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M G Deo

Publications and source records attributed to M G Deo.

At least 19 recordsLinked to original sources
PubMed1998

Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's lymphoma patients from India.

We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to testing the hypothesis that the presence of the L-myc S-allele predisposes towards NHL. We found no significant difference either in the distribution of the LL, LS and SS genotypes or in the allelic frequencies between the patient group and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and 0.46, respectively, in the control group. However, a higher proportion (70%) of the S-allele was observed in our control group of normal healthy volunteers. Thus, the presence of L-myc S-allele did not indicate increased susceptibility or predisposition to the malignancy.

Adolescent↗
PubMed1997

Establishment of a human squamous cell carcinoma cell line of the upper aero-digestive tract.

A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.

Animals↗
PubMed1997

Loss of p53 gene as a biomarker of high risk oral leukoplakias.

We have investigated loss of heterozygosity of p53 tumor suppressor gene in Indian oral cancer patients, individuals with premalignant leukoplakia lesions, and corresponding normal mucosa, to study the status of p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral mucosa from 18 individuals, were analysed. Peripheral blood cells (PBCs) from all the individuals and 47 normal healthy volunteers were also included in the study. Polymerase chain reaction(PCR) of p53 Exon4, followed by restriction enzyme digestion with AccII due to the enzyme polymorphic site at Exon4 codon72, was used to detect homozygosity/heterozygosity of p53 alleles, and compared with the allelic pattern in the corresponding PBC. The PCR product subjected to AccII digestion detected 259 bp, 160/99 bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribution in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 allele in early and advanced stages of oral cancers, as well as leukoplakias, perhaps indicating p53 LOH as one of the early events in oral carcinogenesis. Thus, p53 LOH may be useful as a biomarker in defining a certain population of high risk leukoplakias that may progress to oral cancer.

Adult↗
PubMed1997

Ability of lymphokine-activated killer cells to lyse mycobacteria-infected cells.

Lymphokine-activated killer (LAK) cells were generated by interleukin-2 activation of peripheral blood lymphocytes obtained from lepromatous leprosy (LL) patients and healthy individuals. The ability of LAK cells to lyse targets (macrophages and T-24, a bladder carcinoma cell line) infected with mycobacteria (Mycobacterium leprae and mycobacterial strain ICRC) was assessed in a 51 chromium-release assay. It was observed that LAK cells generated from LL patients and healthy individuals could preferentially lyse M. leprae or ICRC-pulsed macrophages and T-24 cells, compared to non-pulsed targets. The ability of LAK cells to kill intracellular mycobacteria was demonstrated in colony forming assays. These results indicate a promising role for LAK cells in immunotherapy of leprosy.

Carcinoma↗
PubMed1994

Leprosy vaccine.

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Bacterial Vaccines↗
PubMed1994

Detection and cloning of potent transforming gene(s) from chewing tobacco-related human oral carcinomas.

High molecular weight DNA isolated from 14 primary tumour tissues of human oral carcinoma patients was analysed for transforming activity by NIH3T3 co-transfection assay using pSV2neo gene as a selectable marker, followed by nude mouse tumorigenicity assay. Ten of the patient tumour tissues demonstrated molecular lesions in myc, ras or/and EGF-R genes, whereas 4 patients did not show tumour associated aberrations in these oncogenes. The G418-resistant transfected cells from 12 of 14 individual patients demonstrated transforming potential by colony formation in soft agar and tumour induction in nude mice within 25-80 days. DNAs from the transfected cells, consequent nude mice tumours and corresponding cell lines, contained human Alu sequences. Southern blot hybridisation with ras, myc, EGF-R oncogenes demonstrated the presence of human H-ras oncogene in one of the 12 sets of nude mice tumours. In contrast, DNA from the other 11 sets of nude mice tumours indicated absence of c-myc, N-myc, L-myc, H-ras, K-ras, N-ras and EGF-R genes on Southern analysis. Further, DNAs from five first cycle tumorigenic transformants were subjected to a second cycle of transfection, and induced tumours in nude mice with a shorter latency period of 21-50 days. The secondary transformants contained discrete human Alu sequences; however, the DNA did not hybridise with myc/ras/EGF-R probes. A genomic library was constructed from a second cycle nude mice tumour, using EMBL-3 as the vector. Four human Alu sequence positive clones were isolated on screening 2 x 10(5) plaques, and one of the recombinant clones subjected to fine restriction mapping using 16 restriction enzymes. The lack of association of the nude mice tumour DNA with myc/ras/EGF-R showing aberrations in the primary human tumour, implies activation of an alternative potent transforming gene(s) in the chewing tobacco-related oral carcinomas in India.

3T3 Cells↗
PubMed1994

Immunoprecipitation of mycobacterial antigens with sera from patients with leprosy.

Pooled sera from leprosy patients across the clinical spectrum, tuberculosis patients and healthy individuals were tested for their reactivity with antigens of Mycobacterium leprae and a panel of cultivable mycobacteria by immunoprecipitation technique. Sera from lepromatous leprosy patients demonstrated exclusive reactivity with the 26-kDa protein of M. tuberculosis H37Ra, 28-kDa protein of M. kansasii, 45-kDa protein of M. smegmatis, and 158, 40 and 14 kDa proteins of M. phlei. Sera from patients with borderline tuberculoid leprosy, tuberculoid leprosy, tuberculosis and health individuals failed to identify these antigens. Our studies indicate that analysis and characterization of immunodominant antigenic epitopes present on proteins of cultivable mycobacteria, sharing cross-reactive epitopes with M. leprae may prove to be important in the serodiagnosis of multibacillary leprosy as well as for developing vaccines for immunotherapy of leprosy.

Antigens, Bacterial↗
PubMed1994

Restriction fragment length polymorphisms of the human N-myc gene in normal healthy individuals and oral cancer patients in India.

Southern blot hybridization with N-myc oncogene probes coding for different regions of the N-myc gene demonstrated three polymorphic restriction sites in the Indian population. The SphI and PvuII polymorphic pattern due to the SphI polymorphic site in the second intron and the PvuII polymorphic site in the 3'-region of the human N-myc oncogene respectively, was similar to that reported in the Japanese population. The allelic frequency distribution for SphI polymorphism did not differ significantly for the S1 and S2 alleles representing presence (allele S1) or absence (allele S2) of a SphI site. However, the allelic frequency distribution was distorted in the case of PvuII polymorphism, as the frequency of P1 allele (0.7) indicating presence of PvuII site, was higher than the P2 allele (0.3) indicating absence of PvuII site, in the Indian population. An additional polymorphic HindIII site localised in the second intron of the N-myc gene was also observed in both the Indian oral cancer patients and the normal healthy individuals, indicating that this RFLP was not tumor associated and may perhaps represent N-myc alteration in the Indian population.

Genes, myc↗
PubMed1993

Enhancing factor, a Paneth cell specific protein from mouse small intestines: predicted amino acid sequence from RT-PCR amplified cDNA and its expression.

Enhancing factor (EF), a Paneth cell specific growth factor modulator, has been identified in our laboratory from mouse small intestines. In this paper we describe generation of an EF specific cDNA by RT-PCR and its sequence. The predicted amino acid sequence was found to be similar to, and hence confirms, the partial amino acid sequence obtained earlier by protein sequencing. In Northern blot analysis, a 1 kb transcript was observed in intestinal RNA alone. In situ hybridization indicated that the EF gene is expressed exclusively in the Paneth cells. The present study indicates that EF is an isoform of PLA2 type II, with a unique tissue distribution, found predominantly in the Paneth cells of the small intestines. Further, based on the properties of EF, we propose that isoforms of PLA2, belonging to type II, may be involved in regulation of cell proliferation via EGF binding.

Amino Acid Sequence↗
PubMed1993

Enhancing factor protein from mouse small intestines belongs to the phospholipase A2 family.

Enhancing factor (EF), a growth regulatory molecule, isolated from mouse small intestines, has been well characterized in this laboratory. It increases the binding of epidermal growth factor in a unique manner via its own receptor. In the first 20 N-terminal amino acids sequenced, EF showed 50% homology to human Group II phospholipase A2 (PLA2). Here we propose that EF is yet another, unidentified isoform of PLA2 which regulates cell proliferation via modulation of EGF binding. To our knowledge, this is the first report implicating PLA2-II-like molecules in growth regulation.

Amino Acid Sequence↗
PubMed1993

Molecular lesions in human oral cancer: the Indian scene.

Carcinogenesis is a multi-step process including aberrant expression of two interacting classes of genes--oncogenes and tumour suppressor genes. With recent technological advances, it is feasible to identify the various molecular lesions underlying the different stages of neoplasia. Squamous cell carcinomas of the head and neck, although representing 2-4% of the malignancies in the West, comprise a large fraction (40%) of total cancers in India, posing a major health problem. Further, epidemiological and experimental evidence unequivocally confirms a causal association between tobacco chewing habit, highly prevalent in India, and oral cancers. Thus, the oral cancers offer an excellent in vivo system for the study of the environmental tobacco-carcinogen induced molecular alterations in the malignancy, and associated premalignant lesions such as leukoplakia. With a view to elucidating the molecular lesions involving oncogenes in oral carcinogenesis, we have investigated myc/ras/EGF-R activation by amplification, point mutation, gene rearrangement and allelic losses. Further, a functionally activated potent transforming gene was detected in a NIH3T3 transfection/tumorigenicity assay, unrelated to myc/ras/EGF-R. Studies on the involvement of p53 gene in oral cancer, indicates p53 allelic loss as an event observed in leukoplakia and tumour tissues. Advanced oral cancer stages demonstrate cumulative molecular aberrations, with greater than 95% samples showing oncogene involvement, thus indicating a multi-step process of oral carcinogenesis. The review presents a comparative picture of the oral malignancies seen in Western countries and India, significance of molecular lesions and future perspectives of oncogenes and tumour suppressor gene involvement in oral cancer.

3T3 Cells↗
PubMed1993

H-ras-1 restriction fragment length polymorphism in normal individuals and oral cancer patients in India.

Restriction fragment length polymorphism (RFLP) of the human H-ras-1 gene has been indicated as a marker for detection of individuals at high risk of cancer. We have investigated the association of RFLP at the H-ras-1 locus and susceptibility to oral cancer by Southern hybridization analysis in 77 primary oral tumors and 99 healthy donors. The frequency distribution of the BamHI fragments of H-ras-1 revealed homozygous or heterozygous alleles in the two subpopulations. The heterozygous genotype occurred more frequently in the normal subjects (53%) as compared to the cancer patients (36%). Four common alleles-C1 to C4, were noted predominantly in both groups, with rare alleles detected at a lower frequency. The common allele with 7.6 kb BamHI fragment was significantly higher in normals (10%) than in the tumor population (4%) (P < 0.05). However, a similar distribution of rare alleles in both groups indicated that the presence of rare alleles is not indicative of predisposition to oral cancer.

Alleles↗
PubMed1993

Immunoreactivity of mycobacterial strain ICRC and Mycobacterium leprae antigens with polyclonal and monoclonal antibodies.

ICRC, a cultivable mycobacterium, is undergoing clinical trials as an antileprosy vaccine in India. In the present study, we have investigated the crossreactivity between antigens of the mycobacterial strains of ICRC and Mycobacterium leprae using polyclonal and monoclonal antibodies in a radioimmunoprecipitation assay. It was observed that polyclonal anti-ICRC and anti-M. leprae antibodies showed predominant reactivity to a 21-kDa protein of the mycobacterial strain ICRC and the 21- and 14-kDa proteins of M. leprae. Crossreactivity between the antigens of the mycobacterial strains ICRC and M. leprae was established further by using M. leprae-specific monoclonal antibody WML06 (reacting with the 14-kDa protein of M. leprae), which identified the 21- and 14-kDa proteins of the mycobacterial strain ICRC. Thus, our studies demonstrate that the 14-kDa protein of M. leprae, which is known to harbor T- and B-cell epitopes, shares crossreactive antigenic determinants with the 21- and 14-kDa proteins of the mycobacterial strain ICRC. We believe that such proteins may provide important reagents for designing subunit vaccines and for determining skin-test reagents.

Animals↗
PubMed1993

Lymphocyte proliferation, IFN-gamma production and limiting dilution analysis of T-cell responses to ICRC and Mycobacterium leprae antigens in leprosy patients.

Lymphocyte proliferative responses and interferon-gamma (IFN-gamma) production after stimulation with antigens of ICRC, Mycobacterium leprae, and purified protein derivative (PPD) were assessed in leprosy patients and healthy donors. The patients studied were newly diagnosed as having lepromatous leprosy (LL), multidrug therapy (MDT) responders (MDT-R LL), MDT nonresponders (MDT-NR LL), borderline lepromatous (BL), and borderline tuberculoid/tuberculoid (BT/TT) leprosy. The tuberculoid leprosy patients showed increased lymphocyte proliferation and IFN-gamma production in response to stimulation with ICRC, M. leprae, and PPD antigens compared to other groups of LL patients and healthy donors. Although lymphocytes from LL patients showed low responses to ICRC and M. leprae antigens, their responses to PPD were not grossly affected. MDT-R LL patients showed higher lymphocyte proliferative responses and IFN-gamma production after stimulation with ICRC and PPD but not with M. leprae antigens. Tuberculoid leprosy patients showed higher T-cell frequencies to ICRC and M. leprae antigens compared to MDT-R LL and MDT-NR LL patients. The increased lymphocyte proliferative responses to ICRC observed in the MDT-R LL patients was reflected in the increased T-cell frequency to ICRC compared to M. leprae.

Antigens, Bacterial↗
PubMed1992

Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer.

The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers.

Adult↗
PubMed1992

Major proteins of mycobacterial strain ICRC and Mycobacterium leprae, identified by antibodies in sera from leprosy patients and their contacts.

Sera from leprosy patients across the clinical spectrum, healthy contacts, tuberculosis patients, and healthy donors were tested for their reactivity with antigens of mycobacterial strain ICRC (a cultivable mycobacterium) and Mycobacterium leprae by immunoprecipitation technique. Using M. leprae antigens, it was not possible to distinguish between reactivities of sera from lepromatous, borderline lepromatous, borderline tuberculoid, and tuberculoid leprosy patients. All these sera identified M. antigens with molecular masses of 47, 36, 21, and 14 kDa. When the same sera were tested for their reactivities with antigens of mycobacterial strain ICRC, several differences were observed. The 21-kDa antigen of mycobacterial strain ICRC was exclusively precipitated by sera from all lepromatous leprosy patients and from those undergoing erythema nodosum leprosum reaction. Sera from all the other donors tested failed to identify the 21-kDa antigen of mycobacterial strain ICRC. The 14-kDa protein of mycobacterial strain ICRC was identified by sera from a few lepromatous leprosy patients (5 of 26) and all their contacts. Our studies indicate that antigens present on cultivable mycobacteria rather than species-specific antigens may prove to be useful in the serodiagnosis of leprosy.

Antibodies, Bacterial↗