ABSTRACT
Colorectal cancer [CRC] is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes [TSG]. Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis [FAP]. This review provides a venue towards defining candidate genes that can be used as new PCR-based markers for early diagnosis of FAP. In addition to diagnosis, defining the modes of genetic alterations will open door towards genome editing to either suppress the disease or reduce its progression during the course of action
ABSTRACT
This study investigated tissue damages induced by chronic subcutaneous administration of nano- and microparticles of manganese dioxide [MnO2] on the liver, kidneys and testes of rats. Rats [n=210] were divided into three groups: control, MnO2 nanoparticle injected and MnO2 microparticle injected. The experimental groups received subcutaneous injections with either nano- or microparticles of a solution that contained MnO2 [100 microg/kg] once per two weeks for 14 weeks. Once every two weeks, we randomly selected five rats from each group for histological evaluations of the liver, kidneys, and testes. Tissue lesions were initially evaluated by hematoxylin and eosin staining, then kidney and liver tissue sections were stained by the Jones and Masson's trichrome methods, respectively. The changes in diameter of basement membrane and cell numbers of the various parts of the nephrons in different groups were measured by Image Tools version 2 software. The liver tissues of the nano- and microparticle groups exhibited severe damage histopathologically. Cloudy swelling was observed in the cytoplasm of hepatocytes. The liver tissue and its canaliculi structures were severely damaged. Inflammation and ductular reaction signs were seen in liver tissue. Deposition of particles in the basement membrane of the nephrons were observed in the nanoparticle-treated group. There was a significant reduction in glomerular and tubular cells in the nanoparticle-treated group compared to the control and microparticle-treated groups. Some of the structural and functional parameters of the testes in the nanoparticle-treated group had significant pathobiological variations. Administration of MnO2 nanoparticles when compared with the same dose of MnO2 microparticles caused more tissue damage in all examined tissues. Reduction in particle size from micrometer to nanometer appeared to exacerbate the damaging mechanisms of these particles in the examined tissues