured by tissue Doppler imaging TDI, serum high-sensitivity cardiac troponin T (hs-cTnT) levels, and left ventricular ejection fraction (LVEF) by multigated radionuclide angiography (MUGA) were obtained before, after 2-4, and after 6-8 chemotherapy cycles...
September 24, 2017: Echocardiography
https://www.readbyqxmd.com/read/28942432/the-application-and-mechanism-of-pd-pathway-blockade-for-cancer-therapy
#5
REVIEW
Xing Wang, Shan Huang, Ya Zhang, Lin Zhu, Xiaoliang Wu
Research in cancer therapeutics has achieved major progress in the understanding of the tumour-immunity cycle, which controls the delicate balance between the immune system and tumour. Identification of cancer cell T-cell inhibitory signals, including PD-L1, has generated novel insight into how to reinvigorate the patients' immune cells to respond to a variety of tumour types. PD-1 and PD-L1 (PD) inhibitory pathway blockade appears to a highly promising therapy and could accomplish durable anti-tumour responses with a reasonable toxicity profile...
September 23, 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28942428/cancer-stem-cells-in-colorectal-cancer-a-review
#6
REVIEW
Matthew J Munro, Susrutha K Wickremesekera, Lifeng Peng, Swee T Tan, Tinte Itinteang
Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC...
September 23, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28941937/exploiting-homing-abilities-of-cell-carriers-targeted-delivery-of-nanoparticles-for-cancer-therapy
#7
REVIEW
Pamela Tiet, Jacob Berlin
Off target toxicities is one of the hallmarks of conventional chemotherapy as only a tiny percentage of the injected dose actually reaches the tumor(s). Numerous strategies have been employed in attempts to achieve targeted therapeutic delivery to tumors. One strategy that has received immense attention has been the packaging of these chemotherapeutics into nanoparticles and relying on the enhanced permeation and retention (EPR) effect for targeting. However, few, if any, nanoformulations have been used clinically that actually show enhanced drug delivery to tumors...
September 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28941322/stromal-cell-derived-factor-1-mediates-cardiac-allograft-tolerance-induced-by-human-endometrial-regenerative-cell-based-therapy
#8
Xu Lan, Grace Wang, Xiaoxi Xu, Shanzheng Lu, Xiang Li, Baoren Zhang, Ganggang Shi, Yiming Zhao, Caigan Du, Hao Wang
Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation...
September 23, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28941311/endocrinopathies-with-use-of-cancer-immunotherapies
#9
Natalie M Villa, Abtin Farahmand, Lin Du, Michael W Yeh, Stephanie Smooke-Praw, Antoni Ribas, Bartosz Chmielowski, Grace Cherry, Angela M Leung
BACKGROUND: Immunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the down-regulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0-63%. OBJECTIVE: To describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies...
September 23, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28941291/dysregulation-of-circulating-tfr-tfh-ratio-in-primary-biliary-cholangitis
#10
Jiajia Zheng, Tiancheng Wang, Li Zhang, Liyan Cui
Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are critical for the development and maintenance of germinal center (GC) and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh cells or Tfr cells contributes to the pathogenesis of autoimmune diseases. We aim to investigate the roles of circulating Tfh cells and circulating Tfr cells in the pathogenesis of primary biliary cholangitis (PBC). 34 PBC patients and 27 health individuals were enrolled in this study...
September 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28940630/synthesis-molecular-modeling-and-evaluation-of-novel-sulfonylhydrazones-as-acetylcholinesterase-inhibitors-for-alzheimer-s-disease
#11
Thais B Fernandes, Micael R Cunha, Renata P Sakata, Thalita M Candido, André R Baby, Maurício T Tavares, Euzébio G Barbosa, Wanda P Almeida, Roberto Parise-Filho
Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09 μM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains...
September 22, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28940439/detection-of-abcb5-tumour-antigen-specific-cd8-t-cells-in-melanoma-patients-and-implications-for-immunotherapy
#12
Sylvia Borchers, Christoph Masslo, Christina Ann Müller, Anika Tahedl, Jennifer Volkind, Yvonne Nowak, Viktor Umansky, Jasmina Esterlechner, Markus Hermann Frank, Christoph Ganss, Mark Andreas Kluth, Jochen Utikal
ABCB5 has been identified as a tumour initiating cell marker and is expressed in various malignancies, including melanoma. Moreover, treatment with anti-ABCB5 monoclonal antibodies has been shown to inhibit tumour growth in xenotransplantation models. Therefore, ABCB5 represents a potential target for cancer immunotherapy. However, cellular immune responses against ABCB5 in humans have not been described so far. Here, we investigated whether ABCB5-reactive T cells are present in human melanoma patients and tested the applicability of ABCB5-derived peptides for experimental induction of human T cell responses...
September 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28940220/t-helper-immune-phenotype-may-underlie-paradoxical-tumour-necrosis-factor-%C3%AE-inhibitor-therapy-related-psoriasiform-dermatitis
#13
A P Moy, M Murali, D Kroshinsky, T D Horn, R M Nazarian
BACKGROUND: Therapeutics targeting tumour necrosis factor (TNF)-α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF-α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation. AIM: We investigated Th phenotype and expression of K17, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in psoriasis and anti-TNF-α-related PsoD...
September 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28940183/an-increased-cd25-positive-intestinal-regulatory-t-lymphocyte-population-is-dependent-on-cox-2-activity-in-the-apc-min-model
#14
Olusola O Faluyi, Paul Fitch, Sarah E M Howie
Only mismatch repair (MMR)-deficient colorectal cancer (CRC) appears to respond well to PD-1 inhibition at the present time. Emerging evidence suggests a role for micro-environmental factors such as CD25+ve cells modulating response to PD-1 inhibition. In the Apc(Min/+) model of familial adenomatous polyposis (MMR-proficient CRC), increased Cyclooxygenase-2 (Cox-2) expression by cells which include alternatively-activated mononuclear phagocytes promotes intestinal tumorigenesis by mechanisms which may include immune suppression...
September 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28940004/adjuvant-therapy-in-biliary-atresia-hopelessly-optimistic-or-potential-for-change
#15
REVIEW
Mark Davenport
Given that the aetiology of biliary atresia (BA) is complex and that there is a multiplicity of possible pathogenic mechanisms then it is perhaps not surprising that the evidence for effect of a number of different agents is contradictory. Post-operative cholangitis for instance is common, bacterial in origin and various antibiotic regimens have been tested (although none in a randomized trial) but continuation beyond the early post-operative period does not appear to offer any greater protection. There is an inflammatory reaction in about 25-35% of cases of BA illustrated by abnormal expression of class II antigen and upregulation of ICAM, VCAM and E-selectin with an infiltrate of immune-activated T cells (predominantly CD4 + Th1 and Th17) and NK cells and a systemic surge in inflammatory cytokines (e...
September 22, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28939858/adjuvant-il-7-potentiates-adoptive-t-cell-therapy-by-amplifying-and-sustaining-polyfunctional-antitumor-cd4-t-cells
#16
Zhi-Chun Ding, Tsadik Habtetsion, Yang Cao, Tao Li, Chufeng Liu, Michal Kuczma, Tingting Chen, Zhonglin Hao, Locke Bryan, David H Munn, Gang Zhou
Increased availability of homeostatic cytokines is considered a major mechanism by which lymphodepletion enhances the efficacy of adoptive T cell therapy (ACT). IL-7 is one such cytokine capable of augmenting the function of tumor-reactive CD8+ T cells. However, whether host-derived IL-7 plays a role in driving the proper function of CD4+ T cells in an ACT setting remains unclear. Here we report that lymphodepleting chemotherapy by cyclophosphamide (CTX) does not lead to increased availability of the endogenous IL-7 in mice...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#17
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28939663/hepatoma-intrinsic-ccrk-inhibition-diminishes-myeloid-derived-suppressor-cell-immunosuppression-and-enhances-immune-checkpoint-blockade-efficacy
#18
Jingying Zhou, Man Liu, Hanyong Sun, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, John Wong, Charing Ching Ning Chong, Paul B S Lai, Hector Kwong-Sang Wang, Shun-Wa Tsang, Tyler Goodwin, Rihe Liu, Leaf Huang, Zhiwei Chen, Joseph Jy Sung, King Lau Chow, Ka Fai To, Alfred Sze-Lok Cheng
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems...
September 22, 2017: Gut
https://www.readbyqxmd.com/read/28939591/mir-125a-3p-inhibits-er%C3%AE-transactivation-and-overrides-tamoxifen-resistance-by-targeting-cdk3-in-estrogen-receptor-positive-breast-cancer
#19
Lufeng Zheng, Xia Meng, Xiaoman Li, Yan Zhang, Cheng Li, Chenxi Xiang, Yingying Xing, Yufeng Xia, Tao Xi
Tamoxifen (TAM) is a major adjuvant therapy for patients who are diagnosed with estrogen receptor-α (ER)-positive breast cancer; however, TAM resistance occurs often during treatment and the underlying mechanism is unclear. Here, we report that miR-125a-3p inhibits ERα transcriptional activity and, thus, ER(+) breast cancer cell proliferation, which causes cell-cycle arrest at the G1/S stage, inducing apoptosis and suppressing tumor growth by targeting cyclin-dependent kinase 3 (CDK3) in vitro and in vivo In addition, CDK3 and miR-125a-3p expression levels were measured in 37 cancerous tissues paired with noncancerous samples, and their expression levels were negatively associated with miR-125a-3p level...
September 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28939451/hla-haploidentical-stem-cell-transplant-with-pre-transplant-immunosuppression-for-patients-with-sickle-cell-disease
#20
Anna B Pawlowska, Jerry C Cheng, Nicole A Karras, Weili Sun, Leo D Wang, Alison D Bell, Lisa Gutierrez, Joseph Rosenthal
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD) but a significant number of patients lack a HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report, we describe a favorable haploidentical HCT approach in a limited cohort of sickle cell patients with significant co-morbidities...
September 19, 2017: Biology of Blood and Marrow Transplantation
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