Bhagwan Mahavir Medical Research Center

Hyderabad andhra Pradesh, India

Bhagwan Mahavir Medical Research Center

Hyderabad andhra Pradesh, India
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Kesiraju S.,Transimmun | Kesiraju S.,Bhagwan Mahavir Medical Research Center | Paritala P.,Krishna Institute of Medical science | Rao Ch U.M.,Krishna Institute of Medical science | And 2 more authors.
Transplant Immunology | Year: 2014

New onset of diabetes after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported to occur in 2% to 53% of renal transplant recipients. Several risk factors are associated with NODAT, however the mechanisms underlying were unclear. Renal transplant recipients who develop NODAT are reported to be at increased risk of infections, cardiovascular events, graft loss and patient loss. It has been reported that the incidence of NODAT is high in the early transplant period due to the exposure to the high doses of corticosteroids, calcineurin inhibitors and the physical inactivity during that period. In addition to these risk factors the traditional risk factors also play a major role in developing NODAT. Early detection is crucial in the management and control of NODAT which can be achieved through pretransplant screening there by identifying high risk patients and implementing the measures to reduce the development of NODAT. In the present article we reviewed the literature on the epidemiology, risk factors, mechanisms involved and the diagnostic criteria in the development of NODAT. Development of diagnostic tools for the assessment of β-cell function and determination of the role of glycemic control would include future area of research. © 2013 Elsevier B.V.


Nagalakshmi,Bhagwan Mahavir Medical Research Center | Jamil K.,Bhagwan Mahavir Medical Research Center | Usha Rani P.,Nizam's Institute of Medical Sciences
Biology and Medicine | Year: 2013

Single nucleotide polymorphisms (SNP's) in the epidermal growth factor receptor (EGFR) play a crucial role in head and neck cancer (HNC) disease progression and targeted therapies. Hence the present study aims to identify the mutations in EGFR gene (exon 20) in HNC considering their exposure to tobacco and alcohol habits. Mutational analysis was carried out by polymerase chain reaction (PCR) followed by single stranded confirmatory polymorphism (SSCP) techniques on the study group comprising of 129 HNC cases and 150 healthy volunteers. Four different SNP's (R776H, G779G, Q787Q, and L798H) were observed with the overall mutation rate of 75.19% in HNC cases and 46% in controls. Q787Q was found to be more prevalent (p < 0.05) and its genotypes GG, GA, and AA were 24.80%, 61.24%, and 13.95%. The study concluded that EGFR was found to be a polymorphic gene associated with HNC disease, and these SNPs were also prevalent in healthy volunteers with tobacco and alcohol habits.


Natukula K.,Bhagwan Mahavir Medical Research Center | Natukula K.,Nizam's Institute of Medical Sciences | Jamil K.,Bhagwan Mahavir Medical Research Center | Pingali U.R.,Nizam's Institute of Medical Sciences | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.


Natukula K.,Bhagwan Mahavir Medical Research Center | Natukula K.,Nizam's Institute of Medical Sciences | Jamil K.,Bhagwan Mahavir Medical Research Center | Pingali U.R.,Nizam's Institute of Medical Sciences | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: The wide spectrum of clinical features in advanced stages of non-small cell lung cancer (NSCLC) probably contributes to disparities in outcomes because of different prognostic variables significant for stage IIIB/IV patients. Hence the aim of this study was to check for favorable response of patients to various chemotherapeutic combinations with respect to patient survival in stage IIIB and stage IV NSCLC disease. We selected those patients for our study who were receiving treatment with paclitaxel, gemcitabine or etoposide in combination with platinum based drugs. Materials and Methods: Seventy-two patients who visited the hospital from June 2009 to November 2012 with confirmed diagnosis of lung cancer were included, and data were collected for follow up and classified according to treatment received with respect to patients' regimen and response, and overall survival. This study analyzed tumor variables that were associated with clinical outcome in advanced NSCLC patients who were undergoing first-line chemotherapy for stage IIIB/IV NSCLC. Results: Comparative data on various parameters like age, gender, stage, histology, site of disease, metastatic site and chemo-regimens was analyzed; these parameters predicted variable significant improvement for overall survival (p=0.05). One and two year survival rates were 20.8% and 15.3% . Conclusions: In this study we found slight improvement in survival rates in NSCLC and clinical outcomes with one combination (carboplatin+paclitaxel). Overall there were only marginal differences in survival rates for other chemo-regimens evaluated in this study.


Nagalakshmi K.,Bhagwan Mahavir Medical Research Center | Nagalakshmi K.,Nizam's Institute of Medical Sciences | Jamil K.,Bhagwan Mahavir Medical Research Center | Pingali U.,Nizam's Institute of Medical Sciences | And 2 more authors.
Biomarkers | Year: 2014

Context: Mutations in tyrosine kinase domain (TK) of epidermal growth factor receptor (EGFR) lead to signalling interruptions in several cancers. Objective: To understand EGFR mutations in head and neck squamous cell carcinomas (HNSCC), and their role as biomarkers. Methods: Screened 129 HNSCC patients and 150 controls for mutations in the TK domain using polymerase chain reaction (PCR), single strand confirmatory polymorphism (SSCP) and sequencing. Results: 81.39% of HNSCC had four mutations: G2155C, G2176A, C2188G and G2471A among these two mutations were also reported in other cancers where as two novel mutations are being reported for the first time in HNSCC. Mutational frequency was significantly associated with an advanced stage of HNSCC, habits of tobacco/alcohol and ages above 49 years. Conclusion: EGFR single nucleotide polymorphisms could be useful biomarkers of HNSCC. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Kalyani P.,Bhagwan Mahavir Medical Research Center | Jamil K.,Bhagwan Mahavir Medical Research Center
Indian Journal of Cancer | Year: 2015

Background: The three direct factors that could lead cancer patients to anemia, apart from therapy are iron deficiency, inflammatory cytokines surge and decreased erythropoietin (Epo). Our aim was to quantify biochemical and hematologic markers serum Epo, ferritin (Fe) and tumor necrosis factor-alpha (TNF-α) along with hemoglobin (Hb) to understand the associations between these factors, patient characteristics and anemia. Materials And Methods: The study group consisted of 100 anemic cancer patients and 80 controls. Biochemical marker levels were determined by the enzyme linked immunosorbent assay on an autoanalyser. Univarient analysis, t-test, ANOVA, Bonferroni test, linear regression was performed to find correlations and associations among various factors. Results: The baseline serum Epo (153.07 ± 173.88 vs. 23.607 ± 36.462) and Fe levels (233.53 ± 257.12 vs. 23.06 ± 20.04) were adequately high in cases compared with that controls (P ≤ 0.001). Considerable raise in TNF-α levels was also observed (16.26 ± 13.44 vs. 11.2375 ± 4.84) (P = 0.001). TNF-α correlated positively (P = 0.022) with Epo and Fe (P = 0.000), which was also evident from large effect size of Epo (r2 = 0.414), TNF-α (r2 = 0.369), Hb (r2 = 0.226). Epo and Hb were negatively correlated (β = -0.375, P = 0.001) and Epo production was found to be appropriate for the degree of anemia (O/P ratio of 3.51 ± 1.26 vs. 1.43 ± 0.47). A strong association was seen between Hb, Epo and TNF-α in hematological and gynecological malignancies for different grades of anemia. Men were more prone to life-threatening anemia (13%) than women (9%). Conclusion: Anemia in cancers was not because of inadequate Epo or Fe levels, but because of improper Epo response. Further studies on molecular analysis of Epo, biochemical and molecular interplay between Epo and TNF-α could explain a rationale for anemia in cancers.


Nalabolu M.R.,Bhagwan Mahavir Medical Research Center | Palasamudram K.,Bhagwan Mahavir Medical Research Center | Jamil K.,Bhagwan Mahavir Medical Research Center
International Journal of Hematology-Oncology and Stem Cell Research | Year: 2014

Obesity is an important public health problem and major risk factor for postmenopausal breast cancer. Adipose tissue is the major component involved in the control of the metabolism through energy homeostasis, adipocyte differentiation, insulin sensitivity and the activation of anti-inflammatory metabolic and immune pathways. Leptin and Adiponectin pathways are involved in proliferation process in breast cancer. Current review describes potential relationship between the molecular actions and clinical significance of leptin and adiponectin in breast cancer.


Joshi L.,Bhagwan Mahavir Medical Research Center | Chelluri L.K.,Global Hospitals | Gaddam S.,Bhagwan Mahavir Medical Research Center | Gaddam S.,Osmania University
Archivum Immunologiae et Therapiae Experimentalis | Year: 2015

Multi-drug-resistant (MDR) tuberculosis is a major public health problem worldwide. Drug resistance arises due to non-compliance of antibiotic therapy. Herein, we explored the therapeutic options available ranging from conservative treatment approaches to alternate adjunct therapies such as mesenchymal stromal cell (MSC) therapy interventions. It is attractive to understand the scientific rationale of using cells as drugs, in particular mesenchymal stem/stromal cells. The review dwells and attempts to analyze the mechanistic approaches of the current treatment modalities to modern therapies. MSCs have demonstrated profound capacity to regenerate and repair. They appear to modulate that the activities of dendritic cells regulate T cells, both in vivo and in vitro. While there seems to be some benefit of such therapies, its use warrants further research. The merits and de-merits of autologous therapy/allogeneic therapy are ill understood. The challenges of requirement of large number of cells for infusion, the route of administration, choice of timing are complex issues that need to be addressed. Furthermore, the host immune responses, environmental factors and epigenetic mechanisms compound the problem. Although, clinical studies are being performed using autologous MSCs in different inflammatory models, it is important that such an intervention should be based on sound scientific rationale. The current review examines the immunomodulatory properties of MSCs, its interactions with other cell types, in assessing the basis for autologous/allogeneic cell-based therapies in the treatment of XDR/MDR tuberculosis. © 2015, L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.


Sabitha K.,Bhagwan Mahavir Medical Research Center | Vishnuvardhan Reddy M.,P.A. College | Jamil K.,Bhagwan Mahavir Medical Research Center
Cancer Epidemiology | Year: 2010

Background: CYP1A1 is one of the commonest genes which had been widely investigated to find the risk of various malignancies in different ethnic groups. The polymorphism in these genes with a combination of environmental exposure has been hypothesized to confer a differential risk of cancer for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1 activity would be at increased risk of cancer when exposed to high levels of smoke components. The proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by xenobiotics to produce genetic susceptibility for malignancies. Patients and procedures: We performed a case-control study in 205 cases with histopathologically confirmed squamous cell carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers especially among smokers of Hyderabad Indian population. Venous blood samples (5 ml) were collected from patients and control groups; genomic DNA was extracted and used for polymerase chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the variant CYP1A1 alleles. Results and discussion: CYP1A1m1/m1 genotype (OR. = 8.12, 95% CI: 3.27-21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly CYP1A1w2/m2 (OR. = 1.58, 95% CI: 0.94-2.67) and CYP1A1m2/m2 (OR. = 6.31, 95% CI: 2.74-18.69) genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2 site. Conclusion: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2-fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an important determinant in susceptibility to tobacco-induced head and neck carcinogens and there is an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of smoking among Indians. This appears to be a new and important prognostic and diagnostic marker for determining the risk of head and neck cancers genetically. © 2010 Elsevier Ltd.


Ahmed M.,University of Mysore | Jamil K.,University of Mysore | Jamil K.,Bhagwan Mahavir Medical Research Center
Biology and Medicine | Year: 2011

A recent study reports that more than 99% of cases of cervical cancer worldwide contain HPV DNA. Hence, treatment options for cervical cancers are difficult due to multiplicity of the disease. Chemotherapy uses strong anti-cancer chemicals to kill cancer cells but to kill the viruses clinicians administer combination of drugs or higher doses of chemotherapy to control advanced cervical cancer and this practice causes severe side effects. Numerous cancer patients fail standard chemotherapy or develop resistance to chemotherapy during the course of treatment. Hence the aim of this investigation was to determine the chemo sensitivity of the five commonly used neoplastic drugs such as Geftinib, Cisplatin, 5-FU, Gemcitabine and Vinorelbine in vitro, and compare its toxicity on cervical cancer cells (HeLa) using lymphocytes (nucleated cells) as controls. Cytotoxicity in vitro was determined using the MTT assay; LC50 for all the drugs was calculated by regression equation. The morphological change of cells was recorded using Inverted Microscopy. DNA damage studies by comet assay determined the extent of single strand breaks in the DNA and these results were statistically determined using Standard deviation and compared with various treatments in cancer cells (HeLa) and control cells. All the results were statistically analyzed and recorded. From these studies we could determine that cisplatin was the most toxic drug and vinorelbine was least toxic. The order of toxicity (LC50) of the neoplastic drugs was Cisplatin (13 μM) > Gefitinib (20 μM) > Gemcitabine (35 μM) > 5-FU (40 μM) > Vinorelbine (48 μM). Further, we could determine the toxicity of the combination of drugs using sub-lethal doses of each drug.

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