Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of several resistance markers (P-glycoprotein, glutathione S-transferase-pi, thymidylate synthase, dihydrofolate reductase) was analyzed in matched primary tumors and lymph node metastases from 21 patients with lung cancer using immunohistochemistry. The analysis showed that expression of these resistance proteins is generally congruent in primary lung cancer and simultaneously resected lymph node metastases. This suggests that in general the resistance of a primary tumor predicts for the resistance of the metastases and vice versa.
 ...
PMID:Detection of resistance proteins in matched primary lung tumors and lymph node metastases. 791 93

It has been hypothesized that intratumoral thymidylate synthase (TS) gene expression might be used to select therapy for patients with disseminated colorectal cancer. We recently reported the results of a clinical trial in 46 patients with disseminated or recurrent colorectal cancer testing whether expression of TS within the primary tumor, as assessed by quantitative polymerase chain reaction (PCR) methodology, would predict the responsiveness of that cancer of fluoropyrimidine-based therapy. This trial demonstrated that intratumoral TS/beta-actin messenger RNA (mRNA) ratio can accurately predict which metastatic colorectal tumors will be resistant to a leucovorin-modulated 5-FU infusion and which have a high likelihood of responding to such a regimen. Results of other studies of adjuvant therapy in gastric cancer and colorectal cancer also indicated that TS expression within the tumor is predictive of response of 5-FU-based therapy. It may be possible to use this parameter prospectively to decide which patients should receive fluorinated pyrimidine therapy: Patients whose tumors express low TS levels would be likely to benefit from such therapy, whereas limited preliminary data suggest that patients whose tumors express high TS levels may benefit from irinotecan (CPT-11[Camptosar]).
 ...
PMID:Thymidylate synthase as a predictor of response. 972 90

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.
 ...
PMID:A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma. 1049 10

The value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activity in metastatic liver tumor from colorectal cancer as predictive parameters for hepatic artery infusion (HAI) chemotherapy with 5-FU was investigated. Thirteen patients with metachronous liver metastases underwent hepatic resection and primary site colectomy. We measured TS and DPD activity in normal colonic mucosa, primary colon tumor, and metastatic liver tumor in these patients. The TS (pmol/g-tissue) of primary tumor, metastatic tumor, and normal colonic mucosa was 6.6 +/- 1.40 (mean +/- SE), 3.2 +/- 0.83 and 2.5 +/- 0.83 respectively. The DPD (pmol/min/mg/protein) of primary tumor, metastatic tumor, and normal colonic mucosa was 31.7 +/- 5.49, 82.1 +/- 12.5 and 50.6 +/- 8.46, respectively. There was significant relationship between DPD activity level and recurrence. It is suggested that 5-FU catabolism in metastatic liver tumor was increased, and DPD activity may be a valuable predictive marker for tumor response to HAI therapy.
 ...
PMID:[Thymidylate synthase and dihydropyrimidine dehydrogenase activity in a metastatic liver tumor from colorectal cancer]. 1108 36

Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions in metastatic colorectal cancer have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. In this study, we investigated the association between both DPD and TS expressions in primary colorectal tumor and the antitumor effect in patients with metastatic colorectal cancer when treated with a fluoropyrimidine-based protocol. DPD and TS expressions were measured by reverse transcription-PCR in surgically resected materials of primary colorectal tumors from 37 patients who went on to receive oral treatment of uracil and tegafur and leucovorin for either synchronous or metachronous metastatic diseases. Relative mRNA amounts of DPD or TS were expressed as the ratios of targeted gene to glyceraldehyde-3-phosphate dehydrogenase reverse transcription-PCR products. Median values of DPD mRNA expressions were 0.30 and 0.65 for responding tumors and nonresponding ones, respectively, with a statistical significance (P < 0.0001). No responding tumor had a DPD mRNA expression >/= 0.5. A total of 19 tumors had low DPD mRNA expressions of <0.5, and 63% of them showed response. There was no responding tumor with both high DPD and high TS (TS mRNA expression >/= 1.0). However, the response rate was 75% in tumors with both low DPD and low TS. The median survival time was 16.3 months in patients with both low DPD and low TS versus 8.4 months in patients with high DPD or high TS mRNA expression. In conclusion, the combination of DPD and TS mRNA expressions in the primary tumor might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.
 ...
PMID:Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. 1257 51

High intratumoral expression of thymidylate synthase (TS) has been reported as a factor of poor prognosis in patients with advanced colorectal cancer (CRC), but such association is unclear in some studies. Also, TS has been stated as a typical cytosolic enzyme, but nuclear location has been occasionally reported, and data on the clinical meaning of TS intracellular location are scarce. A retrospective study was performed in paraffin-embedded sections of primary tumor from 77 CRC patients treated with surgical resection and adjuvant 5-FU-based chemotherapy. TS levels and expression patterns were determined by immunohistochemistry (IHQ) using TS-106 antibody. Qualitative and quantitative variables were compared respectively by chi2 and Kruskal-Wallis tests; overall survival (OS) and disease-free survival (DFS) were analyzed with the Kaplan-Meier method and compared using the log-rank and Wilcoxon tests. TS was cytoplasmic in 27.1% of positive tumors and both, nuclear and cytoplasmic in 72.9%; specimens from seven patients (9.1%) lacked TS expression. TS levels were high in 21.6% of tumors with nuclear expression and low in 5.6%, whereas 68.4% of cytoplasmic ones showed low immunostaining intensity (p=0.02); cytoplasmic pattern was also associated to longer OS (p<0.009) and DFS (p=0.003). In patients with nuclear expression, low TS expression was associated to shorter OS (p<0.003) and DFS (p<0.04). These results indicate that, in our study, TS immunostaining patterns were related with OS and DFS, the best prognostic corresponding to cytoplasmic one, and, within the subset of patients with nuclear expression, low TS levels were associated to worse clinical outcome.
 ...
PMID:Thymidylate synthase expression pattern is a prognostic factor in patients of colorectal cancer treated with 5-fluorouracil. 1537 35

This study explores the effect of 5-fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate-limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor and liver metastasis samples from patients who were either not pretreated (n = 29) or given one presurgery bolus of 5FU (n = 67). In both groups a wide variation in TS mRNA levels was observed. Median TS mRNA expression in 17 primary tumors of exposed patients was 3.0-fold higher than in 19 primary tumors of unexposed patients (p = 0.015). TS mRNA expression in liver metastasis samples of exposed patients (n = 16) was also higher (5.2-fold) than that of unexposed patients (n = 48; p < 0.001). Also DPD mRNA expression displayed a large degree of interpatient variation. No difference in DPD expression in liver metastasis samples was observed between exposed and unexposed patients. However, median DPD mRNA expression in 15 primary tumors of exposed patients was 3.2-fold lower than in 18 primary tumors of unexposed patients (p = 0.027). In conclusion, administration of 5FU in vivo influences the gene expression of TS and DPD.
 ...
PMID:Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5-fluorouracil to patients with colorectal cancer. 1733 Feb 33

Following resection of hepatic colorectal metastases, there are few criteria for predicting which patients have more aggressive disease and are, therefore, more likely to experience recurrence and reduced survival. Traditionally, primary tumor stage, preoperative carcinoembryonic antigen level, time from primary tumor treatment to diagnosis of hepatic metastases (disease-free interval), hepatic tumor size, number of hepatic metastases, and presence of extrahepatic disease have been reported to be predictors of survival after resection. However, the data regarding the prognostic importance of these clinicopathologic factors are inconsistent and conflicting. Therefore, conventional clinicopathologic factors may be inadequate for the purposes of prognostication. More recently, there has been increased interest in identifying biologic indicators that may help better define patients at risk for recurrence after hepatic resection for colorectal metastases. Recent studies have shown that proliferation markers such as p53 expression, tritiated thymidine uptake, thymidylate synthase, Ki-67, and human telomerase reverse transcriptase may be better predictors of outcome after resection of hepatic colorectal metastases. Moreover, tumor response to preoperative chemotherapy may also prove to be a useful predictor of outcome following liver resection for colorectal metastases.
 ...
PMID:Shifting from clinical to biologic indicators of prognosis after resection of hepatic colorectal metastases. 1743 Jun 90

5-fluorouracil (5-FU) and oxaliplatin play important roles in chemotherapy for patients with colorectal cancer. The expression levels of thymidylate synthase (TS) and excision repair cross-complementing factor 1 (ERCC1) have been reported to be prognostic markers for patients with 5-FU/oxaliplatin chemotherapy. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of TS and ERCC1 in primary colorectal cancer and those in corresponding liver metastasis. Formalin-fixed paraffin-embedded tumor specimens of 31 patients with resection for both colorectal cancer and liver metastasis were dissected by laser capture microdissection. After RNA extraction, TS and ERCC1 mRNA levels in both primary tumor and corresponding liver metastasis were measured by real-time reverse transcription-polymerase chain reaction. Both TS and ERCC1 mRNA levels in primary tumors were significantly associated with those in synchronous liver metastases (TS, rs=0.875, p=0.0024; ERCC1, rs=0.835, p=0.0038). TS mRNA levels in primary tumors were also associated with those in metachronous liver metastases (rs=0.659, p=0.0065), but not in ERCC1 (rs=0.319, p=0.19). In both genes, mRNA levels in metachronous liver metastases were higher than those in primary tumors (TS, p=0.0084; ERCC1, p=0.037). However, there was no difference in the TS and ERCC1 mRNA levels between primary tumors and synchronous liver metastasis. The measurement of TS and ERCC1 mRNA levels in primary colorectal cancer can predict those in synchronous liver metastases, but not in metachronous ones.
 ...
PMID:Messenger RNA expression of TS and ERCC1 in colorectal cancer and matched liver metastasis. 1902 Jul 59

Microdissection is a reliable technique and is extensively used in many cancer studies. We sought to verify the importance of the microdissection technique in molecular analysis of irradiated rectal cancer specimens. Forty patients with rectal cancer underwent 5-fluorouracil based chemoradiotherapy followed by curative surgery. We compared gene expressions that had previously been shown to be involved in chemotherapy or radiation effects; one obtained using RNA extracted from cancer cells by microdissection, and the other from bulky cancer tissues in all patients. More than 50% regression of the primary tumor was seen in 16 patients (40.0%). There was no significant difference in candidate gene expression profiles between tumor and stromal cells except for thymidine phosphorylase (TP). Without microdissection, there was no significant association between distant recurrence and gene expression in specimens. With microdissected sample analysis, however, patients who developed distant recurrence were found to have significantly higher intratumoral thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) compared with patients without recurrence. It is possible that microdissection is essential for gene expression analysis of clinically irradiated rectal specimens because preoperative chemoradiotherapy for rectal cancer affects the tumor-stroma balance in irradiated rectal cancer specimen.
 ...
PMID:Microdissection is essential for gene expression analysis of irradiated rectal cancer tissues. 1972 71


1 2 Next >>