Search results for "progress"
showing 10 items of 1620 documents
Tumor infiltrating T lymphocytes expressing FoxP3, CCR7 or PD-1 predict the outcome of prostate cancer patients subjected to salvage radiotherapy aft…
2016
Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations. Twenty-two patients with resectable prostate cancer, with a mean age of 67 (+/−3.93) years, who receiv…
Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
2018
ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…
A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treat…
2017
Abstract Lessons Learned Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents. The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. Background KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling. The dual-action antibody duligotuzumab (MEHD7945A) inhibits ligand binding to both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). Blockade of EGFR/HER3 and inhibitio…
Genetic systems for a new approach to risk of progression of diabetic retinopathy.
2016
OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG-DR=6; CG=6) by performing next-generation sequ…
Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multice…
2018
Summary Background Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF V600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival. Methods COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF V600E or BRAF V600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had pr…
Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies
2020
Abstract Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. …
Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration
2021
(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by b-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cogni…
Epigenetic changes in localized gastric cancer: the role of RUNX3 in tumor progression and the immune microenvironment
2016
// Marta Jessica Llorca-Cardenosa 1, * , Tania Fleitas 1, * , Maider Ibarrola-Villava 1 , Maria Pena-Chilet 1 , Cristina Mongort 2 , Carolina Martinez-Ciarpaglini 2 , Lara Navarro 2 , Valentina Gambardella 1 , Josefa Castillo 1 , Susana Rosello 1 , Samuel Navarro 2 , Gloria Ribas 1 , Andres Cervantes 1 1 Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain 2 Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain * These authors contributed equally to this work Correspondence to: Gloria Ribas, email: gribas@incliva.es Andres Cervantes, email: andres.cervantes@uv.es Keywords: RUNX3, ARID1A, gastric ca…
Lipidomic profiling identifies signatures of metabolic risk
2020
Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…
Downregulation of intratumoral expression of miR-205, miR-200c and miR-125b in primary human cutaneous melanomas predicts shorter survival
2018
AbstractWhile only 15–25 percent of melanoma patients develop distant metastasis and die, this disease is still responsible for the majority of skin cancer-related deaths. The availability of adjuvant therapies makes the selection of high-risk patients essential. We evaluated the intratumoral expression of ten miRNAs in primary melanomas in relation to its ability to predict melanoma survival. To this end, we correlated miRNA expression in 132 cryopreserved primary and metastatic tumors with clinicopathological factors and clinical outcome. We found sequential downregulation of intratumoral expression of miR-125b, miR-182, miR-200c and miR-205 over the full spectrum of melanoma progression.…