Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of intrahepatic bile duct carcinoma (cholangiocellular carcinoma: CCC) is extremely poor unless detected at an early and curable stage. However, little is known about the clinico-pathological features of CCC resected at a symptom-free stage. We herein report the clinico-pathological findings in two asymptomatic patients who underwent resection. Their liver function tests showed elevated levels of gamma-glutamyl transpeptidase. An intrahepatic mass was first detected by ultrasonography, and subsequent direct cholangiography and cytological examination revealed the presence of carcinoma in both patients. Left or right hepatic lobectomy with caudate lobectomy and lymph node dissection with or without resection of the extrahepatic bile duct was carried out. The lesions were 2.5 and 2.8 cm in maximal size, originating from the intrahepatic bile duct of segment IV and I, respectively. Both were free from extrahepatic bile duct involvement, intrahepatic and lymph node metastases. However, even in a symptom-free stage, perineural invasion, vascular or lymphatic involvements were histologically proved in both cases, which may be an indication of poor prognosis after surgery alone.
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PMID:Clinico-pathological findings of asymptomatic intrahepatic cholangiocellular carcinoma: report of two cases and review of the literature. 860 39

Metastatic renal cell carcinoma (RCC) is a tumor with a poor prognosis resistant to chemotherapy and irradiation. However, in rare cases, spontaneous regressions of metastases after nephrectomy have been reported that were ascribed to destruction of the tumor by the immune system. In earlier studies, we and others identified the expression of modified antigens in RCC. In particular, a concanavalin A-binding isoform of gamma-glutamyltransferase (gamma GT) comprises about 50% of the enzymatic activity found in the tumor tissue of many RCC patients. The monoclonal antibody 138H11, directed against all human gamma GT isoforms, revealed a membranous expression of gamma GT around RCC cells compared to the restricted, apical pattern of renal cells. These data raised the question why the RCC-specific gamma GT, exposed to the immune system in vivo, is not immunogenic in patients with RCC. To address this question, we generated mouse hybridomas against highly purified human RCC gamma GT. Although we obtained a large panel of hybridomas that produced antibodies reacting immunohistochemically in a gamma GT-specific manner, all antibodies stained normal kidney gamma GT as well as RCC gamma GT. These results suggest that the biochemical features specific for RCC gamma GT are not necessarily reflected by specific antigenic determinants that could be differentiated by the immune system of the challenged mice. The lack of immunogenic epitopes different from normal gamma GT enzyme may offer an explanation why gamma GT produced by RCC can escape immunological surveillance.
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PMID:Hybridomas reveal shared immunodominant epitopes of gamma-glutamyltransferase isoforms from human kidney and renal cell carcinoma. 893 53

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.
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PMID:Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study. 904 28

We have studied the efficacy of investigations during follow-up of 430 operable node positive and node negative breast cancer patients. Median follow-up was eight years, and 128 patients had relapsed, 91 with metastatic disease. Eight blood analyses, chest X-ray, limited skeletal X-ray and bone scan examinations were undertaken at regular intervals. Of the patients who had relapsed, 59% had symptoms, 23% were detected by clinical examination and 18% were detected by blood analysis only. X-rays and scintigrams were of little value in proportion to the costs. The combination of three blood analyses was useful. An increase in sedimentation rate (ESR) of more than 10 mm/h, an increase in gamma-glutamyltransferase (GT) of 20 U/l and an increase in alkaline phosphatase (ALP) of 60 U/l or more. By using ESR, gamma-GT, ALP, history and clinical examination, costs could be reduced by 90% while maintaining adequate baseline screening for relapse.
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PMID:[Check up of breast cancer stages 1 and 2]. 914 72

In this study the value of PHI serum measurements in breast cancer as an index of metastases was investigated. Serum CA 15-3 and CEA tumor marker and gamma-glutamyltranspeptidase (gamma-GT) levels were also determined in groups of patients with established distant metastases or in patients on follow-up with no evidence of disease. Fifty-one female breast cancer patients were included in the study. The mean values for each parameter were higher when metastases were present. However, the difference was mostly not meaningful. The only significant difference was observed for CA 15-3. Our data do not support the usefulness of the PHI assay for early detection of the metastases in breast cancer.
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PMID:Evaluation of phosphohexose isomerase as a metastasis marker in breast cancer patients. 937 61

The point mutations occurring in codons 12 and 13 of Ki-ras in 78 patients with colorectal carcinoma (31 Dukes' A and B, 21 Dukes' C, and 26 Dukes' D) have been determined by allele-specific oligonucleotide hybridization and sequencing. Duplicate samples of invasive primary carcinoma, adjacent normal tissue, and available lymph node and liver metastases from the same patients were microdissected from paraffin sections. There were no differences in the mutation rate between primary carcinomas and secondary deposits: 26 of 78 (33 per cent) primary carcinomas, 10 of 32 (31 per cent) lymph node metastases, and 10 of 26 (38 per cent) liver metastases. Multiple sampling revealed frequent heterogeneity within carcinomas: 9 of 26 primaries with Ki-ras mutations also contained areas of carcinoma with only the wild-type gene, implying that Ki-ras mutation, even when present in a colonic carcinoma, may not have been necessary for establishing the malignant phenotype. Also, 2 of 26 (8 per cent) Dukes' D patients had a mutation in their primary carcinoma but none in liver metastases and 6 of 47 (13 per cent) Dukes' C and D patients had mutations in liver or lymph node metastases but none in the primary carcinoma. Such heterogeneity may modify the effectiveness of novel therapies targeting mutant Ki-ras function, such as farnesyltransferase inhibition. Mutation of codon 12 from GGT (glycine) to GTT (valine) was more prevalent in primary and metastatic deposits of Dukes' C/D carcinomas (P = 0.01) than in primary carcinomas from Dukes' A/B patients. Mutations of codon 12 to GAT, AGT, GCT and codon 13 GGC to GAC were also found, but no correlation with carcinoma aggressiveness was apparent. Follow-up of 71/78 patients (up to 12 years) revealed decreased overall survival (P = 0.001) in patients with the GGT to GTT transversion in codon 12, even when the analysis was restricted to Dukes' D cases, supporting the suggestion that this mutation may confer a more aggressive phenotype in colorectal carcinoma.
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PMID:Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality. 971 38

Activities of some enzymes and content of medium-weight molecules in patients with colorectal cancer were studied in order to assess the diagnostic value of these parameters for detection of tumors in the large intestine and development of endogenous intoxication after surgery and for prediction of remote results of treatment. Increased activities of creatine phosphokinase and hexokinase is typical of tumor growth, whereas increased activities of alkaline phosphatase and gamma-glutamyl transpeptidase are observed only in metastases to the liver. The role of medium-weight molecules in the diagnosis of endogenous intoxication during the early postoperative period is shown. The content of these molecules in the sera increases 3 days before clinical manifestation of endotoxicosis, when the traditional parameters are virtually normal.
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PMID:[Diagnostic and prognostic significance of biochemical indicators in colorectal neoplasms]. 986 99

The expression of gamma-glutamyl transpeptidase (GGT), a plasma membrane ectoenzyme involved in the metabolism of extracellular reduced glutathione (GSH), is a marker of neoplastic progression in several experimental models, and occurs in a number of human malignant neoplasms and their metastases. Because it favors the supply of precursors for the synthesis of GSH, GGT expression has been interpreted as a member in cellular antioxidant defense systems. However, thiol metabolites generated at the cell surface during GGT activity can induce prooxidant reactions, leading to production of free radical oxidant species. The present study was designed to characterize the prooxidant reactions occurring during GGT ectoactivity, and their possible effects on the thiol redox status of proteins of the cell surface. Results indicate that: (i) in U937 cells, expressing significant amounts of membrane-bound GGT, GGT-mediated metabolism of GSH is coupled with the extracellular production of hydrogen peroxide; (ii) GGT activity also results in decreased levels of protein thiols at the cell surface; (iii) GGT-dependent decrease in protein thiols is due to sulfhydryl oxidation and protein S-thiolation reactions; and (iv) GGT irreversible inhibition by acivicin is sufficient to produce an increase of protein thiols at the cell surface. Membrane receptors and transcription factors have been shown to possess critical thiols involved in the transduction of proliferative signals. Furthermore, it was suggested that S-thiolation of cellular proteins may represent a mechanism for protection of vulnerable thiols against irreversible damage by prooxidant agents. Thus, the findings reported here provide additional explanations for the envisaged role played by membrane-bound GGT activity in the proliferative attitude of malignant cells and their resistance to prooxidant drugs and radiation therapy.
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PMID:Redox modulation of cell surface protein thiols in U937 lymphoma cells: the role of gamma-glutamyl transpeptidase-dependent H2O2 production and S-thiolation. 1049 Feb 84

Point mutations of c-K-ras in ovarian cancer were detected by replacement of GGT of codon 12 by GAT, AGT, TGT and GTT, polymerase chain reaction, agarose gel electrophoresis and Southern blot hybridization with a digoxigenin detection system. The incidence of four-typed point mutations of c-K-ras oncogene in 37 ovarian cancers was 35.1% (13/37) and the distributions were 32.4% (12/37), 2.7% (1/37), 0% and 0% of GGT to GAT, GGT to AGT, GGT to TGT, and GGT to GTT, respectively. The incidence of c-K-ras point mutations on codon 12 among 37 patients with ovarian cancer was 35.5% (8/22) in those with serous cystadenocarcinomas and 28.6% (2/7) in those with mucinous cystadenocarcinomas. c-K-ras point mutations on codon 12 were detected in 14.3% (1/7) of patients with stage I disease, 28.6% (2/7) with stage II disease, and in 43.5% (10/23) with stage III/IV disease, and there was a statistically significant increase in point mutations of c-K-ras oncogene with advancing clinical stage. The incidence of c-K-ras point mutations on codon 12 among 33 patients who had a pelvic lymph node dissection was 52.4% (11/21) in those with pelvic lymph node metastases and 16.7% (2/12) in those without pelvic lymph node metastases, a statistically significant difference. Furthermore, point mutation of c-K-ras gene was found most frequently in patients with advanced stage disease, and in those with pelvic lymph node metastases. Activation of c-K-ras oncogene seems to be a major factor in ovarian carcinogenesis and tumor progression.
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PMID:Detection of c-K-ras point mutation in ovarian cancer. 1157 63

The effect of piperine on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the compound with tumor induction produced a significant reduction (95.2%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of the control animals compared to normal animals (0.95 microg/mg protein) was significantly reduced (2.59 microg/mg protein) in the piperine-treated animals. The high amount of uronic acid (355.83 microg/100 mg tissue) in the metastasized control animals was significantly reduced (65 microg/100 mg tissue) in the animals treated with piperine. Lung hexosamine content was also significantly reduced in the piperine-treated animals (0.98 mg/100 mg lyophilized tissue) compared to the untreated tumor-bearing animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with piperine. The piperine-treated animals even survived the experiment (90 days). Histopathology of the lung tissue also correlated with the lifespan of the drug-treated animals. Our results demonstrate the antimetastatic activity of piperine, an alkaloid present in plants such as Piper nigrum and Piper longum.
Clin Exp Metastasis 2002
PMID:Effect of piperine on the inhibition of lung metastasis induced B16F-10 melanoma cells in mice. 1255 76


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