Showing papers by "Alok C. Bharti published in 2010"
TL;DR: Investigation of expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis demonstrates that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV 16-mediated cervical carcinogens.
Abstract: Background
Recent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer and cancer tissues were analyzed for the HPV positivity and evaluated for STAT3 expression and its phosphorylation by immunoblotting and immunohistochemistry whereas STAT3-specific DNA binding activity was examined by gel-shift assays.
92 citations
TL;DR: The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions and the development of their potential diagnostic and therapeutic possibilities.
Abstract: Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.
83 citations
TL;DR: It is concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC.
Abstract: Background
Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions.
64 citations
TL;DR: In the authors' opinion, circulating DNA can serve as a diagnostic tool, especially if combined with other more sensitive tumor markers or imaging modalities, and may predict therapeutic efficacy which may help in better management of cancer patients.
42 citations
TL;DR: Monitoring of plasma DNA levels during the course of chemotherapy could identify patients who are likely to exhibit an insufficient therapeutic response and disease progression at an early stage, which may help in individualising treatment, and could lead to better management of advanced-stage lung cancer.
Abstract: Assessment of total plasma DNA can be a promising noninvasive tool for monitoring the effect of cytotoxic therapies in order to predict therapeutic efficacy at an early stage. Cell-free plasma DNA levels were quantified before the first, second and third cycle of chemotherapy in 42 patients with advanced nonsmall cell lung cancer and correlated with response to therapy, as assessed by computed tomography following the third chemotherapy cycle. A significantly lower plasma DNA level, measured before various treatment cycles, was found in patients with remission or stable disease than in those with progression. Higher levels and insufficient decrease in plasma DNA levels during the course of chemotherapy indicated poor outcome. For predicting insufficient therapy response, a sensitivity of 26.9% was achieved at 100% specificity using plasma DNA levels before the first therapy cycle. Prediction of disease progression was achieved with a sensitivity of 35.7% at 100% specificity using plasma DNA levels before the first therapy cycle. Monitoring of plasma DNA levels during the course of chemotherapy could identify patients who are likely to exhibit an insufficient therapeutic response and disease progression at an early stage. This may help in individualising treatment, and could lead to better management of advanced-stage lung cancer.
42 citations
TL;DR: In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years- age.
Abstract: Background
Matrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions.
34 citations
TL;DR: It is concluded that SNPs in the MMP1 promoter region may be associated with susceptibility to oral submucous fibrosis as well as HNSCC in an Indian population and addiction habits such as areca nut chewing and alcohol abuse may enhance the expression of the 2G allele of M MP1 genes in OSMF and H NSCC cases.
Abstract: Matrix metalloproteinases (MMP) are a family of zinc-dependent proteases that degrade the entire component of the extracellular matrix. Our study explores the association of the MMP1 gene promoter (-1607 1G/2G) polymorphisms in oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) in an Indian population. The MMP1single-nucleotide polymorphism (SNP) was genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 412 patients with OSMF, 422 with HNSCC and 426 controls. Our results showed that the frequency of 1G/2G or 2G/2G promoter genotypes having the 2G allele is associated with higher enzymatic activity and significantly increases in OSMF (p<0.001) and HNSCC cases (p<0.00). In this study, results concluded that SNPs in the MMP1 promoter region may be associated with susceptibility to OSMF as well as HNSCC in an Indian population and addiction habits such as areca nut chewing and alcohol abuse may enhance the expression of the 2G allele of MMP1 ...
30 citations
TL;DR: The monitoring of plasma nucleosome levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage, which might help in individualizing treatment and could lead to better management of advanced-stage lung cancer.
25 citations
TL;DR: The status of HPV and the epidemiology of the major disease that it causes in India is reviewed with various opportunities, obstacles and efforts to overcome the roadblocks for the control of cervical cancer in resource-limited settings such as India.
Abstract: Cervical cancer is the principal cause of cancer-related mortality and is a major reproductive health problem in Indian women Despite the successful development of vaccines against its causative agent (human papillomavirus [HPV]), which could be used as primary prevention tool, the highly beneficial effects of cervical screening by visual inspection with acetic acid, cytology and recently HPV DNA detection, and advances in technologies for detection of incipient lesions and HPV infection, the problem of cervical cancer is still prevalent in the country This article reviews the status of HPV and the epidemiology of the major disease that it causes in India with various opportunities, obstacles and efforts to overcome the roadblocks for the control of cervical cancer in resource-limited settings such as India
21 citations
TL;DR: A simple paper smear method for dry collection and storage of cervical specimens was employed to develop an easy multiplex (MPX) PCR for simultaneous detection of generic human papillomaviruses (HPVs) as well as typing of the high-risk HPV-16 and -18, the two clinically most important HPV genotypes, which are responsible for more than 80% of cervical cancers.
Abstract: A simple paper smear (PS) method for dry collection and storage of cervical specimens was employed to develop an easy multiplex (MPX) PCR for simultaneous detection of generic human papillomaviruses (HPVs) as well as typing of the high-risk HPV-16 and -18, the two clinically most important HPV genotypes, which are responsible for more than 80 % of cervical cancers. Multiplexing was performed with a small amount of DNA eluted by boiling from a single PS punch in a single tube and using a mixture of four pairs of primers specific for the HPV L1 consensus sequence, HPV-16, HPV-18 and the β-globin gene. Sixty HPV-positive biopsies and corresponding PS specimens from cervical cancer patients as well as cervical smears from 100 healthy women with or without abnormal cytology were collected both as PSs and in PBS. Detection of HPV DNA from cervical biopsies collected in PBS and corresponding cervical scrapes on a PS or in PBS by conventional and MPX-PCR showed a concordance of 100 % and adequacy of 93 %. A similar comparative study in cervical scrapes from normal women also revealed 100 % concordance. The technique was validated in a multicentric study at four different national laboratories. PSs collected by different centres showed variable adequacy (73–82 %) but the use of multiple PS discs for DNA extraction significantly increased the adequacy. Integration of PSs with MPX-PCR for the detection and typing of HPVs is a highly convenient, efficient, simple and cost-effective method for large-scale clinico-epidemiological studies and is also suitable for HPV vaccine monitoring programmes in resource-poor settings.
17 citations
TL;DR: Plasma levels of TNF-α and TGF-β1 do not appear to be reliable markers for predicting survival and response to therapy in advanced NSCLC.
Abstract: We hypothesized that plasma level of tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 may be a potential tool for diagnosis, prognosis and prediction of treatment outcome in non-small cell lung carcinoma (NSCLC). Plasma levels of TNF-α and TGF-β1 were quantified in 100 NSCLC patients and 100 controls. Association of TNF-α and TGF-β1 with response to therapy and survival was determined in 42 patients. An increased presence of TNF-α and TGF-β1 was observed in NSCLC compared with controls. TNF-α and TGF-β1 levels did not correlate with survival and response to chemotherapy. TNF-α and TGF-β1 do not appear to be reliable markers for predicting survival and response to therapy in advanced NSCLC.
TL;DR: In this article, a change in plasma levels of tumor necrosis factor-α (TNF-α) during the course of chemotherapy in lung cancer may predict therapeutic efficacy at an early stage.
01 Jan 2010
TL;DR: Assessment of total plasma DNA can be a promising non-invasive tool to monitor the effect of cytotoxic therapies for predicting therapeutic efficacy at an early stage.
Abstract: Background: Assessment of total plasma DNA can be a promising non-invasive tool to monitor the effect of cytotoxic therapies for predicting therapeutic efficacy at an early stage.
01 Jan 2010
TL;DR: The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions and the development of their potential diagnostic and therapeutic possibilities.
Abstract: Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.