Relationship between KRAS and NRAS factors with clinicopathologic findings in patients with metastatic colon cancer

Introduction: Colorectal cancer (CRC) is the third common cancer among human and the fourth common reason of mortalities caused by cancers around the world. During recent years, EGFR-related molecular pathways are known as an important therapeutic pathway. High frequency of mutations of RAS family such as KRAS and NRAS and their rapid incidence in colon cancer indicates their high potential as a biomarker for early detection. Materials and Methods: In this cross sectional retrograde study, patients with colorectal cancer referring to Golestan Razi and Poursina Hospitals in Iran were evaluated during years 2009-2018. The rates of KRAS and NRAS factors were evaluated on paraffinized pathology samples of patients with metastatic colon cancer. Then, the correlation between mutation in these two factors with other clinicopathological findings of patients such as age, gender, tumor grade, location of primary lesion, time to progression (TTP), family history and presence or absence of lymphovascular invasion was investigated. Results: There was no significant correlation observed between occurrence of NRAS and KRAS with age group, family history and gender in the present study. But there was a significant statistical correlation between the rate of NRAS gene incidence with location of primary lesion and tumor grade. Finally, there was found a significant correlation between both KRAS and NRAS genes with TTP, so that TTP of patients reported less than patients without mutations in both groups. Conclusion: The present study showed that presence of both mutations in KRAS and NRAS makes the prognosis of disease worth such a way the location of primary lesion and tumor grade are two effective factors in incidence of NRAS gene and lymphovascular invasion is the effective factor on KRAS gene incidence. also, TTP is lower among patients with mutations in both KRAS and NRAS genes

The characterization of oxaliplatin-induced peripheral neuropathy using electromyography in gastrointestinal cancer patients

Oxaliplatin-induced peripheral neuropathy (OIPN) is a common dose-dependent chemotherapy complication in gastrointestinal cancer (GIC). This side effect may restrict therapeutic dose elevation of oxaliplatin. Here, OIPN frequency and determinants of neuropathy appearance in oxaliplatin-treated GIC patients. A total of 102 GIC patients who underwent chemotherapy with fluorouracil, folinic acid and oxaliplatin (FOLFOX4) regimen participated in this longitudinal study. Electromyography (EMG) was accomplished for ulnar, radial, sural, peroneal nerves and superficial peroneal nerve (SPN) before, 3, and 6 months after treatment. National Cancer Institute-Common Toxicity Criteria V.3 and clinical version of the Total Neuropathy Score were used for the neuropathy diagnosis at six months after treatment onset. Of all entered patients, twelve people discontinued this study, and five patients passed away. About 85 patients remained three and six months after chemotherapy onset. Approximately 95% of patients three months after chemotherapy demonstrated OIPN manifestations. Finally, data for 81 patients having neuropathy were analyzed. Mean age of patient 64.0±10.9 years. There were about 3.7%, 30.9%, 63% grade III, II, I of neuropathy, respectively. Interestingly, a significant decrease in action potential (AP) amplitude of SPN, sural and radial nerves but not ulnar and peroneal was observed after treatment onset. However, only the ulnar nerve indicated a substantial deceleration of nerve conduction. Age, sex, weight, past medical diseases, smoking and acute neuropathy were not significantly associated with OIPN. The occurrence of OIPN is detectable by electrophysiological changes of SPN, radial, and sural nerves at three and six months after starting chemotherapy with the FOLFOX4 regimen

Analysis of Ala234Thr Polymorphism SEPP1 gene in Women with Breast Cancer in Guilan Province

Background: Selenoprotein P (Sepp1) is the major selenoprotein in plasma and contains over 50% of the total plasma. The direct and indirect effects of Sepp1 on anti-oxidant defense can be responsible for its role in cancer risk. One of the common polymorphism of SEPP1gene is the Ala234Thr single nucleotide polymorphism (SNP) in coding region. In this research we studied the association between SEPP1 Ala234Thr (rs3877899) polymorphism with the risk of breast cancer. Materials and Methods: In this case-control study, 162 patients with breast cancer were compared with 227 healthy subjects. Genomic DNA was extracted from peripheral blood leukocytes. Determination of DNA genotyping in SEPP1 Ala234Thr (rs3877899) polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) by using MwoI enzyme. Statistical analysis was performed by using the MedCalc program and χ2-test. Results: The genotype frequencies were significantly different between the cases and controls. AA homozygosity subjects were more at risk for breast cancer than others  (OR=3.23; 95%CI, 1.79-5.84; p=0.001). Conclusion:Based on the results of this study,  The Ala234Thr polymorphism of the SEPP1 gene may be associated with the potential for breast cancer in the female population of  northern Iranian women. However, studiesneed to be conducted in larger populations to confirm these results

An Assessment of Spinal Cord Dose Following Radiotherapy of Nasopharyngeal Cancer by TLD and Rando Phantom

Introduction: Nasopharyngeal carcinoma is one of the most common malignancies in the head and neck region and radiotherapy is its treatment of choice. In spite of the fact that it is widely used, due to the presence of many sensitive organs or tissues in this region, patients may suffer from a wide range of side effects. One such sensitive tissue is the spinal cord. If the absorbed dose to spinal cord is greater than its tolerance dose, then myelopathy and Lhermitte’s sign are not avoidable. Material and Methods: Thehead and neck of a Rando phantom (reference man) was employed as a hypothetical patient suffering from nasopharyngeal carcinoma. The full course of treatment consisted of three phases. At the beginning of every phase, an oncologist used a simulator to delineate the surface of the Rando Phantom for treatment. TLD chips (TLD-100) were employed for dose measurement. TLD chips were inserted in the previously made holes on the surface of selected slices adjacent to second cervical to fourth thoracic vertebra. Absorbed dose by TLDs were read by a Harshaw 3500 TLD reader. Results: Total measured dose (in Gy) of various parts of spinal cord adjacent to second cervical to fourth thoracic vertebra varied widely and were as follows respectively: 15.24±1.31, 50.31±1.06, 49.15±2.77, 47.48±1.42, 54.56±2.6, 48.92±0.6, 45.1±0.45. In other words, the range of doses received by different segments of the spinal cord could be as wide as 15.24 to 54.56 Gy. Conclusion: Although the spinal cord was excluded at the end of the first phase, a significant change in the absorbed dose at the end of the first and second phases was not observed. In phase three, the anterior neck field was replaced by a lateral field and the spinal cord absorbed dose was reduced considerably. According to our results, absorbed doses of the spinal cord segments corresponding to the region confined between the third cervical to third thoracic vertebra were more than the 47 Gy recommended tolerance dose value. Therefore, special attention must be paid to protect this sensitive tissue while the treatment is performed. Application of modern techniques such as IMRT, if available, will reduce the unnecessary dose the spinal cord and its consequent biological risks considerably

The assessment of prognostic factors in patients with nonmetastatic rectal Adenocarcinoma referred to Omid Hospital (Mashhad), Iran

Background and Objective: Colorectal carcinoma accounts for nearly 10% of all incident cancers. The stage of the disease is the most important prognostic factor. The main purpose of this study was to evaluate the effect of some presumed prognostic factors on the survival rate of patients with nonmetastatic rectal adenocarcinoma. Materials and Methods: In this retrospective cohort study, 76 patients (m/f:40/36) with nonmetastatic rectal adenocarcinoma whome were referred to oncology department of Omid Hospital between 2001-06 were evaluated. All patients underwent surgical resection and those with T3-T4 and/or lymph node involvement received adjuvant radiotherapy and chemotherapy. Disease free survival was assessed from the date of diagnosis to the date of recurrence using Kaplan-Meyer method. Log-rank test was used to compare survival curves between groups. Multivariate analysis was performed using stepwise backward Cox Proportional Regression method. Results: Stages 1, 2 and 3 were detected in 4, 34 and 38 cases. 48 patients had well differentiated tumors. 11 cases presented with obstruction. With a median follow up time of 18 months, 17 patients experienced recurrence. For all cases 3-year survival rate was 68.2%. The 3-year survival rate was significantly better for stage 1,2 compared to stage 3, patient without obstruction compared to those presented with obstruction, cases older than 50 compared to younger patients and patients with well differentiated tumor compared to moderately or poor differentiated tumors (P<0.05). The gender and the site of tumor had not significant effects on survival. In multivariate analysis only stage of the disease remained significant predictor of survival (p<0.05). Conclusion: This study confirmed that the stage of the disease is the most important predictor of survival. Although younger ages (<50), moderately or poorly differentiated tumor and presence of obstruction at diagnosis were associated with decreased survival in univariate calculations, they lost their significance in multivariate analysis