Biomedical subjects

Prashant Bavi

Publications and source records attributed to Prashant Bavi.

7 recordsLinked to original sources

PubMed2006

Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell lymphoma survival.

Phosphatidylinositol 3'-kinase (PI3K) is a key player in cell-growth signaling in a number of lymphoid malignancies, but its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. Therefore, we investigated the role of the PI3K/AKT pathway in a panel of 5 DLBCL cell lines and 100 clinical samples. Inhibition of PI3K by a specific inhibitor, LY294002, induced apoptosis in SUDHL4, SUDHL5, and SUDHL10 (LY-sensitive) cells, whereas SUDHL8 and OCI-LY19 (LY-resistant) cells were refractory to LY294002-induced apoptosis. AKT was phosphorylated in 5 of 5 DLBCL cell lines and inhibition of PI3K caused dephosphorylation/inactivation of constitutively active AKT, FOXO transcription factor, and GSK3 in LY-sensitive cell lines. In addition, there was a decrease in the expression level of inhibitory apoptotic protein, XIAP, in the DLBCL cell lines sensitive to LY294002 after treatment. However, no effect was observed in XIAP protein levels in the resistant DLBCL cell lines following LY294002 treatment. Finally, using immunohistochemistry, p-AKT was detected in 52% of DLBCL tumors tested. Furthermore, in univariate analysis, high p-AKT expression was associated with short survival. In multivariate analysis, this correlation was no longer significant. Altogether, these results suggest that the PI3K/AKT pathway may be a potential target for therapeutic intervention in DLBCL.

Apoptosis↗

PubMed2006

HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.

AIM: Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated. METHOD: 518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC. RESULTS: Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%). CONCLUSIONS: Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.

Adult↗

PubMed2006

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.

Acid Anhydride Hydrolases↗

PubMed2006

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population.

Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be highly predictive of response to gefitinib (Iressa) therapy in lung cancer. Studies on Western and Japanese lung cancers have indicated substantial differences in the EGFR mutation frequency between these populations. To investigate the prevalence of EGFR in another distinct ethnic group, EGFR alterations were studied in 47 consecutive non small cell lung cancers from Saudi Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing. Detectable EGFR expression was seen in 69.8% of 43 interpretable cancers. Epidermal growth factor receptor amplification, present in 15.3% of 39 analyzable cancers, was strongly associated with high levels of EGFR expression (P = .0047). Only 1 exon 18-21 mutation was seen among 34 lung cancers that could be successfully sequenced. It is concluded that EGFR exon 18-21 mutations are rare in Middle East patients with lung cancer and occur in a similar range as in Western patients. The remarkable high rate of EGFR gene amplifications could potentially facilitate studies on the predictive role of gene copy number changes for response to anti-EGFR therapies in Middle East patient sets.

Adenocarcinoma↗

PubMed2006

Epstein-Barr virus infection is not the sole cause of high prevalence for Hodgkin's lymphoma in Saudi Arabia.

The age-adjusted incidence of Hodgkin's lymphoma (HL) is markedly higher in Saudi Arabia than in the USA, and accounts for 10.5% of all neoplasias in children aged 15 years or older in Saudi Arabia. Epstein-Barr virus (EBV) infection has been suspected to cause high HL incidence in developing countries. To investigate the role of EBV for the high frequency of HL in Saudi Arabia, we analysed 169 HLs from Saudi Arabia and 30 HLs from Europe for EBV infection by in situ hybridization with fluorescence in-conjugated EBV on tissue microarray sections. All Saudi Arabian and European HLs were analysed in one experiment under identical conditions. Unexpectedly, our data show only minor, insignificant differences in EBV infection rates between Saudi Arabian (42 out of 147 informative cases 28.6%) and European HL (nine out of 30 informative cases; 30%; P = 0.8752). Within the Saudi Arabian population, EBV infection was most frequently seen in mixed cellularity HL (52.4%). This was significantly more frequent than in nodular sclerosing HL (26.1%; P = 0.0236). EBV positivity was unrelated to patient prognosis. In conclusion, our data strongly suggest that EBV is not the main cause for the high prevalence of HL in Saudi Arabia. This would be consistent with a major role of genetic susceptibility genes for HL in these populations. The Saudi Arabian population, with high consanguinity and large families, would prove ideal for identifying HL susceptibility genes.

Adolescent↗

PubMed2006

Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis.

AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a tumor suppressor gene for most human cancers. It encodes the most active common human chromosomal fragile region, FRA3B. We studied the prevalence of loss of FHIT expression in various tumors and correlated its loss with various clinicopathologic features. METHODS: To determine whether the absence of FHIT expression correlates with clinical variables such as grade, stage, and survival time, we assessed FHIT expression using immunohistochemistry. More than 1,800 tumors from more than 75 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19% in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like grade, stage, tumor size, and lymph node metastasis showed correlation with loss of FHIT expression in some tumors. No difference was seen in the survival patterns and loss of FHIT expression in any of the tumor groups studied. CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep, multifactorial carcinogenesis process. FHIT may be altered at different stages in different types of cancers. Most of the tumors with a wider prevalence of loss of FHIT expression as an early event show a correlation with clinicopathologic features. However, in some of the tumors, FHIT expression is lost as a late event and is only seen in a fraction of the tumors.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report.

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.

Adult↗