The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats.

Background The adverse effects of methotrexate (MTX) mainly hepatotoxicity restrict its clinical use. This study was designed to investigate the protective effects of saffron (Crocus sativus) (CS) extract on MTX-induced hepatotoxicity. Methods Twenty-eight male Wistar rats randomly divided into four equal groups. Except for control, all groups received a single intraperitoneal (i.p.) injection of MTX on the 3rd day of study. The CS extract was given (80 mg/kg i.p.) to rats 3 days before MTX and continued for the next 7 days (Pre&Post-CS group) or administrated after MTX injection and lasted for 7 days (Post-CS group). On the 11th day, all rats were sacrificed and their plasma levels of liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined. Also, liver histopathology and hepatic levels of malondialdehyde (MDA), nitric oxide (NO) and super oxidase dismutase (SOD) were evaluated. Results The results showed that MTX significantly incremented plasma levels of AST, ALT, ALP and LDH (all p<0.001) and hepatic MDA and NO levels; whereas, decreased SOD activity. Histological alterations such as early fatty changes were evident in the MTX group. Administration of CS extract at both methods could ameliorate liver enzyme elevation, oxidative/nitrosative stresses and morphological alterations of the liver. Pre-and-post treatment with CS extract showed better protective effects than only post-treatment. Conclusion The present findings provide showing CS could effectively alleviate MTX-induced hepatotoxicity in rats. Further investigations are recommended to determine the exact mechanisms underlying the hepatoprotective potential of saffron.

Involvement of the Dysregulation of miR-23b-3p, miR-195-5p, miR-656-5p, and miR-340-5p in Trastuzumab Resistance of HER2-Positive Breast Cancer Cells and System Biology Approach to Predict Their Targets Involved in Resistance.

Resistance to trastuzumab has become a limiting factor for therapeutic efficacy of human epidermal growth factor 2 (HER2)-positive breast cancer. Different expression levels of miRNAs in cancer cells have been associated with poor prognosis and response to chemotherapy. The aim of this study was to evaluate miRNAs that were thought to be associated with HER2-positive breast cancer chemoresistance. In this study, the relative expression of candidate miRNAs to U6 RNA was evaluated in trastuzumab-resistant and trastuzumab-sensitive cells using relative real-time PCR. Our results demonstrated that miR-23b-3p, miR-195-5p, miR-656-5p, and miR-340-5p were significantly dysregulated. For the first time in this study, these miRNAs were identified to be involved in trastuzumab resistance. TargetScan and miRDB were then used for predicting the potential targets of the candidate miRNAs. Our results also revealed that the predicted potential targets of these miRNAs were strongly associated with drug resistance pathways. As a relative expression of candidate miRNAs was statistically different in trastuzumab-resistant and trastuzumab-sensitive cells, their potential targets were involved in drug resistance pathways. We strongly hypothesized the dysregulation of miRNAs as a possible mechanism of trastuzumab resistance. We also assumed that the strategic manipulation of these regulatory networks might be a possible therapeutic strategy to improve the results of chemotherapy for this resistance. However, more research is needed to evaluate the role of these miRNAs in the acquisition of trastuzumab resistance.

Mutations analysis of BRCA1 gene in patients with breast cancer in South Khorasan province, East Iran.

Background: Breast cancer (BC) is well-known as the most common malignancy and the first leading cause of cancer-related death among women worldwide. Evidence suggests that familial history and age are important risk factors for the development of this disease in Iran. Mutations in BRCA1 and BRCA2 genes are the cause of 5 to 10% of hereditary BC. Recent studies demonstrated that mutations in BRCA1 were observed in high-risk women with family histories of BC. However, to date, the mutations have not been elucidated in BC patients from east of Iran. The purpose of this study was to analyze BRCA1 mutations in BC patient from South Khorasan Province. Methods: In the present study, 88 BC patients (11 positive family history) were screened for mutations in BRCA1. The analysis of BRCA1 was carried out by SSCP (single-strand conformation polymorphism) for shorter exons and direct sequencing in the case of longer ones. Results: Twenty-eight of the patients (31.8%) had a synonymous mutation (c.4308T>C) in exon 13. A missense mutation (c. 4837A>G) was presented in exon 16 with a frequency of 56.8 %. In exon 11 three missense mutations were observed, and the frequency rate for c.3113A>G was 32.5%, for c.3119G>A was 5%, and the highest frequency belonged to c.3548A>G with 72.4% in familial BC and 45.4% in the non-familial group. Conclusion: In our study, five mutations were found, but none of the founder mutations were identified in this population. Two missense mutations in exon 16 (56.8%) and in exon 11 (65%) had the highest frequency in South Khorasan Province.

Adjuvant high-dose-rate brachytherapy in the management of oral cavity cancers: 5 years of experience in Iran.

PURPOSE: Brachytherapy is a cost-effective method for the management of oral cavity cancers in low to middle income countries. We aimed to evaluate the clinical outcomes of high-dose-rate interstitial brachytherapy (HDR-IBT) in patients with oral cavity cancer. MATERIAL AND METHODS: From 2009 to 2013, 78 patients (49 combined external beam radiotherapy [EBRT] plus IBT and 29 IBT monotherapy) with oral cavity cancers had been treated in our center. Slightly more than half the patients were male, and the median age was 54 years. The treatment was planned based on the Paris system. The main outcomes were disease-free and overall survival. RESULTS: The median follow-up duration was 36.5 months (range, 1.17-54.23). The actuarial four-year overall and disease-free survival rates were 83% and 65%, respectively. The local and locoregional control was achieved among 89.74% and 87.17% of patients, respectively. None of the factors including tumor size, node status, gender, and radiation modality (IBT alone vs. IBT + EBRT) had a significant statistical correlation to the local control rate. All the patients tolerated the planned treatment in the IBT alone group. Late complications included a case of trismus and three cases of catheter insertion site fibrosis. CONCLUSIONS: HDR-IBT as a monotherapy or in combination with EBRT is an appropriate option for the management of oral cavity squamous cell carcinomas, and supports the improvement in treatment outcomes and toxicity profiles in adjuvant settings.

Comparison of Conventional and Hypofractionated Radiotherapy in Breast Cancer Patients in Terms of 5-Year Survival, Locoregional Recurrence, Late Skin Complications and Cosmetic Results

Bckground: Adjuvant radiation therapy is commonly administered following breast-conserving surgery for breast cancer patients. Hypofractionated radiotherapy can significantly reduce the waiting time for radiotherapy, working load on machines, patient visits to radiotherapy departments and medical costs. Material/Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0) who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy in two arms (hypofractionated radiotherapy arm with 30 patients, dose 42.5 Gy in 16 fractions; and conventional radiotherapy arm with 22 patients, dose 50 Gy in 25 fractions). W compared these two groups in terms of overall survival, locoregional control, late skin complications and cosmetic results. Results: At a median follow-up of 52.4 months (range: 0­64 months), the follow-up rate was 82.6%. Overall, after 60 months, there was no detectable significant differences between groups regarding cosmetic results (p = 0.857), locoregional control or survival. Conclusions: The results confirm that hypofractionated radiotherapy with a subsequent boost is as effective as conventional radiotherapy, is well-tolerated and can be used as an alternative treatment method following breast conservation surgery.