Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer, and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69-1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

A Study of Matrix Metalloproteinase-2 and Interleukin-18 in Preinvasive and Invasive Lesions of Cancer Cervix.

INTRODUCTION: Human Papilloma-Virus infection is the major event for cervical carcinogenesis, whereas host physiological changes may confer individual susceptibility and prognosis. So here, we aimed to compare serum levels of matrix metalloproteinase-2 (MMP-2) and interleukin-18 (IL-18) between cervical cancer patients and healthy controls. MATERIALS AND METHODS: In the present study, we enrolled 168 subjects (10 CIN I, 10 CIN II, 10 CIN III, and 54 invasive cervical cancers with 84 age-matched healthy controls). Serum levels were estimated by enzyme-linked immunosorbent assay. RESULTS AND DISCUSSION: The levels of serum MMP-2 showed a characteristic pattern of increasing trend with statistically significant P value on comparing pre-invasive lesions and cervical cancer versus healthy controls. However, IL-18 levels showed a decreasing trend in serum levels of controls versus cases with a statistically significant P value (P < 0.05). CONCLUSION: MMP-2 accentuates tissue damage and controls many interleukins secretion, which leads invasion and malignancy. Increased levels of MMP-2 and decreased circulating levels of IL-18 were found in cases. Hence, we raise an issue to study MMP-2 and IL-18 further for their diagnostic and prognostic marker role.

Assessment of drug prescribing pattern using world health organization indicators in a tertiary care teaching hospital.

This cross-sectional study was carried out to assess drug prescribing pattern at a tertiary care teaching medical institute. One thousand prescriptions were randomly collected and analyzed using the world health organization prescribing indicators. The average number of drugs per prescription was 2.91. The percentage of drugs prescribed by generic name, from the essential drug list (National) and as fixed dose combinations (FDCs) was 10.05%, 22.57%, and 49.22%, respectively. The total percentage of encounters with antibiotics, injectables, and FDCs was 19.70%, 2.20%, and 73.60%, respectively. The most common group of drug prescribed was gastrointestinal tract drugs (26.38%) followed by Vitamins and Minerals (23.12%), cardiovascular system drugs (11.56%) and antimicrobials (9.63%). The prescribing practices were not appropriate as they consist of polypharmacy, lesser prescription by generic name, and overprescription of FDCs. There is a need for improvement in the standards of prescribing patterns in many aspects.

Levels of IL-8 and TNF-α decrease in Parkinson's disease.

BACKGROUND: Peripheral immune system abnormalities are associated with Parkinson's disease, but role of inflammatory factors in Parkinson's disease has not been consistently proven yet. Thus, population-based studies are needed in the addition of peripheral dysfunction knowledge associated with Parkinson's disease. IL-8 and TNF-α are inflammatory factors that might be involved in PD. The aim of the present study was to evaluate the levels of IL-8 and TNF-α in Parkinson's disease patients from India. METHODS: Serum samples were collected from Parkinson's disease patients (n = 81) and their respective controls (n = 83). The levels of IL-8 and TNF-α were determined using Enzyme-linked immunosorbent assay. RESULTS: The levels of IL-8 (patients = 222.70 ± 200.91 pg/ml, controls = 1584.44 ± 504.44 pg/ml; p < 0.001) and TNF-α (patients = 45.67 ± 24.69 pg/ml, controls = 638.25 ± 511.02 pg/ml; p < 0.001) were lower in the serum of Parkinson's disease patients than controls and the differences were statistically significant. Their levels were also significantly lower in both male and female patients as compared with their respective controls (p < 0.001). IL-8 was significantly lower in the female controls when compared with the male controls (p < 0.001). Their levels were not influenced by disease severity. Significant weak correlation was found between disease duration and the level of IL-8, but not with age at onset among patients. However, the level of TNF-α did not show correlation with disease duration and age at onset among patients. CONCLUSION: The levels of IL-8 and TNF-α were significantly lower in serum of Parkinson's disease patients, which suggested that inflammatory factors might exert their effect and more specifically, inflammation might play crucial role in Parkinson's disease.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

BACKGROUND: Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. MATERIALS AND METHODS: This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. RESULTS: The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. CONCLUSIONS: Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD.

Functional genetic variability at promoters of pro-(IL-18) and anti-(IL-10) inflammatory affects their mRNA expression and survival in prostate carcinoma patients: Five year follow-up study.

BACKGROUND: Inflammation is an important hallmark of all cancers. The net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which, in turn, is determined by the genetic make-up. The present study investigates the role of variations in the promoter regions of IL-18 and IL-10 (anti-inflammatory) cytokines on mRNA expressions and survival in prostate cancer (PCa) patients. METHODS: The study was conducted on 584 volunteer males (291 patients of PCa, between 40-80 years of age. Genetic variants were studied by using RFLP and confirmed by probe based method. Expressions of mRNA were evaluated by real-time PCR (Roche light cycler 480). Relative mRNA and fold change gene expressions were analyzed by ([1/2] (ΔCt) ) and (2(-ΔΔCt) ) methods, respectively, and 5 year follow-ups were evaluated by Log-rank (Mantel-Cox) test with Log-rank test for trends. RESULTS: IL-18 mRNA expression was significantly elevated in GG genotypes (at -137) of PCa with relative mRNA expression of 13.95, that is, 8.48 folds higher (P < 0.05) than controls; and showed a significant median survival of 1243 days. The CC genotypes of IL-10 at both loci (-819 T/C and -592C/A) showed 3.63 and 3.52 higher relative mRNA expressions than controls, but poor survival of 984 and 1052 days than TT of 1359 days and AA of 1371 days. CONCLUSIONS: Genetic variants of pro-inflammatory IL-18 which showed higher relative mRNA expressions have better survival. Genetic variants of anti-inflammatory IL-10 with higher relative mRNA expression showed decreased chances of survival.

Pro-(IL-18) and Anti-(IL-10) Inflammatory Promoter Genetic Variants (Intrinsic Factors) with Tobacco Exposure (Extrinsic Factors) May Influence Susceptibility and Severity of Prostate Carcinoma: A Prospective Study.

BACKGROUND: It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape. MATERIALS AND METHODS: The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods. RESULTS: The findings indicated that the mutant heterozygous and homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI: 0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as -819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants. CONCLUSIONS: We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

Genetic variability at promoters of IL-18 (pro-) and IL-10 (anti-) inflammatory gene affects susceptibility and their circulating serum levels: An explorative study of prostate cancer patients in North Indian populations.

Inflammation is an important hallmark of all types of cancers with a well-established role in carcinogenesis. The net inflammatory response is determined by the balance between pro- and anti-inflammatory cytokines, the levels of which may be affected by the genetic make-up. Interleukin (IL)-18, a pro-inflammatory cytokine expressed by various cells including those of the prostate, is a key mediator of anti-cancer immune response. IL-10, an anti-inflammatory cytokine associated with tumour malignancy, causes escape from immune surveillance. This study hypothesizes that genetic variants of IL-18 (-607 C/A and -137 G/T) and IL-10 (-819 C/T and -592 C/A) may influence the circulating levels of these interleukins, thereby generating susceptibility risk to prostate cancer. The study was conducted on 676 subjects (controls and patients of prostate cancer (PCa): 291 each; and 94 patients with benign prostate hypertrophy (BPH)). Genotyping was performed by PCR-RFLP and Real-Time PCR probe-based method. Circulating interleukin levels were obtained by ELISA. Circulating IL-18 levels were significantly elevated in cancer and BPH patients carrying GG genotypes for -137 of IL-18. The trend of circulating IL-18 levels was GG>GC>CC, observed in all groups. The -137 genetic variants of IL-18 significantly associated with PCa risk were GC, CC, and GC+CC, compared to GG (OR: 1.71, 95% CI: 1.20-2.46; OR: 3.35, 95% CI: 2.03-5.53; and OR: 2.05, 95% CI: 1.46-2.87, respectively). A significant association of AA and CA+AA against CC genotype was observed at -607 locus of IL-18 (OR: 0.46, 95%CI: 0.29-0.72; OR: 0.61, 95% CI: 0.41-0.90, respectively). Significantly elevated levels of IL-10 were observed with TT (wild) genotype at -819 of IL-10, compared to the CC (homozygous mutant) genotype in all three groups of subjects. However, no significant association was found between IL-10 promoter genotypes and PCa risk. We conclude that genetic variants of IL-18 and IL-10 promoters influence the circulating levels of these interleukins. Variations at -137 and -607 loci of IL-18 are associated with susceptibility to PCa.

Tobacco exposure by various modes may alter proinflammatory (IL-12) and anti-inflammatory (IL-10) levels and affects the survival of prostate carcinoma patients: an explorative study in North Indian population.

OBJECTIVE: Inflammation is an important hallmark of all cancers and net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which may be affected by tobacco exposure, so the present study was designed to explore the effect of various modes of tobacco exposure on interleukin-12 (IL-12) and interleukin-10 (IL-10) inflammatory cytokine levels and survival in prostate carcinoma (PCa) patients. METHODS: 285 cancer patients and equal controls with 94 BPH (benign prostatic hyperplasia) were recruited; baseline levels of serum IL-12 and IL-10 were measured and analyzed in various tobacco exposed groups by appropriate statistical tool. Five-year survivals of patients were analyzed by Log-rank (Mantel-Cox) test (graph pad version 5). RESULTS: The expression of serum proinflammatory (IL-12) and anti-inflammatory (IL-10) cytokines was correlated with tobacco exposed group as smokers, chewers, and alcohol users have shown significantly higher levels (P < 0.001) with significantly lower median survivals (27.1 months, standard error = 2.86, and 95% CI: 21.4-32.62); than nonusers. Stages III and IV of tobacco addicted patients have also shown significantly increased levels of IL-12 and IL-10. CONCLUSIONS: IL-12 and IL-10 seem to be affected by various modes of tobacco exposure and inflammation also affects median survival of cancer patients.

A study on risk factors for Parkinson׳s disease in Indian population.

Parkinson׳s disease is the second most common neurodegenerative disorder. The exact cause of selective dopaminergic neurodegeneration is unknown, but it is supposed that etiology of Parkinson׳s disease is multifactorial and consists of an interaction between environmental factors and genetic predisposition. To find out the association between environmental factors and risk of Parkinson׳s disease, a case control study was designed including 97 Parkinson׳s disease patients and 97 controls. Logistic regression analysis was used to determine the risk factors for Parkinson׳s disease. Results from the present study showed that gender, religion, education, place of living, occupation, dietary habits, tobacco chewing, smoking, alcohol intake, and head injury had no association with PD. However, chemical exposure and well water drinking were significantly associated with PD, which concluded that environmental factors could act as a risk factor for PD in some way.

Significance of impaired serum gelatinases activities in metabolic syndrome.

INTRODUCTION: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. MATERIALS AND METHODS: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control. RESULTS: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. CONCLUSIONS: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice.

BACKGROUND: Arsenic is widely distributed in the environment and has been found to be associated with the various health related problems including skin lesions, cancer, cardiovascular and immunological disorders. The fruit extract of Emblica officinalis (amla) has been shown to have anti-oxidative and immunomodulatory properties. In view of increasing health risk of arsenic, the present study has been carried out to investigate the protective effect of amla against arsenic induced oxidative stress and apoptosis in thymocytes of mice. METHODS: Mice were exposed to arsenic (sodium arsenite 3 mg/kg body weight p.o.) or amla (500 mg/kg body weight p.o.) or simultaneously with arsenic and amla for 28 days. The antioxidant enzyme assays were carried out using spectrophotometer and generation of ROS, apoptotic parameters, change in cell cycle were carried out using flow cytometer following the standard protocols. RESULTS: Arsenic exposure to mice caused a significant increase in the lipid peroxidation, ROS production and decreased cell viability, levels of reduced glutathione, the activity of superoxide dismutase, catalase, cytochrome c oxidase and mitochondrial membrane potential in the thymus as compared to controls. Increased activity of caspase-3 linked with apoptosis assessed by the cell cycle analysis and annexin V/PI binding was also observed in mice exposed to arsenic as compared to controls. Co-treatment with arsenic and amla decreased the levels of lipid peroxidation, ROS production, activity of caspase-3, apoptosis and increased cell viability, levels of antioxidant enzymes, cytochrome c oxidase and mitochondrial membrane potential as compared to mice treated with arsenic alone. CONCLUSIONS: The results of the present study exhibits that arsenic induced oxidative stress and apoptosis significantly protected by co-treatment with amla that could be due to its strong antioxidant potential.

Vascular endothelial growth factor 936 c>T polymorphism increased oral cancer risk: evidence from a meta-analysis.

AIM: The vascular endothelial growth factor (VEGF) plays a major role in angiogenesis. The association between VEGF 936 C>T (rs3025039) gene polymorphisms and oral cancer (OC) risk is still contentious and ambiguous. To assess the relationship between the VEGF 936 C>T genotype and the risk of developing OC, we performed a meta-analysis to summarize the possible association. METHODOLOGY: We assessed published studies of the association between 936 C>T polymorphisms and OC risk from four studies with 440 controls and 556 OC cases. We calculated pooled odds ratios (ORs) and 95% confidence interval (CI), considering the frequency of allele, homozygous, heterozygous genotypes and comparison of dominant and recessive genetic models. RESULTS: The combined results showed that the T allele was significantly associated with increased OC risk (T vs. C: p=0.001; OR=1.521, 95% CI=1.194-1.938). The heterozygous genotype CT had a 1.5-fold increased risk (CT vs. CC: p=0.002; OR=1.582, 95% CI=1.184-2.114). In addition the dominant genetic model demonstrated a 1.6-fold increased risk of developing OC (TT+CT vs. CC: p=0.001; OR=1.621, 95% CI=1.226-2.143). CONCLUSION: Our results suggest that the VEGF gene polymorphism (936 C>T) contributes increased susceptibility to OC. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.

Computational analysis of the 3-D structure of human GPR87 protein: implications for structure-based drug design.

The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR which means that the search of their endogenous ligands has been a novel challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was here modeled using two templates (2VT4 and 2ZIY) by a threading method. Functional assignment of GPR87 by SVM revealed that along with transporter activity, various novel functions were predicted. The 3D structure was further validated by comparison with structural features of the templates through Verify-3D, ProSA and ERRAT for determining correct stereochemical parameters. The resulting model was evaluated by Ramachandran plot and good 3D structure compatibility was evidenced by DOPE score. Molecular dynamics simulation and solvation of protein were studied through explicit spherical boundaries with a harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was found at the end of transmembrane helix3, where GPCR binds and thus activation of signals is transduced. In a search for better inhibitors of GPR87, in silico modification of some substrate ligands was carried out to form polar interactions with Arg115 and Lys296. Thus, this study provides early insights into the structure of a major drug target for SCCs.

Tobacco exposure may enhance inflammation in prostate carcinoma patients: an explorative study in north Indian population.

Prostate cancer is responsible for major deaths globally after lung cancer. However, etiology of prostate cancer is still unknown. Individual risk and incidence of prostate cancer may result from the interaction of genetic susceptibility with exposure to environmental factors such as infectious agents, tobacco, occupational exposure, dietary carcinogens, and/or hormonal imbalances leading to injury of the prostate and to the development of chronic inflammation. About 30% of all human cancers are caused by tobacco smoking and inhaled pollutants. Inflammation is now regarded as an important hallmark of cancer. The present study has been aimed to explore the pro-inflammatory levels in prostate carcinoma patients by examining the serum levels of novel cytokine interleukin-18 (IL-18) expression in tobacco exposed population. A total of 578 (n = 284 biopsy proven prostate cancer patients, n = 294 controls with and without tobacco exposed population) were recruited. Serum IL-18 (Interleukin-18) level was done by ELISA. The IL-18 levels between cancer patients and controls within same mode tobacco exposure as tobacco smoking (overall) showed significant difference (P < 0.0001) and further we compared within stratified group, it significantly differ (P < 0.0001) in bidi and cigarette smoking than control non users. Furthermore, IL-18 levels in tobacco chewers (overall) with gutkha and khaini chewers showed significant difference (P < 0.01) than controls non users. Moreover, the IL-18 levels between cancer patients and controls with in of combined mode chewers smokers and alcohol (CSA), smokers with alcohol showed significant difference (P < 0.01) than controls. The IL-18 levels also differed significantly (P < 0.05) with smokers and chewers in higher stages of III and IV, and showed non significant with in lower stages. Tobacco exposure enhance the inflammation in prostate carcinoma patients in stratified group as it have been represented as a risk factors in various cancers, but this study provide further its role that seems to influence inflammation especially in prostate carcinoma.

Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: a prospective study.

BACKGROUND: Prostate cancer is one of the most common cancers afflicting men today. Prostate biopsy, an invasive procedure is generally used for diagnoses but attempts are being made to find accurate and precise non-invasive biomarkers. Diagnostic accuracy of prostate specific antigen (PSA) has been well documented. Serum interleukin-18 (IL-18) and interleukin-10 (IL-10) have shown their diagnostic ability in other cancers but not investigated well in prostate cancer. This study, thus determines the diagnostic and prognostic significance of PSA, IL-18 and IL-10 prospectively in patients with carcinoma prostate. METHODS: A total of 149 patients, aged 40-84 yrs were investigated during April 2007 to July 2010 and recruited for this study after Institutional ethical approval. Of the total of 149 patients, 71 had biopsy proven prostate cancers (TNM stage: T2=17, T3=26 and T4=28) and 78 clinical benign prostate hyperplasia (BPH). Peripheral blood samples of all patients and 71 age matched control subjects were obtained at baseline and estimation of PSA, IL-18 and IL-10 was done by enzyme linked immunosorbent assay (ELISA). Carcinoma prostate patients were followed for three years. Data were analyzed with ANOVA, ROC curve analysis and survival analysis. RESULTS: The baseline levels of PSA, IL-18 and IL-10 in all groups of carcinoma prostate were found to be significantly (p<0.01) higher than both Control and BPH. The levels of IL-18 and IL-10 also found to be elevated significantly in stage T3 (p<0.05) and T4 (p<0.01) as compared to stage T2. The levels especially of IL-18 is found to be well associated with progression of the disease of various groups (r=0.84, p<0.01). In contrast, IL-10 showed significant direct association with progression of carcinoma (r=0.84, p<0.01) while inverse relation with survival duration (r=-0.48, p<0.01) and survival rate (χ2=8.98, p=0.0027; Hazard ratio=0.37, 95% CI=0.18-0.69). CONCLUSIONS: Study concluded that serum IL-18 has potential to be a better diagnostic marker with higher specificity and sensitivity and IL-10 may be valuable as a prognostic marker than PSA in carcinoma prostate.