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T Rajkumar

Publications and source records attributed to T Rajkumar.

At least 19 recordsLinked to original sources

Type 1 (11;22)(q24:q12) translocation is common in Ewing's sarcoma/peripheral neuroectodermal tumour in south Indian patients.

The Ewing's sarcoma family can present diagnostic difficulties. In the past the basis of diagnosis has been a exclusion. Identification of a specific translocation especially t(11;22) (EWS-FLI 1 fusion gene), which is seen in nearly 85 percent of Ewing's sarcoma cases can help in precise diagnosis. We have carried out a study on twenty patient samples diagnosed to have Ewing's sarcoma/peripheral neuroectodermal tumour (PNET)/small round cell malignant tumour. The study involved RT-PCR analysis for the fusion transcript, followed by sequencing to identify the specific type of fusion. Ninety percent (18/20) of the samples tested were found to be t(11;22) translocations involving EWS-FLI 1 genes. Sixty-one percent (11/18) were found to be type 1 fusion and seven were type 2 (39 percentage). This is the first study in India with quantitative information about the types of EWS-FLI 1 translocations present in Ewing's family of tumours in south Indian patients.

Adolescent↗

Role of paan chewing and dietary habits in cervical carcinoma in Chennai, India.

Non-viral factors contribute to human papillomavirus (HPV)-related cervical carcinogenesis. We investigated the role of paan chewing and dietary habits among 205 women with invasive cervical cancer (ICC) and 213 age-matched control women in Chennai, India. Odds ratios (OR) and 95% confidence intervals (CI) were computed by means of unconditional multiple regression, taking into account major correlates of ICC risk. Paan chewing showed a dose-dependent direct association with ICC (OR for >/=5 paan day(-1)=4.0; 95% CI 1.2-13.3). Among dietary habits, the highest vs lowest intake tertile for vegetables and fruit was associated with an OR of 0.5 (95% CI 0.2-1.0). Low education level and low body weight were also risk factors for ICC, but they did not account for the associations of paan chewing and low vegetable and fruit intake. In the analyses restricted to HPV-positive cases and controls, the inverse association with vegetable and fruit intake was confirmed. Conversely, the adverse influence of paan chewing on ICC risk seemed to be attributable to a higher prevalence of cervical HPV infection in women who chewed.

Adult↗

Oral cancer in Southern India: the influence of body size, diet, infections and sexual practices.

Between 1996 and 1999, we carried out a study in Southern India on risk factors for oral cancer. The study included 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women). Height was unrelated to oral cancer risk. Body mass index (weight in kilograms/height in metres squared) was inversely associated with risk (P for trend<0.001). Paan chewers with low BMI were at particularly high risk. Risk was increased among subjects consuming meat (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.00-2.37), ham and salami (OR 4.40, 95% CI 2.88-6.71) two or more times per week. Frequent consumption of fish, eggs, raw green vegetables, cruciferous vegetables, carrots, pulses, apples or pears, citrus fruit, and overall consumption of vegetables and fruit decreased oral cancer risk (P for trend for each of these items less than or equal to 0.001). The risk associated with low consumption of vegetables was higher among smokers than among non-smokers. Men, but not women, who practised oral sex had an increased oral cancer risk (OR 3.14, 95% CI 1.15-8.63). Women with more than one sexual partner during life were at increased oral cancer risk (OR 9.93, 95% CI 1.57-62.9).

Adolescent↗

PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease.

Detection of MRD remains one of the major goals in the treatment of acute lymphoblastic leukemia (ALL). We have used the polymerase chain reaction (PCR)-heteroduplex (HD) analysis to assess and confirm the clonal expansion of T cell receptor (TCR) gamma and delta gene rearrangements in 24 T-ALL patients at diagnosis. 52.4% revealed Vdelta1-Jdelta1; 48% Vdelta2-Ddelta3; 62.5% Vgamma1-Jgamma1 and 46% both Vdelta1-Jdelta1 and Vgamma1-Jgamma1 clonal rearrangements. 6/24 patients had TAL-1 deletion. These clonal markers were used to monitor MRD in remission/relapse bone marrow samples for periods ranging from 6 to 75 months after diagnosis. Patients who relapsed and died revealed a continuous PCR-HD positivity in their clinical remission bone marrow samples. HD analysis established identical diagnostic clone at relapse. Patients who are in long-term clinical and morphological remission achieved PCR-HD negativity in their 8-12 months bone marrow remission samples and continue to be PCR-HD negative. MRD monitored in six patients with two diagnostic PCR--HD positive clonal markers reveal an identical pattern ensuring circumvention of false positive and negative results. Thus, we conclude that PCR followed by HD analysis is a useful technique to monitor MRD in remission/relapse samples in ALL patients.

Adolescent↗

C-myc oncoprotein expression and prognosis in patients with carcinoma of the cervix: an immunohistochemical study.

OBJECTIVE: Evaluation of the prognostic significance of c-Myc expression in carcinoma of the cervix. MATERIALS AND METHODS: 132 patients with carcinoma of the cervix presenting at the Cancer Institute in Chennai from 1996-1999 were included in the study. All the cases were treated with a radical course of radiotherapy and had a median follow-up of 36 months. Paraffin blocks obtained from the punch biopsies from the tumours were used for immunohistochemistry. RESULTS: c-Myc nuclear immunoreactivity was observed in 44/132 (33.3%) of tumours. Patients with tumours in Stages 11 B and III B accounted for 112/132 (84.8%) of the cases. Patients with tumours expressing c-Myc nuclear immunoreactivity were found to have more advanced disease; less likely to achieve complete remission (54.5% vs. 78.4%; p < 0.005) and lower disease-free status (52.3% versus 73.8%; p < 0.014). The poor prognostic feature of c-Myc nuclear immunoreactivity was seen in both stage II B (52.9% vs. 76.3%) and stage III B (38.1% vs. 69.4%; p < 0.025). CONCLUSIONS: c-Myc nuclear immunoreactivity is a predictor of poorer response to radiotherapy and poorer disease free status in stage II B and III B carcinoma of the cervix.

Female↗

Neuregulin 1-alpha expression in locally advanced breast cancer.

The human Neuregulin 1 (NRG1) gene encodes several alternatively spliced ligands that bind to both c-erbB-3 and c-erbB-4, members of the family of type 1 tyrosine kinase growth factor receptors. Antibodies raised to a synthetic peptide recognize selectively the alpha variant of NRG1. The NRG1-alpha isoforms' expression was studied in 115 locally advanced adenocarcinomas of the breast using immunohistochemistry. Absent or low levels of NRG1-alpha were found to be associated with poorer prognosis compared to tumours that had moderate to high levels of the protein.

Journal Article↗

A new dose model for assessment of health risk due to contaminants in air.

The problem of making quantitative assessments of the risks associated with human exposure to toxic contaminants in the environment is a pressing one. This study demonstrates the capability of a new computational technique involving the use of fuzzy logic and neural networks to produce realistic risk assessments. The systematic analysis of human exposure involves the use of measurements and models, the results of which are sometimes used in regulatory decisions or in the drafting of legislation. Because of limited scientific understanding, however, interpretation of models often involves substantial uncertainty. Extensive measurement programs can be very expensive. The high complexity and inherent heterogeneity of exposure analysis is still a major challenge. The approach to this challenge tested here is to use a new model incorporating sophisticated artificial intelligence algorithms. Exposure assessment often requires that a number of factors be evaluated, including exposure concentrations, intake rates, exposure times, and frequencies. These factors are incorporated into a system that can "learn" the relevant relationships based on a known data set. The results can then be applied to new data sets and thus be applied widely without the need for extensive measurements. In this analysis, an example is developed for human health risk through inhalation exposure to benzene from vehicular emissions in the cities of Auckland and Christchurch, New Zealand. Risk factors considered were inhaled contaminant concentration, age, body weight, and activity patterns of humans. Three major variables affecting the inhaled contaminant concentration were emissions (mainly from motor vehicles), meteorology (wind speed, temperature, and atmospheric stability), and site factors (hilly, flat, etc.). The results are preliminary and used principally to demonstrate the technique, but they are very encouraging.

Age Factors↗

Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix.

Cervical cancer is the most common cancer among women in South India. More than 70% of the cases present in stage IIB and IIIB and of these more than 50% fail conventional treatment. The purpose of the present study was to determine the prognostic significance of Bcl-2 and p53 expression in squamous cell carcinomas of the cervix. Using immunohistochemistry, 40 cases of stage IIB and IIIB squamous cell carcinomas of the cervix treated with radiotherapy were studied for the expression of Bcl-2 and p53 protein and their prognostic value ascertained. Bcl-2 was expressed in 65% (n=26) of the tumours. There was a statistically significant association (p=<0.025) between Bcl-2 expression and poorer DFS and OS in stage IIB cases. In stage IIIB, these associations were not obvious probably due to additional genetic events overshadowing the significance of Bcl-2 expression. Only 4/40 (10%) of the cases were positive for p53 protein expression and there was an inverse correlation between p53 expression and Bcl-2 expression. This study suggests that Bcl-2 can be a useful marker to identify the poor prognostic group in stage IIB cases and needs to be confirmed in a larger series.

Biomarkers, Tumor↗

Characterization of mouse fibroblast (NIH3T3) and fibrosarcoma cell lines (WEHI-164 and MFS 8) using PMRS.

Proton magnetic resonance Spectroscopy (PMRS) has been used to study the differences between immortalized fibroblasts and fibrosarcoma cells of different grade. One and two dimensional purged correlation spectroscopy (PCOSY) have been used to assess intact viable fibroblast and fibrosarcoma cells, and differences in the triglyceride, cellular metabolite, and cell surface fucosylation patterns between the three cell lines have been observed. The clinical implication of this study is the potential use of PMRS as an adjunct to conventional histopathology.

3T3 Cells↗

Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c-erbB2 and c-erbB3 in bladder cancer.

Expression of the c-erbB3 protein was determined in transitional cell carcinoma of the bladder by immunohistochemistry. Strong membrane staining was observed in 10 per cent of cases (7/70) and cytoplasmic and membrane overexpression in 20 per cent (14/70). Overexpression of the epidermal growth factor (EGF) receptor (36 per cent, 25/70) and c-erbB2 proteins (9 per cent 6/70) was determined in the same series of cases. c-erbB3 overexpression was positively correlated with EGF receptor expression (P < 0.025) but appeared to be inversely associated with c-erbB2 overexpression.

Biomarkers, Tumor↗

c-erbB3 protein expression in ovarian cancer.

Aims-To study the prevalence of overexpression of c-erbB3 growth factor receptor in ovarian carcinomas and to analyse its relation to histological subtype, stage and grade of the tumours.Methods-Ninety eight ovarian carcinomas were evaluated immunohistochemically using the RTJ1 monoclonal antibody raised against a synthetic peptide, the sequence of which was derived from the cytoplasmic domain of the c-erbB3 protein.Results-Of the tumours, 16% (16/98) overexpressed c-erbB3 protein relative to normal ovarian epithelium, whereas 22% (22/98) were completely negative. There was a statistically significant association between overexpression and well differentiated grade.Conclusions-These findings suggest that c-erbB3 protein overexpression occurs in a significant proportion of ovarian cancers and is correlated with differentiation. Overexpression may merit further investigation as a potential prognostic indicator and as a target for new treatment.

Journal Article↗

The type I growth factor receptors in human breast cancer.

The type 1 family of growth factor receptors includes the EGFR, c-erbB2, c-erbB3, and c-erbB4. All four members of the family are expressed in breast cancer. The EGFR gene and more frequently the c-erbB2 gene are amplified in a proportion of cases. In addition to increased expression as a result of gene amplification, overexpression of perhaps all of the receptors also appears to occur, probably as a result of increased mRNA transcription. Overexpression may have prognostic value and may predict response to current therapies. Finally these GFR proteins represent targets for new types of chemotherapeutic agents.

Animals↗

A monoclonal antibody to the human c-erbB3 protein stimulates the anchorage-independent growth of breast cancer cell lines.

The c-erbB3 protein is a member of the type I growth factor receptor family. It has a widespread pattern of expression in normal tissues and is overexpressed in about 20% of breast cancers. We have raised a specific monoclonal antibody, called SGP1, against the extracellular domain of c-erbB3 which recognises the native form of the protein. The monoclonal antibody was found to modestly but significantly stimulate the anchorage-independent cloning efficiency of the breast tumour cell lines BT483 and T47D, both of which express the c-erbB3 protein. No effect was observed on 293 cells lacking expression, nor did a control isotype-matched antibody promote the growth of any of the cells tested. These results suggest that the c-erbB3 protein may normally act as a growth factor receptor.

Animals↗

Expression of the c-erbB-3 gene product in gastric cancer.

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.

Adult↗

Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1.

We have examined the expression of the c-erbB-3 protein in a wide range of tumours of the gastrointestinal (GI) tract using immunocytochemical staining. Two antibodies were employed, a polyclonal antibody, 49.3, and a new monoclonal antibody, RTJ1, both raised to a synthetic peptide from the cytoplasmic domain of the human c-erbB-3 protein. The antibodies recognize c-erbB-3 by immunoprecipitation and Western blotting of lysate prepared from a cell line engineered to overexpress the protein. Both antibodies also detect expression of the protein in formalin-fixed, paraffin-embedded human tissues. The RTJ1 monoclonal antibody gave superior staining, showing lower background and more pronounced cell surface immunoreactivity. The c-erbB-3 protein was found in normal epithelial cells throughout the GI tract, in squamous epithelium of the oropharanyx and oesophagus, in the parietal cells of the stomach, and in the surface enterocytes of the small and large bowel. Seventy-six tumours arising at these sites were examined for c-erbB-3 protein expression. Widely varying levels of expression were seen, from absent to intense staining with cell membrane accentuation.

Adenocarcinoma↗

Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras.

Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour.

Adolescent↗