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Biomedical subjects

M R Pillai

Publications and source records attributed to M R Pillai.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cellular manifestations of human papillomavirus infection in the oral mucosa.

BACKGROUND AND OBJECTIVES: Human papillomavirus infection has been suggested to play a role in the development of epithelial carcinomas, particularly those of the uterine cervix. Less information is available on the role of the virus in oral lesions. It has been proposed that the viral oncoproteins specifically complex with the products of cellular tumor suppressor gene, namely E6 with p53 and E7 with retinoblastoma gene product. Inactivation or mutation in p53 gene is also known to result in loss of control over the cell cycle and increases in tumor proliferation rates. The present study examines the role of HPV infection in relation to p53 and the extent of the tumor proliferative compartment reflected by cyclin D1 and Ki-67 expression during various phases of tumor progression in the oral epithelium. METHOD: Nonisotopic in situ hybridization (NISH) was performed to detect HPV 6/11 and 16/18. Expression of p53, cyclin D1, Ki-67, and the HPV 16/18 E6 protein were detected by immunocytochemistry. RESULTS: There was significant correlation between the extent of histological abnormality and HPV infection. A correlation (r = 0.250, P = 0.0089) was evident between the presence of HPV 16 and occurrence of invasive cancer. Expression of the tumor suppressor p53 protein also showed significant positive correlation with histology (r = 0.475, P = 0.00004). The tumor proliferative fraction also increased with the extent of histological abnormality (r = 0.387, P = 0.0003 for cyclin D1 and r = 0.463, P = 0.0001 for Ki 67). Accumulation of p53 and increase in tumor proliferation also correlated to the presence of HPV infection (r = 0.511, P = 0.00003 for p53; r = 0.478, P = 0.00002 for cyclin D1 and r = 0.521, P = 0.00004 for Ki-67). CONCLUSIONS: The present study thus demonstrates the importance of HPV infection in oral tissue. Expression of the high-risk HPV 16/18 E6 protein also appears to be a critical event along with aberrant p53 expression. These results are of significance to the molecular epidemiology of oral cancer and may also be used to supplement and elaborate the diagnosis of oral lesions.

Cyclin D1↗
PubMed1999

bcl-2 immunoreactivity but not p53 accumulation associated with tumour response to radiotherapy in cervical carcinoma.

PURPOSE: This study seeks to define the role of pretreatment expression of the tumour-suppressor p53 protein and the anti-apoptotic protein bcl-2 and their relationship to tumour response to radiotherapy in cervical carcinoma. METHODS: A total of 101 patients were evaluated and the possibility of a correlation done between the pretreatment status of the two proteins and clinical outcome following radiotherapy was investigated. Such patients were either disease-free (group 1, n = 65) or had residual/recurrent disease (group 2, n = 36) at a 16-month follow-up. p53 and bcl-2 protein expression was determined by immunocytochemistry. The presence of mutant p53 was detected by a mutant specific p53 enzyme-linked immunosorbent assay. RESULTS: There was no correlation between p53 immunoreactivity or the presence of mutant p53 protein and disease status after treatment. Expression of bcl-2 protein, however, showed significant pretreatment correlations with the final disease outcome (r = 0.643, P = 0.0001). Moreover the odds ratio of a tumour expressing moderate to intense levels of bcl-2 responding poorly to radiotherapy was 27.2 (95% CI 6.0, 123.3). CONCLUSIONS: bcl-2 protein functions in an anti-oxidant pathway to prevent apoptosis. Since radiotherapy efficacy depends on adequate DNA damage caused by free-radical generation, increased expression of bcl-2 may result in tumours becoming less responsive to radiation. Mutation of the p53 gene, however, is a rare event in cervical cancer. Since bcl-2 is negatively regulated by p53, it could be presumed that the p53 detected in the tumour cells may be non-functional or inactive possibly because of interaction with proteins such as E6 or mdm-2.

Cell Nucleus↗
PubMed1999

Increased angiogenesis in the uterine cervix associated with human papillomavirus infection.

We studied the relationship between angiogenesis (using the CD34 antibody), the presence of human papilloma virus (HPV) infection, HPV E6 protein expression and the accumulation of p53 protein at various phases of tumour progression in the uterine cervix. Expression of CD34, p53 and HPV E6 protein was evaluated by immunocytochemistry. Presence of the mutant p53 was detected using a mutant specific ELISA, and the type of HPV was determined by the Polymerase Chain Reaction. A total of 230 cervical tissue samples were analyzed and included 40 cases of apparently normal cervical epithelium, 37 low grade squamous intraepithelial lesions (SILs), 43 high grade SILs, 36 well-differentiated squamous cell carcinomas (DSCC), 31 moderately differentiated (MDSCC) and 43 poorly differentiated carcinomas (PDSCC). There was an excellent correlation between the extent of angiogenesis and histological abnormality (r = 0.912, p = 0.000004). The least extent of angiogenesis was seen in normal cervical tissue and low grade SILs where the mean (low power) intra lesional vascular density (ILVD) was 12 +/- 1.13 and 25.66 +/- 5.20, respectively. In high grade squamous intraepithelial lesions (SILs), the mean ILVD value was 80.84 +/- 25.57. In well-differentiated squamous cell carcinomas (WDSCC's) the mean value was 144.22 +/- 28.67 while in moderately differentiated squamous cell carcinomas (MDSCC's) the mean value was 166.29 +/- 34.95 and in poorly differentiated tumours (PDSCC's) 192.42 +/- 27.98. The extent of angiogenesis also correlated to presence of HPV (r = 0.505, p = 0.00001). Increased CD34 expression was associated with the presence of HPV types 16 and 18. A similar correlation was also evident in HPV, 16/18 infected cases expressing the E6 protein (r = 0.612, p = 0.000001). CD34 expression also correlated well with p53 accumulation (r = 0.859, p = 0.000002). Presence of HPV infection significantly correlated with the extent of histological abnormality (r = 0.467, p = 0.00001). Expression of E6 also showed this significant correlation (r = 0.644, p = 0.00002). Accumulation of p53 was significantly more elevated in HPV 16-infected lesions (r = 0.518, p = 0.00001) and E6-expressing cells (r = 0.650, p = 0.000004). Only 12 of the 230 cases analyzed showed presence of the mutant p53 protein. Angiogenesis appears to increase with histological abnormality in the uterine cervix. Angiogenesis also appears to be influenced by high risk HPV infection, the expression of the E6 transforming protein and the p53 tumour suppressor protein.

Antigens, CD34↗
PubMed1999

Preparation of [186Re]Re-DMSA and its bio-distribution studies.

99mTc(V)-DMSA is widely used for imaging medullary carcinoma and hence 186/188Re(V)-DMSA is suggested as a potential agent for treating medullary carcinoma. In the present paper, we report the work carried out for the preparation of [186Re]Re(V)-DMSA and it's bio-distribution studies in Wistar rats. The complex was prepared by reducing 186Re (100 micrograms, 0.54 microM, approximately 150 MBq) in the presence of DMSA (2 mg, 11 microM) with stannous chloride (0.4 mg, 2.2 microM) in acidic medium at pH 2. The reaction was taken to completion by heating the complex in a boiling water bath for 30 min. Bio-distribution studies carried out revealed that pharmacological behaviour of 186Re(V)-DMSA is similar to that of 99mTc(V)-DMSA except that the kidney uptake is marginally higher. The kidney uptake reduced significantly when the pH of the complex was adjusted to 8 prior to injection. The in vitro stability studies of this complex suggest that the product formed is stable and could be used for clinical trials.

Animals↗
PubMed1999

Preparation, stability studies and pharmacological behavior of [186Re]Re-HEDP.

99mTc-HEDP is widely used as a bone imaging agent and its Re analog [186Re]Re-HEDP is now well established as a therapeutic radiopharmaceutical for palliation of pain due to bone metastases. In the present paper, we report the work carried out for the preparation of stable 186Re-HEDP which retains RC purity up to 5 days when stored at 4 degrees C. 186Re was prepared by irradiation of natural Re metal at a flux of 3 x 10(13) neutrons/cm2/s for seven days and processed after a cooling period of four days. The specific activity of 186Re formed was approximately 35 mCi/mg. A complex with RC purity > 98% could be prepared by varying the reaction conditions. By carefully optimizing the reaction and storage conditions, a complex which was stable for over 4 days could be synthesized. Bio-distribution studies carried out in rats revealed approximately 30% bone uptake of 186Re-HEDP at 3 h postinjection which remained almost constant for 48 h, at which time there was negligible activity in other organs.

Animals↗
PubMed1999

Technetium-99m complexes of polydentate amine-pyrrole and amine-thiophene ligands.

Novel polydentate amine-pyrrole and amine-thiophene ligands were synthesized and characterized by 1H and 13C NMR spectroscopy. Radiochemical studies with 99mTc were carried out at 0.1-100 microM of technetium. Complexation yields were estimated from thin layer chromatography (TLC), paper electrophoresis, and solvent extraction studies. The 99mTc complexes formed were found to be neutral and lipophilic. Complexes with the corresponding imine-ligands were formed in lower yields. Biodistribution studies of the 99mTc complexes of these ligands showed no significant uptake in brain or heart, and the clearance was mainly through the hepatobiliary system.

Animals↗
PubMed1999

Synthesis of heptadentate (N4O3) amine-phenol ligands and radiochemical studies with technetium-99m.

Heptadentate amine-phenol ligands with N4O3 donor atoms for coordination were synthesized by condensing tris(2-aminoethyl)amine with salicylaldehyde or acetophenone and reducing the Schiff bases formed with NaBH4. The ligands were characterized by 1H and 13C nuclear magnetic resonance spectroscopy. Radiochemical studies were carried out with no-carrier-added 99mTc and 99mTc spiked with 0.1-100 microM of 99Tc. Complexation yields were estimated from thin layer chromatography, paper electrophoresis, and solvent extraction studies. 99mTc complexes were formed in yields better than 90% with the amine-phenol ligands. The complexes were found to be neutral and lipophilic. Biodistribution studies of the 99mTc complexes showed that clearance was mainly through the hepatobiliary system.

Animals↗
PubMed1999

Radiochemical studies of 99mTc complexes of modified cysteine ligands and bifunctional chelating agents.

The synthesis of four novel ligands using the amino-acid cysteine and its ethyl carboxylate derivative is described. The synthetic method involves a two-step procedure, wherein the intermediate Schiff base formed by the condensation of the amino group of the cysteine substrate and salicylaldehyde is reduced to give the target ligands. The intermediates and the final products were characterized by high resolution nuclear magnetic resonance spectroscopy. Complexation studies of the ligands with 99mTc were optimized using stannous tartrate as the reducing agent under varying reaction conditions. The complexes were characterized using standard quality control techniques such as thin layer chromatography, paper electrophoresis, and paper chromatography. Lipophilicities of the complexes were estimated by solvent extraction into chloroform. Substantial changes in net charge and lipophilicity of the 99mTc complexes were observed on substituting the carboxylic acid functionality in ligands I and II with the ethyl carboxylate groups (ligands II and IV). All the ligands formed 99mTc complexes in high yield. Whereas the complexes with ligands I and II were observed to be hydrophilic in nature and not extractable into CHCl3, ligands III and IV resulted in neutral and lipophilic 99mTc complexes. The 99mTc complex with ligand II was not stable and on storage formed a hydrophilic and nonextractable species. The biodistribution of the complexes of ligands I and II showed that they cleared predominantly through the kidneys, whereas the complexes with ligands III and IV were excreted primarily through the hepatobiliary system. No significant brain uptake was observed with the 99mTc complexes with ligands III and IV despite their favorable properties of neutrality, lipophilicity, and conversion into a hydrophilic species. These ligands offer potential for use as bifunctional chelating agents.

Animals↗
PubMed1999

De novo programmed cell death in oral cancer.

AIM: The importance of programmed cell death or apoptosis in the maintenance of tissue homoeostasis and the pathogenesis of oral cancer was analysed in relation to apoptosis regulatory proteins, tissue proliferation and tumour histology. METHODS AND RESULTS: The extent of apoptosis was defined by morphological criteria and the TUNEL (terminal deoxy nucleotidyl transferase-mediated dUTP biotin nick end labelling) assay. p53, bax, bcl-2 and cyclin D1 expression was evaluated by immunocytochemistry. The presence of mutant p53 was analysed using a mutant p53-specific ELISA. An inverse correlation was observed between TUNEL reactivity and histology of the lesion (r = -0.555, P = 0.0001). There was also correlation between TUNEL reactivity and immunoreactivity of apoptosis regulatory proteins. p53 (r = 0.641, P = 0.00023), bcl-2 (r = -0.642, P = 0.00014) and bax (r = 0.651, P = 0.00002). The presence of mutant p53 protein showed an inverse correlation to the extent of apoptosis (r = - 0.301, P = 0.00063). Significant correlation was evident between the bax/bcl-2 ratio and TUNEL (r = 0.652, P = 0.00001) as well as between cyclin D1 and TUNEL reactivity (r = 0.577, P = 0.00001). CONCLUSIONS: Results from this study suggest that apoptosis decreases as histological abnormality increases. Apoptotic regulatory proteins are also altered in a histologically dependent manner. Deregulated proliferation occurs simultaneously with decreased apoptosis during tumour progression in the oral mucosa.

Adult↗
PubMed1999

Decreased programmed cell death in the uterine cervix associated with high risk human papillomavirus infection.

The relationship between apoptosis, apoptosis regulatory proteins, cell proliferation and human papillomavirus infection during various phases of tumor progression in the uterine cervix was studied. Apoptosis was defined by morphological criteria and the TUNEL assay. Expression of p53, bcl-2, bax, cyclin D1, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant specific ELISA. Type of HPV infection was determined by PCR using type specific primers. Apoptosis showed significant negative correlation with increasing histological abnormality (p=0.0005). Higher tumor cell proliferation was associated with increasing histological abnormality (p=0.001 for Ki 67 and cyclin D1). There was significant correlation between histological grade and immunoreactivity of p53 (p=0.0001 ) and bcl-2 (p=0.0002). However, mutant p53 was expressed by only 12 of the 230 samples. Expression of bax and the bax/bcl-2 ratio showed an inverse correlation to histological grade (p=0.0003 and 0.0001, respectively). There was also an inverse correlation between extent of apoptosis and immunoreactivity of p53 (p=0.0001) and bcl-2 (p=0. 0001). A significant positive correlation between expression of the bax protein and apoptosis was evident (p=0.0001). HPV infection significantly correlated to the extent of histological abnormality (p=0.0001). High risk HPV-E6 protein also showed this significant correlation (p=0.0002). There was an inverse correlation between apoptosis and HPV infection (p=0.0002). High risk HPV infection was associated with decreased apoptosis and also increased human cell proliferation. Lowest levels of bax/bcl-2 ratio was also associated with HPV 16 and 18 infection (p=0.0001). Modulation of apoptosis and apoptotic regulatory proteins by high risk HPV infection may be an important factor in the development of cervical cancer.

Apoptosis↗
PubMed1999

Immunophenotype of mutant ras p21 and early response to radiotherapy in cancer of the uterine cervix.

Previous studies have postulated that ras gene mutations may influence cellular response to radiotherapy. However, clinical studies have often been limited by the cumbersome methodology associated with DNA analysis. The availability of ELISA method has eventually made clinical evaluation of ras gene mutation feasible. In this study ras mutation by in vitro identification of four mutant forms of p21 ras in cervical tumor tissue extracts was analyzed. Mutant ras proteins were evaluated by an Enzyme Linked Immunosorbent Assay (ELISA). Expression of ras p21 mutations was studied in 101 patients, and a correlation between pre-treatment experimental analyses and the clinical status of the patient after radiotherapy (up to 16 months follow up) was established. There was no correlation between the presence of Val 12 p21 and tumor response to radiotherapy. Yet, presence of the other three mutant proteins had significant relationship to treatment outcome. Detection of Arg 12 mutation was more common in patients who either had residual disease or developed recurrences (28%) as compared to those remaining disease-free (1.5%). The presence of the Arg 12 mutation therefore correlated to poor prognosis (r = 0.445, p = 0.0000). Similarly, the Asp 12 mutation was also more common in patients with residual/recurrent disease (25%) as compared to patients remaining disease-free (3%). Asp 12 mutation also showed a correlation to treatment outcome (r = 0.337, p = 0.00057). Asp 13 mutation was more frequent in patients with residual or recurrent disease (28%) as compared to those remaining disease-free (4.6%). On the basis of laboratory evidence ras genes appear to be involved as modulators of tumor response to radiation therapy. This understanding of the involvement of specific genes in radioresistance will result in the improvement of potential therapies that can be targeted at specific genes, through approaches such as selective inhibition by anti-sense oligonucleotides.

Amino Acid Substitution↗
PubMed1999

Use of Traditional Eye Medicines by corneal ulcer patients presenting to a hospital in South India.

PURPOSE: To investigate the nature and frequency of use of Traditional Eye Medicine (TEM) for corneal ulcer in patients from predominantly rural background. METHODS: We documented the the use of TEM by corneal ulcer patients presenting to a tertiary eye-care centre in South India during two months of 1996. RESULTS: Of 283 patients enrolled in the study, 135 (47.7%) of the patients used TEM. There was no difference with regard to age and sex distribution of patients using TEM and those who did. Patients with history of trauma were more likely to use TEM. Common forms of TEM used were human breast milk 61(45.2%), leafy matter 40(29.6%), castor oil 16 (11.9%), and hen's blood 8 (5.9%). CONCLUSION: Though the awareness of intraocular lens implantation for cataract surgery is very high in this segment of the population, it is still tragic that an awareness of primary eye care following trauma has not been created. Health education is mandatory to prevent this avoidable cause of blindness.

Adolescent↗
PubMed1998

Tumour-proliferative fraction and growth factor expression as markers of tumour response to radiotherapy in cancer of the uterine cervix.

This study seeks to define the role of pretreatment of evaluation of tumour growth fraction in cervical cancer and its relationship to the clinical course of the disease. In addition, it also seeks to explain whether cell kinetics and growth factor expression have an association with tumour response to radiotherapy and hence could be of value in the management of patients. All pre-treatment biopsies were analysed for the tumour-proliferative compartment by evaluation of Ki67 antigen expression and argyrophilic nucleolar organiser region (AgNOR) counts. Growth factor analysis was done by analysing for expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R) and transforming growth factors alpha and beta (TGFalpha, TGFbeta). A total of 152 patients were evaluated and a correlation obtained between pre-treatment status of the tumour-growth-fraction-associated markers and clinical outcome following radiotherapy. Such patients were either disease-free (group 1, n=106) or with residual/recurrent disease (group 2, n=46) at a 16-month follow-up. Pre-treatment analysis of AgNOR significantly correlated to disease status after treatment (r=-0.517, P=0.0000). This may be due to an effect of cell proliferation. Lower AgNOR counts were significantly associated with recurrent/residual tumours, suggesting that increased proliferative activity may be a positive prognostic indicator. Similar results were also obtained for the other proliferation-associated marker Ki67 (r=-0.443, P=0.0000). Expression of EGF and EGF-R also showed significant pre-treatment correlations with the final disease outcome (r=0.248, P=0.031 and r=0.503, P=0.0000 respectively). Both these markers were expressed more by patients belonging to group 2. The opposite was the case for TGFalpha, where patients belonging to group 1 showed higher values (r=0.417, P=0.0001). The other growth factor investigated, TGFbeta, also showed a conspicuous differential expression in the two groups of patients (r=-0.604, P=0.0000). Group 1 patients showed mostly mild to moderate expression while most group 2 patients were negative for the growth factor. It therefore appears that tumours with high AgNOR counts and Ki67 index, along with expression of the two types of transforming growth factor (alpha and beta), responded better to radiotherapy.

Biomarkers, Tumor↗
PubMed1998

Spontaneous programmed cell death in infiltrating duct carcinoma: association with p53, BCL-2, hormone receptors and tumor proliferation.

Recent evidence has emphasized the importance of programmed cell death or apoptosis in the maintenance of tissue homeostasis and pathogenesis of tumors. This study, analyzed in breast cancer, investigates the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, hormone receptors and tumor grade. The extent of apoptosis was defined by morphological criteria and the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay. Immunocytochemistry was performed for p53, bcl-2, estrogen receptor, progesterone receptor and Ki-67 expression. Mutant p53 protein was detected using a mutant specific ELISA. Immunoreactivity of p53 significantly correlated with the presence of mutant p53 protein detected by ELISA (r = 0.654, p = 0.00001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). The extent of apoptosis directly correlated with p53 protein accumulation (r = 0.485, p = 0.00041), Ki-67 immunoreactivity (r = 0.435, p = 0.001), histopathological grade (r = 0.492, p = 0.0003), tumor size (r = 0.326, p = 0.023) and lymph node status (r = 0.287, p = 0.047). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). There was no statistically significant association between estrogen and progesterone receptor status and apoptosis. In addition, the TNM stage of the disease correlated with immunoreactivity of p53 (r = 0.572, p = 0.00012) and Ki-67 (r = 0.3744, p = 0.00818). Bcl-2, by inhibiting apoptosis, may cause a shift in tissue kinetics towards the preservation of genetically aberrant cells, thereby facilitating tumor progression. These results imply that rapidly proliferating tumors appear to have a high "cell turnover state" in which there may be an increased chance of apoptosis amongst the proliferating cells. The ability of apoptosis to also occur in the presence of mutant p53 protein suggests the existence of at least two p53-dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it.

Adult↗
PubMed1998

Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation.

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process.

Antigens, CD34↗
PubMed1998

High-risk human papillomavirus infection and E6 protein expression in lesions of the uterine cervix.

Pathologic and epidemiologic investigations carried out over the past several years have provided evidence that carcinogenesis in the uterine cervix is a multi-step process involving discreet preinvasive stages. Molecular epidemiologic data also indicate that human papillomavirus (HPV) infection is a critical factor in the tumor progression process. In vitro studies have shown that for the initiation and maintenance of the malignant phenotype, the expression of the HPV-transforming protein E6 is required. The E6 protein produced by the high-risk HPV types 16 and 18 can bind to and inactivate the tumor suppressor protein p53 leading to deregulated proliferation and defective apoptosis, thus facilitating tumor progression. Therefore, determination of the HPV genotype alone may not be sufficient in assessing tumor progression in the uterine cervix. In the present study, a total of 623 cervical tissue samples at various phases of tumor progression were assessed for HPV infection by nonisotopic in situ hybridization (NISH) and for HPV 16/18 E6 protein expression by immunocytochemistry. There was significant correlation between the extent of histological abnormality and HPV infection. Significant correlation (r = 0.707, p = 0.000) was observed between the presence of HPV 16 and high-grade squamous intraepithelial lesions (SILs) and invasive cancer. The odds ratio of a cervical tissue infected with HPV 16 falling into these two categories was 44.57 (95% CI: 27.10, 73.30). The E6 protein also was mostly detected in high-grade SILs and cervical cancer tissue expressing either HPV 16 or 18. It was less frequent in low-grade SILs infected with HPV 16/18 and was absent in benign cervical tissue infected with HPV 16. The odds ratio of an HPV-16/18-infected cervical tissue positive for E6 being a high-grade SIL or invasive cancer was 16.20 (95% CI: 6.06, 43.33). These results thus show the clinical utility of HPV characterization along with the analysis of the transforming protein E6 in the assessment of tumor progression in the uterine cervix.

Adult↗
PubMed1998

Bcl-2 protein and apoptosis in pediatric acute lymphoblastic leukemia.

Many chemotherapeutic agents are thought to exert their genotoxic effects through induction of programmed cell death (PCD) (apoptosis) in tumor cells. The bcl-2 is an anti-apoptotic oncoprotein and can confer a survival advantage to tumor cells by preventing apoptosis. Overexpression of bcl-2 may therefore be implicated in resistance to chemotherapy. We studied the significance of bcl-2 expression and the PCD index in pediatric acute lymphoblastic leukemia. Evaluation of bcl-2 by immunocytochemistry and PCD by an enzymatic end labelling technique using biotin-dUTP was carried out in a total of 55 cases and 40 controls. Bcl-2 was found to be expressed in 47% (26/55) of the acute lymphoblastic leukemia cases. The positive cells varied from 0-49% among individual samples. Pre-treatment (spontaneous) apoptosis was observed in 62% (34/55) cases. The mean pre-treatment PCD index was 8.27 1.3%, while the median PCD index was 5. The PCD value for the leukemic samples analyzed were then classified as either high apoptosis values ( 5) and low apoptosis values (<5). PCD index was high in 53% (29/55) and low in 47% (26/55). However, 23% (13/55) of cases did not show presence of either apoptosis or bcl-2. There was no association between clinical and laboratory parameters with the apoptotic index or bcl-2 protein expression. However, evaluation of apoptotic index and bcl-2 expression on day 7 of induction chemotherapy showed a borderline correlation between these markers and initial WBC count, presence of mediastinal mass and hepatosplenomegaly. Follow-up of these patients is being done to look for any association between treatment response and apoptosis.

Antineoplastic Agents↗