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)

We have analyzed the survival data for 117 patients with Ewing's sarcoma treated at the National Cancer Institute since 1964. Treatment consisted of local irradiation to the primary site and a series of increasingly intensive systemic chemotherapy regimens. Four protocols were used with varying numbers of patients in each treatment group. When survival results were compared by treatment group, an overall difference in favor of the most recent treatment regimens was demonstrated (P less than 0.03). When results were evaluated by treatment group according to the site of primary disease, a significant difference was found only for patients who presented with primary lesions of the central axis and without metastases (P less than 0.001). However, we noted a statistically significant correlation of survival with 1) site of primary disease (P less than 0.001), 2) serum lactate dehydrogenase (LDH) level at presentation (P less than 0.0001), and 3) metastatic status at presentation (P less than 0.0001), irrespective of treatment protocol. When the results were reassessed after adjustment for these factors, no significant difference in survival remained. We concluded that further studies, in which stratification for site of primary disease and LDH levels would be used, are necessary to clarify the role of intensive adjuvant chemotherapy in Ewing's sarcoma.
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PMID:Influence of prognostic factors on survival in Ewing's sarcoma. 730 Aug 94

Lysosomal enzymes were elevated about two-fold in primary s.c. Lewis lung carcinoma as compared with metastatic nodules in the lung. In a time course experiment, a general two-fold elevation of acid phosphatase and several glycosidases was observed in the primary tumor between the 14th and 17th postimplant day following s.c. inoculation of Lewis lung carcinoma. This increase in hydrolytic enzyme activity was not due to necrosis in the primary tumor since a comparison of enzyme activities in the nonnecrotic and necrotic areas demonstrated much higher activities in the nonnecrotic areas. No increases in lysosomal enzyme activity were observed with time in Sarcoma 180, a tumor which does not metastasize. There was no change with time in primary Lewis lung tumor lactate dehydrogenase activity while a 7-fold increase in serum lactate dehydrogenase activity was observed in tumor-bearing mice. Mitochondrial succinate-2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium reductase levels fell in the primary Lewis lung tumor as the tumor size increased. A positive correlation was observed between the time of the elevations of tumor lysosomal enzymes in Lewis lung carcinoma and the appearance of micro- and macrometastatic lesions in the lungs. The mechanisms accounting for the increased intratumoral lysosomal enzymes are unknown, but they may be related to macrophage infiltration or other tumor-host interactions which may facilitate the dissemination of tumor cells.
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PMID:Elevation of lysosomal enzymes in primary Lewis lung tumor correlated with the initiation of metastasis. 742 42

Although infants (age less than 1 year) with neuroblastoma have a favorable overall prognosis, metastatic disease is associated with poorer treatment outcome. To assess the role of surgery in these patients, the authors reviewed survival data for 151 infants treated for neuroblastoma, focusing on patient and tumor characteristics, biological markers, and surgical management among the 99 patients with metastatic disease. Patients were divided into early (1961 to 1978) and contemporary (1979 to 1993) treatment eras. Potential prognostic factors were statistically tested to determine their significance in affecting survival. Five-year survival by Pediatric Oncology Group stage was: A, 100% (+/- 0%); B, 94% (+/- 6%); DS, 77% (+/- 9%); C, 73% (+/- 9%); and D, 61% (+/- 8%). Survival for infants with metastatic disease (stages C, D, and DS) was affected significantly by treatment era (P = .0001). Analyses restricted to patients treated during the contemporary era showed prognostic significance for DNA index (P = .02), N-myc copy number (P = .007), serum lactate dehydrogenase level (P = .001), and extent of resection (P = .01). A > or = 95% resection of the primary tumor was found to be associated with improved survival. Significantly more surgical complications were associated with resections performed at the time of diagnosis (P = .007), and delaying surgery until after several courses of chemotherapy did not decrease survival. In conclusion, multiple factors affect the outcome of treatment for infants with metastatic neuroblastoma, and whenever feasible, a > or = 95% resection of the primary tumor should be performed in this patient subgroup.
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PMID:Infants with metastatic neuroblastoma have improved survival with resection of the primary tumor. 747 48

A cohort of 137 patients with completely resected stage I or II adenocarcinoma of the lung was observed from the time of operation; the metastatic pattern determined at autopsy is described in relation to clinical, histologic, and laboratory variables. The pretreatment variables evaluated were performance status, age, gender, lactate dehydrogenase, stage, degree of differentiation, and histologic subtype of adenocarcinoma of the lung. Patients who survived longer than 30 days after operation were eligible for analysis, and 35 autopsies were performed in this patient group (autopsy rate: 39.8%). The most common intrathoracic metastatic sites were mediastinal lymph nodes (43%), lung (31%), pleura (20%), pericardium (9%), and heart (6%). The most common extrathoracic sites were liver (37%), brain (33%), bones (21%), adrenals (17%), and kidneys (17%). Patients undergoing resection for stage I disease had significantly fewer intrathoracic metastases than patients with stage II disease (p = 0.01). Patients who survived less than 1 year had significantly more extrathoracic metastases than patients who survived for a longer period (p = 0.01). Patients with highly differentiated tumors had fewer extrathoracic metastases than patients with less differentiated tumors. No other statistically significant differences were observed. Overall, patients with stage I adenocarcinoma of the lung had better local control of the disease at autopsy than those with stage II disease, but distant metastases are a large problem despite the favorable prognosis of this patient group. The extrathoracic metastatic potential was greatest for less differentiated tumors. An active adjuvant systemic therapy after resection is needed in selected patients with poorly differentiated adenocarcinomas of the lung, even in those with stage I disease.
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PMID:Metastatic pattern in adenocarcinoma of the lung. An autopsy study from a cohort of 137 consecutive patients with complete resection. 747 42

The objective of this study was to identify genes involved in invasion and metastasis using a rat rhabdomyosarcoma model (SMF-A and RMS-B cell lines). The SMF-A cell line was established from a metastatic nodule of an induced rhabdomyosarcoma in syngeneic F344 rats. Two cell lines with defined metastatic potentials, SMF-Ai and SMF-Da, were cloned from the SMF-A line. The cell line SMF-Ai is tumorigenic, highly invasive and highly metastatic. On the other hand, the revertant line SMF-Da is less tumorigenic, non-invasive and non-metastatic. We have isolated from a SMF-Ai cDNA library eight cDNA clones which are differentially expressed by the metastatic SMF-Ai and the non-metastatic SMF-Da cell line using Northern blot analysis. Five of these clones, smf-4, smf-6, smf-41, smf-42 and smf-44, are overexpressed in the SMF-Da cell line and have homology with beta-2-microglobulin, lactate dehydrogenase, ribosomal protein L38, ribosomal protein S4 and acidic ribosomal phosphoprotein P1, respectively. The three other clones, smf-7, smf-40 and smf-61, are overexpressed in SMF-Ai. Clones smf-40 and smf-61 show significant homology with the human TB3-1 gene and the human fus gene respectively. The clone smf-7 has no significant homology with known sequences. We also analyzed the expression of these clones in other rat rhabdomyosarcoma cell lines (RMS-B and their clones) and in tumors obtained by injection of these cell lines into rats or nude mice. Smf-61 and smf-7 were the only clones with a differential expression pattern associated with the invasive or metastatic potential of all cell lines examined. A preliminary study of the expression of smf-7 and smf-61 in other cancer cell lines also showed mRNA expression in two human rhabdomyosarcomas and a human epidermoid carcinoma suggesting the existence of genes homologous to smf-7 and smf-61 clones in human cancers. Our findings suggest an association between the expression of smf-7 and smf-61 and invasive or metastatic potential of rhabdomyosarcoma cells.
Clin Exp Metastasis 1995 Sep
PMID:Cloning and identification of genes differentially expressed in metastatic and non-metastatic rat rhabdomyosarcoma cell lines. 754 34

To assess prognostic factors in patients with metastatic nonseminomatous germ cell tumors, 50 patients with testicular germ cell tumors (TGCT) and 10 patients with extragonadal germ cell tumors (EGGCT) were studied. The clinical staging system for testicular tumors proposed by The Japanese Urological Association and The Japanese Pathological Society was applied. All patients with EGGCT had primary sites in the retroperitoneum. The 3-year survival rates of TGCT and EGGCT were 71.9% and 60.0%, respectively, and there were no differences in patient characteristics. Patients had significantly worse survival rates if the following applied: choriocarcinoma in the primary tumors, serum lactate dehydrogenase level greater than twice the upper limit of normal, liver, brain, or mediastinal metastases, or retroperitoneal tumors greater than 10 cm. It was concluded that the poor-risk group could be defined as those patients having lymph nodal disease only (stage II or III A) with retroperitoneal tumors greater than 10 cm, having pulmonary disease (stage III B) with retroperitoneal tumors greater than 5 cm, or liver, bone or brain metastases (stage III C), and these criteria will predict the prognosis for patients with advanced disease because the good-risk patients (53% of all patients) and poor-risk patients (47%) in this study had 3-year survival rates of 88.7% and 49.7% (p < 0.0001), and complete response rates of 96.9% and 60.7% (p < 0.005), respectively.
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PMID:Survival and prognostic factors associated with metastatic nonseminomatous testicular and extragonadal germ cell tumors. 762 53

Visualization of lactate dehydrogenase (LDH) activity with Neotetrazolium as final electron acceptor under anaerobic conditions and an incubation medium containing polyvinyl alcohol showed that under normal physiological conditions a zonal distribution of LDH activity is present in the liver lobule of male rats. Periportal hepatocytes contain more LDH activity than pericentral hepatocytes. This difference is due to the role of LDH both in gluconeogenesis (periportal cells) and glycolysis (pericentral cells). In livers containing metastases from colon carcinoma, areas of the parenchyma which are not affected by tumour growth maintain such zonation in the lobule, whereas areas close to metastatic foci show increased activity which is distributed uniformly over the lobule. This change may be explained by a Cori's cycle-like relationship between malignant cells and the surrounding hepatocytes due to glucose consumption and lactate production by the tumour cells. Within the metastatic foci, a zonation of LDH activity was also observed. Malignant cells close to the edge of the tumours contained the lowest activity, whereas activity increased inwards. Cancer cells directly surrounding necrotic areas showed the highest activity. Such patterns are in line with increasing anaerobic glycolysis towards the inner metastatic regions. Anaerobic glycolysis supplies limited amounts of ATP with concomitant lactate production but also large amounts of metabolites for RNA, DNA, lipid and complex carbohydrate synthesis. Lactate that is produced by the metastases induces adaptive changes in surrounding hepatocytes to convert this excess of lactate effectively.
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PMID:Changes in the zonation of lactate dehydrogenase activity in lobules of rat liver after experimentally induced colon carcinoma metastases. 787 78

We used the oxygen sensitivity of the histochemical reaction to detect glucose-6-phosphate dehydrogenase (G6PDH) activity based on neotetrazolium (NT) reduction to discriminate cancer cells from normal cells. Formazan generation was strongly reduced in normal but not in malignant cells when the incubation was performed in oxygen instead of nitrogen. Competition for reductive equivalents between NT and oxygen via superoxide dismutase (SOD) has been suggested. Since SOD activity is usually decreased in cancer cells, NT reduction would not be hampered in these cells. We tested this hypothesis by demonstrating NAD-dependent lactate dehydrogenase (LDH) activity instead of NADP-dependent G6PDH activity in normal rat liver and colon, in human colon carcinoma, and in experimentally induced metastases of colon carcinoma in rat livers. Reactions for both enzymes were determined cytophotometrically in an atmosphere of pure oxygen or nitrogen. G6PDH acted as described previously, showing distinct activity in cancer cells but strongly reduced activity in normal cells after incubation in oxygen, but this was not the case with LDH because formazan was also generated in normal tissue in oxygen. It appeared that after 5 min of incubation at 37 degrees C the residual activity of G6PDH in an atmosphere of oxygen compared with nitrogen was 0% in normal liver tissue and 15% in normal colon epithelium, whereas in colon carcinoma and in colon carcinoma metastasis in liver it was 48% and 33%, respectively. The residual activity of LDH in oxygen was 30% in normal female rat liver, 75% in normal male rat liver, and 38% in normal colon epithelium, whereas the residual activity in colon carcinoma and metastases in liver was 54% and 24%, respectively. These experiments clearly indicate that the oxygen sensitivity phenomenon is not solely an effect of competition for reducing equivalents between NT and oxygen via SOD, because NADPH generated by G6PDH and NADH generated by LDH have a similar redox potential. Apparently the system is more complex. The role of specifically NADPH-converting cellular systems such as NADPH-cytochrome P450 reductase was excluded because incubations in the presence of exogenous NADPH as substrate for these systems revealed oxygen sensitivity. Involvement of NADPH-dependent lipid peroxidation in the oxygen sensitivity test is discussed.
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PMID:The histochemical G6PDH reaction but not the LDH reaction with neotetrazolium is suitable for the oxygen sensitivity test to detect cancer cells. 793 May 18

Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.
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PMID:Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities. 798 4

The clinical value of the serum biomarker carcinoembryonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 ng/ml and 2.6-5.0 ng/ml (the standard normal), 5.1-20.0 ng/ml, 20.1-100 ng/ml and greater than 100 ng/ml. 70% of patients had levels less than 5 ng/ml and only 19% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 ng/ml and 22% of patients with limited disease (59 patients) had levels greater than 5 ng/ml. There was a modest relationship of CEA levels to presence of metastases, in that 50% of patients with metastases had levels greater than 20 ng/ml. The average survival for the pathologic and normal category was almost similar, ranging from 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must be applied in conjunction with other biomarkers, particularly LDH and neuron specific enolase (NSE) and is meaningful in only a small proportion of patients.
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PMID:[The importance of measuring plasma carcinoembryonic antigen in small-cell anaplastic carcinoma]. 802 51


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