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Biomedical subjects

N K Hareendran

Publications and source records attributed to N K Hareendran.

11 recordsLinked to original sources

Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.

India has one of the world's highest incidences of oral cancer. The habit of chewing betel quid is widespread and is suspected to play a role in the etiology of this disease. Studies in many other countries have also pointed to a role for human papilloma-viruses (HPVs) in the etiology of some oral cancers. In this study we analyzed biopsies from 91 Indian oral cancer patients, most of whom were betel quid chewers, by PCR amplification and direct DNA sequencing. HPV DNA was detected in 74% of these lesions, of which 41% had multiple HPV infections. Among the lesions from different oral sites, lesions of the tongue had the highest rate (9 of 11) of HPV infection. These HPV prevalences are among the highest ever reported in oral cancers. As to individual HPV types, prevalences of HPV-6, HPV-11, HPV-16 and HPV-18 were 13%, 20%, 42% and 47%, respectively. No additional known or novel HPV types were detected. To understand the unexpectedly high prevalences of the "low-risk" types HPV-6 and HPV-11, we compared the subtypes and variants that were found in oral cancers against those from benign genital warts from the same patient population but found no differences. The high prevalence of HPV in the oral cancers of these Indian patients suggests that viral infection is an important etiological component, with betel quid probably causing additional mutagenic steps in the carcinogenic process.

Areca↗

CD2 related immunoregulation in oral cancer.

Sera from 93 patients with carcinoma of the buccal mucosa were analysed for its regulatory effect on CD2 antigen expression using anti CD2 monoclonal antibodies and sheep erythrocyte rosetting assay. The sera from 55.5% of the patients showed an inhibitory effect (blocker sera) while sera from 44.5% showed an enhancing effect (enhancer sera) on the CD2 antigen expression. An interesting feature observed was the dominance of enhancer sera in the early stages of the cancer, well differentiated squamous cell carcinoma and verrucous carcinoma. The regulatory effect of the sera had no correlation to the concentration of circulating immune complexes (CIC), ferritin, and serum immunoglobulins on an individual basis. Taken as a whole, the concentration of CIC was higher in the enhancer sera while the concentration of IgG and IgM were higher in the blocker sera. The dominance of enhancer sera in groups with better prognosis in clinical practice suggest a correlation with the presence of serum enhancing factors to a good prognosis. The correlation of regulatory status to the prognosis of the patient is examined as the second phase of the study.

Animals↗

Interferon and interleukin-2 induced spontaneous cell-mediated cytotoxicity: a preliminary evaluation.

The contribution of natural cell-mediated cytotoxicity and its modulation with biological response modifiers in antitumour immunity was evaluated in patients with precancers and cancers of the oral cavity. The results were compared to those in normal controls. Both groups of patients showed highly significant depression of the natural killer cell activity. This depression was stage-related, suggesting an influence of tumour or tumour products on this activity. Depression in augmentation of this cytotoxicity was evident in both patient groups with cancers and precancers, suggesting a defect in the response of killer cells to biological response modifiers for reasons other than the tumour per se.

Cells, Cultured↗

Lymphocyte subset distribution after radiation therapy for cancer of the uterine cervix. Possible prognostic implications and correlation with disease course.

An analysis of lymphocyte subpopulations was done in patients with cancer of the uterine cervix before and at different intervals after the commencement of radiation therapy. A common feature was a duration of T-cell and B-cell lymphopenia after therapy. The findings relating to the T-cell subsets were interesting. Although the CD4/CD8 ratio remained unchanged in Stages I/IIA for 24 months after treatment, patients with Stages IIB and III showed a lowering of the ratio immediately after treatment. Distinctive patterns of lymphocyte subset distribution were seen in a comparison between patients who were disease-free and those with recurrent disease. The CD4+ cell counts and CD4/CD8 ratio differed between the two groups, with consistent lowered values during the follow-up associated with recurrent disease. This study demonstrates the effects of radiation therapy in altering lymphocyte subset distribution, resulting in characteristic patterns which could be used as clinical and prognostic indicators.

Antibodies, Monoclonal↗

Interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis: clinical implications for oral precancerous lesions.

Reduced natural killer cell activity was observed in patients with oral leukoplakia and submucous fibrosis compared with normal control subjects. However, the number of target binding lymphocytes was found to be normal in these precancers. Treatment of effector cells with interferon-alpha resulted in highly elevated active killer cell activity, although no change was observed in target binding lymphocyte counts. This finding could imply that precytotoxic cells that are activated by interferon exist in peripheral blood or that direct recruitment of a new cell population takes place. In addition, altered target lysis kinetics was observed, with interferon-activated killer cells demonstrating a tremendous lytic activation that is completed so quickly that a statistical kinetic analysis could not be accurately done. Because natural killer cell activity is an important effector system in immunosurveillance against tumors, its modulation with interferon may be an exciting clinical possibility in the control of malignant transformation or oral precancers.

Analysis of Variance↗

Clinical and prognostic significance of concanavalin-A-induced suppressor cell activity in malignant cervical neoplasia.

Peripheral blood lymphocytes from patients with different stages of cancer of the uterine cervix were analysed for concanavalin-A-induced suppressor cell activity. All cancer patients had high levels of suppressor activity, the increase corresponding to tumour load. Radiotherapy resulted in further increase of suppressor activity. About six months after radiotherapy, patients who remained disease free returned to pretreatment levels of suppressor cell activity and later showed even lewer levels of suppression. On the other hand, patients who developed recurrent disease maintained sustained high levels of suppression and for all stages they always had higher suppressor activity than the patients who remained disease free in the corresponding stage. These results stress the importance of a possible deranged immune system in these patients and also shows the clinical and prognostic significance of the assay.

Female↗

Radiation associated eosinophilia and monocytosis in carcinoma of the uterine cervix: a simple reliable clinical and prognostic indicator.

Clinical and prognostic significance of radiation associated eosinophilia (RAE) and radiation associated monocytosis (RAM) was evaluated in 176 patients with squamous cell carcinoma of the uterine cervix followed up after radiotherapy. Significant RAE was noticed in patients with Stages I/IIA and IIB who remained disease-free after treatment. On the contrary, patients belonging to these two stages but who developed recurrent disease showed absence of RAE. These patients as well as those belonging to Stage III showed considerably higher levels of RAM as compared to those patients remaining disease-free. These observations showed the usefulness of these two simple inexpensively carried out parameters in prognosticating disease course in malignant cervical neoplasia.

Carcinoma, Squamous Cell↗

Immunocompetence in lung cancer. Relationship to extent of tumor burden and histologic type.

In vitro assays of immunocompetence were done in 60 patients with differing extents of tumor load and various histologic types of lung cancer and were compared to values obtained for 60 normal controls. Profound alterations in monoclonal antibody-defined T-lymphocytes and circulating B-cells were seen. All patients showed impaired blastogenic response to the mitogens used with the exception of a normal response to pokeweed mitogen (PWM) in patients with localized disease. Increase levels of serum IgG were seen in patients with localized disease whereas high levels of IgA was seen in patients with more advanced disease. Distant metastases were associated with low IgM levels. All patients studied regardless of stage and histologic type had elevated levels of circulating immunocomplexes. These findings indicate gross immunologic abnormalities in these patients.

Adenocarcinoma↗

Immune reactive proteins as prognostic and clinical markers in malignant cervical neoplasia.

The significance of immune reactive proteins in malignant cervical neoplasia, with particular reference to its prognostic and clinical relevance, was studied in 229 patients. All stages of the disease showed elevated levels of circulating immune complexes (CIC). Patients with stages I/IIA showed elevated levels of IgG, whereas those with stages III and IV showed depressed IgM levels. In the case of IgA, the situation was reversed: patients with advanced disease showed increased levels. Radiotherapy resulted in highly elevated levels of CIC, IgG, and IgA. However, in patients who remained disease-free after radiation treatment, levels of these proteins came down, often falling below pretreatment levels. On the other hand, patients developing recurrent disease showed sustained, high levels of CIC and IgA, with IgG as an isolated case in stage I/IIA. The present study therefore shows that although these increases were non-tumour-specific, patients with persistent elevation of CIC and IgA levels were at much greater risk of developing recurrent disease, thereby proving the merit of these substances as markers in prognosticating the course of disease in malignant cervical neoplasia.

Antigen-Antibody Complex↗

Interleukin 2 production in lymphocyte cultures: a rapid test for cancer-associated immunodeficiency in malignant cervical neoplasia.

Peripheral blood lymphocytes of patients with malignant cervical neoplasia were studied for their capacity to produce interleukin-2 (IL-2) upon in vitro mitogen stimulation. Patients with early disease (Stage I/IIA) showed levels comparable to normal controls but those with advanced disease showed reduced levels, the reduction increasing with tumour load. These findings excellently correlated with our previous observations on a depressed cellular immunity in these patients. On follow up of the patients it was noticed that those who developed recurrent disease showed sustained lower levels of IL-2 production compared to those who remained disease free. These results stress the importance of a deranged immune system in these patients and also shows the clinical and prognostic value of such an assay.

Carcinoma, Squamous Cell↗

Immune function in malignant cervical neoplasia: a multiparameter analysis.

Immunological assessment was carried out in 67 patients with various stages and histological grades of squamous cell carcinoma of the uterine cervix and compared with normal controls to discover whether any of these parameters could be used as an indicator of the patient's clinical status. The results show a gross impairment of the various lymphocyte subpopulations and anti-tumor immunity. This impairment was more pronounced in patients with high tumor load and having a histology of poorly differentiated squamous cell carcinomas. None of the parameters studied (total leukocyte numbers, lymphocyte subpopulations, leukocyte adherence inhibition test, natural killer cell activity, circulating immune complexes, and blocking effect of autologous serum) could be used as a clinical indicator, since no correlation could be noted between immune impairment and either the lymphocyte subpopulations or the circulating immune complexes.

Adult↗