Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer.

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.

Contribution of TGFß1 codon 10 polymorphism to high myopia in an ethnic Kashmiri population from India.

This study looks at novel variants of the TGFß1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176 ethnically matched healthy controls were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using chi-square or Fisher's exact tests. One of the three SNPs in codon 10 showed a significant difference between patients and control subjects (rs1982073: p genotype = 0.003, p allele = 0.001). There were no statistically significant differences between patients and control subjects for the other two SNPs, rs1800471 at codon 25 and a novel variant at codon 52. SNP rs1982073, substituting proline with leucine, appeared to be significantly associated with high myopia (p < 0.05). In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia.

MYP2 locus genes: Sequence variations, genetic association studies and haplotypic association in patients with High Myopia.

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.

A novel G26A variation in 5' half of TGIF1 gene associates with high myopia in ethnic Kashmiri population from India.

This study aims to look at novel variations in TGIF1 gene and explores their potential association with high myopia in an ethnic population from Kashmir (India). Genomic DNA was genotyped for polymorphic variations, and allele frequencies were tested for the Hardy-Weinberg disequilibrium in 240 ethnic Kashmiri cases with high myopia with a spherical equivalent of >-6 diopters (D) and compared with emmetropic controls with spherical equivalent within -0.5D in one or both eyes represented by a sample size of 228. In this study, we found a novel sequence variation G26A (GAT to AAT) in 5' half of TGIF1 gene (p. aspartic acid >asparagine) at a frequency of 62% (148/240, P ≤ 0.0001). Variation appears to associate with high myopia significantly (P ≤ 0.001) as it happens to be present only in high myopia affected individuals. Further, it shows statistical significance for its association with gender and the degree of myopia (P ≤ 0.05). In addition, in silico predictions show that variation likely has an impact on the structure and functional properties of the protein. The assessment of the I-TASSER protein structure showed higher energy for a wild-type protein (-5820.186 kJ/mol) as compared to mutant protein (-6595.593 kJ/mol).

Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

BACKGROUND: The role of common variants in leptin promoter has already been established to play a major role in obesity and diabetes in humans. The study was accordingly focused on leptin promoter variants and their potential association with diabetes and obesity in ethnic population from Kashmir, India. METHODS: Allele frequencies of 620 Kashmiri subjects with diabetes (200), obese subjects (200), and ethnically matched healthy controls (200) were tested for the Hardy-Weinberg disequilibrium. Among 200 obese subjects, a total of 50 persons were with diabetes. The genotype and allele frequencies were evaluated using the Chi-square or Fisher's exact tests. RESULTS: Sequence analysis revealed two reported variations i.e., rs72563764C>T and rs7799039G>A in promoter region. Both variants show homozygous as well as heterozygous genotypes. These variations indicated significant difference with respect to allelic and genotypic frequencies in all groups i.e., persons with diabetes, obese, and obese persons with diabetes (P < 0.05). We also analyzed the association of these variations with biochemical characteristics and found significant association of rs72563764C>T with triglycerides (TG) in obese patients and fasting plasma glucose (FPG) and random blood sugar (RBS) in obese/persons with diabetes. Also rs7799039G>A showed association with postprandial plasma sugar (PPPS) in obese patients and FPG and resting plasma glucose (RPG) in obese persons with diabetes. CONCLUSIONS: Our results are suggestive of the association of leptin promoter gene variations i.e., rs72563764C>T and rs7799039G>A with both diabetes and obesity.

Mutational analysis of the BRCA2 gene in breast carcinoma patients of Kashmiri descent.

Breast cancer demonstrates geographical and ethnic variation in its incidence reflecting the effect of local environmental conditions and lifestyle. The genesis of the disease has further been complexed by the involvement of a number of genes with small effects and above all by population heterogeneity. Accordingly, variations in genes, including breast cancer 1, early onset (BRCA1)/breast cancer 2, early onset (BRCA2), that have been markedly associated with the breast cancer phenotype exhibit a scattered mutational pattern in different populations. The present study was aimed to analyze the sequence variations in BRCA2 gene in a case control manner in ethnically pure Kashmiri population using PCR. Sequencing of BRCA2 exons revealed the presence of five sequence variations, four of which present in exon 11 alone were somatic and one was germline located in the U-terminal region (UTR) of exon 2. Out of these, the two somatic mutations comprised of substitutions, one representing a missense mutation leading to an amino-acid substitution at codon 991 and the other was a silent mutation at codon 1131, whereas the other two mutations located in exon 11 represented a loss of polymorphism. Codons for amino acid position 846 and 868 were demonstrated to be heterozygous polymorphic variants in 66% of the normal breast tissue samples, whereas the heterozygous polymorphic variant codons at the two loci were replaced by a homozygous genotype in associated tumor tissue in 88% of cases. These two mutations were always linked. Germline variation observed in exon 2 was located in the UTR region at contig position 13870572 (rs1799943). Other screened exons of BRCA2 did not demonstrate any sequence variation. These variations may contribute to breast cancer susceptibility along with variations in other low penetrating genes in sporadic types of breast cancer in this cohort of the population.

TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population.

PURPOSE: High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth ß-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. METHODS: Cases with high myopia with a spherical equivalent of ≥-6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using χ(2) or Fisher's exact test. RESULTS: Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p < 0.05) association with the disease phenotype. Since the variant allele frequency of both the single-nucleotide polymorphisms in cases is higher than controls with odds ratio greater than 1.Therefore, variant allele of both the single-nucleotide polymorphisms represents the possible risk factor for myopia in the Kashmiri population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. CONCLUSIONS: TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.

Epidemiological distribution and incidence of different cancers in Kashmir valley--2002-2006.

There are no population-based data available on cancer pattern in Kashmir and our study is the first kind which represents the trend in cancer pattern in the valley. The source of our data were cancer patients registered in the Department of Radiation Oncology, Sheri-Kashmir Institute of Medical Sciences, Srinagar, and Department of Radiation Oncology, SMHS, Srinagar during the period Jan 2002 to Dec 2006. These are leading medical centres in the valley and draw most all of cancer patients from all over Kashmir for treatment. During the period a total of 6,943 cases were registered of which 4,345 were males and 2,598 were females. The age standardized incidence rates were 34.9 per 100,000 for males and 24.8 per 100,000 for females. Oesophagus was the leading site of cancer in both sexes (male ASR 11.2; female ASR 8.3) followed by lung (ASR 6.5), brain (ASR 2.2) and head and neck (ASR 2.2) in males and breast (ASR 5.2), skin (ASR 1.6) and rectum (ASR 0.95) in females. The incidence of cervical cancer in females and prostate cancer in males was lower in Kashmir as compared to other Indian registries. Overall cancer incidence was significantly lower and cancer patterns were markedly different in Kashmir. The observed cancer pattern indicates that awareness campaigns, life style and dietary habit changes, tobacco-control measures and early detection of breast cancer are very important for cancer control in this population.