Short interfering RNA in colorectal cancer: is it wise to shoot the messenger?

Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/ß-catenin, transforming growth factor-ß (TNF-ß), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.

The Survival of Patients with t(15;17)(q22;q12) Positive Acute Promyelocytic Leukemia: A Study in North-East of Iran.

BACKGROUND & OBJECTIVE: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML). Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran. METHODS: Survival rates of 42 APL patients with t(15;17)(q22;q12) were assessed. Clinical information was obtained from archived medical records. Statistical analysis was performed by SPSS 18 software using log-ranked test and Kaplan Maier survival analysis. RESULTS: Females and males comprised 49% and 51%, respectively. The mean age at diagnosis was 34.3 ± 14.1 years old. During the study period, 17 demises occurred in males, while this number was 7 in females. The mean survival of patients (month) was 23.22 ± 3.57 (95% CI: 16.21 ± 30.2). The five-year survival rate obtained 30%. Regarding demographic and clinical features, the highest rates of 5-year survival were recorded in patients with 20-35 years old (47.6%), males (51%), white blood cell count <10 × 10 9 /l (48%), and platelet count >140 × 10 9 /l (100%). CONCLUSION: Younger age, lower WBC count and higher platelet count were significantly associated with longer survival in AML patients with t(15;17)(q22; q12).

Health-related Quality of Life and Associated Factors Among Thalassemia Major Patients, Southeast of Iran.

Low quality of life (QOL) is a feature that has been overlooked in thalassemia major (TM) patients. Our aim was to assess QOL in school-aged TM patients in Zabol city and surrounding rural areas in southeast of Iran. The study was performed in 2014. QOL was evaluated using Pediatric Quality of Life Inventory 4 (PedsQL4) questionnaire addressing physical, emotional, social, and educational, along with psychological health in 80 TM patients. Also, 80 age-matched and sex-matched subjects without any chronic illness served as control group. Mean age of the patients was 11.7±4.1 years old. Total QOL scores was 51.4±13.3 in the patients. In comparison, mean value of total QOL score in controls was 91.1±3.3 (P<0.0001). Poor and moderate QOL were observed in 44.7% and 48.7% of the patients, respectively. Mean functioning scores for physical, emotional, social, educational, and psychological dimensions in the patients were 56.2±119, 69.6.4±23.3, 27.1±22.1, 52.3±18.1, and 48.9±11.8, respectively. The lowest level of QOL was related to the social field (81.3% with less than average score), while the highest QOL was related to the emotional aspect (58.8% with good QOL; >75 scores). Overall, female sex, poor compliance with chelation therapy, and residency in urban areas were significantly associated with poor QOL. In conclusion, providing a psychiatric health package seems to be essential for improving QOL in TM patients, especially in social field.

Diabetes Mellitus in Thalassaemia Major Patients: A Report from the Southeast of Iran.

INTRODUCTION: Diabetes Mellitus (DM) represents a major concern in Thalassaemia Major (TM) patients. AIM: The present study was conducted to evaluate the frequency of Impaired Fasting Glucose (IFG) and DM in TM patients in Southeast of Iran. MATERIALS AND METHODS: Fasting Blood Glucose (FBS) was determined using fasting blood samples in 148 TM patients. Demographical data was collected by a questionnaire. Clinical and laboratory variables including cell blood counts, pre-transfusion Haemoglobin (Hb) level, and five-year ferritin were extracted from medical records. Statistical analysis was performed in SPSS19.0 software using chi-square, student t-test and logistic regression. RESULTS: Females and males comprised 83 (56.1%) and 65 (43.9%) subjects respectively. The mean age and mean five-year ferritin were 17.3±6.1 year-old and 5060.6±2395 ng/ml respectively. Overall, 39 (26.4%) patients had IFG, while 13 (8.8%) were diagnosed with DM. Significant differences were identified in the mean age, volume of transfused blood per occasion, and mean five-years ferritin between the patients with IFG or DM and the patients with normal fasting glucose level. Patients with age >25-year-old had an increased risk of both IFG (OR=4.7,95% CI: 1.3-17, p=0.01) and DM (OR= 7.1, 95% CI: 1-49.2, p=0.04). In addition, splenectomized patients showed a higher risk for IFG (OR=4.3, 95% CI: 1.5-12.1, p=0.005), and ferritin value >6000 ng/ml were associated with an elevated risk of DM (OR=7, 95% CI: 0.8-60.1, p=0.07). CONCLUSION: Our results indicated that higher age, mean five-years ferritin, volume of blood transfused per occasion, as well as splenectomy were risk factors of IFG and DM in TM patients.