Exploring the Relationship Between KRAS, NRAS, and BRAF Mutations and Clinical Characteristics in Iranian Colorectal Cancer Patients.

BACKGROUND: Patients with colorectal cancer can benefit from anti-EGFR (epidermal growth factor receptor) therapy. However, this therapy is not effective for treating colorectal cancers with constitutive activating mutations in the KRAS, NRAS, and BRAF genes. Molecular analysis of tumor tissue frequently informs treatment decisions for colorectal cancer. This study aims to identify KRAS, NRAS, and BRAF mutations in Iranian patients diagnosed with colorectal cancer and to assess the prevalence of these mutations relative to the tumor differentiation stage within these populations. METHODS: From April 2018 to December 2022, 2000 specimens from patients with colorectal cancer were collected. Data on sex, age, and tumor differentiation stage were recorded for all samples. For mutation detection, the KRAS and NRAS exons (2, 3, and 4) were amplified using the Diatech kit, and a specific primer was used to amplify BRAF exon 15. Pyrosequencing was then performed. RESULTS: Analysis of samples revealed that 1105 specimens (55.3%) contained mutations in at least one of the screened genes. Among the genes studied, the highest occurrence was the KRAS mutation at 47.4%, followed by NRAS at 5.3% and BRAF at 2.7%. Most KRAS mutations were found in exon 2 (89.7%), with the G12D mutation being the most prevalent at 32% of cases. There was a significant difference in the rate of KRAS mutations in women (52.5%) compared to men (43.5%) (P = 0.02). For NRAS, the majority mutations were observed in exon 3 (76.2%), with the Q61H mutation being the most prevalent at 28.5% of cases. There were no significant associations between the clinicopathological parameters and mutations. CONCLUSION: The study's findings indicate a rising frequency of mutations in these genes in Iran, highlighting the need to screening mutations in the main exons of all three genes for effective colorectal cancer treatment strategies.

The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients.

The survival rate of lung cancer is low due to the high frequency of drug resistance in patients with mutations in the driver genes. Overexpression of anti-apoptotic genes is one of the most prominent features of tumor drug resistance. EGFR signaling induces the expression of anti-apoptotic genes. Also, microRNAs (miRNAs) have a critical role in regulating biological functions such as apoptosis; a process mostly eluded in cancer progression. The mutation screening was performed on one thousand non-small cell lung carcinoma patients to enroll clinical samples in this study. Bioinformatics analysis predicted that miRNAs (miR-29a, miR-143) might regulate MCL-1 and cIAP-2 expression. We investigated the expression of MCL-1, cIAP-2, miR-29a, and miR-143 encoding genes in adenocarcinoma patients with or without EGFR mutations before treatment. The potential role of miR-29a and miR-143 on gene expression was evaluated by overexpression and luciferase assays in HEK-293T cells. EGFR mutations were found in 262 patients (26.2%) with a greater incidence in females (36.23% vs. 20.37%, P = 0.001). The expression levels of MCL-1 and cIAP-2 genes in patients with mutated EGFR were higher than those of wild-type EGFR. In contrast, compared to those of patients with wild-type EGFR, the expression levels of miR-29a and miR-143 were lower in the patients carrying EGFR mutations. In cell culture, overexpression of miR-29a and miR-143 significantly downregulated the expression of MCL-1 and cIAP-2. Dual-luciferase reporter experiments confirmed that miR-29a and miR-143 target MCL-1 and cIAP-2 mRNAs, respectively. Our results suggest that upregulation of EGFR signaling in lung cancer cells may increase anti-apoptotic MCL-1 and cIAP-2 gene expression, possibly through downregulation of miR-29a-3p and miR-143-3p.

Detection of Legionella Pneumophila in Urine and Serum Specimens of Neutropenic Febrile Patients with Haematological Malignancies.

Background: Legionella pneumophila (L. pneumophila) is a gram-negative bacterium which causes Legionnaires' disease as well as Pontiac fever. The Legionella infections in patients suffering from neutropenia- as a common complication of cancer chemotherapy- can distribute rapidly. We aimed to detect of L. pneumophila in haematological malignancy suffering patients with neutropenic fever by targeting the (macrophage infectivity potentiator) mip gene. Subjects andMethods: Serum and urine specimens were obtained from 80 patients and presence of mip gene of L. pneumophila in specimens was investigated by PCR. Results: The L. pneumophila infection was detected in 21 (26.2%) and 38 (47.5%) of urine and serum specimens, respectively. Conclusion: Our findings indicated that the relative high prevalence of L. pneumophila in the studied patients group which show the necessity of considering this microorganism in future studies from detection and treatment point of view in cancer patients.

Molecular detection of microsporidiosis in various samples of Iranian immunocompromised patients.

Microsporidia infections occur in virtually all invertebrate and vertebrate hosts, including humans. The aim of this study is detection of microsporidiosis in various samples of Iranian immunosuppressed patients during 2011-2012 by molecular methods. The samples included stool samples from the healthy participants and samples from biological fluids of the patients according to consult of their physician and the site of infection. The sample size was determined as 258 for each group. Clinical and demographical data related to each participant was collected. DNA extraction and nested polymerase chain reaction were carried out on all the samples. In the control group, the rates of Encephalitozoon and Enterocytozoon infections were 5.3 and 4 % respectively higher in males and in the age range of 30-45, and all positive cases had gastrointestinal symptoms. In the patient group, most infection cases occurred in male patients and in the age range of 60 and above. Patients with microsporidiosis mostly had the symptoms of chronic diarrhea, vomiting, weight loss, dyspepsia, and malabsorption. In BAL samples from patients 2 % Encephalitozoon and 0.7 % Enterocytozoon, in the sampling bone marrow transplantation from patients 5.7 % Encephalitozoon, 1.43 % Enterocytozoon and from patients who underwent kidney transplantation 5.26 % Enterocytozoon were detected. The most cases of human microsporidiosis are associated with human immunodeficiency virus infection or other states of immunosuppression, particularly in organ transplant recipients; the result of this study confirms this claim.