Search

Background: Lung cancer is the leading cause of cancer deaths worldwide. Pharmacogenomics plays an important role in tailoring cancer patients’ treatment. Pemetrexed is widely used in first- and second-line chemotherapy of non-small cell lung cancer (NSCLC); however, there is no available predictive biomarker for pemetrexed treatment. The present study aimed to investigate the role of polymorphisms in thymidylate synthase and SLC19A1 polymorphisms with clinical outcome in patients with advanced NSCLC treated in first-line with pemetrexed or pemetrexed plus cisplatin.Method: This cohort study included 40 metastatic lung cancer patients treated with pemetrexed plus cisplatin. We utilized the tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction for genotyping of rs3788189 and rs1051298. TYMS 28-VNTR and rs16430 were genotyped in the patients via PCR amplification and PCR-RFLP, respectively. Fisher's exact test and Kaplan-Meier curve were used for statistical analysis.Results: We recruited 40 patients in this research with a median age of 58.9 years. The median survival of all the 40 patients was 11.6 months. The overall survival of the patients, as well as their gender, age, and metastatic sites were not found to be statistically associated with rs1051298, rs3788189, TYMS VNTR, and rs16430.Conclusion: Our study did not identify any associations between the SLC19A1 and TYMS VNTR and rs16430 and clinical outcomes in advanced NSCLC patients. However, further investigation will be conducive to finding effective clinical biomarkers for the treatment of patients with NSCLC.

Introduction. Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban’s ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance. Methods. We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test’s p value was higher than 0.1. We used random models when the p value was less than 0.1. Results. Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations. Conclusion. This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.

Aims: Lung cancer is still the leading cause of cancer mortality in all over the world. Nicotine and its derivatives are the most well-known carcinogens that participate in both etiology and progression of lung cancer. The objective of the current study was to investigate whether single nucleotide polymorphisms (SNPs) rs1051730C > T in CHRNA3 and rs3842A > G in ABCB1, two genes contributing in the mechanism of disposition and metabolism of nicotine and its derivatives, could modify the risk of developing lung cancer, as well as nicotine dependence in Iranian. Main methods: The genotyping analysis for these two SNPs was conducted in a case-control study of 108 lung cancer cases and 120 healthy controls using ARMS-PCR and Tetra-primer ARMS-PCR techniques. The correlation between studied SNPs and lung cancer was assessed by the regression analysis. Key findings: We observed a significant association between lung cancer and rs1051730C > T by using four genetic models: allele (OR:1.83; 95% CI:1.24–2.6; p = 0.002), dominant (OR: 2.19; 95% CI:1.27–3.78; p = 0.005), recessive (OR: 2.25; 95% CI: 1.02–4.95; p = 0.043) and additive (TT vs CC: OR:3.25; 95% CI:1.38–7.60; p = 0.007, CT vs CC: OR:1.96; 95% CI:1.10–3.48; p = 0.021). Furthermore, a significant association between this variant and nicotine dependence (OR: 2.27; 95% CI: 1.52–3.39; p = 0.00005) was reported. However, no association was found for rs3842A > G. Significance: The results suggested that the CHRNA3 rs1051730C > T via a smoking-dependent manner could modify susceptibility to lung cancer among Iranian population.

In the present study, the effects of pretreatment of time (24 and 96 hours) and pH (7 and 9) at extremely limited carbon dioxide concentration were studied on the exponential growth phase, photosynthetic pigments per cell, absorption shift of chlorophyll, structure and function of phycobilisome, the ratio of light harvesting to reaction center pigment, and the ratio of photosystem 1 to photosystem 2 in stigonematalean cyanobacterium Fischerella sp.FS 18. Results showed that pretreatments kept the exponential growth phase at both 24 and 96 hours and also under pHs 7 and 9. Contrary to the absorption peak of chlorophyll, cellular pigments showed no stable pattern regarding pretreatments. Phycobilisomes were the main point of treatment affects. The pattern of the rode part of phycobilisomes was the same at pretreatment reactions. The shift of phycocyanin was about 1 and phycoerythrin about 3. The highest rate of photosystem 1 to photosystem 2 ratio was observed at 24 hours and under neutral condition. This changed by the time and led to decreased efficiency of energy transport in photosynthesis system. The change in the phycobilisome operation may be a compensation mechanism to mitigate the degree of such a decrease.

Background: The Micronuclei has been discussed as an indicator of chromosomal damage in radiotherapy. This study aimed to investigate the changes of micronuclei in peripheral blood lymphocytes of patients with of the gastrointestinal cancers pre- and post-chemo-radiation. Methods: This cross-sectional study was conducted in patients with gastrointestinal cancers who referred to oncology ward of Rasool Akram Hospital in Tehran from January to March, 2016. After obtaining informed consent from all patients, 3 cc of peripheral blood samples was obtained for cytogenetic assessment in two stages, before treatment and 4 weeks after treatment. The frequency of micronuclei was examined per 1,000 lymphocytes with two nuclei. Results: Sixty-one patients were evaluated and 11 patients were excluded at the end of study. Fifty patients (34 males, 16 females) with a 59.74±13.34 years old were evaluated. 24 (48%) and 26 patients (52%) were in the less than 60 years’ age group and more than one, respectively. 37 cases (74%) with gastric cancer and 13 cases (26%) with esophageal cancer enrolled in the study. The significant differences were meaningful pre- and post-treatment (44.88 vs. 364.4 /1000 cells) (P=0.005). Also, there were no significant differences of the mean number of micronuclei between pre- and post-treatment according the type of cancer, sex and age groups. Further analysis according by age, sex and cancer of the esophagus or stomach showed no statistically significant differences between the groups in micronuclei number. In other words, chemotherapy and radiation in patients, regardless of age, sex and type of gastrointestinal cancer is very significant impact on the micronuclei production in peripheral blood of patients. Conclusion: The number of micronuclei in peripheral blood increased significantly in patients with gastrointestinal tract cancer (esophagus and stomach) under the chemo-radiation therapy. It seems that this increase was not correlated with age, sex and type of cancer (stomach or esophagus).

Stable molecular changes during cell division without any change in the sequence of DNA molecules is known as epigenetic. Molecular mechanisms involved in this process, including histone modifications, methylation of DNA, protein complex and RNA antisense. Cancer genome changes happen through a combination of DNA hypermethylation, long-term epigenetic silencing with heterozygosis loss and genomic regions loss. Different combinations of N-terminal’s changes cooperate with histone variants with a specific role in gene regulation. It have led to load a setting histone that determine transcription potential of a particular gene or genomic regions. DNA methylation analysis in genome region using methylation-specific digital karyotyping of normal breast tissue detect gene expression patterns and DNA specific methylation can be found in breast carcinoma too more than 100 genes in breast tumors or cell lines of breast cancer are reported hypermethylated. Important of DNA methylation on cancer has been concentrated CpG islands hypermethylation. Most of the techniques are able to identify hypermethylated areas. Often, methylated genes play important role in cell cycle regulation, apoptosis, metastasis and tissue invasion, angiogenesis and hormonal signaling. Cyclin D2 (CCND2) gene is an important regulator of cell cycle and increased of expression inhibits the transition from G1 to S cell cycle. This gene is frequently methylated in breast cancer and has been proposed as the first event. Other cell cycle regulator is p16ink4A / CDKN2A that methylated in a large number of human cancers, including breast cancer. Another regulator of the proliferation of breast cancer that methylated is tumor suppressor RAR-β cancer that has been found in lobular and ductal carcinoma. Recent studies have showed the role of epigenetic silencing in the pathogenesis of breast cancer in which tumor suppressor genes have been changed by acetylation and DNA deacetylation. Histone deacetylase inhibitors have different roles in cancer cells and could show the ways of new treatment for breast cancer. In this review, various aspects of breast cancer epigenetics and its applications in diagnosis, prediction and treatment are described.

Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU) if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years) were enrolled in this study. Convulsion was seen in 104 patients (69.3%). In 8 out of 104 patients (7.6%) two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3%) were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.

Lymphedema is sometimes accompanied by high degrees of anxiety and depression. This study aimed to assess the effects of relaxation techniques on the level of edema, anxiety and depression in women undergoing Comprehensive Decongestive Therapy (CDT).This clinical trial compared two treatment methods in 31 women with post-mastectomy lymphedema, including 15 cases who received CDT and 16 who received RCDT (Relaxation plus CDT). The edema volume, anxiety and depression scores were compared at the first and last sessions of the first phase of the treatment and six weeks afterwards.The edema, anxiety and depression scores were 63.6%, 54.1% and 65.5% in the RCDT group and 60.7%, 31.4% and 35.2% in the CDT group. There were significant differences between the two groups in terms of the reduction in depression (p = 0.024) and anxiety (p = 0.011) scores throughout the study. This significant relationship was due to the differences in the depression score in the 3rd and 9th weeks of the study between the two groups. Similarly, anxiety levels differed significantly between the two groups at the 9th week of the study (P = 0.013).Relaxation techniques reduced the anxiety and depression scores and the volume of edema in the patients with lymphedema. The addition of this intervention to the therapeutic package for lymphedema patients requires further studies in terms of cost-effectiveness.