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https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#1
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#2
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27909274/-three-mitral-valve-operations-in-a-patient-with-trousseau-syndrome-and-nonbacterial-thrombotic-endocarditis-caused-by-ovarian-cancer
#3
Masahito Saito, Naoki Asano, Kazunori Ota, Kazuho Niimi, Koyu Tanaka, Shigeyoshi Gon, Hiroshi Takano
A 52-year-old woman was admitted to our hospital for acute right hemi-paresis, left homonymous hemianopia, and fever. Magnetic resonance imaging of the brain showed multiple cerebral infarctions and transesophageal echocardiography (TEE) revealed a vegetation on the posterior leaflet of her mitral valve. Mitral valve repair was performed under a diagnosis of infective endocarditis (IE). Further multiple cerebral infarctions occurred on the 11th postoperative day, resulting in left hemiplegia and dysarthria...
December 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/27907881/effect-of-toad-skin-extracts-on-the-pain-behavior-of-cancer-model-mice-and-its-peripheral-mechanism-of-action
#4
Tao Chen, Shen-Jun Yuan, Xue-Qin Yu, Liang-Bo Jiao, Wei Hu, Wang-Long Chen, Bo Xie
The changes in thermal and mechanical hyperalgesia in paw cancer pain model mice and the action mechanism of toad skin extracts (TSE) was investigated. Eighty female mice were subcutaneously injected with saline or inoculated with H22 hepatoma cells in the right hind paw and administration with saline, vehicle, morphine and TSE. The pain behavior was recorded before treatment and at 0.5, 1.0, 1.5, 3 and 6h after initial administration, and thereafter on the 2nd, 4th, 6th, and 8th day after administration. On the last day, samples were collected after the euthanasia for the detection of β-END, CRF, IL-1β, POMC, μ-OR, CD3+, CD8+ and CD4+ in sera and the tumor tissues...
November 28, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#5
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27904752/the-role-of-immune-checkpoint-inhibition-in-the-treatment-of-ovarian-cancer
#6
REVIEW
Stéphanie L Gaillard, Angeles A Secord, Bradley Monk
The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10-15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade...
2016: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/27901470/sinomenine-prevents-the-development-of-cardiomyopathy-in-diabetic-rats-by-inhibiting-inflammatory-responses-and-blocking-activation-of-nf-%C3%AE%C2%BAb
#7
Cheng Jiang, Yun-Long Tong, Dan Zhang, Li-Zhi Liu, Ju-Fei Wang
Diabetic cardiomyopathy is a severe complication of diabetes mellitus (DM). The goal of current work was to study the effects of sinomenine on streptozotocin-induced cardiomyopathy in rats. DM in rats was induced by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by measuring left ventricle end-diastolic diameter, left ventricle end-systolic diameter and ejection fraction. Cardiac inflammation was evaluated by the degree of infiltration of T lymphocytes and the levels of pro-inflammatory cytokines...
November 30, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27899977/nahco3-enhances-the-antitumor-activities-of-cytokine-induced-killer-cells-against-hepatocellular-carcinoma-hepg2-cells
#8
Ya Hong Yuan, Chun Fang Zhou, Jiang Yuan, Li Liu, Xing Rong Guo, Xiao Li Wang, Yan Ding, Xiao Nan Wang, Dong Sheng Li, Han Jun Tu
The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytes in vitro and promotes tumor cell invasion. In the present study, both in vitro and in vivo experiments were conducted to investigate how NaHCO3 would affect the antitumor activities of cytokine-induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For the in vitro experiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell-conditioned medium (CMCIK)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896569/anti-pituitary-antibodies-against-corticotrophs-in-igg4-related-hypophysitis
#9
Naoko Iwata, Shintaro Iwama, Yoshihisa Sugimura, Yoshinori Yasuda, Kohtaro Nakashima, Seiji Takeuchi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Patrizio Caturegli, Teruhiko Koike, Yoshiharu Oshida, Hiroshi Arima
PURPOSE: IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors...
November 28, 2016: Pituitary
https://www.readbyqxmd.com/read/27895816/clinical-impact-of-chemotherapy-to-improve-tumor-microenvironment-of-pancreatic-cancer
#10
REVIEW
Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Toshiaki Shichinohe, Satoshi Hirano
A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells...
November 15, 2016: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/27894751/polymerase-%C3%AE%C2%B5-pole-ultra-mutation-in-uterine-tumors-correlates-with-t-lymphocyte-infiltration-and-increased-resistance-to-platinum-based-chemotherapy-in-vitro
#11
Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger, Pei Hui, Salvatore Lopez, Christopher de Haydu, Elena Bonazzoli, Federica Predolini, Luca Zammataro, Emiliano Cocco, Federico Ferrari, Antonella Ravaggi, Chiara Romani, Fabio Facchetti, Enrico Sartori, Franco E Odicino, Dan-Arin Silasi, Babak Litkouhi, Elena Ratner, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC...
November 25, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27893413/kir-2d-l1-l3-l4-s4-and-kir-3dl1-protein-expression-in-non-small-cell-lung-cancer
#12
Yayi He, Paul A Bunn, Caicun Zhou, Dan Chan
BACKGROUND: Nature killer (NK) cells are the immune system's first line of defense against both viral infections and tumors. Killer cell immunoglobulin-like receptors (KIRs) are associated with susceptibility to different types of cancers. We investigated KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression and their association with survival in non-small cell lung cancer (NSCLC). METHODS: The expression of KIR 2D (L1, L3, L4, S4) (BC032422/ ADQ31987/ NP_002246/ NP_036446, ABCAM) and KIR 3DL1 (AA 1-444, ABCAM) protein was assessed by immunohistochemistry (IHC) in 62 NSCLC patients...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888708/prognostic-value-of-tumor-infiltrating-lymphocytes-for-patients-with-head-and-neck-squamous-cell-carcinoma
#13
Qiaoshi Xu, Chong Wang, Xiaohong Yuan, Zhien Feng, Zhengxue Han
BACKGROUND: The prognostic value of tumor-infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) remains controversial. Additionally, there is no standardized approach or cutoff value for evaluating TIL levels. The aim of this study was to establish a feasible method and criterion to assess TIL levels for future clinical practice and research use and to explore the relationship between TIL levels and prognosis. PATIENTS AND METHODS: This retrospective cohort study reviewed the records and pathological sections of 202 patients with HNSCC who were surgically treated at Beijing Stomatological Hospital, Capital Medical University, from January 1998 to January 2011...
November 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27882092/the-influence-of-exendin-4-intervention-on-obese-diabetic-mouse-blood-and-the-pancreatic-tissue-immune-microenvironment
#14
Jinshui He, Chaowei Lian, Yanling Fang, Jinzhi Wu, Huowang Zhou, Xiaoling Ye
The aim of the study was to determine the influence of exendin-4 intervention on non-obese diabetic (NOD) mouse blood and the pancreatic tissue immune microenvironment. A total of 40 clean NOD mice were used in the study and randomly divided into 4 groups (n=10/group). The first group was blank control group D with normal saline intervention, and with different doses of exendin, i.e.,-4 2, 4 and 8 µg/kg/day. The three remaining groups were: i) Low-dose group A; ii) medium-dose group B; and iii) high-dose group C...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27879973/application-of-the-immunoscore-as-prognostic-tool-for-hepatocellular-carcinoma
#15
EDITORIAL
Annacarmen Petrizzo, Luigi Buonaguro
To date, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification represents the standard system for evaluation of prognosis in solid tumors. However, the clinical outcome can be significantly different in patients with the same TNM stage. Therefore, many efforts have been made aiming to define new prognostic parameters. Indeed, analyses conducted in large cohorts of colorectal cancer patients emphasized the prognostic value of tumor-infiltrating lymphocytes, leading to the development of a prognostic score referred to as "Immunoscore"...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27872951/immunogenicity-and-efficacy-of-a-rationally-designed-vaccine-against-vascular-endothelial-growth-factor-in-mouse-solid-tumor-models
#16
Aizhang Xu, Li Zhang, Yangyang Chen, Zhibing Lin, Rongxiu Li
Vascular endothelial growth factor (VEGF) plays an important role in the progression of various cancers. The VEGF-specific antibody bevacizumab combined with chemotherapy was shown to significantly improve progression-free survival in certain cancers. However, repeated administration is necessary for effective suppression of VEGF, thereby making the therapy expensive and cumbersome. Thus, it is urgent to develop alternative reagents such as VEGF vaccines. Here we report that DTT-VEGF, a VEGF-based antigen consisting of the receptor-binding domain of VEGF and diphtheria toxin T domain (DTT), not only stimulated neutralizing antibody response, but also induced type 1 immune response as well as anti-tumor cytotoxic T lymphocytes in mice when administered with aluminum hydroxide adjuvant...
November 21, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27872095/t-cells-redirected-to-a-minor-histocompatibility-antigen-instruct-intratumoral-tnf-%C3%AE-expression-and-empower-adoptive-cell-therapy-for-solid-tumors
#17
Teresa Manzo, Tabea Sturmheit, Veronica Basso, Elisabetta Petrozziello, Rodrigo Hess Michelini, Michela Riba, Massimo Freschi, Angela R Elia, Matteo Grioni, Flavio Curnis, Maria Pia Protti, Ton N Schumacher, Reno Debets, Melody A Swartz, Angelo Corti, Matteo Bellone, Anna Mondino
Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR-gene engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27869446/-oncopathological-aspects-of-brca1-and-brca2-genes-inactivation-in-tumors-of-ovary-fallopian-tube-and-pelvic-peritoneum
#18
Petr Škapa, Pavel Dundr
Ovarian carcinoma represents a heterogeneous group of malignant epithelial tumors which could be divided into two fundamental groups: Type I (endometrioid carcinoma, clear cell carcinoma, low grade serous carcinoma, mucinous carcinoma and more rare seromucinous carcinoma and malignant Brenner tumor) and type II (high grade serous carcinoma - HGSC). HGSC is the most frequent ovarian carcinoma which may be etiologically linked to inactivation of tumor suppressor genes BRCA1/2 and TP53 and differs from type I carcinomas by higher aggressiveness, tendency to peritoneal spread and worse prognosis...
2016: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/27868286/a-high-number-of-stromal-tumor-infiltrating-lymphocytes-is-a-favorable-independent-prognostic-factor-in-m0-stages-i-iii-esophageal-squamous-cell-carcinoma
#19
Jing Li, Yang Tang, Liu Huang, Qianqian Yu, Guangyuan Hu, Yanmei Zou, Xianglin Yuan
Esophageal cancer is a highly invasive tumor with a poor prognosis. Lymphocytes play an important role in systemic immune responses, but their role in cancers varies depending on the specific tumor microenvironment. The aim of this study was to provide evidence for tumor-infiltrating lymphocytes (TILs) as a prognostic biomarker in esophageal squamous cell carcinoma. TIL analysis was retrospectively performed on full-face hematoxylin and eosin-stained sections from 127 patients. A majority (92.6%) of tumors had at least 10% stromal TILs (sTILs) (range, 10%-90%), and 84...
November 21, 2016: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
https://www.readbyqxmd.com/read/27865851/pathological-%C3%AE-synuclein-exacerbates-the-progression-of-parkinson-s-disease-through-microglial-activation
#20
Qiu-Shuang Zhang, Yang Heng, Yu-He Yuan, Nai-Hong Chen
Parkinson's disease (PD) is characterized by α-synuclein accumulation, dopaminergic neuron loss and inflammation. α-Synuclein can be secreted by neurons and activate microglia to different degrees. Excessive microglial activation can increase the production of tumor necrosis factor alpha (TNF-α), interleukin-1-β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and nitric oxide (NO), and can also enhance microglial phagocytosis and migration as well as lymphocyte infiltration...
November 16, 2016: Toxicology Letters
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