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Biomedical subjects

M R Pillai

Publications and source records attributed to M R Pillai.

At least 73 records · Page 4Linked to original sources

Alterations in expression of basement membrane proteins during tumour progression in oral mucosa.

Expression of three basement membrane proteins--collagen IV, laminin and fibronectin--was studied in normal, hyperplastic, dysplastic and neoplastic conditions of the oral mucosa using immunohistochemistry. Collagen IV and laminin exhibited similar staining patterns, while fibronectin showed a different pattern of expression. The expression of collagen IV and laminin also demonstrated an inverse correlation between staining intensity, thickness and basement membrane continuity in various stages of tumour progression. In contrast to the continuous and intense staining of basement membrane in normal oral mucosa with collagen IV and laminin antibodies, severe dysplasia and carcinoma exhibited discontinuous, thin and weakly stained basement membrane. The expression of fibronectin showed a direct correlation with extent of tumour progression. In normal mucosa, expression of fibronectin was almost absent, whereas in carcinoma intense expression of fibronectin was evident in the basement membrane and basal cells. These results emphasize the value of basement membrane proteins as biological markers for assessing oral carcinogenesis.

Antibodies, Monoclonal↗

Alterations in expression of terminal differentiation markers of keratinocytes during oral carcinogenesis.

Expression of cytoskeletal proteins has been shown to be dependent on the differentiation status of the tissue. In the present study, expression of two cytoskeletal proteins normally present in terminally differentiated keratinocytes, namely cytokeratin types 10/11 and involucrin, were studied in different stages of tumour progression in the oral mucosa. Results showed that cytokeratins 10/11 and involucrin strongly correlated with the differentiation status of cells. High expression was observed in non-dysplastic hyperplastic epithelium as compared to normal, dysplastic and neoplastic epithelium. In addition, various grades of dysplasia showed an inverse correlation with expression of these proteins. Statistical analysis of the results also showed a negative correlation between the differentiation of upper spinal cells and the stage of tumour progression. It therefore appears that the proteins studied may be useful as markers for epithelial carcinogenesis.

Biomarkers, Tumor↗

Co-expression of ras p21 and epidermal growth factor receptor during various stages of tumour progression in oral mucosa.

Ras p21 and epidermal growth factor receptor (EGFR) have commonly been implicated in a variety of malignancies. The present study immunohistochemically analysed the relationship between the expression of ras p21 and EGFR in normal, premalignant and malignant lesions of the oral mucosa. Except for normal mucosa, all other lesions showed a more or less similar expression pattern of both ras p21 and EGFR. It was also observed that the expression of both proteins was mostly confined to the basal or basaloid cells of the leucoplakia and carcinoma lesions, respectively. Normal keratinizing type mucosa showed expression of ras p21 and EGFR in the basal and lower spinal cells. However, in non-keratinizing mucosa the expression of ras p21 was totally negative while EGFR was restricted to the basal cells. Statistical analysis revealed a good correlation between the expression of ras p21 and EGFR with the various histological stages of tumour progression. The presence of these proteins in immature dividing cells of premalignant and malignant lesions thus emphasizes their relationship with cell proliferation.

ErbB Receptors↗

Differential expression of cytokeratin proteins during tumour progression in oral mucosa.

The expression pattern of cytokeratin filaments in epithelia has been shown to be dependent on their type and grade of differentiation. The type of expression of cytokeratin in a cell may also be altered during carcinogenesis or other pathological conditions. The present study examined the alterations in expression of various cytokeratin types during different stages of tumour progression in the oral mucosa. Six monoclonal anti-cytokeratin antibodies were used for the study. Conspicuous staining differences with these antibodies were evident between normal keratinizing and non-keratinizing mucosa. These differences can be correlated to the differentiation pattern of the normal mucosa types. Antibodies specific to cytokeratin types 10/11, 19 and 14 showed significant correlation with stage of tumour progression. In addition cytokeratin type 18 also showed prominent differences in expression between different stages of tumour progression. These alterations in cytokeratin expression suggest that the terminal differentiation pathway of keratinocytes is disturbed during oral carcinogenesis. The results of the present study also emphasize the potential of using cytokeratin filaments as markers in the biological staging of oral premalignant and malignant lesions.

Antibodies, Monoclonal↗

99mTc-complexes of a pentadentate amine-oxime ligand.

Synthesis and characterization of a new pentadentate amine-oxime ligand, 3,3,11,11-tetramethyl-7-benzyl-4,7,10-triazatridecane-2,12- dionedioxime is reported. The technetium complexes of this ligand was formed by direct reduction of TcO4- in the presence of the ligand at pH 9. The radiochemical yield of the complex is greater than 95% with 10(-7) M 99TcO4-. The technetium complex formed is a positively charged chelate that elutes as a single peak on a reverse phase HPLC. Biodistribution studies in rats showed an uptake of 1.4% of the injected activity at 15 sec p.i. in heart, but the wash-out was fast. The high radiochemical purity and stability of this 99mTc-chelate indicate that these types of chelates hold potential for development of bifunctional chelating agents (BFCAs).

Animals↗

Oral cancer and human papillomaviruses: is there a link?

Cancer of the oral cavity accounts for almost 56,000 new cases in India each year totalling almost 30% of all cancer cases in the country. Despite the numerous advances in etiology and epidemiology, the mechanisms involved in oral carcinogenesis remain obscure. Current research has provided some provocative results, suggesting an association between human papillomavirus (HPV) and development of squamous cell tumors including oral cancer. Evidence has been presented showing HPV infection of the oral mucosa and its relation to neoplastic changes. However a clear cut association as is evident in the uterine cervix is not yet available. However, considering the many similarities between oral and cervical oncogenesis, many of the HPV induced changes in the cervix may also be applicable to the oral mucosa. This paper studies the evidence for the possible role of HPV infection in oral carcinogenesis, the uterine cervix as a model for HPV mediated carcinogenesis, and tries to determine if similar mechanisms could exist in both cases.

Female↗

Expression of lectin-specific cellular glycoconjugates during oral carcinogenesis.

The binding pattern of two lectins, concanavalin A (ConA) and peanut agglutin (PNA), in various phases of tumour progression in the oral epithelium was studied. These included non-dysplastic, dysplastic and neoplastic lesions as well as normal tissue. ConA and PNA showed intense staining in the basement membrane of all types of lesions. Little difference was observed in the staining patterns between different stages of oral carcinogenesis, either with ConA or PNA. ConA showed mild cytoplasmic and membrane staining in all types of lesions while PNA showed moderate to intense staining in both the cytoplasm and membrane of lower-layer cells in all histological groups. The present study therefore shows that these lectins have limited value in the elucidation of oral carcinogenesis and are of insignificant diagnostic value.

Carcinoma↗

Ultrastructural variations and assessment of malignant transformation risk in oral leukoplakia.

Oral cancer is the most common malignancy in India, having a well defined precancerous state, leukoplakia. Various follow-up studies have shown that only 4 to 18% of oral leukoplakia lesions subsequently progress into invasive malignancy over a period of time. This study evaluates the potential of electron microscopy in the early detection of malignant changes in leukoplakia. The study revealed that of the 25 leukoplakia lesions examined, 7 showed changes akin to malignancy. Predominant ultrastructural alterations observed were reduplication and discontinuity of the basal lamina, basal cells with pleomorphic and bizarre nuclei containing perichromatin and interchromatin granules, prominent intercellular spaces and poorly formed desmosomes. Since none of these changes were evident under light microscopy the study demonstrates the value of electron microscopy in evaluating oral carcinogenesis. A long term follow-up of such patients is needed to understand the prognostic implications of these ultrastructural variation and how they can be used as a base line for better light microscopic evaluation.

Cell Transformation, Neoplastic↗

Immuno-pathological and immunological features of oral precancers.

Cancer of the oral cavity and oropharyngeal regions constitute about 30% of all cancers seen in India, with Trivandrum District in southern India having one of the highest incidence. Despite easy accessibility for examination and diagnosis, these tumours still cause high mortality, emphasizing the need for better methods of diagnosis and more importantly prognosis. Most oral carcinomas initially present as premalignant lesions and hence understanding their biology and behaviour is vital to the management and control of the disease. This review presents some of the clinico-pathological, immuno-pathological and immunological aspects of oral precancers.

Antibody Formation↗

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↗

Biolocalization and cell labeling properties of neutral-lipophilic 99mTc-amine-phenol chelates.

99mTc-diamine-diphenol chelates are neutral lipophilic chelates exhibiting good stability in aqueous solutions. The cell labeling and biolocalization properties of four different 99mTc-amine-phenol complexes were determined. All four chelates readily labeled leukocytes and RCBs in high yields. Even though 99mTc was retained by the cells, the elution rate of 99mTc from the labeled cells in plasma at 37 degrees C was unacceptably high for potential utility in scintigraphic imaging. The uptake of 99mTc in brain or heart following i.v. injection of the chelates in rats was low and clearance of activity from the blood was slow.

Animals↗

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↗

Labeling of human serum albumin with 105Rh-cysteine complexes.

The conjugation of a complex formed by reacting RhCl3 with cysteine to human serum albumin has been investigated. Approximately 50% of the rhodium (labeled with 105Rh) was converted to the complex. Conjugation of the complex to HSA via the ECDI method resulted in yields of approximately 40% of the total rhodium or approximately 80% of the Rh-cysteine complex. No conjugation was observed in the absence of the ECDI. At approximately equal molar concentrations of rhodium and HSA, an average of approximately 0.4 rhodium atoms per HSA molecule was achieved.

Cysteine↗

Labeling of hematoporphyrin with 105Rh and binding studies with human gamma globulin.

Labeling of hematoporphyrin with 105Rh at stoichiometric concentrations is described. Labeling efficiencies of up to 93% could be obtained at pH 9.0 in bicarbonate buffer. Solvent extraction of 105Rh-hematoporphyrin into methyl isobutyl ketone was used to estimate the complex yield. The complex showed high stability and no loss of 105Rh was seen throughout the 6 days of study. 105Rh-hematoporphyrin when incubated with human gamma globulin was seen to be quantitatively bound to the protein. This procedure may be used for labeling monoclonal antibodies with 105Rh for therapeutic applications.

Hematoporphyrins↗

Labeling of proteins using [105Rh]Rh-4-(p-aminobenzyl)-diethylenetriamine.

A bifunctional ligand 4-(p-aminobenzyl)-diethylenetriamine has been synthesized. 105Rh complexes with this ligand were prepared with an overall yield of 79% at pH 9.0 in bicarbonate buffer. The preformed complex was converted to the isothiocyanate derivative using thiophosgene. Conjugation yields of 75% with IgG and 85% with HSA could be obtained for a 4 h conjugation reaction. Affinity chromatography of human-IgG coupled to the rhodium complex in an anti-human IgG agarose gel indicated no denaturation of the labeled protein. The procedure reported here can be adapted for the preparation of 105Rh-labeled antibodies for therapeutic applications.

Immunoglobulin G↗

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 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↗