Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells.

The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs.

Regulation of miRNAs Expression by Mutant p53 Gain of Function in Cancer.

The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants.

Deciphering the epigenetic network in cancer radioresistance.

Radiotherapy, in addition to surgery and systemic chemotherapy, remains the core of the current clinical management of cancer. Radioresistance is one of the major causes of disease progression and mortality in cancer; therefore, it is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancer. Epigenetic mechanisms that control hallmarks of cancer have a key role in the development of radiation resistance of cancer cells.

Nanostructured oleic acid/polysorbate 80 emulsions with diminished toxicity in NL-20 cell line: Insights of potential drug carriers.

Nanoemulsions (NE) are nowadays required drug nanocarriers. We have selected i) oleic acid (OA) as oil (O), ii) polysorbate 80 (PS) as surfactant (S), and iii) water (W) in a prototype NE. Our best formulation had O:S ratio [OA]/[PS] = 0.

Design of a synthetic miniR1 plasmid and its production by engineered Escherichia coli.

A synthetic plasmid consisting of the minimal elements for replication control of the R1 replicon and kanamycin resistance marker, which was named pminiR1, was developed. pminiR1 production was tested at 30 °C under aerobic and microaerobic conditions in Escherichia coli W3110 recA (W1). The plasmid DNA yields from biomass (Y) were only 0.

New insights into radioresistance in breast cancer identify a dual function of miR-122 as a tumor suppressor and oncomiR.

Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR-122 was observed to be up-regulated.

A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.

Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus.

Cooperative multi-targeting of signaling networks by angiomiR-204 inhibits vasculogenic mimicry in breast cancer cells.

RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia.

Evaluation of HIF-1α and iNOS in ischemia/reperfusion gastric model: bioimpedance, histological and immunohistochemical analyses.

Unlabelled: Gastrointestinal ischemia/reperfusion (I/R) generates pathological alterations that could lead to death. Early ischemic damage markers could be used to guide therapy and improve outcomes.

Aim: To relate hypoxia-inducible factor 1α (HIF-1α) activation and inducible nitric oxide synthase (iNOS) expression to gastric impedance changes due to I/R damage.

Tumor suppressor miR-29c regulates radioresistance in lung cancer cells.

Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells.

Aerobic expression of Vitreoscilla hemoglobin improves the growth performance of CHO-K1 cells.

Inefficient carbon metabolism is a relevant issue during the culture of mammalian cells for the production of biopharmaceuticals. Therefore, cell engineering strategies to improve the metabolic and growth performance of cell lines are needed. The expression of Vitreoscilla stercoraria hemoglobin (VHb) has been shown to significantly reduce overflow metabolism and improve the aerobic growth of bacteria.

All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription-Independent Mechanism.

All-trans retinoic acid (ATRA) has been used as an antineoplastic because of its ability to promote proliferation, inhibition, and differentiation, primarily in leukemia; however, in other types of cancer, such as lung cancer, treatment with ATRA is restricted because not all the patients experience the same results. The ERK signaling pathway is dysregulated in cancer cells, including lung cancer, and this dysregulation promotes proliferation and cell invasion. In this study, we demonstrate that treatment with ATRA can activate the ERK signaling pathway by a transcription-independent mechanism through a signaling cascade that involves RARα and PI3K, promoting growth, survival, and migration in lung cancer cells.

Activation of Akt pathway by transcription-independent mechanisms of retinoic acid promotes survival and invasion in lung cancer cells.

Background: All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment.

Randomized phase II trial of All-trans-retinoic acid with chemotherapy based on paclitaxel and cisplatin as first-line treatment in patients with advanced non-small-cell lung cancer.

Purpose: This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel (PC) plus all-trans retinoic acid (ATRA) increases response rate (RR) and progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of retinoic acid receptor beta 2 (RAR-beta2) as a response biomarker.

Patients And Methods: Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m(2)/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-beta2 expression was analyzed in tumor and adjacent lung tissue.

Wood-smoke exposure as a response and survival predictor in erlotinib-treated non-small cell lung cancer patients: an open label phase II study.

Introduction: Erlotinib, a tyrosine kinase inhibitor, has improved survival and quality of life in patients with non-small cell lung cancer (NSCLC) after first- or second-line chemotherapy. Asian origin, adenocarcinoma histology, female gender, lack of tobacco use, and expression of epidermal growth factor receptor are significant independent predictors of response to Erlotinib. Although tobacco use is considered a major cause of NSCLC, other risk factors such as wood-smoke exposure (WSE) are associated.

Novel structural and functional findings of the ehFLN protein from Entamoeba histolytica.

The ehFLN protein (previously known as EhABP-120) is the first filamin to be identified in the parasitic protozoan Entamoeba histolytica. Filamins are a family of cross-linking actin-binding proteins that organize filamentous actin in networks and stress fibers. It has been reported that filamins of different organisms directly interact with more than 30 cellular proteins and some PPIs.

EhGEF3, a novel Dbl family member, regulates EhRacA activation during chemotaxis and capping in Entamoeba histolytica.

Rho GTPases are critical elements involved in the regulation of signal transduction cascades from extracellular stimuli to cytoskeleton. The Rho guanine nucleotide exchange factors (RhoGEFs) have been implicated in direct activation of these GTPases. Here, we describe a novel RhoGEF, denominated EhGEF3 from the parasite Entamoeba histolytica, which encodes a 110 kDa protein containing the domain arrangement of a Dbl homology domain in tandem with a pleckstrin homology domain, the DH domain of EhGEF3 is closely related with the one of the Vav3 protein.

EhGEF2, a Dbl-RhoGEF from Entamoeba histolytica has atypical biochemical properties and participates in essential cellular processes.

Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activation of Rho small GTPases. This paper reports the molecular, structural, biochemical and functional characterization of EhGEF2, a new member of the Dbl family. EhGEF2 is the second GEF studied in parasites and in the protozoan Entamoeba histolytica, and it is also the first member of the Dbl family that was found to have Arm repeats.