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Biomedical subjects

K N Naresh

Publications and source records attributed to K N Naresh.

At least 19 recordsLinked to original sources
PubMed2003

Inhibition of nitrosodiethylamine-induced hepatocarcinogenesis by dietary turmeric in rats.

Turmeric, widely used in food and medicine has been shown to prevent benzo(a)pyrene [B(a)P] or dimethylbenz(a)anthracene (DMBA)-induced forestomach, skin and mammary tumors in mice and/or rats. In this study we examine the modulatory effects of turmeric on nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats. Female Wistar rats were administered NDEA (200 ppm) through drinking water (5 days per week) for 4 weeks. Control and/or NDEA-treated rats received 0, 0.2, 1.0 or 5.0% turmeric diet (w/w) either before (2 weeks), during (4 weeks) and after NDEA exposure (10 weeks) or starting from 24 h after NDEA exposure for 10 weeks. NDEA-treated rats receiving 1 or 5% turmeric before, during and after carcinogen exposure showed significant decrease in number of gamma glutamyl transpeptidase (GGT) positive foci measuring >500 or >1000 microm and decrease in the incidence of NDEA-induced focal dysplasia (FD) and hepatocellularcarcinomas. Decrease in the number of GGT positive foci measuring >1000 microm was also observed in NDEA-treated rats receiving 0.2% turmeric, although no decrease in tumor incidence was noted. On the other hand, similar levels of turmeric treatment (0.2, 1 and 5%) after exposure to NDEA did not show any protective effects. The underlying mechanism(s) of chemoprevention of NDEA-induced hepatocarcinogenesis need to be explored.

Animals↗
PubMed2003

Demonstration of cytokeratin-5 non-expression in tobacco related oral carcinogenesis--use of reverse transcriptase polymerase chain reaction as a sensitive assay.

Cytokeratins (CK) are the epithelia specific intermediate filament proteins. We have shown consistent non-expression of CK-5 protein in human oral pre-cancer and cancer, in earlier studies. To investigate whether non-expression of CK-5 protein is the result of transcriptional or translational block and to evaluate the possibility if CK-5 non-expression can be used as a marker for early diagnosis of tobacco related oral cancer, RT-PCR using CK-5 specific primers was conducted. Out of 36 precancerous lesions and 29 squamous cell carcinomas (SCC) of buccal mucosa (BM) samples studied, 11 and 13 samples respectively of precancer and SCC did not show CK-5 product in RT-PCR. Down regulation of CK-5 mRNA expression was also observed in some samples. Thus, in conclusion, our results have shown that CK-5 non-expression is the result of transcriptional block. We proposed CK-5 non-expression as a potential marker for the early diagnosis of tobacco related oral cancer.

Carcinoma, Squamous Cell↗
PubMed2003

Benign metastasizing meningioma.

Meningiomas represent about one sixth of all primary neoplasms of the central nervous system. They rarely metastasize outside the intracranial compartment. There are no clear criteria to identify the subset of aggressive tumors which recur locally or metastasize. Histological tumor grade is the most important predictor of recurrence or metastases. We report an unusual case of recurrent metastasis in an extrapleural location and review the literature. Our patient developed recurrent thoracic metastases from an intracranial benign meningioma after a disease-free interval of 8 years. She was successfully managed by wide excision of the metastasis and is currently asymptomatic.

Adult↗
PubMed2002

Do metastatic tumours from an unknown primary reflect angiogenic incompetence of the tumour at the primary site?--a hypothesis.

Metastases from unknown primary tumours (MUP) are not an uncommon clinical problem. A hypothesis that discusses the plausible role of neoangiogenesis, as a central theme in the development of MUPs, is presented. Invasive cancers, which cannot or do not switch to the angiogenic phenotype, remain subclinical. In situations where a non-angiogenic tumour attempts to grow beyond the volume that can be supported by the vasculature, marked apoptosis and cell turnover result. Tumours with a high cell turnover are biologically advanced. Thus, such subclinical tumours acquire a metastatic phenotype. In the viscera, metastases may remain dormant for varying periods until subclones with an angiogenic phenotype arise due to tumour evolution or they burn out. Visceral MUPs, due to their longer evolution, are biologically advanced and have dismal prognosis. Contrary to this, tumour cells reaching lymph nodes (LN) grow without acquiring any phenotypic or genotypic change, as angiogenesis is redundant for growth within the metastatic LNs.

Angiogenesis Inducing Agents↗
PubMed2002

Regional variation in the distribution of subtypes of lymphoid neoplasms in India.

Lymphoid malignancies (LM) are a heterogeneous group of tumours. The relative frequencies of the various types of LMs vary across geographic regions. The pattern in India shows significant differences from the rest of the world. As India is a vast country, we set out to investigate whether there are regional differences in the relative frequencies of the various LMs. A total of 562 LMs from three different regions in India--Barshi (western India, 102 cases), Pondicherry (southern India, 156 cases) and Jaipur (northern India, 304 cases) were analysed according to the WHO classification. The non-Hodgkin lymphoma (NHL) to Hodgkin disease (HD) ratio was 6.28 in Barshi, 1.26 in Pondicherry and 2.27 in Jaipur. The frequency of HD's various subtypes did not significantly differ among the three regions. While T-cell NHLs constituted only 12.5% of NHLs at Barshi, they accounted for 31 and 27.5% of all NHLs at Pondicherry and Jaipur, respectively. There were also notable differences in the specific subtypes of NHL between the three different geographic regions in India.

Demography↗
PubMed2002

Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic implications.

In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment with MCP-842 protocol, a short duration intense protocol, yields worse survival in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas. In order to identify both favourable and unfavourable subgroups in pts with T-cell LL (T-LL) with respect to relapse free survival following treatment with MCP-842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53 protein overexpression was noted in 59% cases and bcl-2 overexpression was noted in 29.4% cases. p53 expression correlated with a higher rate of relapse (p = 0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In conclusion, in this study, overexpression of p53 protein was common in patients with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in these patients.

Adolescent↗
PubMed2001

Apoptosis index is a predictor of metastatic phenotype in patients with early stage squamous carcinoma of the tongue: a hypothesis to support this paradoxical association.

BACKGROUND: Patients with squamous carcinoma of the oral tongue in clinical stages TIN0M0 and T2N0M0 with a tumor thickness < or = 3 mm usually do not have lymph node (LN) metastasis. However, factors that are useful in predicting LN metastasis in thicker tumors (> 3 mm thick) need to be identified. The authors investigated the clinical relevance of the apoptotic index (AI), the proliferation index, and tumor grade in relation to LN metastasis in patients with early stage squamous carcinoma of the oral tongue. METHODS: Twenty-three patients with squamous carcinoma of the anterior two-thirds of the tongue measuring < 2 cm in height and > 3 mm in thickness were evaluated for tumor grade, AI (by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique), and proliferation index (by proliferating cell nuclear antigen [PCNA] expression). RESULTS: The mean AI value was significantly higher in LN positive patients compared with LN negative patients (P = 0.012). The LN positive and LN negative subgroups did not differ in the mean PCNA index, and there was no significant difference in the distributions of tumor grade between LN positive and LN negative subsets. Four of 12 tumors with an AI < or = 5% and 10 of 11 tumors with an AI > 5% had LN metastasis (P = 0.009; risk ratio, 20). The AI maintained its significance with respect to LN metastasis in the multivariate analysis (P = 0.003). The 4-year recurrence free survival was significantly better in patients with tumors that had an AI value < or = 5% compared with patients with tumors that had an AI > 5% (92% vs. 32%) (P = 0.033). However, the AI lost its impact on recurrence free survival within a Cox proportional hazards model (P = 0.068). CONCLUSIONS: A higher AI value is a predictor of LN metastasis and may serve as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather surprising finding.

Apoptosis↗
PubMed2001

Angiogenesis is redundant for tumour growth in lymph node metastases.

AIMS: Angiogenesis is essential for the growth of solid tumours. As the role of angiogenesis is unclear in the pathogenesis of primary lymph node (LN) tumours, we wondered whether neoangiogenesis was important in supporting and promoting the growth of tumours in LNs. METHODS AND RESULTS: We investigated 16 cases of squamous carcinoma involving oral cavity (n=9) and larynx/pyriform fossa (n=7), all of whom had lymph node metastases. Sections of the primary tumour, uninvolved mucosa, metastatic LN and nonmetastatic LN were double-immunostained with factor VIII-related antigen and MIB-1. Proliferating blood vessels, i.e. neoangiogenesis, was identified by coexpression of factor VIII-related antigen-stained blood vessels and MIB-1 staining of the endothelial cell nuclei. Counts were performed in an area of 4 mm2. Primary tumours (127-188.7), uninvolved mucosa (54-84.5) and metastatic LNs (123.5-167) had significantly lower vessel counts than nonmetastatic LNs (194-253.9) (P=0.003; P < 0.001; P < 0.001, respectively). With regard to neoangiogenesis, primary tumours (1.7-5) had significantly higher counts than uninvolved mucosa (0-0.4), nonmetastatic LNs (0-0.4) and metastatic LNs (0.9-2.4) (P < 0.001; P < 0.001; P=0.047, respectively). CONCLUSIONS: Our data suggest that because of the rich native vascularity of lymph nodes, neoangiogenesis is redundant for the growth of metastatic tumour.

Blood Vessels↗
PubMed2001

CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease.

The expression of CD40L was investigated in HD involved lymph nodes by flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR). Also an investigation of the role of CD40L in upregulation of the anti-apoptotic gene BclxL in a Hodgkin's disease (HD) derived cell line was undertaken. HD patients (n = 18) had significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment as compared to controls (n = 8). HD patients also demonstrated higher numbers of CD4+, CD8+ and CD19+ lymphocytes co-expressing CD40L as compared to controls. The CD40L signal was consistently and significantly upregulated in HD patients (n = 5) as compared to controls (n = 3) at the mRNA level. RT-PCR and FCM analysis revealed that soluble CD40L upregulated BclxL levels in the Fas-sensitive HD cell line HDLM2. We conclude that CD40L can act as an important anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells of HD and may be partly responsible for their survival 'in-vivo'.

Apoptosis↗
PubMed2001

Hodgkin's disease involving Waldeyer's ring: a study of four cases.

We report four cases of Hodgkin's disease who presented with involvement of Waldeyer's ring. Their clinical, morphological and immunohistochemical features are discussed. The patients were immuno-competent, were between 17 and 65 years of age and presented with symptoms related to swelling in the nasopharynx or oropharynx and cervical lymphadenopathy. The nasopharyngeal biopsy and the cervical lymph node in all four cases showed features of classical Hodgkin's disease. The Reed Sternberg cells expressed CD15 and CD30, and in three cases, CD20 and Epstein-Barr virus--latent membrane protein -1 (EBV-LMP-1). Extranodal involvement by Hodgkin's disease which is not in continuity with nodal disease is rare in immunocompetent patients. Morphologically, such extranodal lesions, especially in locations like the oropharynx and nasopharynx, should be differentiated from EBV-associated lymphoproliferations.

Adolescent↗
PubMed2001

Primary extranodal mucosa associated lymphoid tissue (MALT) lymphoma of the prostate.

Low-grade B-cell mucosa associated lymphoid tissue (MALT) lymphoma can rarely present primarily in extranodal sites other than stomach, which is the most common site for it. Until now only four cases of primary prostatic MALTomas have been described in the literature and we report the fifth. We describe a case of primary prostatic MALToma in a 67-year-old man and the diagnosis was made on the trans-urethral resection specimen of the prostate. As the disease was limited to prostate (stage IEA), the patient was treated with external beam radiation therapy to a total dose of 4400cGy in 22 fractions. The patient achieved completed remission and has remained free of disease in the following 36 months.

Disease-Free Survival↗
PubMed2000

Ceramide-induced apoptosis in fas-resistant Hodgkin's disease cell lines is caspase independent.

We investigated whether cell-permeable, synthetic ceramide (C6 ceramide) could induce apoptosis in Fas-resistant Hodgkin's disease (HD)-derived cell lines. Despite strongly expressing the Fas-receptor, two of three HD-derived cell lines were resistant to Fas-mediated apoptosis. This resistance to Fas could not be attributed to differential Fas isoform generation patterns between the Fas-resistant and the Fas-sensitive cell lines. The Fas-resistant cell lines did not demonstrate the presence of Fas exon 8 deletion. Bcl-2 and BclxL levels were comparable between the Fas-resistant and the Fas-sensitive cell lines. C6 ceramide could induce apoptosis in both Fas-resistant cell lines and this was associated with a decrease in BclxL level. Caspase-1, caspase-3, or pan-caspase inhibitors could not prevent ceramide-induced apoptosis. Furthur, ceramide treatment did not lead to cleavage of caspase 3 or poly(ADP-ribose) polymerase, but caused a loss in mitochondrial transmembrane potential which could not be prevented by caspase inhibitors. Thus, we conclude that ceramide-induced apoptosis in Fas-resistant HD cell lines is caspase independent.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Circulating levels of TNF alpha and TNF receptor superfamily members in lymphoid neoplasia.

We have correlated the serum levels of TNF alpha and soluble TNF receptor superfamily members with clinico-pathologic parameters in patients of Hodgkin's disease (HD, N = 26) and non-Hodgkin's lymphoma (NHLs, N = 35). HD patients had significantly higher levels of TNF alpha, sTNFRI, and sTNFRII in serum while NHL patients had significantly higher levels of sTNFRI, sTNFRII, sCD27, and sFas as compared to controls. In NHL patients the levels of sCD27 correlated directly and significantly with the high-stage disease, bone marrow involvement, lymph nodal presentation, and serum LDH levels. Similarly in NHL patients, levels of sFas also correlated directly and significantly with the presence of high stage disease. HD patients with B symptoms had significantly higher levels of sTNFRII.

Adolescent↗
PubMed2000

Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.

BACKGROUND: Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival. PATIENTS AND METHODS: We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. RESULTS: EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model. CONCLUSIONS: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.

Adolescent↗