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https://www.readbyqxmd.com/read/28934305/the-prognostic-value-of-interleukin-17-in-lung-cancer-a-systematic-review-with-meta-analysis-based-on-chinese-patients
#1
Xiao-Fei Wang, Yi-Tong Zhu, Jia-Jia Wang, Da-Xiong Zeng, Chuan-Yong Mu, Yan-Bin Chen, Wei Lei, Ye-Han Zhu, Jian-An Huang
BACKGROUND: Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung cancer (LC) prognosis. To comprehensively and quantitatively summarize the prognostic value of IL-17 expression in LC patients, a systematic review and meta-analysis were performed. METHODS: We identified the relevant literatures by searching the PubMed, EMBASE, Cochrane Library, SinoMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases, up until April 1, 2017...
2017: PloS One
https://www.readbyqxmd.com/read/28933526/impact-of-radioguided-occult-lesion-localization-roll-in-the-management-of-cervical-recurrences-from-differentiated-thyroid-cancer
#2
Viviana Garbaccio, Massimo Menga, Giovanni Mensa, Roberto Passera, Antonello Galati, Alessandra Codegone, Monica Finessi, Emanuela Pilati, Désirée Deandreis, Riccardo E Pellerito
BACKGROUND: Surgery is the elective treatment for cervical relapse from differentiated thyroid cancer (DTC) but it is technically challenging, with risk of failure and morbidity. We explored the feasibility and the efficacy of Radioguided Occult Lesion Localization (ROLL) with intratumoral 99mTc radiolabeled human albumin macroaggregates ([99mTc]MAA) injection in this setting. METHODS: Fifteen patients who underwent ROLL by ultrasonography (US)-guided intratumoral injection of [99mTc]MAA between December 2013 and October 2016 for DTC recurrence were considered for this study...
September 20, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28932645/intratumor-heterogeneity-of-immune-checkpoints-in-primary-renal-cell-cancer-focus-on-hla-g-ilt2-ilt4
#3
Nathalie Rouas-Freiss, Joel LeMaoult, Jérôme Verine, Diana Tronik-Le Roux, Stéphane Culine, Christophe Hennequin, François Desgrandchamps, Edgardo D Carosella
The establishment and maintenance of anti-tumor immune responses are the objectives of cancer immunotherapy. Despite recent promising advances, the effectiveness of these approaches has been limited by the multiple immunosuppressive mechanisms developed by tumors (checkpoint). The aim of the present study was to demonstrate intratumor heterogeneity at the levels of immune escape strategies and tumor-host relationships. We focused on well-known checkpoints such as PD1/PDL1 and on a new checkpoint involving HLA-G and its receptors ILT2/ILT4...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932636/cd103-tumor-infiltrating-lymphocytes-are-tumor-reactive-intraepithelial-cd8-t-cells-associated-with-prognostic-benefit-and-therapy-response-in-cervical-cancer
#4
Fenne L Komdeur, Thalina M Prins, Stephanie van de Wall, Annechien Plat, G Bea A Wisman, Harry Hollema, Toos Daemen, David N Church, Marco de Bruyn, Hans W Nijman
Human papilloma virus (HPV)-induced cervical cancer constitutively expresses viral E6/E7 oncoproteins and is an excellent target for T cell-based immunotherapy. However, not all tumor-infiltrating T cells confer equal benefit to patients, with epithelial T cells being superior to stromal T cells. To assess whether the epithelial T cell biomarker CD103 could specifically discriminate the beneficial antitumor T cells, association of CD103 with clinicopathological variables and outcome was analyzed in the TCGA cervical cancer data set (n = 304) and by immunohistochemistry (IHC) in an independent cohort (n = 460)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932631/tadalafil-has-biologic-activity-in-human-melanoma-results-of-a-pilot-trial-with-tadalafil-in-patients-with-metastatic-melanoma-tame
#5
Jessica C Hassel, Huanhuan Jiang, Carolin Bender, Julia Winkler, Alexandra Sevko, Ivan Shevchenko, Niels Halama, Antonia Dimitrakopoulou-Strauss, Walter E Haefeli, Dirk Jäger, Alexander Enk, Jochen Utikal, Viktor Umansky
Myeloid-derived suppressor cells (MDSCs) are known to play a critical role in the suppression of T cell antitumor responses. Our preclinical data showed that the phosphodiesterase (PDE)-5 inhibitor sildenafil impaired MDSC functions, enhanced intratumoral T cell activity and prolonged survival of melanoma-bearing mice. In this study, we evaluated biologic effects, safety and efficacy of palliative treatment with the PDE-5 inhibitor tadalafil in metastatic melanoma patients. We conducted an open-label, dose de-escalation trial with tadalafil in pretreated metastatic melanoma patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931759/combination-immunotherapy-with-tlr-agonists-and-checkpoint-inhibitors-suppresses-head-and-neck-cancer
#6
Fumi Sato-Kaneko, Shiyin Yao, Alast Ahmadi, Shannon S Zhang, Tadashi Hosoya, Megan M Kaneda, Judith A Varner, Minya Pu, Karen S Messer, Cristiana Guiducci, Robert L Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Dennis A Carson, Tomoko Hayashi, Ezra Ew Cohen
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931654/cancer-immunotherapy-with-recombinant-poliovirus-induces-ifn-dominant-activation-of-dendritic-cells-and-tumor-antigen-specific-ctls
#7
Michael C Brown, Eda K Holl, David Boczkowski, Elena Dobrikova, Mubeen Mosaheb, Vidya Chandramohan, Darell D Bigner, Matthias Gromeier, Smita K Nair
Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer immunotherapy potential of the recombinant poliovirus/rhinovirus chimera PVSRIPO. PVSRIPO is currently in clinical trials against recurrent World Health Organization grade IV malignant glioma, a notoriously treatment-refractory cancer. Cytopathogenic infection of neoplastic cells releases the proteome and exposes pathogen- and damage-associated molecular patterns...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28931370/association-between-tumour-infiltrating-lymphocytes-histotype-and-clinical-outcome-in-epithelial-ovarian-cancer
#8
Fiona R James, Mercedes Jiminez-Linan, Jennifer Alsop, Marie Mack, Honglin Song, James D Brenton, Paul D P Pharoah, H Raza Ali
BACKGROUND: There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. METHODS: We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study...
September 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28930684/tumor-derived-mesenchymal-stem-cells-use-distinct-mechanisms-to-block-the-activity-of-natural-killer-cell-subsets
#9
Sabine Galland, Joanna Vuille, Patricia Martin, Igor Letovanec, Anne Caignard, Giulia Fregni, Ivan Stamenkovic
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28929220/-pathogenesis-and-genetics-of-osteosarcoma-current-concepts-and-developments
#10
REVIEW
D Baumhoer
Osteosarcomas are genetically complex tumours for which the cell of origin and the molecular pathogenesis are still poorly understood. Despite intensive multimodal treatment protocols only two thirds of patients currently survive the disease which is at least partly due to the early occurring chromosomal instability resulting in marked inter- and intratumoral heterogeneity. This review article outlines the current state of osteosarcoma research with a particular focus on exome- and genome-wide sequencing analyses and potential impacts on new therapeutic opportunities...
September 19, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28927692/prognostic-influence-of-tumor-stroma-on-breast-cancer-subtypes
#11
Sandra Cid, Noemi Eiro, Berta Fernández, Rosario Sánchez, Alejandro Andicoechea, Pablo Ignacio Fernández-Muñiz, Luis O González, Francisco J Vizoso
INTRODUCTION: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS: A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status)...
August 19, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28927083/expression-of-thymidylate-synthase-predicts-clinical-outcomes-of-s-1-based-chemotherapy-in-squamous-cell-lung-cancer
#12
Yuichiro Honma, Shinsaku Togo, Kazue Shimizu, Miniwan Tulafu, Takuo Hayashi, Toshimasa Uekusa, Shigeru Tominaga, Kenji Kido, Yuichi Fujimoto, Yukiko Nanba, Kazuya Takamochi, Shiaki Oh, Kenji Suzuki, Kazuhisa Takahashi
Non-small cell lung cancer (NSCLC) patients with squamous cell carcinoma (SCC) histology have limited chemotherapeutic options. Treatment with S-1 combined with carboplatin (CBDCA) has been shown to provide a significant survival benefit in SCC patients compared with treatment with combined CBDCA and paclitaxel. The aim of the present study was to investigate the association between the expression of molecular markers related to the pharmacological action of S-1, including thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD), and the clinical efficacy of S-1-based chemotherapy in SCC patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926893/-effect-of-intratumor-heterogeneity-of-esophageal-squamous-cell-carcinoma-on-chemotherapy-sensitivity
#13
L Sun, W Wu, M Yan, P L Han, X Zhan, X W Ma, X G Cao, S Zhao, F Gao, Y Qi, W Cao
Objective: To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity. Methods: Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28925392/atypical-e2fs-inhibit-tumor-angiogenesis
#14
B G M W Weijts, B Westendorp, B T Hien, L M Martínez-López, M Zijp, I Thurlings, R E Thomas, S Schulte-Merker, W J Bakker, A de Bruin
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28923858/anti-cd137-suppresses-tumor-growth-by-blocking-reverse-signaling-by-cd137-ligand
#15
Sang W Kang, Sang Chul Lee, So H Park, Juyang Kim, Hyeon H Kim, Hyeon-Woo Lee, Su-Kil Seo, Byoung S Kwon, Hong R Cho, Byungsuk Kwon
CD137 (4-1BB) is a T cell co-stimulatory molecule and agonstic CD137 antibodies are currently being evaluated in clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#16
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28923105/genetic-engineering-of-human-nk-cells-to-express-cxcr2-improves-migration-to-renal-cell-carcinoma
#17
Veronika Kremer, Maarten Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
BACKGROUND: Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#18
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#19
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920000/oncolytic-peptide-ltx-315-induces-an-immune-mediated-abscopal-effect-in-a-rat-sarcoma-model
#20
Janne Nestvold, Meng-Yu Wang, Ketil A Camilio, Severin Zinöcker, Torunn Elisabeth Tjelle, Alf Lindberg, Bengt Erik Haug, Gunnar Kvalheim, Baldur Sveinbjørnsson, Øystein Rekdal
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8(+) T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis...
2017: Oncoimmunology
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