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https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#1
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923573/neoadjuvant-buparlisib-plus-trastuzumab-and-paclitaxel-for-women-with-her2-primary-breast-cancer-a-randomised-double-blind-placebo-controlled-phase-ii-trial-neophoebe
#2
Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee, Sabine Turri, Patrick Urban, Sherko Kümmel, Guenther Steger, Andrea Gombos, Michael Lux, Martine J Piccart, Gunter Von Minckwitz, José Baselga, Sherene Loi
AIM: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer. METHODS: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel...
September 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#3
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28919130/the-nuts-and-bolts-of-cognitive-remediation-exploring-how-different-training-components-relate-to-cognitive-and-functional-gains
#4
Matteo Cella, Til Wykes
BACKGROUND: Cognitive Remediation (CR) is an evidence based treatment targeting cognitive and functional difficulties in people with psychosis. Despite the large number of effectiveness studies, only limited evidence exists for the active ingredients of this therapy. This study begins to fill this gap by exploring the relationship between CR ingredients, including alliance with a therapist, and therapy outcomes. METHOD: This is a secondary analysis based on data from a published randomised controlled trial comparing CR+treatment-as-usual (TAU) to TAU alone...
September 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28917695/the-impact-of-gabaergic-drugs-on-tms-induced-brain-oscillations-in-human-motor-cortex
#5
Isabella Premoli, Til O Bergmann, Matteo Fecchio, Mario Rosanova, Andrea Biondi, Paolo Belardinelli, Ulf Ziemann
Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30-200 ms after TMS) synchronization in the α- and β-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200-400 ms) α- and β-desynchronization over the stimulated and contralateral sensorimotor cortex...
September 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#6
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915679/prognostic-role-of-tumor-infiltrating-lymphocytes-in-gastric-cancer-a-meta-analysis
#7
Xiao Zheng, Xing Song, Yingjie Shao, Bin Xu, Lujun Chen, Qi Zhou, Wenwei Hu, Dachuan Zhang, Changping Wu, Min Tao, Yibei Zhu, Jingting Jiang
BACKGROUND: In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. MATERIALS AND METHODS: We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914593/effects-of-local-administration-of-tiludronic-acid-on-experimental-periodontitis-in-diabetic-rats
#8
Nara L T Nunes, Michel R Messora, Luiz Fernando Oliveira, Mario Lisboa, Marina Costa Barcellos Garcia, Rodrigo O C C Rêgo, Arthur Belém Novaes, Sérgio Luís Scombatti de Souza, Edilson Ervolino, Flávia A C Furlaneto
BACKGROUND: Tiludronic acid (TIL) presents antiresorptive and anti-inflammatory properties and it has not been evaluated in the association periodontitis-diabetes mellitus (DM) to date. This study evaluated the effects of local administration of TIL on experimental periodontitis (EP) in rats with streptozotocin-induced DM. METHODS: Thirty-two animals (Rattus norvegicus, albinus, Wistar) were divided into groups DM/C (Control), DM/EP, DM/EP/TIL1 and DM/EP/TIL3. In groups EP, a ligature was placed around mandibular molars (MM)...
September 15, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28913760/impact-of-histopathology-tumor-infiltrating-lymphocytes-and-adjuvant-chemotherapy-on-prognosis-of-triple-negative-breast-cancer
#9
Roberto A Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A Gilbert, Victoria Cafourek, David W Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew P Goetz
BACKGROUND: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. METHODS: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs...
September 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28913367/efficacy-of-tumor-infiltrating-lymphocytes-combined-with-ifn-%C3%AE-in-chinese-resected-stage-iii-malignant-melanoma
#10
Wei Li, Linping Xu, Yaomei Wang, Lingdi Zhao, Daniel B Kellner, Quanli Gao
BACKGROUND: This study aims to explore the efficacy of tumor-infiltrating lymphocytes (TIL) along with interferon-α (IFN-α) to treat stage III malignant melanoma (MM) patients in China. METHODS: Between May 2010 and October 2014, 77 patients of stage III MM who underwent surgery were collected in this study. These patients were divided into two groups: patients who received TIL + IFN-α ± RetroNectin-activated cytokine-induced killer cells (R-CIK) in Arm 1 (n = 27) and IFN-α ± R-CIK in Arm 2 (n = 50) as adjuvant therapy...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#11
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28911908/enhancement-of-mouse-hematopoietic-stem-progenitor-cell-function-via-transient-gene-delivery-using-integration-deficient-lentiviral-vectors
#12
Maria E Alonso-Ferrero, Niek P van Til, Kerol Bartolovic, Márcia F Mata, Gerard Wagemaker, Dale Moulding, David A Williams, Christine Kinnon, Simon N Waddington, Michael D Milsom, Steven J Howe
Integration-deficient lentiviruses (IdLV) effectively deliver genes to tissues but are rapidly lost from dividing cells. This property can be harnessed to transiently express transgenes to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of Hematopoietic Stem/Progenitor Cells (HSPC) during transplantation by delivering HOXB4 and Angptl3 using IdLV to enhance the engraftment of HSPC. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells...
September 11, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28911063/stromal-lymphocyte-infiltration-after-neoadjuvant-chemotherapy-is-associated-with-aggressive-residual-disease-and-lower-disease-free-survival-in-her2-positive-breast-cancer
#13
A-S Hamy, J-Y Pierga, A Sabaila, E Laas, H Bonsang-Kitzis, C Laurent, A Vincent-Salomon, P Cottu, F Lerebours, R Rouzier, M Lae, F Reyal
Background: The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905250/tumour-infiltrating-lymphocytes-tils-related-genomic-signature-predicts-chemotherapy-response-in-breast-cancer
#14
Mariko Kochi, Takayuki Iwamoto, Naoki Niikura, Giampaolo Bianchini, Shinobu Masuda, Taeko Mizoo, Tomohiro Nogami, Tadahiko Shien, Takayuki Motoki, Naruto Taira, Yutaka Tokuda, Hiroyoshi Doihara, Junji Matsuoka, Toshiyoshi Fujiwara
PURPOSE: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. METHODS: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS...
September 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28904066/pd-1-status-in-cd8-t-cells-associates-with-survival-and-anti-pd-1-therapeutic-outcomes-in-head-and-neck-cancer
#15
Benjamin A Kansy, Fernando Concha-Benavente, Raghvendra M Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jessica Moskovitz, Jennifer Moy, Jing Li, Sven Brandau, Stephan Lang, Nicole C Schmitt, Gordon J Freeman, William E Gooding, David A Clump, Robert L Ferris
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1(+) TIL has been reported in human papillomavirus (HPV)(+) HNC patients, despite the role of PD-1 in T cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T cell function and prognostic impact, since PD-1(high) T cells may be more exhausted than PD-1(low) T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903377/pd-l1-pd-1-expression-and-tumor-infiltrating-lymphocytes-in-conjunctival-melanoma
#16
Jinfeng Cao, Niels J Brouwer, Kate E Richards, Marina Marinkovic, Sjoerd van Duinen, Daan Hurkmans, Els M E Verdegaal, Ekaterina S Jordanova, Martine J Jager
Conjunctival melanoma (CM) is an infrequent but potentially lethal malignancy, with limited therapeutic options for metastases. Recent inhibitors of the interaction of programmed cell death protein 1 (PD-1) and its ligand PD-L1 are associated with good clinical responses in many malignancies. To investigate the therapeutic potential of targeting the PD-1/PD-L1 axis in CM, we analyzed the expression of PD-1 and PD-L1 and the density of various types of tumor-infiltrating lymphocytes (TILs) in primary CM (n = 27), using immunofluorescence staining...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902789/prognostic-significance-of-tumor-infiltrating-lymphocytes-in-patients-with-pancreatic-ductal-adenocarcinoma-treated-with-neoadjuvant-chemotherapy
#17
Reza Nejati, Jennifer B Goldstein, Daniel M Halperin, Hua Wang, Nazila Hejazi, Asif Rashid, Matthew H Katz, Jeffrey E Lee, Jason B Fleming, Jaime Rodriguez-Canales, Jorge Blando, Ignacio I Wistuba, Anirban Maitra, Robert A Wolff, Gauri R Varadhachary, Huamin Wang
OBJECTIVES: The aim of this study was to examine tumor-infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy. METHODS: Intratumoral CD4, CD8, and FOXP3 lymphocytes were examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathological parameters and survival...
October 2017: Pancreas
https://www.readbyqxmd.com/read/28900472/predictive-and-prognostic-impact-of-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer-treated-with-neoadjuvant-chemotherapy
#18
Carmen Herrero-Vicent, Angel Guerrero, Joaquin Gavilá, Francisco Gozalbo, Abraham Hernández, Sergio Sandiego, Maria Asunción Algarra, Ana Calatrava, Vicente Guillem-Porta, Amparo Ruiz-Simón
INTRODUCTION: In locally and locally advanced triple-negative breast cancer (TNBC), neoadjuvant chemotherapy (NAC) only induces a pCR in 30-35% of patients. Clinical and pathological factors are not enough to distinguish the patients who have no chance of a pCR or not. The tumour microenvironment is critical for cancer and tumour-infiltrating lymphocytes (TIL). Moreover, the NAC scenario is the perfect setting to study possible changes in TIL levels. MATERIAL AND METHODS: Using our prospective maintained breast cancer (BC) database, we identified 164 TNBC patients treated with NAC between 1998 and 2015 with enough samples of diagnostic biopsy and after surgery...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28899967/circulating-cell-free-dna-for-metastatic-cervical-cancer-detection-genotyping-and-monitoring
#19
Zhigang Kang, Sanja Stevanović, Christian S Hinrichs, Liang Cao
PURPOSE: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. PATIENTS AND METHODS: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet (dd) PCR...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28899890/what-is-the-impact-of-research-champions-on-integrating-research-in-mental-health-clinical-practice-a-quasiexperimental-study-in-south-london-uk
#20
Sherifat Oduola, Til Wykes, Dan Robotham, Tom K J Craig
OBJECTIVES: Key challenges for mental health healthcare professionals to implement research alongside clinical activity have been highlighted, such as insufficient time to apply research skills and lack of support and resources. We examined the impact of employing dedicated staff to promote research in community mental health clinical settings. DESIGN: Quasiexperiment before and after study. SETTING: South London and Maudsley National Health Service Foundation Trust...
September 11, 2017: BMJ Open
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