Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compared to either compound alone, the combination of acivicin and cis-diamminedichloroplatinum(II) markedly enhanced the inhibition of the activities of thymidylate synthase and thymidine kinase, the enzymes involved in the final steps of the de novo and salvage pathways in pyrimidine metabolism in A549 lung cancer cells. The enhancement of enzymic inhibition paralleled that of cell growth inhibition. These results indicate that the combination of these drugs can inhibit the capacities of the pyrimidine pathways, resulting in an efficient reduction of DNA synthesis.
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PMID:Effects of the combination of acivicin and cis-diamminedichloroplatinum(II) on thymidylate synthesis of A549 lung cancer cells. 273 Jun 61

Interactions between fluorinated Pyrimidine derivatives and anticoagulants were studied experimentally and clinically, using transplanted tumor tissues of Donryu rats and tissues from lung cancer patients. In rats, which were given 5-FU, uracil, tegafur and UFT respectively, the higher tumor concentrations of 5-FU and uracil were observed when given warfarin and ticlopidine beforehand, on the other hand, the concentrations of tegafur were almost the same between rats with and without anticoagulants. In patients with lung cancer, who were given UFT and anticoagulants, the higher concentrations of 5-FU and uracil in plasma, tumor and lymph nodes were observed than those who were given UFT alone. The 5-FU concentrations in normal lung tissues were about a half of those in tumor. These results suggest a existence of the synergistic effects between fluorinated pyrimidine derivatives and anticoagulants in plasma and tissue concentrations of 5-FU.
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PMID:[Experimental and clinical study of interactions between fluorinated pyrimidine derivatives and anticoagulants]. 313 97

Activities of pyrimidine nucleoside phosphorylase in brain tumors were measured and their relationship to a clinical course of the patients was investigated. Pyrimidine nucleoside phosphorylase is said to exist more quantitatively in malignant tumors such as Sarcoma 180, Ehrlich ascites carcinoma, Walker 256, and hepatoma, and very little in normal tissues. In brain tumors the activities were measured by bioassay and compared to that of Sarcoma 180. When the activity of Sarcoma 180 was expressed to be 100%, those of brain tumors were as follows: ten cases of normal brain less than 8.5; six cases of glioblastoma 39.3 +/- 30.7; five cases of astrocytoma 22.0 +/- 13.8; five cases of meningioma 22.4 +/- 13.7; two cases of oligodendroglioma 8.1 and 11.3; two cases of sarcoma 94.3 and 145.4; chordoma 48.0; ependymoblastoma 3.7; plexus papilloma 22.5; parotid cancer 43.4; ten cases of metastatic brain tumors from lung cancer 61.5 +/- 41.6; two cases from breast cancer 28.0 and 68.8; that from thyroid cancer 10.0; that from gastric cancer 13.5; malignant melanoma 77.2. In 12 cases of gliomas (glioblastoma, astrocytoma, oligodendroglioma) the mean activity was highest in glioblastoma (39.3), followed by astrocytoma (22.0) and oligodendroglioma (9.7). The postoperative survival time became shorter in gliomas with the higher activities. In metastatic brain tumors from lung, breast, and gastric cancer, the average time from the diagnosis of primary cancer to brain metastasis was shorter in cases with high activities and longer in cases with low activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activities of pyrimidine nucleoside phosphorylase in brain tumors and antitumor effect of 5'-DFUR]. 622 41

The pyrimidine antimetabolite gemcitabine is an analogue of cytosine arabinosid. Gemcitabine is well tolerated when given in doses of 1000-1250 mg/m2 weekly x 3 followed by 1 weeks rest, with mild myelosuppression as the major toxicity. In five studies, including a total of 250 patients with previously untreated non-small cell lung cancer (NSCLC), response rates from 20 to 28% were observed, ranking gemcitabine among the active agents in NSCLC. Gemcitabine should be further explored in combination therapy for NSCLC.
Lung Cancer 1995 Apr
PMID:Gemcitabine in non-small cell lung cancer. 755 26

Angiogenesis is a recently described prognostic factor in non-small-cell lung cancer. Platelet-derived endothelial cell growth factor (PD-ECGF), shown to be the enzyme thymidine phosphorylase (TP), induces angiogenesis in vitro and in vivo. High intracellular levels of the enzyme are associated with increased chemosensitivity to pyrimidine antimetabolites. PD-ECGF/TP expression was evaluated immunohistochemically in surgically resected specimens from 107 patients with operable non-small-cell lung cancer using the P-GF,44C monoclonal antibody. High expression of PD-ECGF/TP was found in 25% of cases and was associated with high vascular grade (P = 0.01). Fourteen of 32 (44%) high vascular grade tumours showed a positive reactivity for PD-ECGF/TP vs 13/75 (17%) of low/medium vascular grade. Positive expression was observed more frequently in T2-staged cases than in T1 (P = 0.04). While overall survival was not affected (P = 0.09), subset analysis revealed that node-negative patients with positive PD-ECGF/TP expression had a worse prognosis (P = 0.04). The results suggest that PD-ECGF/TP may be an important molecule involved in angiogenesis in non-small-cell lung cancer. Up-regulation of the enzyme defines a more aggressive tumour phenotype in patients with node-negative disease. Assessment of vascular grade and PD-ECGF/TP expression should be taken into account in the design of randomized trials assessing the role of adjuvant chemotherapy in non-small-cell lung cancer.
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PMID:Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer. 905 96

Lung cancer, which is the leading cause of cancer mortality, remains a significant health-care problem among men and women in the United States, despite an overall 20-year decline in the incidence of cigarette smoking. Non-small cell lung cancer (NSCLC) comprises 75 to 80% of all lung cancer cases. The metastatic nature of this disease has been responsible for the poor survival statistics reported to date and emphasizes the need for effective systemic treatment. Prior to 1993, attempts to identify new chemotherapeutic agents and combinations with activity against NSCLC met with little success. Recently, however, several new compounds and classes of compounds have offered some hope for at least small improvements in response and survival while being relatively well tolerated in patients with this disease. This article presents current findings for some of these agents, including the taxanes paclitaxel and docetaxel, the topoisomerase inhibitors irinotecan and topotecan, and the novel pyrimidine analogue gemcitabine. In addition, the University of Southern California/Norris Cancer Center experience with the combination of carboplatin and paclitaxel is presented.
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PMID:Experience with new chemotherapeutic agents in non-small cell lung cancer. 943 88

The pyrimidine (uracil) analogue 3-oxauracil (OU) previously had been shown to completely inhibit the growth of E. coli B and decrease by 96% the replication of herpes simplex virus type 2 when present in the culture fluid at a concentration of 10(2) microM. Limited in vivo studies in mice demonstrated antiviral effects without significant toxicity when given i.p. daily for two weeks at a concentration of 3.23 mg/kg. However, the antineoplastic properties of OU were unknown. We assessed the ability of OU to inhibit the proliferation of various human tumor cell lines (3 pancreatic, 1 colon, 1 neuroendocrine, and 1 lung) in an in vitro radiometric (Bactec) system. In the pancreatic lines (RWP-2, MiaPaCa-2, and PANC-1), the colon line (HT-29), the neuroendocrine line (COLO 320DM), and the lung cancer cell line (SK-MES-1), OU at a concentration of 10(3) microM, produced a dramatic decrease in percent cell survival. When compared with cytotoxic drugs of choice for these tumor cells (gemcitabine, 5-fluorouracil, and adriamycin, respectively) a significantly higher concentration of OU was required usually to achieve comparable results with two exceptions. These were the HT-29 and the COLO 320DM cell lines. These results indicate OU has significant (p < 0.05) cytotoxic activity against pancreatic, colon, neuroendocrine, and nonsmall cell lung cancer lines, when compared to untreated control cultures. Additional in vivo testing of this potential antineoplastic agent is warranted.
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PMID:An in vitro assessment of the antineoplastic potential of 2H-1,3-oxazine-2,6(3H)-dione (3-oxauracil), a novel pyrimidine. 954 71

There have been exciting new developments in anticancer therapy over the past few years. One such therapy uses gemcitabine (GemzarR), an antimetabolite approved in 1996 by the Food and Drug Administration (FDA) for first-line treatment of locally advanced (nonresectable stage II or stage III) or metastatic (stage IV) adenocarcinoma of the pancreas. This novel nucleoside analog resembles the naturally occurring pyrimidine nucleoside deoxycytidine, but it has a unique mechanism of action. Clinical studies with gemcitabine have demonstrated anticancer activity in pancreatic cancer; non-small-cell lung cancer; breast, bladder, and ovarian cancers; and small-cell lung cancer. Clinical trials in patients with cancer of the pancreas used a novel study end point called clinical benefits response (CBR) to measure gemcitabine's effect on disease-related symptoms. The CBR is a composite assessment of performance status, pain, and weight gain. Studies show that gemcitabine has a relatively mild safety profile, with myelosuppression as the major dose-limiting toxicity. The aim of this review is to provide the oncology nurse with an overview of gemcitabine's pharmacology, innovative clinical trial end points, and clinical performance, as well as the nursing care required for the patient receiving this drug.
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PMID:Gemcitabine: a pharmacologic and clinical overview. 1021 35

A series of 6- and 7-acrylamide derivatives of the 4-(phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6-acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better-positioned, when bound to the enzyme, to react with the critical cysteine-773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6-acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However the pyrido[3,2-d]pyrimidine analogues were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB-453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than intraperitoneally. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions.
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PMID:Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. 1034 32

Pemetrexed disodium (ALIMTA) is a novel antimetabolite that inhibits at least three folate-dependent enzymes, thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed disodium is broadly active in a wide variety of solid tumours, including non-small cell lung, breast, bladder, head and neck and ovarian cancers. Gemcitabine is a broadly active pyrimidine nucleoside antimetabolite, which is approved for the treatment of pancreatic and non-small cell lung cancers. Three preclinical studies have been reported that show cytotoxic synergy between gemcitabine and pemetrexed. Clinical activity with this combination has been observed in a phase I study, with partial responses in three of five patients previously treated for non-small cell lung cancer. An international phase II study of this combination in non-small cell lung cancer is ongoing.
Lung Cancer 2001 Dec
PMID:Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. 1174 12


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