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Biomedical subjects

M K Nair

Publications and source records attributed to M K Nair.

At least 19 recordsLinked to original sources

Mutagen sensitivity as a predisposing factor in familial oral cancer.

Pedigree analysis of the oral cancer (OC) patients registered at our Centre had disclosed familial aggregation of oral cancer which hitherto has not been largely reported. There is a paucity of information on the genetic determinism for familial oral cancer predisposition. Therefore, we investigated constitutional chromosome abnormalities and bleomycin-induced chromosome sensitivity of 7 familial and 10 sporadic oral cancer patients and 14 unaffected family members (first-degree relatives) to determine whether these factors could give any clues regarding cancer-predisposing factors. Neither the oral cancer patients nor the unaffected family members showed any constitutional chromosomal abnormalities. However, with regard to bleomycin sensitivity, there was significant difference between the oral-cancer patients and unaffected relatives. The mean b/c value was 1.68 +/- 0.48 for familial OC patients, 1.12 +/- 0.36 for sporadic OC patients and 0.52 +/- 0.18 for the unaffected family members (p < 0.001). A noteworthy observation was that one unaffected family member also showed bleomycin hypersensitivity and expressed a mean b/c value of 1.32, at the initiation of the study. That patient later developed oral carcinoma. This clearly demonstrates that mutagen hypersensitivity among unaffected relatives in OC families may be related to cancer predisposition. The mutagen sensitivity study is being continued in a larger series of subjects, for the development of a cytogenetic marker for prediction of cancer susceptibility.

Adolescent

Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions.

With the ultimate goal of characterizing the molecular pathogenesis of oral cancer, the most predominant malignancy in India, immunocytochemical evaluation of p53 and bcl-2 proteins was carried out in hypeplastic oral mucosa, dysplastic oral mucosa and invasive oral cancer. All subjects gave a similar and almost uniform history of prolonged use of betal quid and tobacco. Expression of p53 was insignificant while bcl-2 was absent in hyperplastic leukoplakia lesions. Both proteins were however expressed in leukoplakia with apparent dysplasia. Almost all invasive cancer lesions showed high levels of both p53 and bcl-2. Good correlation was therefore evident between expression of these two proteins and increasing histologic abnormality. Moreover relative risk evaluation revealed that lesions expressing p53 and bcl-2 had a high probability of having a histology of dysplasia or worse. Since it has been previously shown that wild type p53 regulates the expression of bcl-2, it may be presumed that the protein detected in the dysplastic and malignant oral tissue is of the mutant type. It is also known that p53 is a positive regulator of programmed cell death or apoptosis while bcl-2 is an anti-apoptotic protein. This suggests the possibility that alterations in p53 followed by over-expression of bcl-2 occur early in oral carcinogenesis resulting in defective apoptosis and subsequent tumor progression.

Cell Count

Differential expression of jackfruit-lectin-specific glycoconjugates in metastatic adenocarcinoma and reactive mesothelial cells-a diagnostic aid in effusion cytology.

Distinguishing reactive mesothelial cells from adenocarcinoma cells in serous effusions on the basis of morphological criteria alone is often difficult. Interest has therefore been focused on identifying reliable methods to supplement the conventional cytological techniques. Plant lectins have been reported as diagnostic markers for malignant cells. We studied 51 aspirated samples of benign and malignant effusions using horseradish-peroxidase-conjugated jackfruit lectin. No significant difference was observed between the cells of pleural and peritoneal fluids. The reactively proliferated mesothelial cells of benign effusions showed a predominance of mild staining while moderate and intense staining was predominant in malignant effusions. Intense and irregular lectin binding was observed in macrophages irrespective of the cause of effusion. The lectin staining method therefore appears to have some clinical significance as an additional diagnostic aid for use in effusion cytology.

Adenocarcinoma

Clinical implications of cytogenetic classification in adult acute lymphoblastic leukaemia patients.

Cytogenetic analysis performed on pretreated unstimulated, bone marrow/peripheral blood samples of 46 adult patients with acute lymphoblastic leukaemia (ALL) showed sufficient metaphases in 39 patients and insufficient metaphases in 7 patients. G-banded karyotype analysis of these 39 patients revealed non-random clonal chromosome abnormalities in 31 patients and apparently normal karyotypes in 8 patients. Numerical abnormalities involving chromosome trisomies and structural abnormalities involving different types of chromosomal translocations and deletions were encountered in varying percentages. These patients were grouped into various cytogenetic subsets on the basis of their karyotype pattern and followed-up to evaluate their prognosis. Patients with apparently normal karyotypes showed good prognosis and those with 6q- showed intermediate prognosis. But all other patients with hyperdiploid, pseudodiploid and hypodiploid karyotypes were associated with poor prognosis. Cytogenetic classification of ALL patients is thus of clinical importance, as it helps the early identification of clinically important prognostic groups.

Adolescent

Lectin histochemistry of oral premalignant and malignant lesions: correlation of JFL and PNA binding pattern with tumour progression.

The expression of glycoconjugates specific to Jack fruit lectin (JFL) and peanut agglutinin (PNA) in various clinicopathological stages of tumour progression in the oral mucosa were studied. These included various clinical forms of dysplastic and non-dysplastic oral leucoplakias, carcinomas, normal keratinising (gingiva) and non-keratinising (buccal mucosa) epithelia. It was seen that the binding patterns of PNA and JFL in the epithelial cells of various types of oral lesions were more or less similar. Normal non-keratinising epithelium showed mild membrane staining only in the spinal layers, while normal keratinising epithelium showed a moderate membrane staining and mild cytoplasmic staining in all layers. Moderate membrane and mild cytoplasmic staining were observed in leucoplakias, irrespective of various clinical or histological types. In carcinomas, the intensity of lectin binding was high, particularly in the membrane of differentiated cells. Correlation analysis of the binding pattern of PNA and JFL showed significant correlation in the membrane and cytoplasm of all layers with histological stages of tumour progression. The present study thus showed that PNA and JFL may be used as cytochemical probes in differentiating malignancy from benign lesions of the oral mucosa.

Carcinoma, Squamous Cell

Is oral cancer susceptibility inherited? Report of five oral cancer families.

All the oral cancer patients registered at the Regional Cancer Centre, Trivandrum, during January to July 1995 were subjected to detailed pedigree analysis. This revealed that oral cancer tends to aggregate in families. Like other familial cancers, a family history of oral cancer was associated mostly with an early age of onset of the disease. Family members without habits such as tobacco chewing, smoking or alcohol consumption were also affected. These observations prompt us to suggest the probable inheritance of an oral cancer susceptibility gene in these families. The familial aggregation, mostly site-specific, with an autosomal dominant mode of inheritance, was observed in 0.94% of the total oral cancers. This necessitates the need to undertake studies to elucidate the molecular lesions responsible for oral cancer susceptibility in families.

Adult

Ultrastructural analysis of the adjacent epithelium of oral squamous cell carcinoma.

Fifteen biopsies of the immediate adjacent epithelium of oral squamous cell carcinoma were examined under light and electron microscopy. Light microscopic examination of one micron thick sections revealed that the majority of lesions (67%) had hyperplastic or mildly dysplastic epithelium while the remaining (33%) had moderate to severe dysplasia. Ultrastructural observations showed that all these lesions had subcellular alterations similar to those seen in frank malignant oral tissue, particularly in the lower half of the epithelium. Important ultrastructural changes observed included bizarre nuclei of basal and lower spinal cells, enlarged and multiple nucleoli, presence of interchromatin and perichromatin granules, loss of desmosomes and marked spongiosis as well as disturbed cellular maturation sequences in the keratinocytes evidenced by abnormal and irregular distribution of maturation markers such as keratohyalin granules and tonofilaments. The present study thus shows the value of electron microscopy in the detection of malignant changes in the adjacent epithelium of oral squamous cell carcinoma.

Carcinoma, Squamous Cell

Nonrandom karyotype abnormalities in 36 multiple myeloma patients.

G-banded analysis performed on pretreated bone marrow samples of 36 multiple myeloma patients allowed the identification of clonal chromosome abnormalities. Abnormalities consisting of trisomies, monosomies, translocations, deletions, and marker chromosomes apparently followed a nonrandom pattern. The chromosomes involved in the production of abnormal karyotypes were numbers 1,2,3,11,12,14,17, and 18. Even though no specific chromosome pattern has been identified, the involvement of chromosomes 1, 3, and 14 was found to be more frequent. Many of the chromosomes and chromosomal breakpoints involved in these abnormalities correspond to the location of identified oncogenes or tumor suppressor genes. Hence, it is presumed that these chromosome abnormalities may be playing an important role in the genesis of multiple myeloma by altering the structure or function of oncogenes or tumor suppressor genes.

Adult

Evaluation of utilisation of health workers for secondary prevention of oral cancer in Kerala, India.

The utilisation of primary health workers (HWs) for cancer control in developing countries has often been suggested, based on the experience of feasibility studies in India and Sri Lanka. We initiated a project in 1988 to evaluate the long-term feasibility of using trained HWs in secondary prevention of oral cancer, to bring about earlier detection of oral cancer in the communities served by them. Two hundred and eighty-two HWs attached to 14 primary health centres (PHCs), serving approximately 0.92 million rural population in the northern half of Trivandrum district in Kerala, India, were trained in oral visual inspection to detect precancerous, malignant and other suspicious lesions of the oral cavity and refer them for confirmation and treatment. They were asked to examine subjects aged 35 years and above and to give person to person health education on tobacco in their target population. The HWs belonging to the PHCs serving approximately 1 million rural population in the southern half of Trivandrum district were not trained, and this region served as the control area. In addition to several process measures, stage distribution of oral cancer in subjects reporting from the intervention and control areas, as well as oral cancers referred by the HWs, as a proportion of total oral cancers from the intervention area, were the outcome measures evaluated. Only 9/282 (3.2%) trained HWs were motivated and they examined 17,812 eligible subjects in 3 years and referred 408 subjects with lesions; 258/408 (63.2%) referred subjects reported for further examination and ten oral cancers were detected among them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cervical cancer in Kerala: a hospital registry-based study on survival and prognostic factors.

The survival experience of 452 cervical cancer patients registered during 1984 by the hospital registry of the Regional Cancer Centre, Trivandrum, Kerala, India, is described in this paper. Eighty per cent of the patients completed the prescribed treatment, which was predominantly radiotherapy. The vital status of each patient was established by scrutiny of case records and by reply-paid postal enquiries. The observed survival rates were estimated by the Kaplan-Meier method and prognostic factors were assessed using Cox's proportional hazards regression analysis. The overall 5 year observed survival rate was 47.4% (95% CI, 41.6-52.9%). Socioeconomic status, performance status and the clinical stage of disease emerged as independent predictors of survival. Low survival was associated with advanced stages of disease, low socioeconomic status and poor performance status. The problems in studying survival from cancer in developing countries and the strategies used to improve follow-up rates in India are discussed. It is stressed that trends in survival rates may be used to evaluate cancer control programmes in developing countries in the absence of reliable mortality statistics and, even when mortality data are available, survival rates are valuable comparative statistics. Earlier detection by improving the awareness of the population and the physicians will improve survival rates, but a more effective and prudent approach would be to prevent invasive cervical cancer, and thereby reduce mortality, by implementing feasible and effective screening programmes in India.

Adult

Evaluation of mouth self-examination in the control of oral cancer.

This study was planned to evaluate the feasibility of mouth self-examination (MSE). Some 450 college students distributed to 9000 households a brochure describing the risk factors of oral cancer, the appearance of premalignant and malignant lesions of the oral cavity and the methods of MSE with pictures. All subjects with tobacco habits and/or aged 30 years or over were asked to read the brochure carefully and to report to the clinic conducted in their locality on fixed days, if they suspected an abnormality while practising MSE. Out of the approximately 22,000 eligible subjects, 8028 (36%) practised MSE. Among the 247 subjects reporting to the clinics seven (3%) had oral cancer and 85 (34%) had oral precancerous lesions; the others had either benign lesions or normal anatomical variations. Six of the seven subjects with oral cancer had stage I disease, five of whom accepted treatment and were alive disease-free 5 years later. The detection rates of oral cancer compared favourably with the previously reported detection rates using trained health workers. Although this study demonstrated that MSE is feasible, larger studies are required to evaluate whether health education could result in a sustained practice of MSE resulting in reduction in incidence of and mortality from oral cancer.

Adult

Evaluation of chemoprevention of oral cancer with Spirulina fusiformis.

The blue-green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p < 0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol or beta-carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

Adult

Implications of gynaecological abnormalities in pre-selection criteria for cervical screening: preliminary evaluation of 3602 subjects in south India.

Early detection and eradication of cervical cancer and its precursor lesions through organized mass cytological screening programmes have recently gained considerable attention in developing countries. Strategies for both cost saving and effective implementation are however required for mass cervical screening in developing countries. In an early cancer detection programme conducted in South India, we analysed cytological abnormalities in 3602 women and correlated the results with other factors, including age, gynaecological complaints, number of years of married life and parity to see if pre-selection for cytologic screening was possible. Only lower grades of dysplasia were found in asymptomatic women below the age of 40 years. In asymptomatic women, malignancy and higher grades of dysplasia were confined to women with a clinically abnormal cervix only. Univariate analysis also revealed that subjects with a parity of more than 3 and a married life of more than 20 years had a significantly higher number of cytological abnormalities. However, on a multivariate analysis the increased number of marital years was not found to be an independent variable. These results suggest that asymptomatic women below the age of 40 years with a married life of less than 20 years and parity below 3, may be excluded from screening campaigns, and that pre-selection for cytologic screening is possible by introducing a programme of clinical and speculum examination of the cervix.

Adult

Case report: brain metastases from papillary carcinoma thyroid.

Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of 0.1-5% in reported series. The clinical details of two cases of histologically proven brain metastases from papillary thyroid cancer treated in our centre are presented. In one patient, the lesion was in the cerebellar hemisphere, and in the other, the frontal lobe. Also presented is a review of the literature of this unusual clinical presentation.

Brain Neoplasms

Case report: spinal metastasis from carcinoma of the penis.

Carcinoma of the penis has a well documented metastatic pattern, regional lymph nodes being the predominant site of involvement. Distant metastasis is extremely rare, with a reported incidence of 1-10%. Osseous metastasis is even rarer and no case of metastasis to the spine has been reported previously. We present a case of carcinoma of the penis metastasizing to the spine.

Humans

Expression of galactoside-specific endogenous lectins and their ligands in human oral squamous cell carcinoma.

Human endogenous lectins have a wide spectrum of biological functions. The present study analyses the expression of beta-galactoside specific and N-acetyl-D-galactosamine specific endogenous lectins in oral squamous cell carcinomas using biotinylated neoglycoproteins. The expression pattern of beta-galactosyl-containing glycoconjugates or ligands of beta-galactoside specific lectins in these tissues was also studied using an endogenous biotinylated lectin, the human 14-kDa lectin. For comparison a galactoside specific plant lectin from mistletoe, Viscum album was also employed. The results demonstrate that oral squamous cell carcinomas mainly express accessible binding sites for lactosylated neoglycoprotein (90%) while few carcinomas expressed mild amount of N-acetyl-D-galactosamine specific binding sites (40%). There was no difference in the binding patterns of these probes between well and less differentiated carcinomas. Expression of these neoglycoprotein binding sites were mostly concentrated in immature basaloid cells, indicating a possible association with cell proliferation. The binding pattern of D-galactosyl specific lectins (human 14-kDa and mistletoe lectins) showed conspicuous differences. This feature emphasizes the caution that needs to be exercised in interpreting the biological significance of results attained using plant lectins on human tissue.

Acetylgalactosamine

A case-control study of diet and lung cancer in Kerala, south India.

A total of 281 male lung-cancer patients were identified from the hospital cancer registry in the Regional Cancer Centre in Trivandrum. The controls were selected from the visitors and patients' bystanders in the hospital. The recruitment of cases and controls started in 1990, and the present study used the cases registered in the first year. The questionnaire administered to cases and controls collected information on tobacco smoking and alcohol habits. Dietary data were collected using a food frequency questionnaire and were analyzed by multiple logistic regression producing odds ratio estimates of the relative risk and deviance chi-squared tests of significance. Analysis was done on the computer package, EGRET. All models included age, education, religion and smoking to adjust for the effect of confounding. Green vegetables and bananas were found to have a protective association with lung cancer. The odds ratio associated with the highest quartile of vegetable consumption compared with the lowest was 0.32 (95% confidence interval 0.13, 0.78). Forward stepwise regression analysis indicated pumpkins and onions as the most consistently significant protective factors. Animal protein foods and dairy products were found to have a predisposing effect on lung cancer in this study. The expected influence of smoking on lung cancer (a considerable increase in risk among smokers) provided evidence of the reliability of the data. In conclusion the results from this study show that diet has a role in lung cancer aetiology, although the association is weak compared to the effects of smoking.

Adult