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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The comparison of the gene expression profiles between two subpopulations of melanoma cells (1C8 and T1C3) derived from the tumor of one patient by cDNA array revealed differences in GAPDH and beta-actin gene levels. These two housekeeping genes were up-regulated in invasive T1C3 melanoma cells compared to noninvasive 1C8 cells. Since cDNA array results were not confirmed by conventional RT-PCR throughout the exponential phase of amplification, we performed duplex relative RT-PCR using ribosomal 18S RNA as internal standard including competimer technology. Statistical analyses provided significant evidence that invasive T1C3 melanoma cells exhibited a twofold higher mRNA level of both GAPDH and beta-actin than noninvasive 1C8 cells. This study demonstrates that the duplex relative RT-PCR procedure including ribosomal 18S RNA as internal standard and competimer technology is precise for RNA quantification and is tailored for cDNA array validation. Our data provide molecular evidence that cellular subpopulations of the same pathological origin are highly heterogeneous and extend the concept that the selection of an appropriate internal control for comparative mRNA analysis should be adapted to each model of human cancers.
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PMID:Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes as internal standard for quantitative comparison of mRNA levels in invasive and noninvasive human melanoma cell subpopulations. 1147 40

The suitability of "real-time" quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8, CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone marrow specimens from noncancer patients, and 30 bone marrow specimens from patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow specimens from noncancer patients demonstrated background transcription of CK8 (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1 copies/10(3) copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly lower. When maximal background values were used as a threshold value to define positivity in tumor cell dilution experiments, sensitivity levels of one tumor cell in 10(4) bone marrow cells were determined for CK7 and CK20 RT-PCR assays. Maximal background expression values of the different CKs as obtained in the control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times (CK7) in bone marrow specimens from cancer patients, with none of these specimens exceeding the maximal background expression value of CK8. We conclude that RT-PCR for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor cells in bone marrow of cancer patients. On the other side, the limited number of gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that assay sensitivity for these CKs might be limited because of their selective expression by carcinoma cells.
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PMID:Transcription of cytokeratins 8, 18, and 19 in bone marrow and limited expression of cytokeratins 7 and 20 by carcinoma cells: inherent limitations for RT-PCR in the detection of isolated tumor cells. 1159 48

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel sensitive to apoptosis gene, SAG, may be expressed in tumors of patients with nonsmall cell lung cancer (NSCLC) and may affect their clinical outcome. Expression of SAG messenger RNA was evaluated by reverse transcription polymerase chain reaction in 80 nonsmall cell lung carcinomas and 65 adjacent histologic nonmalignant lung samples using a LightCycler. The data were analyzed in reference to clinicopathologic data and survival. The SAG/GAPDH mRNA level in 80 NSCLC was 2.337 +/- 1.972. Of 65 paired NSCLC and nonmalignant lung samples, SAG/GAPDH mRNA levels were 2.313 +/- 2.064 and 1.696 +/- 1.910, respectively. The SAG mRNA level was significantly higher in NSCLC compared with nonmalignant lung tissue (p = 0.0169). There was no relationship between SAG gene expression and age, gender, T- or N-status or clinical stages. The NSCLC patients with high SAG/GAPDH expression (>1.8) had significantly poorer survival than the patients with low SAG/GAPDH expression (<1.8, p = 0.0227). Thus we suggest that SAG gene expression in NSCLC may be a useful prognostic marker.
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PMID:Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer. 1166 20

To identify novel tumor suppressor genes involved in ovarian carcinogenesis, we generated four down-regulated suppression subtraction cDNA libraries from two early-stage (stage I/II) and two late-stage (stage III) primary ovarian tumors, each subtracted against cDNAs derived from normal ovarian epithelial cell brushings. Approximately 600-700 distinct clones were sequenced from each library. Comparison of down-regulated clones obtained from early- and late-stage tumors revealed genes that were unique to each library which suggested tumor-specific differences. We found 45 down-regulated genes that were common in all four libraries. We also identified several genes, the role of which in tumor development has yet to be elucidated, in addition to several under expressed genes, the potential role of which in carcinogenesis has been described previously (Bagnoli et al., Oncogene, 19: 4754-4763, 2000; Yu et al., Proc. Natl. Acad. Sci. USA, 96: 214-219, 1999; Mok et al., Oncogene, 12: 1895-1901, 1996). The differential expression of a subset of these genes was confirmed by semiquantitative reverse transcription-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control in a panel of 15 stage I and 15 stage III tumors of mixed histological subtypes. Chromosomal sorting of library sequences revealed that several of the genes mapped to known regions of deletion in ovarian cancer. Loss of heterozygosity (LOH) analysis revealed multiple genomic regions with a high frequency of loss in both early- and late-stage tumors. To determine whether loss of expression of some of the genes corresponds to loss of an allele by LOH, we used a microsatellite marker for one of the novel genes on 8q and have shown that loss of expression of this novel gene correlates with loss of an allele by LOH. In conclusion, our analysis has identified down-regulated genes, which map to known as well as novel regions of deletions and may represent potential candidate tumor suppressor genes involved in ovarian cancer.
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PMID:Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. 1178 86

In order to identify genes associated with metastasis of ductal pancreatic adenocarcinoma we investigated pancreatic tumor cell lines derived from an orthotopic pancreatic tumor model in SCID mice. Transcriptional profiling (Affymetrix Gene Chip Technology) was performed with cell lines derived from the primary tumor and metastatic lesions such as mesentery, liver and lungs. We scored for genes commonly deregulated in the cell lines derived from the metastatic lesions. Of 7070 genes investigated, 59 (0.83%) were found to be deregulated in the cell lines derived from the metastatic lesions. We grouped these genes into different categories such as transcription, translation, cytoskeleton, cell adhesion, chromosome instability, tumor suppressor genes, enzymes and "others". The most remarkable features of the system are the up-regulation of high mobility group protein HMG-I (Y), twenty-one ribosomal proteins, GAPDH and the laminin receptor in the cell lines derived from the metastatic lesions, whereas tumor suppressor genes such as maspin and RB1 were down-regulated. Inhibition or reconstitution of the activity of these targets are an emerging strategy for inhibition of metastasis in this system.
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PMID:Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genes. 1184 76

The role of the bcl-2 gene family members in promoting or antagonizing apoptosis in malignant tumors, including soft tissue sarcomas (STS), is well known. However, the impact of mRNA expression of bcl-2 family genes on prognosis has not been thoroughly investigated in STS. Samples from 82 STS patients were analyzed for mRNA expression of bad, bax, bcl-xL and bcl-2 by a high-throughput quantitative RT-PCR approach, using validated assays based on TaqMan technology. The mRNA data, related to glyceraldehyde-3-phosphate dehydrogenase expression measured in the same sample, were analysed for their correlation to tumor stage and overall survival of patients. In a Kaplan-Meier analysis none of the mRNA levels investigated differed significantly with regard to their impact on survival (log-rank test). However, after including the tumor stage in the statistical analysis, a borderline significance was observed for bad mRNA expression (p=0.068) indicating a stage-specific impact of mRNA expression on prognosis. Considering STS patients of tumor stage 2, multivariate Cox analysis revealed that bad mRNA values > or = 10 (p=0.0039; RR=9.08), bcl-xL > or = 1.5 (p=0.067; RR=4.59), bax > or = 0.005 (p=0.1; RR=2.84) and bcl-2 < 3 (p=0.42; RR=1.7) were associated with a poor prognosis. Combined high bad/bcl-xL mRNA expression levels revealed a 20-fold increase in the relative risk of tumor-related death (p=0.016) when comparing the poor and good prognosis groups. There was a 14.5-fold and 6.5-fold increase in the risk for the combinations of high bax/bcl-xL mRNA (p=0.018) and bax/bcl-2 mRNA expression (p=0.017), respectively. In conclusion, high bad mRNA levels and combined values of bad/bcl-xL bax/bcl-xL and bax/bcl-2 appear to be independent prognostic factors at least for stage 2 STS patients. In the combinations of mRNA levels there was more than an additive effect pointing to different pathways of prognostic relevance.
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PMID:High bad and bcl-xL gene expression and combined bad, bcl-xL, bax and bcl-2 mRNA levels: molecular predictors for survival of stage 2 soft tissue sarcoma patients. 1216 36

Oesophageal squamous cell carcinoma is one of the most malignant tumours. To identify patients with a high risk of recurrence of oesophageal squamous cell carcinoma, we investigated the prognostic significance of survivin mRNA expression in oesophageal squamous cell carcinoma, which has recently been reported to be a good marker for unfavourable prognosis in various tumours. Tumours and non-cancerous epitheliums adjacent to tumours were obtained by surgical resection from 57 patients with oesophageal squamous cell carcinoma. Expression levels of survivin and glyceraldehyde-3-phosphate dehydrogenase mRNA were analysed quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The survivin/glyceraldehyde-3-phosphate dehydrogenase ratios of tumours were higher than those of non-cancerous tissues (P=0.0003). Tumour-survivin/glyceraldehyde-3-phosphate dehydrogenase ratio did not correlate with histologic type, lymph node metastasis, and stage of tumours. In 53 surviving patients, the 5-year survival rate of 17 patients with high survivin mRNA expressed oesophageal squamous cell carcinoma (14.1%) was significantly poorer than that of 36 with low survivin mRNA expressed oesophageal squamous cell carcinoma (46.8%, P=0.0018). In these patients, tumour-survivin mRNA expression was recognised as a good marker of cancer recurrence independently from tumour stage. These findings indicate that survivin mRNA expression in oesophageal squamous cell carcinoma may be a good biomarker for identifying patients with high risk of cancer recurrence.
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PMID:survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. 1237 3

Mitochondrial H+-ATP synthase is required for cellular energy provision and for efficient execution of apoptosis. Almost one century ago, Otto Warburg proposed the hypothesis that mitochondrial function might be impaired in cancer cells. However, his hypothesis was never demonstrated in human carcinomas. In this study, we have analyzed the expression of the beta-catalytic subunit of the H+-ATP synthase (beta-F1-ATPase) of mitochondria in carcinomas of the human liver, kidney, and colon. We show that carcinogenesis in the liver involves a depletion of the cellular mitochondrial content, as revealed by reduced content of mitochondrial markers, whereas in kidney and colon carcinomas, it involves a selective repression of the expression of the beta-F1-ATPase concurrent with an increase in the expression of the glycolytic glyceraldehyde-3-phosphate dehydrogenase. Both mechanisms limit mitochondrial cellular activity in cancer, strongly supporting Warburg's hypothesis, and suggest a mechanism for the resistance and compromised apoptotic potential of tumor cells. Furthermore, we show that the metabolic state of the cell, as defined by a bioenergetic mitochondrial index relative to the cellular glycolytic potential, provides a signature of carcinogenesis of prognostic value in assessing the progression of colorectal carcinomas.
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PMID:The bioenergetic signature of cancer: a marker of tumor progression. 1243 66

We used real-time reverse-transcription polymerase chain reaction (RT-PCR) to assay expression of the mRNA of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in gastric cancer tissue with the objective of establishing a system to measure TS and DPD in ultra-low-volume samples. Nude mouse xenografts of 5 human gastric cancer cell lines and 85 clinical samples were used as the specimens in this study. Sensitivity to 5-fluorouracil (5-FU) was determined on the basis of the relative tumor proliferation rate in mice and the results of ATP assay using serum-free cultures of the clinical samples. mRNA expression was measured in tumor tissue by real-time RT-PCR using the ABI PRISM 7700 system. The values for expression of the mRNA for TS and DPD were corrected according to the level of glyceraldehyde-3-phosphate dehydrogenase mRNA expression. The xenografts yielded correlations between TS and DPD mRNA expression and the activity of the enzymes (TS: rs=0.700, DPD: rs=0.900), and an inverse correlation was noted between the mRNA levels and sensitivity to 5-FU (TS: rs=-0.900, DPD: rs=-0.800). The clinical samples showed an inverse correlation between 5-FU sensitivity and mRNA expression (TS: rs=-0.518, DPD: rs=-0.564). Sensitivity to 5-FU was noted only in cases in which TS mRNA expression and DPD mRNA expression were both low. Real-time RT-PCR can provide a highly sensitive assessment of TS and DPD mRNA expression in gastric cancer, and it was useful for predicting 5-FU sensitivity.
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PMID:Quantitative measurement of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level in gastric cancer by real-time RT-PCR. 1249 74

Gene therapy clinical trials for cancer frequently produce inconsistent results. Some of this variability could result from differences in transcriptional regulation that limit expression of therapeutic genes in specific cancers. Systemic liposomal delivery of a nonviral plasmid DNA showed efficacy in animal models for several cancers. However, we observed large differences in the levels of gene expression from a CMV promoter-enhancer between lung and breast cancers. To optimize gene expression in breast cancer cells in vitro and in vivo, we created a new promoter-enhancer chimera to regulate gene expression. Serial analyses of gene expression data from a panel of breast carcinomas and normal breast cells predicted that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter is highly active in breast cancers. Furthermore, GAPDH is up-regulated by hypoxia, which is common in tumors. We added the GAPDH promoter, including the hypoxia enhancer sequences, to our in vivo gene expression plasmid. The novel CMV-GAPDH promoter-enhancer showed up to 70-fold increased gene expression in breast tumors compared to the optimized CMV promoter-enhancer alone. No significant increase in gene expression was observed in other tissues. These data demonstrate tissue-specific effects on gene expression after nonviral delivery and suggest that gene delivery systems may require plasmid modifications for the treatment of different tumor types. Furthermore, expression profiling can facilitate the design of optimal expression plasmids for use in specific cancers.
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PMID:Enhanced gene expression in breast cancer cells in vitro and tumors in vivo. 1249 74


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