Do IL-4 Intron 3 VNTR and IL-6 (-174) G/C Variants Reflect Ethnic Variation? A Comparative Study Between the Global and North Indian Populations

Variations in the production and activity of cytokines have been reported by several investigators which influence the susceptibility and/or resistance to various infectious agents and cancer. Differences in the cytokine production between individuals are often caused by single nucleotide polymorphism (SNP) in the promoter or coding regions of cytokine genes. Although the SNP cytokine gene variations are basically mutations, they are designated as polymorphisms, because these changes do not modify the alleles to rare or abnormal variants. The two important cytokine genes IL-4 and IL-6 of 343 unrelated healthy individuals from North India were compared with the published polymorphism of other populations. It was seen that our population differs from South Indian population as well as from other Caucasian populations except, Taiwanese population at IL-4 locus and Spanish and Polish population at the IL-6 gene locus. This study may be helpful for predicting clinical outcome of various infectious and immunoregulated disorders as well as explore for risk alleles for various cancers.     

XRCC1 codon 399 mutant allele: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy

XRCC1 protein plays crucial role in base excision repair (BER)by acting as a scaffold for other BER enzymes. Variants in XRCC1 gene might alter protein structure/function or create alternatively spliced protein influencing BER efficiency and affect individual susceptibility/recurrence to urinary bladder cancer (BC). We tested whether polymorphisms in XRCC1 gene were associated with BC risk and further to substantiate risk of recurrence after Bacillus Calmette-Guerin (BCG) immunotherapy. Genotyping for three polymorphic sites of XRCC1 gene at codon Arg194Trp (PvuII), Arg280His (RsaI) and Arg399Gln (MspI) in 140 BC cases and 190 controls by PCR-RFLP method was done. We observed significant association in heterozygous genotype (GA) of codon 280 and 399 with BC risk (OR = 1.96, p = 0.021 and OR = 1.81, p = 0.021, respectively), however no association was seen for variant AA genotype. A trend of increased risk with high stage and grade in patients with codon 194 variant genotypes (CT + TT) was observed. Haplotype analysis showed that individuals with haplotype 194C-280G-399A were at >3-fold higher risk for BC (OR = 3.48, p = 0.01). The A/A genotype of codon 399 was associated with high risk for recurrence in BCG treated patients (HR = 5.05, p = 0.01) thus, showing reduced recurrence free survival (AA/GG = 12/60 months; log rank p = 0.004). The study suggested no association of variant genotypes with the susceptibility to BC. Haplotype analysis however, revealed that XRCC1 399 A allele may have a major role as patients with haplotype 194C-280G-399A carrying variant allele of 399 were at higher risk.     

Existing antiviral vaccines

The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever.     

Varicella zoster vaccines

In the past, the varicella zoster virus affected virtually the entire population and had substantial morbidity and mortality associated with both primary varicella and herpes zoster reactivation. Since the varicella vaccine was first approved in 1995, there has been a significant decline in incidence, morbidity, and mortality caused by primary varicella. Breakthrough disease with the one-dose vaccine schedule led to the recommendation in 2006 that children receive a two-dose vaccine series. Older adults have also benefited from the development of the zoster vaccine. In 2006, the Food and Drug Administration approved the zoster vaccine, a higher concentration of the same live attenuated virus used in the primary varicella vaccine, for persons 60 years of age or older. It has the potential to help millions of people avoid the pain associated with reactivation of the varicella zoster virus by reducing the incidence and severity of herpes zoster and postherpetic neuralgia.     

HIV vaccines under study

Human immunodeficiency virus (HIV) infection is a worldwide epidemic, with over 42 million people currently infected. Since the discovery of HIV as the causative agent of the acquired immune deficiency syndrome (AIDS), many potential vaccines have been created. The first of these vaccines presented disappointing results; however, that has not deterred researchers from continuing to develop more potential HIV vaccines. This article will review the various current HIV vaccine candidates under study.     

BCG response prediction with cytokine gene variants and bladder cancer: where we are?

Purpose  

Bladder cancer (BC) is one of the most widespread cancers afflicting men and women and also has major philosophical impact on health care worldwide. Despite elaborate characterization of the risk factors and treatment options, BC is still a major epidemiological problem worldwide and its incidence lingers to upswing each year. Over the last three decades, intravesical immunotherapy with the biological response modifier Mycobacterium bovis–Bacillus Calmette Guerin (BCG) has been established as the most effective adjuvant treatment for averting local recurrences and tumor progression following transurethral resection of non-muscle-invasive bladder cancer.     

Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis

Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ‐H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD‐45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 284–297, 2014.