Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and enzymatic activities of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in human gastric cancer specimens. Forty-one patients with advanced gastric cancer gave informed consent and were enrolled in the study. Biopsy specimens of gastric cancer were obtained preoperatively through gastrofiberscopy and used to determine TS and DPD messenger RNA (mRNA) levels. TS and DPD enzyme activity and mRNA levels were also measured in resected tumor tissue samples obtained after surgical resection. TS and DPD activity were measured using the TS-binding assay and a radioenzymatic assay, respectively, while mRNA levels were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), with co-amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. 5-FU sensitivity of resected tumor specimens was measured by the tetrazolium-based colorimetric assay (MTT assay). Both TS and DPD mRNA levels correlated well between biopsied and resected tumor specimens. A statistically significant correlation was also observed between mRNA levels in biopsied specimens and enzymatic activities in resected specimens. DPD levels significantly correlated with 5-FU sensitivity, such that high DPD activity and high DPD mRNA levels resulted in low sensitivity to 5-FU. In contrast, no correlation was observed between TS activity or TS mRNA levels and 5-FU sensitivity. We conclude that tumor DPD mRNA level, as assessed from biopsy specimens obtained by gastrofiberscopy, may be a useful indicator in predicting tumor sensitivity to 5-FU in patients with gastric cancer.
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PMID:Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: possible predictor for sensitivity to 5-fluorouracil. 1074 51

Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proliferation of parathyroid cells. Vitamin D deficiency and reduced parathyroid VDR expression has been associated with development of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger RNA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR mRNA relative to glyceraldehyde-3-phosphate dehydrogenase mRNA levels were determined by RNase protection assay in 42 single parathyroid adenomas of patients with primary HPT, 23 hyperplastic glands of eight patients with uremic HPT, and 15 normal human parathyroid glands. The adenomas and hyperplasias demonstrated similar VDR mRNA levels, which were reduced (42 +/- 2.8% and 44 +/- 4.0%) compared with the normal glands (P < 0.0001). Comparison of parathyroid adenoma with a normal-sized parathyroid gland of the same individual (n = 3 pairs) showed a 20-58% reduction in the tumor. Nodularly enlarged glands represent a more advanced form of secondary HPT and showed greater reduction in the VDR mRNA levels than the diffusely enlarged glands (P < 0.005). The reduced VDR expression is likely to impair the 1,25(OH)2D3-mediated control of parathyroid functions, and to be of importance for the pathogenesis of not only uremic but also primary HPT. Circulating factors like calcium, PTH, and 1,25(OH)2D3 seem to be less likely candidates mediating the decreased VDR gene expression in HPT.
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PMID:Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism. 1134 51

The MSV-MDCK-INV invasive variant of Moloney sarcoma virus (mos) transformed MDCK cells express multiple beta-actin-rich pseudopodia (P. U. Le et al., Cancer Res. 58, 1631-1635, 1998). We show here that the tips of these actively protruding cellular domains are morphologically distinct presenting numerous blebs and selectively pass through 1-microm-pore filters. The pseudopodia were purified from the underside of the filters and a major protein component was identified as the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). By confocal microscopy, GAPDH colocalized with actin in MSV-MDCK-INV pseudopodia localizing this glycolytic enzyme to this site of active actin polymerization. Inhibition of glycolysis with 2-deoxyglucose or oxamate induced a rapid transformation of beta-actin-rich pseudopodia into extended lamellipodia and prevented cell motility. A localized glycolytic supply of energy therefore regulates the formation of beta-actin-rich pseudopodial protrusions and thereby the motility of invasive tumor cells.
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PMID:Purification and characterization of beta-actin-rich tumor cell pseudopodia: role of glycolysis. 1091 99

Thymidylate synthase (TS) is thought to be one of the target genes that the E2F1 transcription factor binds to and regulates. However, the relationship between the expressions of TS and E2F1 in primary colon cancer specimens remains unclear. The aim of this study was to define the relation of TS and E2F1 gene expressions in tumor samples from 23 colon cancer patients. TS and E2F1 gene expressions were measured by TaqMan reverse transcription-PCR assay using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard and expressed as a TS:GAPDH or E2F1:GAPDH mRNA ratio. A close relationship was found between TS gene expression and E2F1 gene expression (r2 = 0.598, P < 0.001) in 23 tumor samples analyzed. Surprisingly, a high correlation between TS gene expression and E2F1 gene expression was observed even in advanced tumors from stage IV colon cancer patients. These results suggest that transcription of the TS gene may be regulated by E2F1 in primary colon cancer specimens and that this gene-regulatory pathway from E2F1 to TS may be highly conserved during malignant progression. Four of the 23 patients showed TS overexpression with increased E2F1 expression. These results suggest that the ability of a tumor to increase TS expression may possibly be due to an overexpression of E2F1. Although the number of patients was relatively small, our study provides new insights into the molecular mechanisms underlying the regulation of TS expression in colon cancers.
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PMID:Thymidylate synthase expression correlates closely with E2F1 expression in colon cancer. 1091 14

Tumor-derived circulating DNA has been found in the plasma of cancer patients. Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylation of several genes. RNA has also been found circulating in the plasma of normal subjects and cancer patients. Tyrosinase mRNA has been extracted from the serum of melanoma patients and subjected to RT-PCR. Moreover, the presence of cell-free EBV-associated RNA has been reported in the plasma of patients with nasopharyngeal carcinoma. Human telomerase comprises two RNA subunits, telomerase RNA template (hTR) and its catalytic component, telomerase reverse transcriptase protein (hTERT). Expression of these subunits correlates with telomerase activity. Using RT-PCR, we investigated whether these RNA subunits were present in the serum of 18 patients with breast cancer, 2 patients with benign breast disease, and 21 normal subjects. The presence of amplifiable RNA was confirmed in all tissue and serum samples using RT-PCR of glyceraldehyde-3-phosphate dehydrogenase RNA. hTR was found in 17 of 18 tumors (94%) and 5 of 18 serum samples (28%). hTERT was also detected in 17 of 18 tumors (94%) and in 4 of 16 available serum samples (25%). hTR and hTERT were undetectable in tissues and sera taken from 2 patients with benign disease and in the sera of 21 normal subjects. We conclude that RNA is detectable in the serum of breast cancer patients and that tumor-derived mRNA can be extracted and amplified using RT-PCR, even in patients with localized disease. This may have implications for cancer diagnosis and follow-up in the future.
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PMID:Telomerase RNA as a detection marker in the serum of breast cancer patients. 1105 Dec 24

Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ERalpha and ERbeta, mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ERbeta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ERalpha and ERbeta isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ERbeta levels were further studied in Caco-2 cells using Northern and Western analyses. ERbeta mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ERbeta1 and ERbeta2 isoform mRNA levels were significantly decreased in tumors from female patients, and ERbeta1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ERalpha mRNA levels were much lower than ERbeta levels and were similar between normal mucosa and tumor samples in both genders. ERbeta mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ERalpha mRNA. Caco-2 cells coexpressed ERbeta1, ERbeta2, and ERbeta5 mRNA, though a single protein transcript was observed. ERbeta protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ERbeta is the predominant ER subtype in the human colon and that decreased levels of ERbeta1 and ERbeta2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ERbeta-mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage.
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PMID:Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. 1121 61

The relationships between gene expression, protein expression, and enzymatic activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have not been clarified in tumor and non-tumor tissues of human. In this study, we compared three different parameters by evaluating TS and DPD levels, mRNA expression assessed by RT-PCR, protein expression evaluated by immunohistochemical examination, and enzymatic activity measured by biochemical assay, in the tumor tissue and adjacent normal mucosa of 43 patients with gastrointestinal cancer. TS enzymatic activity in the tumor tissue was significantly higher than in normal tissue in both the stomach (median activity: 81.0 and 38.0 pmol/mg protein, respectively, p=0.012) and the colorectum (49.8 and 30.8, respectively, p=0.023). Similarly, TS mRNA expression in the tumor tissue was significantly higher than in normal tissue in both the stomach (median TS/GAPDH ratio: 6.0 and 2.0, respectively, p=0.009) and the colorectum (3.20 and 0.91, respectively, p=0.001). But no significant differences in DPD activity were observed between the tumor and normal tissue in either stomach (median activity: 41.3 and 41.6 pmol/min/mg protein, respectively) or colorectum (34.9 and 49.0, respectively). On the other hand, DPD mRNA levels in normal tissue were significantly higher than in tumor tissue only in the colorectum (DPD/GAPDH ratio: 0.83 and 0.20, respectively, p=0.003). No linear relationships were found between the enzymatic activity and mRNA expression of TS or DPD either in tumor or normal tissue. Nor were any correlations found between protein expression and either mRNA expression or enzymatic activity for either TS or DPD. These results suggest that tissue TS and DPD levels may vary with differences in the methods used to measure them. These discrepancies must be taken into account when interpreting correlation between TS and DPD levels and clinical outcome.
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PMID:Discrepancies between the gene expression, protein expression, and enzymatic activity of thymidylate synthase and dihydropyrimidine dehydrogenase in human gastrointestinal cancers and adjacent normal mucosa. 1125 Nov 64

Alpha-feto protein (AFP) mRNA levels increase in hepatocellular carcinoma (HCC) cells as compared with non-neoplastic tissue. Therefore, detection of AFP mRNA in blood nuclear cells is useful for the evaluation of treatment efficacy and prognosis of HCC. In this study, simple and reproducible methods were developed to quantify AFP mRNA using the real-time RT-PCR assay (Taq Man assay). By using in vitro synthesized AFP and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA, the sensitivity and dynamic range of the RT-PCR assay were established. AFP mRNA in both HCC and non-neoplastic tissue, as well as in cell lines, were measured using this assay system. The expression of the AFP mRNA level was normalized using the GAPDH house keeping gene product as an endogenous reference. AFP and GAPDH mRNA can be quantified in the range of 10-10(8) copies when using this quantitative assay. Among HCC cell lines, Huh 7 and HepG2 cells, respectively, represented 1.5x10(6) and 6.0x10(5) AFP mRNA/10(6) GAPDH mRNA, in contrast to 6, 23 and 230 AFP mRNA/10(6) GAPDH mRNA for HLE, HLF and PLC/PRF/5 cells, respectively. Other cell lines derived from stomach, pancreas, and colon cancers have 10 AFP mRNA copies/10(6) GAPDH mRNA. In liver tissue from patients with chronic hepatitis, and the non-neoplastic portion of the liver from HCC patients, AFP mRNA distributes from 2.5x10(3) to 5.8x10(4)/10(6) GAPDH transcripts. In contrast, AFP mRNA in tumor cells were more than 100-fold higher than that found in corresponding non-neoplastic portions in two patients who had a high level of AFP in serum. The establishment of the TaqMan quantifying system for AFP mRNA may have important clinical implications.
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PMID:Simple quantitative assay of alpha-fetoprotein mRNA in liver tissue using the real-time detection polymerase chain reaction assay - its application for clinical use. 1128 88

It is well known that iron plays an essential role in many biochemical reactions and that rapidly growing cells require more iron for their growth and metabolism than resting cells. Transferrin and its receptor are required for entry of iron into the cell. In contrast, ferritin is a cellular storage protein whose main function is to sequester excess ferric iron and thus prevent high concentrations of soluble ferric iron from becoming toxic to the cell. However, the clinical significance of both transferrin receptor and ferritin mRNA levels have not previously been described in tumors from breast cancer patients. In this study, tumor tissue mRNA levels of transferrin receptor and ferritin were quantitated on forty-two breast cancer patients. A highly sensitive non-radioisotopic cDNA polymerase chain reaction assay was used to quantitate expression of mRNA. The expression of glyceraldehyde-3-phosphate dehydrogenase served as the control. In the tumor tissue from the 42 breast cancer patients the transferrin receptor mRNA levels were significantly correlated to the ferritin H-chain mRNA levels (Spearman correlation r = 0.5433, p = 0.0002; Pearson correlation r = 0.6276, p < 0.0001). The level of amplified transferrin receptor complementary DNA was related to differentiation (ANOVA, p = 0.042) with poorly differentiated tumors having high levels of transferrin receptor mRNA. Further, the levels of amplified gene for ferritin heavy chain complementary DNA was directly related to axillary lymph nodes status (Student's t-test, p = 0.044), presence of metastatic disease (Student's t-test, p = 0.046) and clinical stage (stage I + stage II versus stage III + stage IV; Student's t-test, p = 0.0181). These results demonstrate that non-radioisotopic RT-PCR is a very sensitive method for determining mRNA levels in tumor tissue. Additionally, the quantitation of expression of transferrin receptor and ferritin heavy chain mRNA may be useful for assessing prognosis and guiding therapeutic decisions in breast cancer patients.
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PMID:Expression of transferrin receptor and ferritin H-chain mRNA are associated with clinical and histopathological prognostic indicators in breast cancer. 1129 1

The four members of the fibroblast growth factor receptor (FGFR) family are cell-surface membrane-spanning tyrosine kinase receptors involved in a wide spectrum of biologic processes. Much evidence also indicates that mutations in FGFR genes result in several craniosynostotic disorders and chondrodysplasias, and that changes in qualitative and quantitative FGFR expression profiles are implicated in tumor induction or progression. Here, we describe a precise and reliable competitive PCR-based assay to evaluate human FGFR1-4 gene expression. A single multispecific synthetic competitive template was designed to amplify FGFR1-4 homologous stretches and constructed to contain FGFR1/FGFR2/FGFR3/FGFR4/GAPDH tandemly arranged forward and reverse primers that allow competition for cDNA-specific primer annealing. The housekeeping GAPDH transcript was utilized as a reference for comparing the expression profiles of different RNA pools. The assay herein described allows the comparison of relative FGFR expression levels, both within a single RNA pool and among multiple RNA pool samples. The major advantages of such a PCR-based approach are its ability to obtain unbiased FGFR mRNA expression patterns and to detect transcripts present in low copy number. Qualitative and semiquantitative analyses of the FGFR1-4 transcript repertoire in mesenchymal- and epithelial-derived primary cell cultures and cell lines demonstrated the utility of such a method to investigate the FGFR1-4 functional role in FGF signal transduction.
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PMID:A competitive PCR-based method to measure human fibroblast growth factor receptor 1-4 (FGFR1-4) gene expression. 1144 8


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