RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition.

Related Articles

RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition.

Cancer Cell Int. 2017;17:111

Authors: Rubio MF, Lira MC, Rosa FD, Sambresqui AD, Salazar Güemes MC, Costas MA

Abstract
Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition of apoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents. The aim of this study was to investigate its role in chemoresistance of colorectal cancer.
Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines, expressing high or low natural levels of RAC3, was investigated using viability assays.
Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy was strongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cells expressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with control cells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce an increase of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlier after stimulation.
Conclusions: Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs. Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to design new improved therapeutic strategies in the future.

PMID: 29209153 [PubMed]

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2joDwsZ

Metastasis suppressor 1 (MTSS1) expression is associated with reduced in-vivo metastasis and enhanced patient survival in lung adenocarcinoma

Abstract

Metastasis suppressor 1 (MTSS1) has been shown to be a metastasis suppressor in a number of cancers. However, its role in lung adenocarcinoma is largely unknown. To evaluate the significance of MTSS1 expression on lung adenocarcinoma metastatic properties, the gain or loss of MTSS1 in in vivo and in vitro experiments were employed. Using an in vivo orthotopic mouse xenograft model mimicking human disease progression, stable overexpression of MTSS1 in lung adenocarcinoma cells resulted in a significant decrease in metastatic burden. Stable overexpression of MTSS1 in NCI-H1299 decreased in vitro lung adenocarcinoma invasion and migration while knockdown of MTSS1 in A549 resulted in a significant increase in cell invasion and migration. Using The Cancer Genome Atlas dataset of over 500 patient lung adenocarcinoma specimens, we demonstrated a 20% increase in 5-year survival associated with preserved intratumoral MTSS expression. MTSS1 expression in lung adenocarcinoma is associated with decreased metastatic burden, as assessed by an in vivo orthotopic model, and correlates with a 20% survival advantage at 5 years following diagnosis. In vitro data suggests MTSS1 regulates lung adenocarcinoma through augmentation of cell invasion and migration.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2iz1nFq

Use of HuH6 and other human-derived hepatoma lines for the detection of genotoxins: a new hope for laboratory animals?

Abstract

Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line. The sensitivity of twelve hepatic cell lines was investigated in single cell gel electrophoresis assays. Furthermore, characteristics of these lines were studied which are relevant for their use in genotoxicity assays (mitotic activity, p53 status, chromosome number, and stability). Three lines (HuH6, HCC1.2, and HepG2) detected representatives of five classes of promutagens, namely, IQ and PhIP (HAAs), B(a)P (PAH), NDMA (nitrosamine), and AFB₁ (aflatoxin), and were sensitive towards reactive oxygen species (ROS). In contrast, the commercially available line HepaRG, postulated to be a surrogate for hepatocytes and an ideal tool for mutagenicity tests, did not detect IQ and was relatively insensitive towards ROS. All other lines failed to detect two or more compounds. HCC1.2 cells have a high and unstable chromosome number and mutated p53, these features distract from its use in routine screening. HepG2 was frequently employed in earlier studies, but pronounced inter-laboratory variations were observed. HuH6 was never used in genotoxicity experiments and is highly promising, it has a stable karyotype and we demonstrated that the results of genotoxicity experiments are reproducible.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ACz8Ag

Ecthyma Gangrenosum

Figure 1.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BRKjTx

Necrotizing Soft-Tissue Infections

Necrotizing fasciitis is a surgical diagnosis characterized by friability of the superficial fascia, dishwater-gray exudate, and a notable absence of pus. This and other necrotizing soft-tissue infections have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms, but all…

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BR4X6j

Necrotizing Soft-Tissue Infections

Necrotizing fasciitis is a surgical diagnosis characterized by friability of the superficial fascia, dishwater-gray exudate, and a notable absence of pus. This and other necrotizing soft-tissue infections have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms, but all…

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BR4X6j

Subcutaneous phaeohyphomycosis caused by Veronaea botryosa in a Japanese patient with adult T-cell lymphoma

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2AB54os