Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties.

Temozolomide is an alkylating agent which is used in glioblastoma treatment. We aimed to investigate the effects of different concentrations of temozolomide and exposure time on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9 and VEGF. U87MG cells were cultured in different temozolomide concentrations and incubation time and the effects of temozolomide on inducing apoptosis was investigated. The levels of VEGF and CXCR4 expression were measured by RT-PCR and flowcytometry. Moreover, MMP2 and MMP9 activity and expression were assessed by ELISA and zymography. CXCR4 and VEGF expression levels decreased upon applying higher concentration of temozolomide. MMP2 and MMP-9 had lower activity in cells with longer exposure time or higher doses of temozolomide. Temozolomide induces the apoptosis in U87MG glioblastoma cells at therapeutic or higher dose. It is capable of decreasing their expression levels of VEGF and CXCR4.

Association of AHSG gene polymorphisms with serum Fetuin-A levels in individuals with cardiovascular calcification in west of Iran.

Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.

Association of Angiotensin-converting Enzyme Gene Polymorphism with Susceptibility to Asthma Disease in Western Iran.

Asthma is a complex disease caused by a combination of multiple genetic and environmental factors. Angiotensin-converting enzyme (ACE) is involved in the pathogenesis of asthma by inactivating bradykinin, substance P, and neurokinin A. It has been shown that the level of ACE variation in serum is associated with an insertion-deletion (I/D) polymorphism. So, this study aimed to investigate the association of these polymorphisms with asthma in western Iran. In this case-control study, 111 asthmatic patients as a case group and 80 healthy subjects as a control group were evaluated. The ACE gene polymorphism was determined by the PCR method. The relationship between genotypes done by the χ2 test and the relative risk of disease with genetic polymorphism (Odds Ratio) was performed using logistic regression. The frequency of I/D genotypes (included in II, ID, and DD) between patient and control groups had no significant difference. In addition, none of the genotypes in the patient and control groups show any significant differences between men and women. However, the frequency of ID and DD genotypes was considerably different between the male patient groups (over and under 40 years old). Hence, these genotypes are suggested to be a risk factor for asthma. The results of our study indicate that ACE gene polymorphism is not significantly associated with asthma in the west of Iran.

Erratum to epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world.

[This corrects the article DOI: 10.21037/jtd.2016.03.91.].

A Practical Non-Extraction Direct Liquid Chromatography Method for Determination of Thiopurine S-Methyltransferase Activity in Inflammatory Bowel Disease.

Thiopurine drugs remain pivotal therapies for the wide varieties of diseases such as inflammatory bowel disease (IBD). Here, thiopurine S-methyltransferase (TPMT) phenotype, the main metabolizing enzyme of thiopurine-drugs, was studied. This is for the first time that TPMT activity is measured in Iranian IBD patients. We used an improved direct liquid chromatography assay without need for solvent extraction and minimize excess labor handling making it ideal for use in routine referral medical centers. TPMT activity in whole blood was determined by a non-extraction HPLC method. We evaluated 427 individuals including 215 IBD patients and 212 unrelated healthy individuals as control group from Iran's western population. TPMT phenotyping of this study demonstrated no frequency for deficient, 2.8 % for low and 97.2% for normal activity, which is different with results of other studies. There was a significant negative correlation between TPMT activities as calculated based on nmol/grHb/h and the Hb-levels in IBD and control groups (r= -0.54, P<0.001 and r= -0.27, P<0.001), respectively. Interestingly a significant positive correlation between Hb levels and TPMT-activities were seen when the activity calculated in mU/L in IBD patients and control subjects (r=0.14, P=0.05 and r=0.43, P<0.001), respectively. We strongly suggest the use of international unit (mU/L) is more appropriate than nmol6MTG/grHb/h for expressing TPMT-activity in IBD patients. In addition, in comparison with other providers of TPMT test activity and centers around the world the risk of toxicity is much lower after utilizing thiopurine drugs for IBD patients in this region.

Silymarin (Livergol®) Decreases Disease Activity Score in Patients with Rheumatoid Arthritis: A Non-randomized Single-arm Clinical Trial.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which can lead to joint destruction and disability. Pannus formation due to chronic synovitis is the hallmark of RA. Oxidative stress as a consequence of immune cell activation and disease-modifying anti-rheumatic drugs can prevent inflammation and tissue destruction. Silymarin, an antioxidant extract from Silybum marianum, has been traditionally used for the treatment of liver diseases for decades. In the present non-randomized single-arm clinical trial (NRSACT) study we evaluated the effects of silymarin tablet (Livergol®) on inflammatory markers in stable RA patients. Disease activity score (DAS-28) was measured before and after adding silymarin to standard drug regimen used for controlling inflammation in RA patients. Silymarin significantly reduced the DAS28 related symptoms in 44 RA patients after 90 days (3.02±0.98 versus 2.3±0.74, p<0.001). The exact mechanism of therapeutic effects of silymarin in RA patients is not clear but it could be as the results of its anti-inflammatory and anti-oxidative properties. Conducting the study on larger number of patients and also measuring cytokines levels including TNF-α and IL-1ß may clarify the underlying mechanisms of the anti-inflammatory effects of silymarin in RA patients.

Study of Serum Malondialdehyde Level in Opioid and Methamphetamine Dependent Patients.

Opioid compound and methamphetamine are commonly used in drug abuse; these can disrupt the normal function of cellular and molecular systems, leading to several events such as oxidative stress, aging, apoptosis, and necrosis. Malondialdehyde (MDA) is the most important biomarker for evaluation of oxidative stress and determination of lipid peroxidation. In this study, 42 drug abusers and 22 healthy persons participated as case and control groups, respectively. MDA in volunteer sera was determined by high-performance liquid chromatography (HPLC) with fluorescence detection after pre-column derivatization using thiobarbituric acid. The analysis was performed on a ODS column by spectrofluorometer detection, operated at excitation of 515 nm and emission of 535 nm. A mixture of phosphate buffer (0.05 M, pH 6.8), containing potassium monobasic phosphate and methanol (60:40, v/v) at a flow rate of 1 ml/min, was used as the mobile phase. The retention time of MDA-TBA was 3.2 min. Our findings showed that the MDA level increased in the opioid and methamphetamine abusers when compared to the control group (P<0.05); however, no significant difference was observed between the opioid and methamphetamine groups. A state of oxidative stress during biological processes leads to lipid peroxidation, DNA damage, biomolecule dysfunctions, and many other diseases. Since it is impossible to eradicate the drug addiction, we should reduce the side effects of drug abuse, such as oxidative stress, by intake of proper nutrition and antioxidants.

Incidence and Mortality of Nasopharynx Cancer and Its Relationship With Human Development Index in the World in 2012.

BACKGROUND: One of the most common cancers in head and neck is nasopharynx. Knowledge about the incidence and mortality of this disease and its distribution in terms of geographical areas is necessary for further study, better planning and prevention. Therefore, this study aimed to determine the incidence and mortality of nasopharynx cancer and its relationship with human development index (HDI) in the world in 2012. METHODS: This study was an ecological study conducted based on GLOBOCAN project of World Health Organization (WHO) for the countries in world. The correlation between standardized incidence rates (SIRs) and standardized mortality rates (SMRs) of nasopharynx cancer with HDI and its components was assessed with correlation coefficient by using SPSS 15. RESULTS: In 2012, 86,691 nasopharynx cancer cases occurred in the world, so that 60,896 new cases were seen in men and 25,795 new cases in women (sex ratio = 2.36). SIR of the cancer was 1.2 per 100,000 (1.7 in men and 0.7 in women per 100,000) in the world. In 2012, 50,831 nasopharynx death cases occurred in the world, so that 35,756 death cases were seen in men and 15,075 death cases in women (sex ratio = 2.37). SIR of mortality from the cancer was 0.7 per 100,000 (0.7 in women and 1 in men per 100,000) in the world. The results of correlation analysis showed a negative correlation between the SIR and HDI (r = -0.037, P = 0.629), and also the results of correlation analysis showed a negative correlation between the SMR and HDI (r = -0.237, P = 0.002). CONCLUSION: Nasopharyngeal cancer is native to Southeast Asia and the highest incidence and mortality were seen in countries with moderate and low HDI. It is suggested that studies are conducted on determining the causes of the cancer incidence and mortality in the world and the differences between various regions.

Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world.

BACKGROUND: The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. METHODS: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. RESULTS: Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. CONCLUSIONS: The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI.

Primary pulmonary lymphoma and cutaneous metastasis: a case report.

Diffuse large B cell lymphoma is the most common type of non-Hodgkin's lymphoma, representing nearly one-third of all cases. Any organ can be involved, making a diagnostic biopsy imperative. When the lungs are the involved organs, it is called primary pulmonary lymphoma (PPL). Hereby, we present a case of PPL that demonstrated a single large mass on chest CT and had metastatic skin lesions. The diagnosis of PPL was performed by histopathology and immunohistochemistry staining of the transthoracic lung biopsy and skin lesion specimens. This case highlighted an unusual and subtle clinical presentation, and the importance of new onset pulmonary symptoms and a large lung mass on chest X-ray. Review of the literature on the patient`s radiographic presentation revealed various findings, the most common of which were single or multiple nodular lesions in one or two lungs. It highlighted the fact that this diagnosis should be considered in all cases with a lung mass and skin lesions.