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https://www.readbyqxmd.com/read/28544923/unfavorable-prognostic-role-of-tumor-infiltrating-lymphocytes-in-hormone-receptor-positive-her2-negative-metastatic-breast-cancer-treated-with-metronomic-chemotherapy
#1
Emilia Montagna, Andrea Vingiani, Patrick Maisonneuve, Giuseppe Cancello, Federica Contaldo, Giancarlo Pruneri, Marco Colleoni
BACKGROUND: High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown. PATIENTS AND METHODS: We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination)...
May 22, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28539467/b7-h3-expression-in-nsclc-and-its-association-with-b7-h4-pd-l1-and-tumor-infiltrating-lymphocytes
#2
Mehmet Altan, Vasiliki Pelekanou, Kurt A Schalper, Maria I Toki, Patricia Gaule, Konstantinos N Syrigos, Roy S Herbst, David L Rimm
Background and Purpose: <p>The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members.  Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor infiltrating lymphocytes (TILs), PD-L1, B7-H4 and major clinico-pathological characteristics is in 3 NSCLC cohorts.</p> <p>Experimental design:</p> <p>We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4 and TILs in 634 NSCLC cases with validated antibodies...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28535297/antihypertensive-adherence-trajectories-among-older-adults-in-the-first-year-after-initiation-of-therapy
#3
Jennifer L Hargrove, Virginia Pate, Carri H Casteel, Yvonne M Golightly, Laura R Loehr, Stephen W Marshall, Til Stürmer
BACKGROUND: Adherence to antihypertensives is suboptimal, but previous methods of quantifying adherence fail to account for varying patterns of use over time. We sought to improve classification of antihypertensive adherence using group-based trajectory models, and to determine whether individual factors predict adherence trajectories. METHODS: We identified older adults initiating antihypertensive therapy during 2008-2011 using a 20% sample of Medicare (federal health insurance available to US residents over the age of 65) beneficiaries enrolled in parts A (inpatient services), B (outpatient services), and D (prescription medication)...
May 23, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#4
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#5
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
May 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28529568/a-different-representation-of-natural-t-cells-and-natural-killer-cells-between-tumor-infiltrating-and-periphery-lymphocytes-in-human-hepatocellular-carcinoma
#6
Xiao-Feng Li, Dong Dai, Xiu-Yu Song, Jian-Jing Liu, Lei Zhu, Xiang Zhu, Wenchao Ma, Wengui Xu
Natural T cells [cluster of differentiation (CD) 3(+)CD56(+)] and natural killer (NK) cells (CD3(-)CD56(+)) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28526026/a-qualitative-study-of-telehealth-patient-information-leaflets-tils-are-we-giving-patients-enough-information
#7
Reem Kayyali, Iman Hesso, Evelyn Ejiko, Shereen Nabhani Gebara
BACKGROUND: The provision of patient information leaflets regarding telehealth has been perceived by potential consumers as a strategy to promote awareness and adoption of telehealth services. However, such leaflets need to be designed carefully if adoption and awareness among potential users is to be promoted. Therefore, the aims of this study were: first, to see how telehealth was portrayed in some of the existing telehealth leaflets (THLs). Second, to explore patients' perceptions of the existing THLs and their engagement with the concept and how THLs can be optimised...
May 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28525810/tumor-infiltrating-lymphocytes-in-patients-with-her2-positive-breast-cancer-treated-with-neoadjuvant-chemotherapy-plus-trastuzumab-lapatinib-or-their-combination-a-meta-analysis-of-randomized-controlled-trials
#8
REVIEW
C Solinas, M Ceppi, M Lambertini, M Scartozzi, L Buisseret, S Garaud, D Fumagalli, E de Azambuja, R Salgado, C Sotiriou, K Willard-Gallo, M Ignatiadis
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination...
May 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#9
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28508354/patient-and-public-preferences-for-treatment-attributes-in-parkinson-s-disease
#10
Marieke G M Weernink, Janine A van Til, Catharina G M Groothuis-Oudshoorn, Maarten J IJzerman
BACKGROUND: Patient and public preferences for therapeutic outcomes or medical technologies are often elicited, and discordance between the two is frequently reported. OBJECTIVE: Our main objective was to compare patient and public preferences for treatment attributes in Parkinson's disease (PD). METHODS: A representative sample from Dutch PD patients and the general public were invited to complete a best-worst scaling case 2 experiment consisting of six health-related outcomes and one attribute describing the specific treatment (brain surgery, pump, oral medication)...
May 15, 2017: Patient
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#11
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507712/redox-non-innocence-permits-catalytic-nitrene-carbonylation-by-dadi-ti-0000000000000000000000000000000000-0000000000000000000000000000000000-0000000000000000000000000000000000-0000000000000000000000000000000000-0000000000000000000000000000000000-0000000000000000000000000000000000
#12
Spencer P Heins, Peter T Wolczanski, Thomas R Cundari, Samantha N MacMillan
Application of the diamide, diimine {-CHN(1,2-C6H4)N(2,6-(i)Pr2-C6H3)}2(m) ((dadi) (m) ) ligand to titanium provided adducts (dadi)TiL x (1-L x ; L x = THF, PMe2Ph, (CNMe)2), which possess the redox formulation [(dadi)(4-)]Ti(iv)L x , and 22 πe(-) (4n + 2). Related complexes containing titanium-ligand multiple bonds, (dadi)TiX (2 X; X = O, NAd), exhibit a different dadi redox state, [(dadi)(2-)]Ti(iv)X, consistent with 20 πe(-) (4n). The Redox Non-Innocence (RNI) displayed by dadi (m) impedes binding by CO, and permits catalytic conversion of AdN3 + CO to AdNCO + N2...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28506244/early-eeg-for-outcome-prediction-of-postanoxic-coma-prospective-cohort-study-with-cost-minimization-analysis
#13
Lotte Sondag, Barry J Ruijter, Marleen C Tjepkema-Cloostermans, Albertus Beishuizen, Frank H Bosch, Janine A van Til, Michel J A M van Putten, Jeannette Hofmeijer
BACKGROUND: We recently showed that electroencephalography (EEG) patterns within the first 24 hours robustly contribute to multimodal prediction of poor or good neurological outcome of comatose patients after cardiac arrest. Here, we confirm these results and present a cost-minimization analysis. Early prognosis contributes to communication between doctors and family, and may prevent inappropriate treatment. METHODS: A prospective cohort study including 430 subsequent comatose patients after cardiac arrest was conducted at intensive care units of two teaching hospitals...
May 15, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28505618/use-of-epinephrine-in-patients-with-drug-induced-anaphylaxis-an-analysis-of-the-beijing-pharmacovigilance-database
#14
Tiansheng Wang, Xiang Ma, Yan Xing, Shusen Sun, Hua Zhang, Til Stürmer, Bin Wang, Xiaotong Li, Huilin Tang, Ligong Jiao, Suodi Zhai
BACKGROUND: Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine...
May 16, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28503494/intratumoral-and-peritumoral-mast-cells-in-malignant-melanoma-an-immunohistochemical-study
#15
Parvin Rajabi, Azam Bagheri, Mohssen Hani
BACKGROUND: The aim of the current study was to determine mast cell infiltration in malignant melanoma by immunohistochemistry method and its relationship with some of the cancer prognostic factors, including age, sex, and depth of the tumor. MATERIALS AND METHODS: In this retrospective analytic cross-sectional study, paraffin-embedded tissue blocks of patients with cutaneous malignant melanoma who had undergone excisional biopsy were studied. Mast cells count in studied cases in different stages of the tumor depth was evaluated by mast cell tryptase immunohistochemistry method...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28501937/expression-of-pd-l1-in-keratoacanthoma-and-different-stages-of-progression-in-cutaneous-squamous-cell-carcinoma
#16
Thilo Gambichler, Martha Gnielka, Ines Rüddel, Eggert Stockfleth, Markus Stücker, Lutz Schmitz
BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major role in the immune responses of a variety of cancers. OBJECTIVES: To investigate the expression of PD-L1 in different progression forms of cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen´s diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using the tumour proportion score and staining intensity evaluation...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501560/the-immune-microenvironment-and-hpv-in-anal-cancer-rationale-to-complement-chemoradiation-with-immunotherapy
#17
REVIEW
Daniel Martin, Franz Rödel, Panagiotis Balermpas, Claus Rödel, Emmanouil Fokas
Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world, and 70-90% of all cases originate from infection with human papilloma viruses (HPV). Primary chemoradiotherapy (CRT) is the standard treatment for ASCC, but local and/or distant failure still occurs in up to 30% of patients. HPV-associated ASCC and tumors with a higher density of tumor infiltrating lymphocytes (TIL) carry a better prognosis. Furthermore, HPV can render tumors more immunogenic, whereas it correlates with elevated TIL densities...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28493410/expression-and-prognostic-significance-of-programmed-death-protein-1-and-programmed-death-ligand-1-and-cytotoxic-t-lymphocyte-associated-molecule-4-in-hepatocellular-carcinoma
#18
Hyeyoon Chang, Wonkyung Jung, Aeree Kim, Han Kyeom Kim, Wan Bae Kim, Ji Hoon Kim, Baek-Hui Kim
Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry...
May 11, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28491135/highlights-from-the-15th-st-gallen-international-breast-cancer-conference-15-18-march-2017-vienna-tailored-treatments-for-patients-with-early-breast-cancer
#19
Consuelo Morigi
The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28488168/the-therapeutic-candidate-for-immune-checkpoint-inhibitors-elucidated-by-the-status-of-tumor-infiltrating-lymphocytes-tils-and-programmed-death-ligand-1-pd-l1-expression-in-triple-negative-breast-cancer-tnbc
#20
Nobumoto Tomioka, Manabu Azuma, Mayuko Ikarashi, Mitsugu Yamamoto, Masako Sato, Ken-Ichi Watanabe, Katsushige Yamashiro, Masato Takahashi
BACKGROUND: The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression...
May 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
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