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Biomedicines
The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly u... more The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Te...
Oral oncology, Dec 1, 2017
The purpose of this study was to determine association between cancer stem cells (CSCs) and their... more The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p < 0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of pati...
Environmental toxicology and pharmacology, Jan 29, 2015
Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual an... more Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual and interethnic differences in DNA repair capacity and drug disposition respectively. In the present study, we determined the allele and genotype frequencies of four single nucleotide polymorphisms (SNPs) located in the DNA repair genes, XRCC1, XRCC3, XPD, OGG1, namely XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, and OGG1 Ser326Cys, respectively and two SNPs located in the multidrug resistance gene, ABCB1, namely ABCB1 C3435T and ABCB1 C1236T, in 33-35 healthy and unrelated Sindhi individuals, residing in the Vidarbha region of Central India and compared them with the Maharashtrian population from the same geographical region and some other HapMap populations from the HapMap database. The study findings reveal that the Indian Sindhis are closely related to the Maharashtrians as well as Utah residents with Northern and Western European ancestry and Gujarati Indians in Houston, Texas in ...
Chemical Research in Toxicology, 2014
In the present study, we attempt to shed light on the underlying molecular mechanism of the antic... more In the present study, we attempt to shed light on the underlying molecular mechanism of the anticancer activity of pterostilbene (PTS) in HepG2 cells through the proteomic approach. PTS was found to induce apoptosis by altering the expression of apoptotic genes and the G2/M phase of cell cycle arrest. Further, the 2-DE map showed the expression of 72 differentially regulated proteins in PTS-treated HepG2 cells, of which 8 spots with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 fold up- or down-regulated level were identified by MALDI-TOF analysis, which has a regulatory role in apoptosis. These findings for the first time offer valuable insights into the mechanism of apoptotis by PTS in HepG2 cells.
Xenobiotica, 2014
1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P-gp) encoded by t... more 1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P-gp) encoded by the gene ABCB1 (also, known as Multidrug resistance gene, MDR1), plays a major role in drug disposition. Single nucleotide polymorphisms (SNPs) in the ABCB1 gene might contribute to inter-individual and ethnic differences in drug disposition and thereby, could influence the outcome and prognosis of certain diseases. 2. India is one of the most ethnically and genetically diverse regions of the world. This study was undertaken with a view to determine the allele and genotype frequencies of C3435T and C1236T polymorphisms in the ABCB1 gene among the Maharashtrian population, residing in the Vidarbha region of central India and compare them with HapMap and other Indian populations. The common synonymous C3435T polymorphism has been found to be associated with lower P-gp functional expression and drug uptake, alone or in conjunction with a few other linked SNPs like C1236T. 3. The genotypes of C3435T and C1236T SNPs were determined by PCR-RFLP in 222 healthy and unrelated Maharashtrian individuals. 4. According to the findings of this study, the Maharashtrians were found to be not significantly different from the Gujarati Indians in Houston, Texas in the HapMap database.
Environmental Science and Pollution Research, 2012
Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. Th... more Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.
Chemosphere, 2011
Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inheri... more Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.
Chemosphere, Feb 1, 2011
Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inheri... more Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.
Biomedicines
The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly u... more The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Te...
Oral oncology, Dec 1, 2017
The purpose of this study was to determine association between cancer stem cells (CSCs) and their... more The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p < 0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of pati...
Environmental toxicology and pharmacology, Jan 29, 2015
Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual an... more Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual and interethnic differences in DNA repair capacity and drug disposition respectively. In the present study, we determined the allele and genotype frequencies of four single nucleotide polymorphisms (SNPs) located in the DNA repair genes, XRCC1, XRCC3, XPD, OGG1, namely XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, and OGG1 Ser326Cys, respectively and two SNPs located in the multidrug resistance gene, ABCB1, namely ABCB1 C3435T and ABCB1 C1236T, in 33-35 healthy and unrelated Sindhi individuals, residing in the Vidarbha region of Central India and compared them with the Maharashtrian population from the same geographical region and some other HapMap populations from the HapMap database. The study findings reveal that the Indian Sindhis are closely related to the Maharashtrians as well as Utah residents with Northern and Western European ancestry and Gujarati Indians in Houston, Texas in ...
Chemical Research in Toxicology, 2014
In the present study, we attempt to shed light on the underlying molecular mechanism of the antic... more In the present study, we attempt to shed light on the underlying molecular mechanism of the anticancer activity of pterostilbene (PTS) in HepG2 cells through the proteomic approach. PTS was found to induce apoptosis by altering the expression of apoptotic genes and the G2/M phase of cell cycle arrest. Further, the 2-DE map showed the expression of 72 differentially regulated proteins in PTS-treated HepG2 cells, of which 8 spots with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 fold up- or down-regulated level were identified by MALDI-TOF analysis, which has a regulatory role in apoptosis. These findings for the first time offer valuable insights into the mechanism of apoptotis by PTS in HepG2 cells.
Xenobiotica, 2014
1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P-gp) encoded by t... more 1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P-gp) encoded by the gene ABCB1 (also, known as Multidrug resistance gene, MDR1), plays a major role in drug disposition. Single nucleotide polymorphisms (SNPs) in the ABCB1 gene might contribute to inter-individual and ethnic differences in drug disposition and thereby, could influence the outcome and prognosis of certain diseases. 2. India is one of the most ethnically and genetically diverse regions of the world. This study was undertaken with a view to determine the allele and genotype frequencies of C3435T and C1236T polymorphisms in the ABCB1 gene among the Maharashtrian population, residing in the Vidarbha region of central India and compare them with HapMap and other Indian populations. The common synonymous C3435T polymorphism has been found to be associated with lower P-gp functional expression and drug uptake, alone or in conjunction with a few other linked SNPs like C1236T. 3. The genotypes of C3435T and C1236T SNPs were determined by PCR-RFLP in 222 healthy and unrelated Maharashtrian individuals. 4. According to the findings of this study, the Maharashtrians were found to be not significantly different from the Gujarati Indians in Houston, Texas in the HapMap database.
Environmental Science and Pollution Research, 2012
Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. Th... more Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.
Chemosphere, 2011
Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inheri... more Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.
Chemosphere, Feb 1, 2011
Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inheri... more Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.