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

Satisfactory therapeutic effects are rarely obtained with oral chemotherapy for gastric cancer. We have experienced successful treatment for synchronous hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan. The patient was a 78-year-old female, diagnosed as having gastric cancer with multiple hepatic metastases, who underwent gastrectomy. Immunohistochemistry of the resected specimens with anti-thymidine phosphorylase (dThdPase) antibody yielded positive results for dThdPase in the primary tumor as well as the hepatic metastases. Two months after surgery, administration of 400 mg of 5'-DFUR per day and 2 mg i.v. of Lentinan every other week was started. Four months after discharge, carcinoembryonic antigen (CEA) in plasma showed an abrupt logarithmic decline. Furthermore, a 99% reduction in hepatic metastases was demonstrated by abdominal CT. At present, 22 months after surgery, the patient is managed on an outpatient basis with no complaints of any side effects. Immunochemotherapy using 5'-DFUR and Lentinan may be effective against gastric malignancies expressing dThdPase activity.
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PMID:[Successful treatment of hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan]. 946 40

5-Fluorouracil (5-FU) plays an important role in the treatment of several tumor types, particularly colorectal cancer and breast cancer. Xeloda (capecitabine; 5'-deoxy-5-fluoro-N-[(pentyloxy)carbonyl-cytidine]) is a new rationally designed fluoropyrimidine carbamate. It is administrated orally and after absorption it is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase from the liver and then converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase from the liver and tumor tissues. Finally, thymidine phosphorylase (TP) converts 5'-DFUR to 5-FU. TP is more active in tumor tissues than in normal tissue. This tissue localization pattern results in preferential metabolism and generates higher levels of 5-FU in malignant tissue, thus enhancing efficacy but minimizing side effects. The tumor tissue selectivity was confirmed in a study of 19 patients with colorectal cancer. After Xeloda administration, concentrations of 5-FU were 2.5 times higher in the primary tumor compared with adjacent healthy tissue. Xeloda was highly active in human tumor xenografts. It was more active than 5-FU, 5'-DFUR and tegafur plus uracil (UFT) and had a better therapeutic index. Xeloda also demonstrated synergistic or additive activity when used in combination with cyclophosphamide, methotrexate, doxorubicin, paclitaxel and docetaxel. This may be in part a result of up-regulation of TP by the cytotoxic agents. Phase I and II clinical trials have shown that Xeloda is active across a range of tumor types, and phase III studies are ongoing.
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PMID:Rational design of new tumoractivated cytotoxic agents. 1043 11

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) are predictive markers for tumor response to 5-fluorouracil-based therapies. To determine whether gene expression values measured in primary cancer tissue would be useful for prediction of response of lymph node metastases, the expressions of these genes were quantitatively analyzed in 35 pairs of primary colorectal cancer (CRC) and corresponding lymph node metastases using real-time PCR. DPD and TP mRNA levels were significantly lower in the primary colorectal tumor and lymph node metastases compared with the normal adjacent stroma tissue (p<0.01), whereas TS mRNA levels were significantly higher in the primary tumor and lymph node metastases than in the normal adjacent tissue (p<0.001). Median gene expression levels of TP and TS did not differ significantly between primary colorectal tumor and corresponding lymph node metastasis but median DPD gene expression levels in the lymph node metastases were significantly higher compared to matched primary colorectal tumors (p=0.015). There was a significant correlation for DPD, TP and TS gene expression levels between primary colorectal tumor specimens and the matched lymph node metastasis. These results suggest that biopsies of the tumor of origin may be valid for determining predictive markers for chemotherapy response in patients with metastatic CRC.
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PMID:Molecular factors of 5-fluorouracil metabolism in colorectal cancer: analysis of primary tumor and lymph node metastasis. 1639 9

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.
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PMID:Microdissection is essential for gene expression analysis of irradiated rectal cancer tissues. 1972 71

Lactate dehydrogenase (LDH), adenosine deaminase and thymidine phosphorylase activity was analyzed in the blood serum, primary tumor and adjacent uninvolved breast tissues from 49 women with adenocarcinoma and from 10 ones with benign adenofibroma. The LDH activity was increased in both cancerous and adjacent tissues. Serum LDH level reflects cell membrane alterations not only in the tumor node cells but also to a greater extent--in the surrounding unmalignant tissues. The discovered changes in nucleosides catabolic enzyme's activity in patients with breast cancer are correlated with LDH activity and its level in the blood serum.
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PMID:[Lactate dehydrogenase, adenosine deaminase and thymidine phosphorylase activity of blood and tissues in breast cancer]. 2038 38