Mesenchymal Stem Cells Genetically Modified by Lentivirus-Express Soluble TRAIL and Interleukin-12 Inhibit Growth and Reduced Metastasis-Relate Changes in Lymphoma Mice Model.

BACKGROUND: Cancer treatment has many side effects; therefore, more efficient treatments are needed. Mesenchymal stem cells (MSC) have immunoregulatory properties, tumor site migration and can be genetically modified. Some proteins, such as soluble TRAIL (sTRAIL) and interleukin-12 (IL-12), have shown antitumoral potential, thus its combination in solid tumors could increase their activity. MATERIALS AND METHODS: Lentiviral transduction of bone marrow MSC with green fluorescent protein (GFP) and transgenes (sTRAIL and IL-12) was confirmed by fluorescence microscopy and Western blot. Soluble TRAIL levels were quantified by ELISA. Lymphoma L5178Y cells express a reporter gene (GFP/mCherry), and TRAIL receptor (DR5). RESULTS: An in vivo model showed that combined treatment with MSC expressing sTRAIL+IL-12 or IL-12 alone significantly reduced tumor volume and increased survival in BALB/c mice (p < 0.05) with only one application. However, at the histological level, only MSC expressing IL-12 reduced tumor cell infiltration significantly in the right gastrocnemius compared with the control group (p < 0.05). It presented less tissue dysplasia confirmed by fluorescence and hematoxylin-eosin dye; nevertheless, treatment not inhibited hepatic metastasis. CONCLUSIONS: MSC expressing IL-12, is or combination with BM-MSC expressing sTRAIL represents an antitumor strategy for lymphoma tumors since they increase survival and reduce tumor development. However, the combination did not show significative additive effect. The localized application did not inhibit metastasis but reduced morphological alterations of tissue associated with liver metastasis.

Chemosensitivity analysis and study of gene resistance on tumors and cancer stem cell isolates from patients with colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of mortality. Recent studies suggest that cancer stem cells (CSCs) can survive after chemotherapy and promote tumor invasiveness and aggression. According to a higher hierarchy complexity of CSC, different protocols for isolation, expansion, and characterization have been used; however, there are no available resistance biomarkers that allow predicting the clinical response of treatment 5­fluorouracil (5FU) and oxaliplatin. Therefore, the primary aim of the present study was to analyze the expression of gene resistance on tumors and CSC­derived isolates from patients CRC. In the present study, adenocarcinomas of the colon and rectum (CRAC) were classified based on an in vitro adenosine triphosphate­based chemotherapy response assay, as sensitive and resistant and the percentage of CD24 and CD44 markers are evaluated by immunohistochemistry. To isolate resistant colon­CSC, adenocarcinoma tissues resistant to 5FU and oxaliplatin were evaluated. Finally, all samples were sequenced using a custom assay with chemoresistance­associated genes to find a candidate gene on resistance colon­CSC. Results showed that 59% of the CRC tissue analyzed was resistant and had a higher percentage of CD44 and CD24 markers. An association was found in the expression of some genes between the tumor­resistant tissue and CSC. Overall, isolates of the CSC population CD44+ resistant to 5FU and oxaliplatin demonstrated different expression profiles; however, the present study was able to identify overexpression of the KRT­18 gene, in most of the isolates. In conclusion, the results of the present study showed overexpression of KRT­18 in CD44+ cells is associated with chemoresistance to 5FU and oxaliplatin in CRAC.

Family and social environment associated with traits of antisocial personality disorder in the prison population of Peru.

INTRODUCTION: The prison environment in Peru is one of the worst in the continent. In situations such as these, where there is considerable stress, many inmates can develop antisocial disorders, especially if they come from a conflictive family setting. OBJECTIVES: To determine the association between family relationships, social environment and features of antisocial personality disorder (ASPD) in the Peruvian prison population in 2016. MATERIAL AND METHOD: Analytical cross-sectional study based on a sub-analysis of the First National Penitentiary Census of Peru in 2016. The sample is the prison population (≥18 years old) that participated in said census, which was carried out in 66 correctional facilities nationwide and reached a coverage of 98.8%. RESULTS: Of the 77,086 prisoners, 76,152 participated in the analysis. The prevalence of antisocial traits was 96% and half of the population met two criteria for the disorder. Independently associated factors were, being male (RPa: 1.35; 1.30-1.40), born outside the capital (RPa: 0.89; 0.88-0, 91), friends in the neighborhood who committed offences (RPa: 1.01; 1.00-1.02) and not living with a father (RPa: 1.00; 1.00-1.01). DISCUSSION: The prevalence of antisocial personality disorder traits in the Peruvian prison population was 96%. We found greater association with the male sex, in those born in Lima and in those who escaped from their home before the age of 15.

Understanding the colon cancer stem cells and perspectives on treatment.

An area of research that has been recently gaining attention is the relationship between cancer stem cell (CSC) biology and chemo-resistance in colon cancer patients. It is well recognized that tumor initiation, growth, invasion and metastasis are promoted by CSCs. An important reason for the widespread interest in the CSC model is that it can comprehensibly explain essential and poorly understood clinical events, such as therapy resistance, minimal residual disease, and tumor recurrence. This review discusses the recent advances in colon cancer stem cell research, the genes responsible for CSC chemoresistance, and new therapies against CSCs.

Environmental light conditions alter gene expression of rat catecholamine biosynthetic enzymes and Neuropeptide Y: differential effect in superior cervical ganglia and adrenal gland.

The hypothalamic suprachiasmatic nuclei (SCN) comprise the main site in the brain involved in the control of the homeostatic mechanism which respond to environmental daily light changes. The sympathetic nervous system and hypothalamic releasing or inhibiting factors mediate the SCN control of a number of peripheral organs and tissues. In this work we analyzed the involvement of two environmental light conditions, constant light (LL) and constant dark (DD) for 20 days, on the expression of mRNAs for catecholamines biosynthetic enzymes and neuropeptide Y (NPY) genes in rat superior cervical ganglia (SCG) and adrenal gland. The results of Northern blot analysis show that LL exposure reduces mRNA levels for tyrosine hydroxylase (TH) the rate limiting catecholamine biosynthetic enzyme and also of dopamine beta-hydroxylase (DBH) as well as for NPY in SCG to about half the levels in control animals. In contrast, exposure of the rats to DD did not elicit any change in the SCG. In the adrenal gland, both, LL and DD conditions increased the TH, DBH as well as phenylethanolamine N-methyltransferase (PNMT) mRNA levels. Under the same conditions, adrenal NPY mRNA levels were decreased by either LL or DD. The results show, for the first time, that prolonged changes in environmental light can alter the gene expression of catecholamine biosynthetic enzymes and of NPY. There was differential response in SCG and adrenal gland.

[Polychaetes as bioindicators of organic pollution on the beaches of São Paulo]. / Poliquetas bioindicadores de poluição orgânica em praias paulistas.

This study consisted of an analysis of the occurrence of bioindicator polychaete species of organic pollution along beaches of the north coast of São Paulo State, southeastern Brazil, taking into account the importance of benthic species as indicators of organically enriched environments. A comparison was established between the frequence and abundance of these species in areas qualified as impacted and improper for bathing. The study area comprehends 17 beaches of the Caraguatatuba Bay and the Channel of São Sebastião. The data about the macrobenthos were collected from March, 1988 to March, 1991 and the data on bathing conditions came from reports published by CETESB. The biological samples were obtained with an iron core of 0.025 m2 surface area. The results show markedly the presence of species considered as indicators of organically enriched places, such as Capitella capitata, Heteromastus filiformis, Laeonereis acuta, and Scolelepis squamata. The high density of Capitella and Heteromastus in beaches considered improper for bathing consist in a strong indication of the degree of damage to these areas.