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Biomedical subjects

P Pande

Publications and source records attributed to P Pande.

14 recordsLinked to original sources

Coexpression of Ets-1 and p53 in oral carcinomas is associated with P-glycoprotein expression and poor prognosis.

PURPOSE: To determine the association between the expression of P-gp with Ets-1 and p53 proteins in oral squamous cell carcinomas (SCCs). MATERIALS AND METHODS: Immunohistochemical analysis of Ets-1, P-glycoprotein (P-gp), and p53 proteins was carried out in 40 formalin-fixed, paraffin-embedded tissue sections from oral SCCs using specific antibodies for these proteins. RESULTS: Expression of Ets-1 protein was observed in 27/40 (68%) cases, P-gp was overexpressed in 27/40 (68%) cases, and p53 accumulation was observed in 26/40 (65%) cases. Twenty-two of 27 (82%) SCCs showed concomitant overexpression of Ets-1 and P-gp underpinning an association between the expression of these two proteins ( P=0.007). Twenty-one of 27 (78%) Ets-1 overexpressing oral SCCs showed accumulation of p53 protein ( P=0.015). Nineteen of the 27 (70%) P-gp expressing tumours showed p53 accumulation. Concomitant Ets-1 and P-gp overexpression was significantly associated with poor prognosis ( P=0.002). In multivariate analysis using Cox's proportional hazards model, P-glycoprotein emerged as the most significant adverse predictor of disease-free survival (HR=6.2, P=0.003). The hallmark of the study was the significant association between the expression of Ets-1, P-gp, and p53 proteins in oral SCCs and their association with poor prognosis. Oral cancer patients showing concomitant expression of Ets-1, P-gp, and p53 proteins had shorter disease-free survival (median time of no recurrence=18 months) and worst prognosis ( P=0.001) as compared to the cases overexpressing any of these proteins. CONCLUSION: Concomitant expression of Ets-1, P-gp, and p53 proteins adversely affects the clinical outcome in oral SCCs.

ATP Binding Cassette Transporter, Subfamily B↗

Prognostic factors in betel and tobacco related oral cancer.

Paucity of well-defined prognostic molecular markers severely hampers prediction of the clinical course of squamous cell carcinoma (SCC) of oral cavity. The aim of the study was to evaluate the prognostic significance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread in oral SCC of habitual betel and tobacco chewers. A prospective study was performed in 105 betel and tobacco consumers with oral SCCs during the period 1988-1999, to evaluate the prognostic relevance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread. Alterations in the expression of p53, pRb, p16, MDM2, p21, and Ets-1 proteins were determined by immunohistochemical analysis in formalin fixed, paraffin embedded tissue sections from oral SCCs. Analysis of multiple molecular biological factors showed overexpression of p53 in 69/105 (66%) cases, MDM2 in 72/105 (69%) cases, p21 in 57/105 (54%) cases and Ets-1 in 64/105 (61%) cases. Loss of pRb was observed in 58/105 (55%) cases and p16 loss was observed in 72/105 (69%) cases. Interestingly, multivariate analysis revealed loss of pRb as the most significant predictor of advanced tumour stage [P=0.001; Odd's Ratio (OR)=3.5] and overexpression of Ets-1 protein was an independent risk factor for lymph node metastasis (OR: 10.1; P<10(-6)). Multiple logistic regression models showed that pRb loss [Hazard's Ratio (HR): 3.93] and p53 overexpression (HR: 2.97) may serve as adverse prognosticators for disease free survival of the patients. The data demonstrate multiple impairments in p53/MDM2/p21/Ets-1 and p16/pRb pathways in betel and tobacco related oral tumourigenesis.

Adult↗

Sequence-specific delivery of a quinone methide intermediate to the major groove of DNA.

Silyl-protected phenol derivatives serve as convenient precursors for generating highly electrophilic quinone methide intermediates under biological conditions. Reaction is initiated by addition of fluoride and has previously exhibited proficiency in DNA alkylation and cross-linking. This approach has now been extended to the modification of duplex DNA through triplex recognition and fluoride-dependent quinone methide induction. Both oligonucleotides of a model duplex were alkylated in a sequence specific manner by an oligonucleotide conjugate that is consistent with triplex association. Optimum reaction required the presence of the two complementary target sequences and a pH of below 6.5. In addition, one guanine in each strand adjacent to the triplex region was the predominant site of alkylation. The yield of modification varied from approximately 20% for the purine-rich strand to only 4% for the pyrimidine-rich strand. This surprising difference indicates that the linker between the recognition and reactive elements may limit productive interaction between the quinone methide and the reactive nucleophiles of DNA. Restricted orientation of this intermediate may also be responsible for the lack of target cross-linking at detectable levels.

Alkylation↗

Prognostic impact of Ets-1 overexpression in betel and tobacco related oral cancer.

In oral squamous cell carcinoma (SCC), the presence of lymph node metastasis is one of the most important prognostic factors, correlating locoregional spread, recurrence, distant metastasis and survival. However, the biological factors implicated and the mechanisms underlying these events are not completely elucidated. We reported Ets-1 expression in oral SCC and proposed that it may serve as a plausible marker of invasive potential and lymph node metastasis. Herein, we investigate the prognostic significance of Ets-1 expression in oral cancer. One hundred oral SCCs assessed for Ets-1 expression showed significant association with tumor stage (P = .027), lymph node involvement (P < 10(-6)) and distant organ metastasis (P = .007). The transcription factor Ets-1 regulates the expression of several genes involved in extracellular matrix remodeling that may account for its association with lymph node and distant organ metastasis. Kaplan-Meier survival analysis entailed significant association of Ets-1 expression in oral SCCs with reduced disease free survival (P = .0041), suggesting its utility as a prognosticator for oral cancer. In conclusion, these findings underscore the role of Ets-1 in oral tumor invasion and metastasis and may thus account for its association with diminished disease free survival.

Areca↗

Plumbism--a mimicker of common childhood symptoms.

Lead poisoning is a preventable entity that can affect almost every system of the body. Its toxic effects range from subtle common childhood symptoms to even death. In a prospective study forty six children with at least one symptom compatible with plumbism were enrolled after screening patients attending medical services at AIIMS. The work-up included a detailed clinical history and examination including intelligence quotient (IQ) and behaviour. Blood lead levels were estimated in all with due precautions. Their ages ranged from 2.5 to 18 years and M:F ratio was 2:1. The common symptoms included unexplained recurrent colic (39), anorexia (21), sporadic vomiting and constipation (13), pigmented gum lines (11), growth failure (11), history of pica (9) etc. None of the children had acceptable blood lead levels (< 10 micrograms/dl). Ninety three per cent children had levels > 20 micrograms/dl and 47.8% had > 45 micrograms/dl. Statistically significant correlation with blood lead levels was seen with most symptoms. Plumbism can mimic common childhood illnesses and should be investigated in children with a clinically compatible profile. Community awareness with regard to pica reduction may be an important preventive measure. This silent epidemic needs to be aggressively tackled by a multipronged approach.

Adolescent↗

Ets-1: a plausible marker of invasive potential and lymph node metastasis in human oral squamous cell carcinomas.

The proto-oncogene Ets-1 is a transcription factor known to regulate the expression of a number of genes involved in extracellular matrix remodelling. It has been postulated to play a role in angiogenesis, cell migration, and regulation of tumour invasion. In betel and tobacco-related oral tumourigenesis, oral squamous cell carcinomas (SCCs) having a poor prognosis often exhibit extensive local disease with spread into regional lymph nodes. At present, no tumour marker is available to predict the metastatic potential of oral carcinomas. To elucidate the involvement of Ets-1 in human oral tumourigenesis, 60 cases of oral SCC, 30 potentially malignant lesions, and 30 samples of normal oral mucosa were examined by immunohistochemistry and the findings corroborated with immunoblotting. The relationship of Ets-1 expression with the degree of differentiation, lymph node metastasis, and tumour stage was determined in oral SCCs. Ets-1 was not detected in the normal oral epithelium. Among the 60 cases of oral SCC, 35 cases (58 per cent) showed positive staining for the Ets-1 protein in tumour cells. In potentially malignant lesions, 14 of 30 cases (47 per cent) showed Ets-1 immunopositivity. Ets-1 expression correlated significantly with tumour stage ( p=0.01) and lymph node metastasis ( p=0.005). The presence of Ets-1 mRNA in oral SCCs was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). These findings suggest that overexpression of Ets-1 in potentially malignant lesions may be related to angiogenesis and its expression in oral SCCs may be one of the factors involved in tumour progression and lymph node metastasis.

Biomarkers, Tumor↗

pRb and p16 protein alterations in human oral tumorigenesis.

Cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTS1) and retinoblastoma (Rb) tumour suppressor genes play important roles in the regulation of the cell cycle. The protein products of these genes p16INK4 (p16) and pRb, respectively, like p53 protein inhibit progression from G1 to S phase. p16 exerts its function through inhibition of CDK4-mediated phosphorylation of pRb. The pRb/p16 pathway is a critical target for molecular aberration at the G1-S checkpoint in a wide range of primary human tumours. The expression of p16 and pRb proteins was analyzed by immunohistochemistry in 35 cases of oral squamous cell carcinomas (SCCs), 22 cases of premalignant oral lesions and 30 normal oral tissues. Lack of pRb expression was observed in 23/35 (66%) oral SCCs and 14/22 (64%) premalignant lesions. Lack of p16 expression was observed in 22/35 (63%) oral SCCs and 13/22 (59%) premalignant lesions. Weak p16 and pRb immunoreactivities were observed in normal oral mucosal epithelium. The status of p16 and pRb was correlated with clinicopathological characteristics of the patients. Alteration in p16 expression showed significant correlation with tumour staging and progression (P = 0.024). Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco. Our results suggest that alterations in the p16/pRb pathway are early events in oral tumorigenesis and may be involved in the development of betel- and tobacco-related oral malignancies.

Adult↗

Behavior problems in nephrotic syndrome.

OBJECTIVES: To evaluate the adaptive competences and behavioral problems in children with nephrotic syndrome, and whether their mothers also showed features of psychosocial stress. DESIGN: Prospective case-control study. SETTING: Pediatric Out-Patient Department. SUBJECTS: Seventy consecutive patients of nephrotic syndrome, between the ages of 4 to 14 years, and their mothers constituted cases. The control group, matched for age, sex and socioeconomic status comprised of 46 children and their mothers. The mother's description of the child's behavior, on the Child Behavior Checklist (CBCL), was obtained to assess behavioral problems and social competences. The level of anxiety in the mother was assessed using the PGI Health Questionnaire N2. RESULTS: Children with nephrotic syndrome showed features of depressed, hyperactive or aggressive behavior. Somatic complaints, social withdrawal and poor school performance were also observed. These problems did not interfere with compliance to treatment and only 7 patients required psychological interventions. Boys with nephrotic syndrome had more hyperactive and aggressive behavior as compared to girls. The scores on the CBCL were well correlated with the anxiety scores of the mother. CONCLUSIONS: These observations suggest the presence of minor behavior problems in a significant proportion of children with nephrotic syndrome. The severity of these problems may be related to the attitude of the mother towards the child's illness.

Adaptation, Psychological↗

Behavioral training for mothers of mentally handicapped children: teaching of self-help skills.

Deficits in self help skills are an inevitable problem with the mentally handicapped. The acquisition of self-help skills, learned effortlessly by more intelligent children, is a crucial aspect of the overall development of the mentally handicapped child. In the present study, thirty seven mothers of mentally handicapped children aged between 3 1/2 and 8 years, with an IQ of less than 70, were trained in behavioral techniques such as shaping, task analysis, prompting, and modelling, to develop independent self-help functioning in their children. The self-help areas were toileting, feeding, bathing, washing, and dressing. Thirty two per cent of mothers reported complete skill learning. The problems encountered in the course of training and the subsequent evaluation of its efficacy are discussed.

Adult↗

Electromyography in voluntary posterior instability of the shoulder.

Electromyographic (EMG) activity of selected shoulder girdle muscles was analyzed during voluntary posterior subluxation of the glenohumeral joint in four subjects. Although there was a great deal of variation in the muscle activation patterns during subluxation, subjects either pushed the humeral head backwards with the anterior muscles (deltoid, biceps) or pulled the humeral head backwards with the infraspinatus and/or posterior deltoid. In all cases, inhibition of the scapular rotators and winging of the scapula accompanied this maneuver. The method used in this study is presented as an objective technique for quantifying EMG activity during subluxation and relocation phases of shoulder instability.

Adolescent↗