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A Maitra

Publications and source records attributed to A Maitra.

At least 19 recordsLinked to original sources
PubMed2001

Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers.

A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors. hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70%) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60%) of 5 primary breast tumors and 11 (79%) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5'azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.

Amino Acid Sequence↗
PubMed2001

Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas.

BACKGROUND: Recent reports have described overexpression of p185(c-erbB2), the product of the HER-2/neu oncogene, in more than 40% of archival osteosarcomas that were examined by immunohistochemistry (IHC). However, IHC can be influenced by the method of fixation, extent of antigen retrieval, specificity and sensitivity of the antibody clone, and the use of an arbitrary semiquantitative scoring system. In contrast, fluorescence in situ hybridization (FISH) assays that assess HER-2/neu gene copy numbers in individual cells are more consistent, more reproducible, and less subjective than IHC. METHODS: The authors examined pretreatment nondecalcified archival tissue from 21 high-grade pediatric osteosarcomas for amplification of the HER-2/neu oncogene using an Food and Drug Administration (FDA)-approved FISH assay (PathVysion, Vysis Inc., Downers Grove, IL). Additionally, IHC for p185(c-erbB2) was performed in all cases using the Dako polyclonal antibody clone A0485 (Dako Co., Carpinteria, CA). RESULTS: None of the 21 osteosarcomas had evidence of HER-2/neu gene amplification by FISH, whereas p185(c-erbB2) IHC was negative in all cases. CONCLUSIONS: HER-2/neu gene amplification appeared to be an uncommon event in pediatric osteosarcomas. The reason(s) for discordance between previous IHC data and the current FISH and IHC results was unknown, but might reflect intrinsic variations in antibody clones, or might suggest that, in some cases, the occurrence of protein overexpression is independent of gene amplification.

Bone Neoplasms↗
PubMed2001

5' CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer.

Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5' CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung and 86% of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.

Acid Anhydride Hydrolases↗
PubMed2001

Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma.

Although gallbladder carcinoma (GBC) is a highly malignant neoplasm, there is very limited information about the molecular changes involved in its pathogenesis. To identify the chromosomal locations of putative tumor suppressor gene loci involved in the pathogenesis of GBC, we conducted a genome-wide allelotyping or loss of heterozygosity (LOH) analysis of GBCS: Microdissected tissue from 24 archival GBCs and their matched control DNAs were analyzed for PCR-based LOH using 169 microsatellite markers spanning all nonacrocentric autosomal arms and the X chromosome. The chromosomal arms with the greatest frequencies of LOH (> or = 60%) were 3p, 6q, 7q, 8p, 9p, 9q, 11q, 12q, 17p, 18q, 19p, 22q, and XQ: The average fractional allele loss index in GBC cases was high (0.43) and frequent breakpoints were detected in gallbladder tumors. Of interest, 21 different regions of frequent LOH (hot spots) defined as > or = 50% for individual GBC samples were detected in this neoplasm, nearly half of them confined to one microsatellite marker. We conclude that in GBC at least 21 chromosomal regions with frequent allele losses are involved, suggesting that several putative tumor suppressor genes are inactivated in its pathogenesis. Overall, these data provide global estimates of the extent of genetic changes leading to GBC and will be useful for the identification of new tumor suppressor genes and for multiple new markers for translational research.

Adenocarcinoma↗
PubMed2001

Expression of the RNA component of human telemorase (hTR) in ThinPrep preparations from bladder washings.

BACKGROUND: The enzyme telomerase is associated with cellular immortality and is expressed in the vast majority of human neoplasms. The expression of the RNA component of human telomerase (hTR) shows excellent concordance with enzyme activity. METHODS: In this study, hTR expression was analyzed in a series of 18 perioperative bladder washings and compared with histologic diagnoses from material obtained in the same setting. The hTR expression analysis used an 35S-based in-situ hybridization assay. ThinPrep preparations fixed in PreservCyt solution (Cytyc Corporation, Boxborough, MA) were hybridized with sense and antisense hTR probes. A 1-4+ grading scheme was used, with appropriate positive and negative controls. RESULTS: Five of six (83%) lesions with benign histology had hTR expression that was 2+ or less in the exfoliated urothelial cells. In contrast, 11 of 12 (93%) lesions with malignant histology had an hTR expression that was focally 3+ or more, with 7 of 12 (58%) lesions having 4+ hTR expression in at least some urothelial clusters. Although increased hTR expression was present in smears with malignant urothelial cells, a similar trend was not seen with muscularis propria invasion or higher grades of TCC on subsequent histology. CONCLUSIONS: The use of in situ hybridization technique bypasses the need for stringent specimen processing and allows identification of the specific cell type that expresses telomerase. Cancer (Cancer Cytopathol)

Carcinoma, Transitional Cell↗
PubMed2001

Loss of p16(INK4a) expression correlates with decreased survival in pediatric osteosarcomas.

Abnormalities of the G1 cell-cycle checkpoint are commonly reported in cancers at various anatomic sites. pRB, p16(INK4a) and cyclin D1 are critical G1-checkpoint proteins responsible for maintaining the balance of cellular proliferation. We examined a series of 38 pediatric osteosarcomas for abnormal expression of pRB, p16(INK4a) and cyclin D1 by immunohistochemical analysis of archival biopsy specimens. Overall, 17/38 (45%) osteosarcomas showed evidence of G1-checkpoint abrogation, including 11/38 (29%) with loss of pRB expression and 6/38 (16%) with loss of p16(INK4a) expression. Cyclin D1 over-expression was not detected. There was an inverse correlation between loss of pRB and p16(INK4a) expression (p = 0.07). pRB and p16(INK4a) abnormalities were independent of site of disease, presence of metastasis at diagnosis and percentage of tumor necrosis in the resection specimen. Clinical follow-up was available on all patients (median 31.6 months, range 5.9-116 months). Absence of p16(INK4a) expression significantly correlated with decreased survival in univariate analysis (p = 0.03), while loss of pRB expression did not affect survival. Immunohistochemical analysis of p16(INK4a) expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis.

Adolescent↗
PubMed2001

High-resolution chromosome 3p allelotyping of breast carcinomas and precursor lesions demonstrates frequent loss of heterozygosity and a discontinuous pattern of allele loss.

We performed high-resolution allelotyping for loss of heterozygosity (LOH) analysis on microdissected samples from 45 primary breast cancers, 47 mammary preneoplastic epithelial foci, and 18 breast cancer cell lines, using a panel of 27 polymorphic chromosome 3p markers. Allele loss in some regions of chromosome 3p was detected in 39 of 45 (87%) primary breast tumors. The 3p21.3 region had the highest frequency of LOH (69%), followed by 3p22-24 (61%), 3p21.2-21.3 (58%), 3p25 (48%), 3p14.2 (45%), 3p14.3 (41%), and 3p12 (35%). Analysis of all of the data revealed at least nine discrete intervals showing frequent allele loss: D3S1511-D3S1284 (U2020/DUTT1 region centered on D3S1274 with a homozygous deletion), D3S1300-D3S1234 [fragile histidine triad (FHIT)/FRA3B region centered on D3S1300 with a homozygous deletion], D3S1076-D3S1573, D3S4624/Luca2.1-D3S4597/P1.5, D3S1478-D3S1029, D3S1029 (with a homozygous deletion), D3S1612-D3S1537, D3S1293-D3S1597, and D3S1597-telomere; it is more than likely that additional localized regions of LOH not examined in this study also exist on chromosome 3p. In multiple cases, there was discontinuous allele loss at several 3p sites in the same tumor. Twenty-one of 47 (45%) preneoplastic lesions demonstrated 3p LOH, including 12 of 13 (92%) ductal carcinoma in situ, 2 of 7 (29%) apocrine metaplasia, and 7 of 25 (28%) usual epithelial hyperplasia. The 3p21.3 region had the highest frequency of LOH in preneoplastic breast epithelium (36%), followed by 3p21.2-21.3 (20%), 3p14.2/FHIT region (11%), 3p25 (10%), and 3p22-24 (5%). In 39 3p loci showing LOH in both the tumor and accompanying preneoplasia, 34 (87%) showed loss of the same parental allele (P = 1.2 x 10(-6), cumulative binomial test). In addition, when 21 preneoplastic samples showing LOH were compared to their accompanying cancers, 67% were clonally related, 20% were potentially clonally related but were divergent, and 13% were clonally unrelated. Overall this demonstrated the high likelihood of clonal relatedness of the preneoplastic foci to the tumors. We conclude that: chromosome 3p allele loss is a common event in breast carcinoma pathogenesis; involves multiple, localized sites that often show discontinuous LOH with intervening markers retaining heterozygosity; and is seen in early preneoplastic stages, which demonstrate clonal relatedness to the invasive cancer.

Adult↗
PubMed2001

Deletions of chromosome 4 occur early during the pathogenesis of colorectal carcinoma.

Allelic losses at one or both arms of chromosome 4 are frequent in several tumor types, but information about colorectal carcinoma is limited. We have previously defined 4 nonoverlapping regions of frequent deletions in several tumor types. In an effort to more precisely locate the putative tumor suppressor gene(s) on chromosome 4 involved in the multistage pathogenesis of colorectal carcinomas, we performed loss of heterozygosity (LOH) studies using 19 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we determined LOH in DNA obtained from 23 colorectal adenocarcinomas, 20 colorectal adenomas, and from corresponding histologically normal-appearing colonic epithelial samples adjacent to the tumors and at the resection margins. We observed localized deletions of chromosome 4 at multiple regions in both carcinomas and adenomas. We identified deletions at 4 previously identified regions: R1 at 4q33-34 (18%-33%), R2 at 4q25-26 (45%-65%), R3 at 4p15.1-15.3 (35%-47%), and R4 at 4p16.3 (40%-49%). Six of fifteen (40%) cases examined with deletions of chromosome 4 in either adenocarcinomas or adenomas had loss of the same parental alleles in adjacent histologically normal epithelium but not in epithelial samples from the surgical resection margins. The deletions, which commenced on the short arm of chromosome 4 (regions R3 and/or R4), were more extensive in adenocarcinomas, intermediate in length in adenomas, and least extensive in histologically normal epithelium. Our results suggest that there may be multiple putative tumor suppressor genes located on both arms of chromosome 4 whose inactivation are important early events in the pathogenesis of colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

Primary mammary small-cell carcinoma: a molecular analysis of 2 cases.

Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma whose genetic profile has not been previously investigated. We report the molecular features of 2 cases of small-cell carcinoma of the breast: 1 with an adjacent intraductal carcinoma, and 1 with prior pleomorphic lobular carcinoma in situ. Laser capture microdissection followed by loss of heterozygosity (LOH) analysis revealed identical molecular alterations at multiple chromosomal regions, including BRCA-1, BRCA-2, p53, and retinoblastoma gene loci, in 1 case of small-cell carcinoma and its adjacent intraductal component. Additionally, LOH in 1 or both small-cell carcinomas was detected at 3p, 4q31.2-qter, 8p21-24, 11q13 (MEN-1 locus), 11q23.3, 11q24.1-25, 16q24.1 (H-cadherin locus), and 17q25. The results of our molecular analysis suggest that genetic changes in mammary small-cell carcinoma resembled those seen in both invasive ductal carcinomas and pulmonary small-cell carcinoma. Second, mammary small-cell carcinoma is clonally related to ductal carcinoma in situ and might represent an example of divergent differentiation occurring in a multipotential neoplastic stem cell.

Adult↗
PubMed2001

Small cell carcinoma of the gallbladder: a clinicopathologic, immunohistochemical, and molecular pathology study of 12 cases.

Small cell carcinomas of the gallbladder are unusual neoplasms that have been characterized only recently. The authors describe the clinical, histopathologic, immunohistochemical, and molecular features of 12 small cell carcinomas of the gallbladder. The mean age at diagnosis was 69 years, and the male-to-female ratio was 5:7. The neoplasms had an average size of 3 cm, and 90% showed invasion of the muscularis propria and perimuscular connective tissue. Seventy-five percent of the carcinomas had metastasized or extended locally beyond the gallbladder at surgery. Survival was uniformly poor, with a mean survival of 10.7 months (range, 3-25 months). Half the small cell carcinomas were combined with other neoplasms. Four had foci of adenocarcinoma, one contained areas of squamous differentiation, and another had a component of carcinosarcoma. Immunohistochemical analysis showed focal reactivity for chromogranin (six of six cases), neuron-specific enolase (six of six cases), and Leu-7 (three of three cases). The molecular changes in small cell carcinomas were similar to those of adenocarcinomas occurring at this site, with a high frequency of p53 (75%) and p16INK4a (33%) abnormalities, and a low frequency of deleted in pancreatic carcinoma-4 inactivation (0%) and K-ras codon 12 mutations (17%). In contrast to pulmonary small cell carcinomas, p16INK4a function appears to be abrogated more frequently in these carcinomas.

Adenocarcinoma↗
PubMed2001

Immunoreactivity for hepatocyte paraffin 1 antibody in hepatoid adenocarcinomas of the gastrointestinal tract.

Hepatocyte paraffin 1 (Hep Par 1) is a monoclonal antibody considered almost specific for normal and neoplastic hepatocytes, that can be used on formalin-fixed paraffin-embedded tissues. Hep Par 1 reactivity has been demonstrated consistently in hepatocellular carcinomas and hepatoblastomas but only rarely in cholangiocarcinomas and metastatic tumors to the liver. Although its role as a marker of hepatocytic differentiation in primary liver tumors has been studied extensively, Hep Par 1 expression has not been explored in extrahepatic lesions, especially rare adenocarcinomas with hepatoid morphologic features. We studied 7 hepatoid adenocarcinomas of the gastrointestinal tract (6 gastric and 1 from the gallbladder) for Hep Par 1 immunoreactivity. Focal Hep Par 1 expression was seen in 6 of 7 tumors. These hepatoid adenocarcinomas also showed reactivity for alpha-fetoprotein and carcinoembryonic antigen. The presence of Hep Par 1 reactivity in extrahepatic hepatoid adenocarcinomas underscores the fact that Hep Par 1 expression is not unique to primary hepatocellular neoplasms. Adenocarcinomas with hepatoid features must be considered in the differential diagnosis of Hep Par 1-positive lesions.

Adenocarcinoma↗
PubMed2001

Precursor B-cell lymphoblastic lymphoma. A study of nine cases lacking blood and bone marrow involvement and review of the literature.

We describe 9 cases of precursor B-cell lymphoblastic lymphoma (LYL) without evidence of marrow or blood involvement. Four patients had superficial nodal disease, 2 cutaneous involvement, and 1 each ovarian, retroperitoneal, or tonsillar primary tumor. Six patients had limited disease; 3 patients were stage III. Immunophenotyping revealed a terminal deoxynucleotidyl transferase (TdT)-positive, immature B-cell population with variable expression of CD10, CD20, and CD45. All patients are in complete clinical remission (median follow-up, 14 months). A literature review yielded 105 patients with a diagnosis of precursor B-cell LYL based on less than 25% marrow involvement. Of these, 64% were younger than 18 years. Skin, lymph nodes, and bone were the most common sites of disease. Mediastinal involvement was uncommon. TdT, CD19, CD79a, CD10, and HLA-DR were the most frequently expressed antigens, while CD45 and CD20 were expressed in only two thirds of the cases. Cytogenetic analysis showed additional 21q material as a recurring karyotypic abnormality. At a median follow-up of 26 months, 74% of patients were alive; the median survival was 19 months for patients dying of disease. Comparison with precursor B-cell acute lymphoblastic leukemia showed several overlapping features, although distinct differences were identified.

Adult↗
PubMed2001

Microdissection and the study of cancer pathways.

Abstract: The study of genetic alterations in tumors and their precursor lesions is often hampered by the presence of a heterogeneous background of non-neoplastic elements such as stromal cells, inflammatory cells, and angiogenic elements. Microdissection involves the extraction of specific populations of cells under direct visualization. In this article, we will discuss the currently available techniques of microdissection, and briefly review how this material is being utilized in the study of cancer pathways. Microdissected tissue is amenable for the study of cancer genomics, expression analysis and most recently, cancer proteomics. The purity of reagents obtained from microdissected material has resulted in the successful identification of tumor suppressor genes as well as novel transcripts and proteins that are altered in neoplastic cells. Improved techniques of tissue fixation and microdissection, supplemented with ancillary technology such as pre-amplification, have permitted the use of increasingly smaller quantities of material for the study of cancer pathways. Importantly, it is now possible to analyze many of the genetic changes that precede cancer, thereby identifying populations "at risk" for developing malignancies in the future.

Cell Separation↗
PubMed2001

Fine-needle aspiration biopsy features in a case of giant cell fibroblastoma of the chest wall.

Giant cell fibroblastoma is an unusual tumor of childhood, primarily occurring in the superficial soft tissues. We describe the fine-needle aspiration biopsy features of a case of giant cell fibroblastoma of the chest wall in a 3-year-old child. The aspirates comprised bland spindle to oval cells entrapped in a metachromatic matrix, accompanied by rare multinucleated giant cells with wreathlike nuclei. Although we were unable to render a definitive diagnosis on fine-needle aspiration biopsy, surgical resection of the mass established the diagnosis of giant cell fibroblastoma. We review the distinctive cytologic features of some common soft tissue tumors arising in this age group that may give rise to a diagnostic conundrum on fine-needle aspiration biopsy.

Biopsy, Needle↗
PubMed2001

Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.

BACKGROUND: Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs). DESIGN: We examined a series of 20 pediatric EFTs for abnormal expression of p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5-103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy). RESULTS: Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21(WAF1) expression, 4 (20%) with down-regulation of p16(INK4a), 2 (10%) with absence of pRB, and one case (5%) with loss of p14(ARF) expression. Loss of p16(INK4a) expression correlated with metastatic disease at presentation (P =.026), and showed a trend toward shortened survival (P =.20). The p21(WAF1), p14(ARF), and pRB status was not significantly correlated with either metastatic disease at presentation or outcome. CONCLUSION: Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21(WAF1) and p16(INK4a) were the most frequent findings. Loss of p16(INK4a) expression may identify a subset of cases with a more aggressive phenotype.

Adolescent↗
PubMed2001

Malignancies arising in oncocytic schneiderian papillomas: a report of 2 cases and review of the literature.

Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases--a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.

Aged↗
PubMed2000

Ketorolac entrapped in polymeric micelles: preparation, characterisation and ocular anti-inflammatory studies.

Polymeric micelles made of copolymer of N-isopropylacrylamide (NIPAAM), vinyl pyrrolidone (VP) and acrylic acid (AA) having cross-linkage with N,N'-methylene bis-acrylamide (MBA) were used as host carrier in which up to 30%w/w ketorolac (free acid) was entrapped to make the formulation. The lyophilised powder was used for physical characterisation. The drug entrapment was found to be about 80% and the formulation was stable for 8-10 days at room temperature. The smaller the amount of ketorolac dissolved into the micelles, the longer was the formulation shelf life. The size of the particles as measured by dynamic light scattering was found to be around 35 nm diameter at 25 degrees C. TEM picture showed spherical particles. The structure of the polymer and its morphology were characterised by FTIR, NMR and XRD measurements. IR data indicated weak interaction between polymer and ketorolac in the encapsulated system. NMR spectra indicated rigid polymer backbone with intermittent iso-propyl group in the chain. XRD spectra showed significant loss of crystallinity of the drug while being entrapped in the polymeric micelles. The release of drug in aqueous buffer (pH 7.2) from the polymeric micelles at 25 degrees C were 20 and 60% after 2 and 8 h respectively and is temperature and pH dependent. In vitro corneal permeation studies through excised rabbit cornea indicated two fold increase in ocular availability with no corneal damage compared to an aqueous suspension containing same amount of drug as in nanoparticles. The formulation showed significant inhibition of lid closure up to 3 h and PMN migration up to 5 h compared to the suspension containing non-entrapped drug, which did not show any significant effect.

Acrylamides↗