PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genes, Neoplasm”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2003

Aberrant hypermethylation of tumor suppressor genes in pancreatic endocrine neoplasms.

OBJECTIVE: Because histologic features can be unreliable in determining the malignant potential of pancreatic endocrine neoplasms (PENs), we characterized the methylation patterns of PENs to develop a molecular marker system useful for clinical prognosis. SUMMARY BACKGROUND DATA: Aberrant promoter methylation of tumor suppressor genes is associated with a loss of gene function that can afford selective growth advantages to neoplastic cells. Gene hypermethylation, coupled with sporadic genetic mutations, defines the heterogeneous biology of human neoplasms. METHODS: Forty-eight well-differentiated PENs were subjected to methylation-specific polymerase chain reaction to detect aberrant methylation associated with 11 candidate tumor suppressor genes (INK4a/p16, APC, O6-MGMT, hMLH1, p73, E-cadherin, RAR-beta, p14ARF, GST-pi, TIMP3, and RASSF1A). Methylation differences among PENs, subdivided according to tumor size, lymph node status, or liver metastasis, were analyzed, and the association of gene methylation with tumor recurrence and patient survival was evaluated. RESULTS: Aberrant hypermethylation of any of the 11 tumor suppressor genes was detected in 87% of the PENs. In decreasing order of frequency, the 5 most commonly methylated genes were: RASSF1A (75%), INK4a/p16 (40%), O6-MGMT (40%), RAR-beta (25%), and hMLH1 (23%). In general, tumors larger than 5 cm and those associated with lymph node or hepatic metastases exhibited a higher frequency of methylation at each promoter site compared with PENs without malignant histologic features. The methylation of specific tumor suppressor genes was an independent predictor of early PEN recurrence and decreased 5-year survival following surgical resection. The accumulation of methylation of multiple tumor suppressor genes was associated with early tumor recurrence and reduced survival among a subpopulation of patients with lymph node-negative PENs. CONCLUSIONS: Aberrant methylation of multiple tumor suppressor genes is associated with advanced tumor stage and identifies molecularly distinct PENs with identical histologic characteristics. The methylation status of specific tumor suppressor genes is predictive of PEN behavior.

Carcinoma, Islet Cell↗
PubMedDate not supplied

Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms.

Identification of multiple clinical and pathologic prognostic factors in differentiated thyroid cancer has permitted some degree of risk stratification. However, these clinical indices fail to distinguish potential intrinsic differences in tumor virulence. The nm23 gene has been identified as a potential metastasis suppressor gene that is homologous to nucleoside diphosphate kinases. Studies in human breast cancer have shown a significant inverse correlation between nm23 levels and nodal involvement/tumor recurrence. Given the possible clinical utility of a marker of metastatic potential in the management of thyroid carcinoma, we examined 34 thyroid neoplasms and a human medullary thyroid cancer (MTC) cell line (TT) for nm23 expression. Normalized nm23 expression was assessed by Northern analysis of tumor RNA. nm23 Expression (tumor expression/TT cell expression, mean +/- SE) was 1.14 +/- 0.15* in MTCs (n = 5), 0.70 +/- 0.10* in follicular cancers (n = 6), 0.51 +/- 0.11 in papillary cancers (n = 19), and 0.31 +/- 0.03 in follicular adenomas (n = 4) (*p < 0.05 when compared to adenomas). Within histologic groups, we found no correlation between nm23 expression and nodal involvement of distant metastases. Our results indicate that thyroid neoplasms of different histologies express varying levels of the nm23 transcript. Although nm23 expression seems diminished in metastatic breast cancer, it appears not to be the case in metastatic thyroid cancer. The nm23 gene may therefore have different roles in the evolution and metastases of different neoplasms.

Adenocarcinoma, Follicular↗
PubMed1999

Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms.

Ten percent of fine-needle aspirations (FNAs) of the thyroid are deemed "indeterminate" or "suspicious" for malignancy by the cytopathologist, but most of these lesions are benign. Therefore, additional markers of malignancy may prove to be a useful adjunct. The catalytic component of telomerase, human telomerase reverse transcriptase (hTERT), has been found to be reactivated in immortalized cell lines. Reverse transcription-PCR of the hTERT gene revealed expression in 15 (79%) of 19 malignant thyroid neoplasms, including 6 of 6 follicular carcinomas and 9 of 13 papillary carcinomas. In contrast, hTERT gene expression was detected in only 5 (28%) of 18 benign thyroid nodules, including 2 of 7 follicular adenomas and 3 of 11 hyperplastic nodules. All five benign thyroids exhibiting hTERT gene expression had lymphocytic thyroiditis. No normal thyroids exhibited hTERT gene expression. Telomerase enzyme activity was examined in all 37 nodules and was found to correlate with hTERT gene expression in 35 (95%) nodules. The two cases in which telomerase activity and hTERT expression results were discrepant were in two papillary carcinomas that were telomerase activity negative and hTERT positive. Finally, we have demonstrated that hTERT gene expression can be measured in in vivo FNA samples. These results suggest that hTERT expression may be more accurate than telomerase activity in distinguishing benign from malignant and may be measured in FNA samples from suspicious thyroid lesions.

Biomarkers, Tumor↗
PubMed1998

[TP53 gene aberrations in chondromatous neoplasms: correlation with immunohistochemical p53 accumulation and MDM2 expression].

Histological differentiation between chondroma and chondrosarcoma is a common problem in surgical pathology. In a former study (3) we were able to show, that immuno-histochemical p53-accumulation in chondromatous neoplasias might be an additional hint for malignancy. Now we tried to find out, whether p53-accumulation is caused by TP53-aberrations or functional inactivation of p53-wildtype protein by MDM2. For this purpose, paraffin-embedded material of 80 chondromatous neoplasms (18 chondromas, 18 chondromatous neoplasms of uncertain dignity (i.e. cytologically suspicious but without definite invasive growth), and 44 chondrosarcomas (24 GI, 13 GII, 7 GIII)) were screened for TP53 gene-aberrations by means of DGGE (denaturing gradient gel electrophoresis; exons 5-8). The results were correlated with immunohistochemical p53-accumulation (DO-7, DAKO) and MDM2-expression (AB-1, Oncogene). A total of 43% of all chondromatous neoplasms showed TP53-aberrations in DGGE-analysis, i.e. 27% of chondromas, 50% of chondromatous neoplasms of uncertain dignity, 46% of GI-, 46% of GII- and 71% of GIII-chondrosarcomas. Exon 6 (58% of all cases with aberrations) and exon 8 (47%) were affected most frequently. No significant correlation between TP53-aberration and either p53-accumulation or MDM2-expression was present. A statistically significant correlation could be found between p53-accumulation and MDM2-expression (p < 0.0001). Regarding histological tumor-classification, p53-accumulation and MDM2-expression discriminated between chondromas/chondromatous neoplasms of uncertain dignity and well differentiated chondrosarcomas in a statistically significant manner. In the subgroup of p53-positive and MDM2-negative cases significantly more TP53-aberrations were detected by DGGE-analysis than in the other groups. Interestingly, the subgroup of p53- and MDM2-negative cases showed the second highest rate of TP53-DGGE-aberrations. Nearly 50% of these aberrations, however, were localized in exon 8, a mutation that is known to cause no p53-protein-accumulation. In conclusion, TP53-aberrations occur frequently in chondromatous neoplasms and show no significant association to either immunohistochemical p53-accumulation or MDM2-expression. Functional inactivation of p53 wildtype protein by MDM2-expression seems to be the major cause of p53-accumulation in chondromatous neoplasms and emphasizes the role of these parameters as additional hint for malignancy.

Bone Neoplasms↗
PubMed1984

Nuclear structure and higher order gene structure: their role in the control of chemically-induced neoplastic transformation.

An overview is hereby given of the physical and physicochemical alterations at the level of nuclear structures in rat liver cells, following a chemically-induced neoplastic transformation. These alterations refer to chromatin-DNA structure, from secondary (B- versus A- and Z-form) to tertiary-quanternary up to quinternary (in situ), and to the physical state of water. Possible molecular mechanisms-linking global chromatin changes to single gene expression in the control of neoplastic transformation-are discussed in terms of the degree of negative superhelicity of fibrosomes, recently identified single repeating structural subunits and hereby associated with single functional genes.

Animals↗
PubMed2007

Favorable histology, MYCN-amplified 4S neonatal neuroblastoma.

We report a neonate with 4S neuroblastoma and MYCN amplification, but favorable Shimada histology, successfully treated with chemotherapy and 13-cis-retinoic acid without stem cell transplantation. MYCN amplification in neuroblastoma is usually associated with unfavorable Shimada histology; the presence of these features in infants with 4S disease confers a poor prognosis. A small number of infants with 4S neuroblastoma and MYCN amplification have favorable Shimada histology. In this subgroup of infants, histopathology may be equally important in predicting outcome.

Adrenal Gland Neoplasms↗
PubMed1992

Overexpression of the ras-related rab2 gene product in peripheral blood mononuclear cells from patients with hematological and solid neoplasms.

The rab2 gene product belongs to the rab branch of the ras-related GTP-binding protein family. The rab2 gene mRNA analysis in 70 tumor samples from various origins showed no obvious difference between malignant tissues and their normal counterparts. However, an over-expression has been observed at the RNA or protein levels in peripheral blood mononuclear cells from the nine patients with Sézary syndromes studied. Subsequent investigations in mycosis fungoides and solid tumor patients allowed us to link these high protein levels to immune reactive rather than to malignant cells. Circulating monocyte and lymphocyte populations from cancer patients are under analysis to correlate the Rab2 protein overexpression to a peculiar subset of cells.

Adult↗
PubMed2005

Mismatch repair genes in renal cortical neoplasms.

Mutation of human mutL homolog 1 (MLH-1) and human mutS homolog 2 (MSH-2) has been linked with the pathogenesis of colorectal carcinoma in hereditary nonpolyposis colorectal cancer syndrome and other carcinomas. Mutations of these genes in renal cell carcinomas were recently described. The aim of this study was to examine the expression of MLH-1 and MSH-2 in renal cortical neoplasms of various histological types by immunohistochemistry. Thirty-eight (n = 38) resected renal tumors were obtained from the surgical pathology files of the UMass Memorial Healthcare, including clear cell carcinomas (CLEARs, n = 20), papillary carcinomas (PAPs, n = 8), chromophobe carcinomas (CHRs, n = 4), and oncocytomas (ONCs, n = 6). Positive immunostaining for MLH-1 and MSH-2 was graded by the number of positive tumor cell nuclei, as follows: 0, negative; 1, up to one third of positive nuclei; 2, one to two thirds positive; and 3, greater than two thirds positive. Loss of MLH-1 or MSH-2 was defined as a tumor with grade 0 or 1, compared with the normal tubules. Normal tubules and intercalated ducts contained cells positive for MLH-1 and MSH-2 in all cases. For both antibodies, positive staining in tumors ranged from grade 1 to 3 in the CLEAR and PAP but was only grade 2 to 3 in the CHR and ONC. Loss of MLH-1 and/or MSH-2 occurred in malignant tumors but not in ONC. Loss of MLH-1 was present in 8 (40%) of 20 CLEARs and 4 (50%) of 8 PAPs, compared with loss of MSH-2 in 4 (20%) of 20 CLEARs and 1 (25%) of 4 CHRs. Our results suggest that loss of mismatch repair genes is involved in the malignant transformation in some renal carcinomas, particularly those derived from the proximal tubules.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.

Animals↗
PubMed1995

No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms.

The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.

Adolescent↗
PubMed1999

[IFN alpha- and IFN gamma-induced differentially expressed genes].

OBJECTIVES: It was previously found that IFN alpha could reduce, while IFN gamma could enhance metastatic potential of a mouse mammary adenocarcinoma cell line MA891. The aim of this study was to identify the sequence of cDNA fragments that were differentially expressed by the two types of IFN, respectively. METHODS: Total RNA was extracted from MA891 cells treated with IFN alpha or IFN gamma. Northern blotting was used to confirm the differentially expressed gene fragments. DNA sequencing was then carried out. RESULTS: The Northern blots indicated that among the 10 cDNA fragments obtained by mRNA differential display technique, 4(G15 gamma, C4 alpha, T2 gamma, and T11 gamma) were shown to be unequivocally differentially expressed. Among them, the nucleotide sequence of G15 gamma did not show homology with any of the existing genes, while that of C4 alpha, T2 gamma and T11 gamma was highly homolgous to mouse minor histocompatility complex gene, mouse beta-actin gene and hamster high blood pressure gene, respectively. CONCLUSIONS: Four differentially expressed cDNA fragments by IFN alpha- and IFN gamma-treated MA891 cells have been ascertained. Regardless of sequence homology, none of them is reportedly related to tumor cell metastasis. The results herein reported provide basis for the elucidation of new metastasis-associated gene(s).

Adenocarcinoma↗
PubMed2003

Microarrays bring new insights into understanding of breast cancer metastasis to bone.

Using a microarray approach, Kang and colleagues identified several genes involved in the generation of breast cancer metastasis in bone and demonstrated their roles in bone colonization in vivo. Their findings and interpretations are reviewed in the context of recent array studies that compared gene expression in primary tumors and metastases. RNA expression array results have already demonstrated value in predicting whether metastases will develop in patients. They have also shown that expression patterns are similar in primary tumors and metastases. The latter data have invited re-examination of long-held notions related to mechanisms of metastasis. While the arrays show promise for improving diagnostic capability in breast cancers, ascribing mechanistic interpretations to correlative data should be done with extreme caution. Kang and colleagues' paper in Cancer Cell elegantly reinforces the concepts that efficiency of the metastatic process is dependent on the coordinated expression of multiple genes and that the expression of metastasis-associated genes is sometimes dependent on the microenvironment in which cells find themselves.

Bone Neoplasms↗
PubMed2006

Activation of multiple cancer-associated genes at the ERBB2 amplicon in breast cancer.

During the past decade the role of the ERBB2 (neu/HER2) oncogene as an important predictor of patient outcome and response to various therapies in breast cancer has been clearly established. This association of ERBB2 aberrations with more aggressive disease and poor clinical outcome, together with the high prevalence of such alterations in breast cancer, has also made ERBB2 an attractive target for therapy. A specific antibody-based therapy, Herceptin, directed against the extracellular domain of the ERBB2 receptor tyrosine kinase, was recently developed and several clinical trials have shown the therapeutic efficacy of this drug against ERBB2-positive breast cancer. However, a relatively large fraction of patients does not benefit from Herceptin treatment, indicating that other factors beyond ERBB2 itself must influence therapy response in ERBB2-positive tumors. It is well known that amplification of the 17q12-q21 region is the most common mechanism for ERBB2 activation in breast cancer and that it leads to simultaneous activation of several other genes. These co-amplified and co-activated genes may have an impact on disease progression and the clinical behavior of ERBB2-positive tumors and thus represent important targets of research. In this paper we discuss the current knowledge on the structure of the ERBB2 amplicon, the genes involved, and their possible contribution to breast cancer pathogenesis.

Breast Neoplasms↗
PubMed1993

Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms.

Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6/8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13% (2/15) of those CNS tumors that are not commonly associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.

Base Sequence↗
PubMed1996

Sensitivity to cis-diamminedichloroplatinum in human cancer cells is related to expression of cyclin D1 but not c-raf-1 protein.

Although several oncogenes, including c-myc, ras and c-raf-1, have been implicated in cellular resistance to ionising radiation, there is less information relating oncogene expression to cis-diamminedichloroplatinum (CDDP) resistance. However, transfection of c-myc or v-H-ras and activation of protein kinase C (PKC), which contributes to the RAF-1, MAP kinase signal transduction pathway, can influence therapeutic response to CDDP. Activation of PKC increases CDDP sensitivity, whilst transfected c-myc or v-H-ras induce CDDP resistance. We have previously reported that human in vitro cell lines show different patterns of sensitivity to CDDP and 4 MeV X-irradiation. In these cells radiation sensitivity is related to high levels of expression of the C-raf-1 proto-oncogene. We thus predicted that cells sensitive to CDDP might show a different relationship to c-raf-1 expression. In addition, because cyclin D1 expression can be upregulated by the myc or ras oncogenes, we also chose to study putative relationships between cyclin D1 protein levels and intrinsic cellular sensitivity to CDDP and gamma-irradiation. We report that in the 16 human cell lines which we have studied, high cyclin D1 expression is related to CDDP resistance but has no relationship with radiation responsiveness, whereas high c-raf-1 expression, although related to radiosensitivity has no relationship with CDDP responsiveness.

Antineoplastic Agents↗