Occurrence of large-scale mitochondrial DNA deletions in human colorectal cancer

Introduction: The aim of this study was to determine the mutation patterns of colon cancers through screening of different regions of mitochondrial DNA (mtDNA) in colon cancer patients. Material and methods: In order to investigate whether deletions exist in the mitochondrial DNA of colon cancer patients, we used a PCR assay to assess the presence of large-scale deletions. We screened four regions of the mitochondrial genome by PCR amplification and Southern blot analysis followed by DNA sequencing. Previously, deficiency in mitochondrial complex I has been reported; therefore we focused on the region of mtDNA that encodes the genes of this complex. Results: In 11 out of 90 patients, we found an 8.7 kb deletion. Large-scale deletions of mtDNA are common events that have been found to occur in human ageing and in patients with mitochondrial myopathies. Based on our results the mtDNA 8.7 kb deletion occurs in 12.2% of the colorectal cancer (CRC) samples. Conclusions: As reactive oxygen species (ROS) are continuously generated by the respiratory chain, they may cause significant oxidative damage to mtDNA (for example mtDNA deletions or mutations) if not efficiently eliminated. Defective respiratory enzymes containing protein subunits encoded by the deleted mtDNA may further enhance free radical production, resulting in more profound oxidative damage in CRC patients. Copyright © 2008 Termedia & Banach

Therapeutic impacts of microRNAs in breast cancer by their roles in regulating processes involved in this disease

Breast cancer is the most common cancer in women around the world. So far, many attempts have been made to treat this disease, but few effective treatments have been discovered. In this work, we reviewed the related articles in the limited period of time, 2000–2016, through search in PubMed, Scopus database, Google Scholar, and psychology and psychiatry literature (PsycINFO). We selected the articles about the correlation of microRNAs (miRNAs) and breast cancer in the insight into therapeutic applicability from mentioned genetics research databases. The miRNAs as an effective therapy for breast cancer was at the center of our attention. Hormone therapy and chemotherapy are two major methods that are being used frequently in breast cancer treatment. In the search for an effective therapy for breast cancer, miRNAs suggest a promising method of treatment. miRNAs are small, noncoding RNAs that can turn genes on or off and can have critical roles in cancer treatment; therefore, in the near future, usage of these biological molecules in breast cancer treatment can be considered a weapon against most common cancer-related concerns in women. Here, we discuss miRNAs and their roles in various aspects of breast cancer treatment to help find an alternative and effective way to treat or even cure this preventable disease

Analysis of PTEN in two BRCA1 and BRCA2 wild-type familial breast cancer patients

O portal da primeira rede editorial de blogues em Portugal é apresentado publicamente hoje, conforme já havia anunciado aqui.No endereço TubarãoEsquilo, vai mostrar-se "o rosto dos mais de vinte autores que desde o Outono têm vindo a aderir ao projecto pioneiro, bem como os seus trabalhos. Com um jornalista como pivot, a TubarãoEsquilo assume-se como um projecto editorial profissionalizante: os autores são remunerados em função dos resultados alcançados, remuneração esta assente, na fase de a..

Evaluation of DNA repair capacity in parents of pediatric patients diagnosed with autism spectrum disorder using the comet assay procedure

Background: Autism Spectrum Disorder (ASD) is characterized by impairments in social communication, limited repetitive behaviors, impaired language development, and interest or activity patterns, which include a group complex neurodevelopmental syndrome with diverse phenotypes that reveal considerable etiological and clinical heterogeneity and are also considered one of the most heritable disorders (over 90%). Genetic, epigenetic, and environmental factors play a role in the development of ASD. Aim: This study was designed to investigate the extent of DNA damage in parents of autistic children by treating peripheral blood mononuclear cells (PBMCs) with bleomycin and hydrogen peroxide (H2O2). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll method and treated with a specific concentration of bleomycin and H2O2 for 30 min and 5 min, respectively. Then, the degree of DNA damage was analyzed by the alkaline comet assay or single cell gel electrophoresis (SCGE), an effective way to measure DNA fragmentation in eukaryotic cells. Results: Our findings revealed that there is a significant difference in the increase of DNA damage in parents with affected children compared to the control group, which can indicate the inability of the DNA molecule repair system. Furthermore, our study showed a significant association between fathers’ occupational difficulties (exposed to the influence of environmental factors), as well as family marriage, and suffering from ASD in offspring. Conclusion: Our results suggested that the influence of environmental factors on parents of autistic children may affect the development of autistic disorder in their offspring. Subsequently, based on our results, investigating the effect of environmental factors on the amount of DNA damage in parents with affected children requires more studies

Molecular characterization and SNP development for the porcine IL6 and IL10 genes

Different cytokines are secreted in response to specific microbial molecules referred to as pathogen associated molecular patterns (PAMPs). Interleukin 6 (IL6) and interleukin 10 (IL10), both secreted by macrophages and lymphocytes, play a central role in the immunological response. In this work we obtained the genomic structure and complete DNA sequence of the porcine IL6 and IL10 genes and identified polymorphisms in the genomic sequences of these genes on a panel of ten different pig breeds. Comparative intra- and interbreed sequence analysis revealed a total of eight polymorphisms in the porcine IL6 gene and 21 in the porcine IL10 gene, which include single nucleotide polymorphisms (SNPs) and insertion deletion polymorphisms (indels). Additionally, the chromosomal localization of the IL10 gene was determined by FISH and RH mapping

CTNS molecular genetics profile in a Persian nephropathic cystinosis population

Purpose: In this report, we document the CTNS gene mutations of 28 Iranian patients with nephropathic cystinosis age 1–17 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Methods: Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular analysis, which involved polymerase chain reaction (PCR) amplification to determine the presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: The common 57-kb deletion was not observed in any of the 28 Iranian patients. In 14 of 28 patients (50%), mutations were observed in exons 6 and 7. No mutation was detected in exon 5, and only one (3.6%) patient with cystinosis showed a previously reported 4-bp deletion in exon 3 of CTNS. Four patients (14.3%) had a previously reported mutation (c.969C>A; p.N323K) in exon 11, and five (18%) had novel homozygous deletions in exon 6 leading to premature truncation of the protein. These deletions included c.323delA; p.Q108RfsX10 in three individuals and c.257-258delCT; p.S86FfsX37 in two cases. Other frame-shift mutations were all novel homozygous single base pair deletion/insertions including one in CTNS exon 9 (c.661insT; p.V221CfsX6), and four (14.3%) in exon 4, i.e., c.92insG; p.V31GfsX28 in two and c.120delC; p.T40TfsX10 in two. In total, we identified eight previously reported mutations and eight novel mutations in our patients. The only detected splice site mutation (IVS3-2A>C) was associated with the insertion mutation in the exon 9. Conclusion: This study, the first molecular genetic analysis of non-ethnic-specific Iranian nephropathic cystinosis patients, may provide guidance for molecular diagnostics of cystinosis in Iran