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Biomedical subjects

A Munshi

Publications and source records attributed to A Munshi.

At least 19 recordsLinked to original sources
PubMed2006

A case of Hodgkin's disease presenting with recurrent laryngeal nerve palsy and tracheoesophageal fistula.

Malignancy is the most common cause of tracheoesophageal fistulas. The malignancies commonly implicated in the development of tracheoesophageal fistulas are primary bronchial or esophageal carcinomas. Hodgkins disease rarely leads to such a fistula. We report a case of Hodgkin's disease with a tracheoesophageal fistula as well as a left recurrent nerve palsy at presentation. This presentation has no precedent in literature. The patient was treated with systemic chemotherapy and involved field radiotherapy. On follow up 1 year after the completion of treatment, he was clinically and radiologically disease free.

Adult↗
PubMed2005

Carcinoma of the tonsil with bilateral breast metastasis: a rare presentation.

With increasing local regional control and survival rates, the incidence of distant metastasis is increasing. Head and neck malignancies traditionally metastasize to the lung, liver and bone. We present a case of an elderly woman who was loco-regionally controlled after radiotherapy for carcinoma of the tonsil, but later presented with breast metastasis. To our knowledge, this metastatic pattern has never been reported in published literature. We also discuss the management of breast metastasis and the need to avoid unnecessary mastectomies in such patients.

Breast Neoplasms↗
PubMed2002

Chemotherapeutic agents enhance TRAIL-induced apoptosis in prostate cancer cells.

PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family that preferentially kills tumor cells. In this study, we sought to determine whether chemotherapeutic agents augment TRAIL-induced cytotoxicity in human prostate cancer cells, and whether this sensitivity can be blocked by overexpression of bcl-2. METHODS: Prostate cancer cells, PC3 and LNCaP, were treated with TRAIL alone, drug alone or a combination of both for 24 h. Cytotoxicity was determined by DNA fragmentation and clonogenic survival assay. RESULTS: Treatment with the conventional chemotherapeutic agents cisplatin (2 and 5 microg/ml), etoposide (10 microM and 20 microM) and doxorubicin (30 and 60 n M) dramatically augmented TRAIL-induced apoptosis in LNCaP and PC3 cells. TRAIL-induced apoptosis was partially abrogated by overexpression of bcl-2 in these two cell lines when it was used in combination with the above agents. Similar results were obtained using clonogenic survival assays where bcl-2 overexpression was also found to marginally protect against TRAIL- and chemotherapy-induced cell killing. CONCLUSIONS: This study demonstrates that combination treatment of prostate cancer cells with TRAIL and chemotherapeutic agents overcomes their resistance by triggering caspase activation. This greater than additive effect of cotreatment with TRAIL and chemotherapy may provide the basis for a new therapeutic approach to induce apoptosis in otherwise resistant cancer cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Unusual presentation of talon cusp: two case reports.

Talon cusp is an uncommon odontogenic anomaly comprising of an accessory cusp-like structure, usually observed on the palatal surfaces of maxillary incisors. Two uncommon presentations of talon cusp, occurring on a mandibular incisor and on a supernumerary tooth in the maxilla, are reported.

Child↗
PubMed2001

TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2.

To determine if TRAIL-induced apoptosis in human prostate tumor cells was suppressed by bcl-2, we compared the levels of apoptosis induced by recombinant human TRAIL in pairs of isogenic cell lines that do or do not express bcl-2. Three human prostate tumor cell lines (PC3, DU145 and LNCaP) and their bcl-2-expressing counterparts were tested for their susceptibility to TRAIL. Cells were exposed to TRAIL in the presence of cycloheximide which acted as a sensitizer. Apoptosis was induced rapidly in PC3 and DU145 neo-control transfected cells, whereas induction in LNCaP required 24 h. All three cell line variants expressing bcl-2 were resistant to the apoptotic effects of TRAIL. Caspase 3 and 8 activation was also detected in the neo control cells after treatment with TRAIL, demonstrating the rapid activation of the caspase cascade similar to that seen with other death receptors. Bcl-2 overexpression in these cells blocked activation of these caspases, suggesting that bcl-2 expression of human cancer cells may be a critical factor in the therapeutic efficacy of TRAIL.

Antineoplastic Agents↗
PubMed2001

Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line.

PURPOSE: To restore radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant murine lymphoma cell line (LY-ar) by pretreatment with paclitaxel (Taxol). Because this cell line also has high intracellular levels of glutathione (GSH), reportedly due to the bcl-2 expression and involved in the cell's antioxidant functions, paclitaxel treatment was correlated with GSH levels. METHODS AND MATERIALS: LY-ar cells were pretreated with paclitaxel and then irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h later. Dose response and time course experiments were performed. Intracellular GSH levels were measured after treatment. Cell survival analysis was performed for various paclitaxel concentrations +/- 5 Gy. RESULTS: LY-ar cells pretreated with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel for 20 h underwent apoptosis at 2%, 15%, 25%, and 22%, respectively. With the addition of 5-Gy irradiation, LY-ar cell apoptosis increased to 4%, 30%, 49%, and 57%. Maximal apoptosis was detected with a paclitaxel pretreatment time of 20 h. Intracellular GSH levels were reduced by nearly 50% with paclitaxel pretreatment. Surviving fractions (SFs) with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05, respectively. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were 0.009, 0.003, 3 x 10(-5), and 1 x 10(-5), respectively. CONCLUSION: Radiation-induced apoptosis in LY-ar cells was restored by pretreatment with paclitaxel. This correlated with lowered levels of intracellular GSH. Cell survival analysis indicated that the combination of Taxol and radiation on cell killing was greater than additive.

Animals↗
PubMed2001

The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.

Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here that the LxCxE binding site in Rb mediates both cell survival and cell-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protective effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damage in an Rb-dependent manner.

Amino Acid Motifs↗
PubMed2001

Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell lung cancer cells but not normal lung fibroblasts.

PURPOSE: We compared the ability of adenoviral-mediated wild-type p53 RPR/INGN201(Ad5/CMV/p53) to radiosensitize non-small cell lung carcinoma (NSCLC) and normal lung fibroblast cells. MATERIALS AND METHODS: NSCLC cell lines (A549 and H322) and human lung fibroblast cells (MRC-9 and CCD-16) were used in this study. Radiosensitivity was determined by clonogenic assay and tumor growth delay. Expression of p53, Bax, and p21WAF1 protein were evaluated by immunoblot. A FITC conjugate of annexin V was used for flow cytometric detection of apoptosis. RESULTS: Clonogenic and apoptotic assays indicated that Ad5/CMV/p53 enhanced the radiosensitivity of both NSCLC cell lines. On the other hand, the two normal human fibroblast cell lines appeared to be resistant to the cytotoxic effects of Ad5/CMV/p53 and were not radiosensitized compared to the NSCLC cells. According to immunoblot analysis, Bax expression was increased in the NSCLC cells treated with the combination therapy; Bax expression, however, was unchanged in normal cells. In in vivo studies, tumor growth suppression was enhanced by this combination strategy in xenograft tumors growing in nude mice compared to Ad5/CMV/p53 or radiation therapy when used alone. CONCLUSIONS: Our data indicate that therapy using Ad5/CMV/p53 and irradiation in combination is more effective than either treatment when used alone on NSCLC cells, is not limited to cells with defective endogenous p53, and does not enhance the radiosensitivity of normal cells.

Adenoviridae↗
PubMed2001

Midline space closure in the mixed dentition: a case report.

Supernumerary teeth which occur both in the primary and the permanent dentition are seen more frequently in the permanent dentition causing a variety of pathological disturbances. Presented herewith is a case report of a patient with a mesiodens which had caused flaring of the maxillary central incisors and impeded normal eruption of the maxillary lateral incisors. Extraction of the mesiodens was carried out; subsequently followed by the space closure utilizing simple fixed orthodontic therapy.

Child↗
PubMed1999

Effect of p21waf1/cip1 transgene on radiation induced apoptosis in T cells.

The cyclin kinase inhibitor p21WAF1/Cip1 is upregulated by the tumor suppressor p53. While p21 is central for the G-1 arrest mediated by p53, it is still unclear if p21 also functions as a downstream effector of p53 dependent apoptosis. Apoptosis induced by DNA damage but not dexamethasone is p53 dependent in thymocytes. To investigate the physiological role of p21 in apoptosis, we have generated transgenic mice in which the p21 transgene is targeted for restricted expression in the T cell lineage. Thymocytes from p21 transgenic mice were hypersensitive to cell death induced by DNA damaging agents such as ionizing radiation and UV, but not be dexamethasone. Irradiated p21 transgenic thymocytes had approximately twofold more apoptotic cells as compared to irradiated age matched littermate control mice. Radiation induced death is comparable in thymocytes from p21 + Bcl2 + double transgenic mice and age matched littermate controls, indicating that the Bcl2 transgene rescues the radiation hypersensitivity imposed by p21. However, thymocytes from p53-/- mice even when they expressed the p21 transgene, were resistant to death induced by radiation. Together these results show that thymocytes from p21 transgenic mice are hypersensitive to radiation induced programmed cell death and suggest that the radiation hypersensitivity of p21 transgenic thymocytes involves p53 dependent pathway and signals in addition to p21.

Animals↗
PubMed1999

Enhancement of tumor killing using a combination of tumor immunization and HSV-tk suicide gene therapy.

Tumor cells genetically modified with the herpes simplex virus thymidine kinase (HSV-tk) gene in combination with ganciclovir (GCV) demonstrate a "bystander effect". Previous attempts to enhance the bystander tumor killing by combining cytokine genes with HSV-tk/GCV have met with varying results. The present study was designed to determine the effects of tumor immunization in combination with HSV-tk gene-modified tumor cells and GCV on tumor killing and to determine if the bystander tumor killing could be enhanced. Tumor-bearing mice immunized with syngeneic tumor (KBALB) prior to treatment with an i.p. injection of xenogeneic HSV-tk gene-modified tumor cells (PA-1STK) had prolonged animal survival (group 4, 56.4 days). In contrast, unimmunized tumor-bearing mice (group 2) or tumor-bearing mice immunized to the xenogeneic PA-1STK tumor cells (group 5) showed a mean survival of about 27 days after receiving an i.p. injection of PA-1STK cells and GCV. Control groups, which were either not immunized and did not receive HSV-tk cells (group 1) or immunized but treated only with GCV (group 3) showed short survival (16-18 days). Analysis of tumors for cytokine mRNA expression revealed increased TNF-alpha and IL-1alpha mRNA expression in group 4 mice. Furthermore, IL-2 mRNA expression was detectable on days 2 and 4 only in group 4 mice. Immunophenotypic analysis for tumor-infiltrating lymphocytes demonstrated an increase in macrophage (4%, p = 0.0001) and T cells (1.8%, p < 0.001) in group 4 mice with an enhanced T-cell response as compared with mice from groups 1, 2 and 3. Our results demonstrate that tumor immunization combined with HSV-tk/GCV treatment results in increased animal survival with enhanced immune response. Furthermore, the cytokine milieu observed in the present study can modulate the tumor micro-environment in vivo from one that is immunosuppressive to one that is immune-stimulatory.

Animals↗
PubMed1999

Integrin-dependent tyrosine phosphorylation and growth regulation by Vav.

The proto-oncogene product p95Vav (Vav) undergoes rapid phosphorylation on tyrosine following stimulation of the T or B cell antigen receptor, and in response to a variety of other cell surface stimuli. Vav contains, among other, a guanine nucleotide exchange factor domain with homology to the Rho/Rac/CDC42 exchange protein Db1. It has been recently shown that Vav is functionally linked to small GTPases of the Rho family, suggesting that it is an activator of Rho GTPases and may participate in regulation of cytoskeletal organization. The present study shows that cell adhesion to fibronectin triggers rapid phosphorylation of Vav on tyrosine in Vav-transfected CHO cells and in Jurkat T cells. Vav phosphorylation is strongly dependent on adhesion and is mediated by beta 1 integrins. Furthermore, Vav overexpression enhances the adhesion-dependent increase in the rate and extent of phosphorylation on focal adhesion kinase and paxillin, and the formation of stress fibers and lamellipodia. In addition, there is a marked increase in the amount of Vav localized to the triton-insoluble fraction following 1 h of incubation on FN. Finally, Vav increases the growth rate of the cells in an adhesion-dependent manner. Our results strongly implicate Vav as a mediator of integrin signal transduction.

Actins↗
PubMed1999

Leopard syndrome--report of a variant case.

This case report presents a patient with Leopard syndrome, with multiple lentigines all over the body and face, ocular hypertelorism, delayed secondary sexual characteristics, mild cardiac abnormalities and supernumerary teeth. Clinical relevance of this syndrome lies in its early recognition and precautions to be taken during any invasive dental procedure, which if not performed under antibiotic prophylaxis and premedication, could lead to infective endocarditis. Additionally, a multidisciplinary approach with pediatric and medical consultants is mandatory during the management of such cases.

Abnormalities, Multiple↗
PubMed1999

Relationship between the existing caries status, plaque S. mutans and Cariostat caries activity test in children.

An attempt was made in this study to find out the sensitivity and specificity of a caries activity test, CARIOSTAT and its relationship to the existing caries status and the plaque S. mutans level. The test proved to be highly sensitive and specific with significant relationship to the S.mutans count in the dental plaque. There also was a significant relationship between both the cultured microorganisms on MSB agar and the plaque in the Cariostat medium.

Adolescent↗
PubMed1998

p53 molecule as a prognostic marker in human malignancies.

The tumor suppressor gene, p53, is the most commonly mutated gene associated with cancer. Mutation of p53 plays a critical role in the multiple stages of carcinogenesis. The functional inactivation of p53 by missense mutations has been described in various cancers and the majority of these mutations occur in exons 5 through 9 of the p53 gene. Mutations leading to the overexpression of p53 have been found to affect the patient survival outcome in several human malignancies. Our experience with more than 200 samples of breast and prostate carcinoma is presented. Our results strongly suggest that the type and location of the p53 mutations within the molecule may affect and dictate the outcome of cancer.

Biomarkers, Tumor↗
PubMed1997

Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma.

Cytokines and growth factors are powerful modulators of the immune response. Their aberrant expression either by the tumor cells or by the tumor infiltrating lymphocytes confers a selective advantage to the tumor to grow and suppress the cytotoxic activity of the infiltrating lymphocytes. Therefore, analysis of these soluble factors in the tumor microenvironment can provide an insight into the understanding of the tumor behavior and may be used as a prognostic factor. In the present study the nature of the tumor infiltrating lymphocytes (TILs) and cytokine profile was examined in 36 and 19 mammary carcinoma tissues, respectively, by immunohistochemistry and PCR. Phenotypic differences in the number of cytotoxic T lymphocytes (CD8+) and lymphokine activated killer cells (CD16) was observed among TILs when patients with either early disease stage (39% and 46.6%, respectively) or those alive with no residual disease (31% and 52%, respectively) were compared with late stage (9.7% and 22.8%, respectively) or those dead of disease (14.6% and 15.6%, respectively). Furthermore, analysis of the 19 tumor samples for cytokine mRNA expression by RT-PCR revealed the presence of TNF-alpha, IL-10, TGF-beta1, and IL-2. However, semi-quantitative PCR analysis demonstrated TGF-beta1 expression to be significantly higher in patients with a favorable outcome (1.0246 attomoles/micromoles) as compared to patients with a poor prognosis (0.1157 attomoles/micromoles). Our results demonstrate the potential biological significance of certain host factors, particularly TILs and TGFbeta1 expression, on the outcome of breast cancer.

Adult↗
PubMed1997

Differential expression of HLA-DQA1 alleles associated with promoter polymorphism.

The promoter regions of DQA1 alleles are polymorphic, with some of the nucleotide sequence polymorphisms being located within X and Y motifs essential for the regulation of HLA class II gene transcription. In the present study, we demonstrate that polymorphisms in the promoter regions of three DQA1 alleles influence constitutive and inducible transcription of reporter gene constructs in epithelial, B-, and T-cell lines. Promoter strength in transient transfection assays generally followed a pattern of DQA1(*)03011>DQA1(*)0101>DQA1(*)05011, and was not affected by the endogenous HLA haplotype of the recipient cells. TNFalpha significantly activated the DQA1(*)05011 promoter, but had little effect on the DQA1(*)03011 promoter. Mutagenesis of the X and Y motifs of DQA1(*)03011 and DQA1(*)05011 demonstrated that nucleotide sequence polymorphisms in the Y element had the greatest effect on the promoter strength and differential TNFalpha inducibility. The finding that alleles of the DQA1 gene differ in promoter strength and responsiveness to TNFalpha suggests a mechanism for the association of certain alleles of this gene with susceptibility to autoimmune disease.

Alleles↗