Search results for " Line"

Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation

2017

MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR- 29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b…

Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy

2020

Gastroesophageal adenocarcinoma (GEA) and squamous esophageal cancer (ESCC) are responsible for1 million deaths annually globally. Until now, patients with metastatic GEA and ESCC could anticipate survival of1 year. Anti- programmed cell death protein 1 (anti-PD-1) monotherapy has demonstrated modest efficacy in previously treated GEA and ESCC. In 2020, four pivotal trials have established anti-PD-1 therapy as a new standard of care for selected GEA and ESCC patients as first-line advanced and adjuvant therapy. In this review, we discuss the recent results of the CheckMate 649, ATTRACTION-4, KEYNOTE-590 and CheckMate 577 trials. We consider these results in the context of current standards …

Aflibercept in combination with irinotecan, fluorouracil and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal cancer (mCRC) p…

2018

The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis

2018

Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled…

A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

2019

Background Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K arra…

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 …

Mid-region parathyroid hormone-related protein is a genome-wide chromatin-binding factor that promotes growth and differentiation of HB2 epithelial c…

2018

Human parathyroid hormone-related protein (PTHrP) is a polyhormone that undergoes proteolytic cleavage producing smaller peptides which exert diversified biological effects. PTHrP signalization is prominently involved in breast development and physiology, but the studies have been focused onto either N-terminal species or full-length protein introduced by gene transfer techniques. Our present work investigates for the first time the effect of the mid-region PTHrP secretory form, that is, the fragment [38-94], on HB2 non-tumoral breast epithelial cells. We examined viability/proliferation of cells grown in PTHrP-containing media supplemented with different serum concentration and on differen…

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation

2017

Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalcife…

Identification of potential therapeutic compounds for Parkinson's disease using Drosophila and human cell models.

2017

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5–10% of them are familial forms caused by mutations in certain genes. One of these genes is the DJ-1 oncogene, which is involved in an early…

The human meibomian gland epithelial cell line as a model to study meibomian gland dysfunction

2016

The meibomian gland dysfunction (MGD) is the leading cause of dry eye disease (DED) throughout the world. The investigation of MGD lacks suitable in vivo and in vitro models. In 2010 a human meibomian gland epithelial cell line (HMGEC) was established, so far the only available meibomian gland cell line. The characterization of HMGEC is of major importance to clarify its suitability for studying the meibomian gland (patho)physiology in vitro. The current culture protocol and new concepts of HMGEC culture will be compared. Hormones are believed to be a key factor in meibomian gland dysfunction thus HMGEC responsiveness to hormone stimulation is crucial to elucidate the hormonal influence on …