Search results for "response"

Protein misfolding, amyotrophic lateral sclerosis and guanabenz: Protocol for a phase II RCT with futility design (ProMISe trial)

2017

IntroductionRecent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumula…

Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a…

2020

Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA’s. Using specific cut-offs determined…

Discontinuation of braf/mek-directed targeted therapy after complete remission of metastatic melanoma : a retrospective multicenter adoreg study

2021

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-res…

Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence…

2021

The introduction of checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC) treatment landscape, resulted in improvements in overall survival (OS) in metastatic patients. Brain metastases (BMs) are a specific metastatic site of interest representing a predictive factor of poor prognosis. Patients with BMs were usually excluded from prospective clinical trials in the past. Despite recent evidence suggest the efficacy and safety of ICIs, the BMs treatment remains a challenge; the immunotherapy responsiveness seems to be multifactorial and dependent on several factors, such as the genetic intratumor heterogeneity and the immunosuppressive role of the brain tumor microenvironment. This revie…

The Value of Liquid Biopsies for Guiding Therapy Decisions in Non-small Cell Lung Cancer

2019

Targeted therapies have allowed for an individualized treatment approach in non-small-cell lung cancer (NSCLC). The initial therapeutic decisions and success of targeted therapy depend on genetic identification of personal tumor profiles. Tissue biopsy is the gold standard for molecular analysis, but non-invasive or minimally invasive liquid biopsy methods are also now used in clinical practice, allowing for later monitoring and optimization of the cancer treatment. The inclusion of liquid biopsy in the management of NSCLC provides strong evidence on early treatment response, which becomes a basis for determining disease progression and the need for changes in treatment. Liquid biopsies can…

Analysis of miRNA expression profile induced by short term starvation in breast cancer cells treated with doxorubicin

2017

// Sergio Rizzo 1, * , Antonina Cangemi 1, * , Antonio Galvano 1, * , Daniele Fanale 1 , Silvio Buscemi 2 , Marcello Ciaccio 3 , Antonio Russo 1 , Sergio Castorina 4, 5, # and Viviana Bazan 1, # 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Department of Internal and Specialistic Medicine (DIBIMIS), Laboratory of Clinical Nutrition, University of Palermo, Palermo, Italy 3 Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnology, University of Palermo, U.O.C. Laboratory Medicine, Policlinico University Hospital, Palermo, Italy 4 Fondazione Mediterranea…

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

2018

Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The g…

Anticancer properties of 4-thiazolidinone derivatives depend on peroxisome proliferator-activated receptor gamma (PPARγ)

2017

Peroxisome proliferator-activated receptors (PPARs) play an important role in numerous chronic diseases such as diabetes, obesity, atherosclerosis and cancer, and PPAR modulators are among the approved drugs and drug-candidates for their treatment. The aim of this study was to elucidate the involvement of PPARs in the mechanism of cytotoxic and pro-apoptotic action of novel anticancer 4-thiazolidinone derivatives (Les-2194, Les-3377, Les-3640) and approved 4-thiazolidinones (Rosiglitazone, Pioglitazone) towards the human squamous carcinoma (SCC-15) cell line. Experiments with 4-thiazaolidinone derivatives and PPAR-specific siRNA were conducted and PPARα, PPARβ and PPARγ mRNA expression was …

Modulating allergic response by engineering the major Parietaria allergens.

2017

Parvovirus B19V Nonstructural Protein NS1 Induces Double-Stranded Deoxyribonucleic Acid Autoantibodies and End-Organ Damage in Nonautoimmune Mice

2018

Abstract Background Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model. Methods BALB/c mice were inoculated with (1) pristane-induced, (2) B19V NS1-induced, or (3) staurosporine-induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and enzyme-linked immunosorbent assay. Brain, heart, liver, and kidney pathology was examined. Deposition of self-antigens…