Digumarti R.,Nizams Institute of Medical Sciences |
Sinha S.,Institute of Oncology and Regional Cancer Center |
Nirni S.S.,Indo American Cancer Institute and Research Center |
Patil S.G.,Bangalore Institute of Oncology |
Pedapenki R.M.,King George Hospital
Indian Journal of Cancer | Year: 2014
Background: Patients with hematological malignancies that are highly proliferative and have high tumor burden are at high risk of developing hyperuricemia and tumor lysis syndrome (TLS), spontaneously and while undergoing chemotherapy. Aim: To assess the safety and efficacy of a new generic formulation of recombinant rasburicase in prevention and treatment of malignancy-associated hyperuricemia. Materials and Methods: An open-label, multicenter, phase-III study was conducted on 100 eligible patients with high risk for TLS. Rasburicase was administered 0.2 mg/kg intravenously over 30 min, daily, for 4 days. The outcome measures were percentage of reduction in plasma uric acid at 4 h after rasburicase, plasma uric acid area under the curve (AUC)0-96 h and incidence of adverse events. Results: Eighty eight patients completed the study period of 10 days. After rasburicase administration, there was a 75.3 ± 28.5% of reduction in plasma uric acid at 4 h as compared to baseline. The plasma uric acid AUC 0-96 h was 259.9 ± 215.5 mg/dL h. Safety of rasburicase was assessed on the basis of changes in vitals, hematological, and biochemical parameters from baseline to termination. Except for the plasma uric acid level, there was no significant difference in any of the parameters. Mild to moderate adverse events were reported in 29 patients. Three patients had serious adverse events (SAEs) unrelated to rasburicase. Conclusions: These results demonstrated that recombinant rasburicase that is indigenously developed is effective for prevention and management of hyperuricemia in patients who are at high risk of developing TLS.
Sowjanya A.P.,Institute of Genetics |
Rao M.,Sir Ronald Ross Institute of Tropical and Communicable Diseases |
Vedantham H.,Mediciti Institute of Medical science MIMS Campus |
Kalpana B.,Mediciti Institute of Medical science MIMS Campus |
And 3 more authors.
Nitric Oxide - Biology and Chemistry | Year: 2016
Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. © 2015 Published by Elsevier Inc.
Sushma P.S.,National Institute of Nutrition ICMR |
Jamil K.,Bhagwan Mahavir Medical Research Center |
Kumar P.U.,National Institute of Nutrition ICMR |
Satyanarayana U.,Dr Pinnamaneni Siddhartha Institute Of Medical Science |
And 2 more authors.
Tumor Biology | Year: 2015
Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer. © 2015 International Society of Oncology and BioMarkers (ISOBM)
Anil Kumar A.,Andhra University |
Akula R.R.,International Cancer Center |
Ayyangar K.,International Cancer Center |
Krishna Reddy P.,Institute of Oncology and Regional Cancer Center |
And 3 more authors.
Journal of Applied Clinical Medical Physics | Year: 2016
This paper presents a new approach towards the quality assurance of external beam plans using in-house-developed DICOM import and export software in a clinical setup. The new approach is different from what is currently used in most clinics, viz., only MU and point dose are verified. The DICOM-RT software generates ASCII files to import/export structure sets, treatment beam data, and dose-volume histograms (DVH) from one treatment planning system (TPS) to the other. An efficient and reliable 3D planning system, ROPS, was used for verifying the accuracy of treatment plans and treatment plan parameters. With the use of this new approach, treatment plans planned using Varian Eclipse planning system were exported to ROPS planning system. Important treatment and dosimetrical data, such as the beam setup accuracy, target dose coverage, and dose to critical structures, were also quantitatively verified using DVH comparisons. Two external beam plans with diverse photon energies were selected to test the new approach. The satisfactory results show that the new approach is feasible, easy to use, and can be used as an adjunct test for patient treatment quality check.
Raman R.,DNA Diagnostics Center |
Kotapalli V.,DNA Diagnostics Center |
Adduri R.,DNA Diagnostics Center |
Gowrishankar S.,Apollo Hospitals |
And 14 more authors.
Molecular Carcinogenesis | Year: 2014
Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS, and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. © 2012 Wiley Periodicals, Inc.