Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients with nonparasitic hepatic cysts underwent surgery to relieve abdominal complaints, at the First Surgical Department, Tokyo University Hospital between 1966 and 1989. Total removal of the cyst was carried out in 14 of the patients, while puncture and aspiration only were performed in the other patient in whom a cyst had ruptured spontaneously, after which hemoperitoneum was observed at emergency laparotomy. The size of the cysts varied from 7-19 cm with a mean of 12.4 cm. Histological study revealed a congenital cyst in 14 patients and a cystadenoma in one. The epithelium lining of the internal surface of the congenital cysts was highly atrophic and desolated and often disappeared. Examination of the cyst fluid revealed the same concentration of electrolytes as in the serum. Hepatic enzyme levels were usually lower than in the serum, but lactic dehydrogenase and aminotransferase levels were elevated in a few cases. Tumor marker levels of the cyst fluid were higher than those in the serum in four of five patients examined.
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PMID:Surgical experience with nonparasitic cysts of the liver--the characteristics and constituents of cyst fluid. 181 89

Expression of TGF-alpha mRNA, which correlates well with the ability of cells to condition medium with an EGF-like activity, clonally segregates best with tumorigenicity among the several single phenotypes considered in this study. The results of unreported studies in which we have analyzed the quantitative relationships between the expression of selected phenotypes and tumorigenicity, suggest that the elevated expression of myc and TGF-alpha mRNAs interact in their associations with tumor yield. These results suggest that elevated myc expression sensitizes hepatic epithelial cells to the possible tumorigenic action of TGF-alpha. This observation may explain why the correlation between the qualitative expression of TGF-alpha and tumorigenicity, described here, is not perfect. Conventionally applied markers of transformation in hepatocytes in vivo and in cultured liver epithelial cells in vitro that we studied -histochemical expression of GGT, ability to grow in medium containing low levels of calcium, and ability to grow in soft agar- clonally segregated with tumorigenicity poorly in liver epithelial cells transformed in vitro. We conclude that these phenotypes are not adequate markers for determining the lineage of hepatic epithelial neoplasms (including, probably hepatocellular cancers arising in vivo). This study appears to be the first to attempt to analyze clonally the association of these markers with tumorigenicity, and to quantify the sensitivity, specificity, and predictive value of the associations. Our study suggests that the relatively weak associations of these phenotypes with tumorigenicity may be related only to their stronger associations with expression of TGF-alpha, or to some other property that is strongly associated with tumorigenicity. Expression of TGF-alpha is more strongly associated with expression of GLC, for example, than is the GLC phenotype with tumorigenicity. At least for GLC, autocrine stimulation by TGF-alpha is likely, since EGF increases growth of WB cells in low calcium medium. This observation may explain the perfect correlation between expression of TGF-alpha and GLC. EGF also stimulates lactate dehydrogenase, pyruvate kinase, and glucose 6-phosphate dehydrogenase in WB cells. However, quantitative correlation between GGT activity and TGF-alpha is less strong. Thus, our data from these studies suggest that the tumorigenic phenotype of cultured hepatic epithelial cells is intimately dependent on the expression of the TGF-alpha gene, possibly producing autocrine stimulation of growth via the cells' EGF receptors. This is the most simple view of the potential relationship between TGF-alpha expression and tumorigenicity in liver epithelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clonal analysis of neoplastic transformation in cultured diploid rat liver epithelial cells. 181 88

Primary cultured rat epidermal keratinocytes were used as an experimental model to detect oxidant-mediated adverse effects of dithranol (anthralin), a widely used antipsoriasis drug with tumor-promoting and skin-irritating properties. Keratinocytes were isolated and prepared from the skin of neonatal rats by a trypsin flotation method. Highly proliferative monolayer cells cultured in a serum-free medium were exposed to the test compound at concentrations (5-100 microM) used therapeutically for the treatment of skin disorders. Cytotoxicity was evaluated by changes in plasma membrane integrity (lactate dehydrogenase leakage), lysosomal function (neutral red uptake), and mitochondrial metabolic activity (reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, MTT). Exposure of keratinocytes to dithranol produced time- and concentration-related toxic responses. MTT reduction was found to be a more sensitive endpoint of cytotoxicity, showing significant toxic effects at 2 hr, while significant leakage of lactate dehydrogenase did not result until 6 hr. Oxygen consumption in keratinocytes and isolated mitochondria showed a similar pattern after exposure to dithranol. Increased cyanide-insensitive respiration was also noted. Oxidative stress, measured by superoxide anion-dependent reduction of nitroblue tetrazolium, occurred before dithranol produced cytotoxicity in the keratinocyte cultures. Superoxide formation, which increased with time after dithranol exposure, was detected both extracellularly and intracellularly and was inhibited by the addition of superoxide dismutase. Dithranol-induced cell injury was partially prevented by treatment with superoxide dismutase, and greater protection was shown by concurrent treatment with superoxide dismutase plus catalase. These findings suggest that the superoxide anion and hydrogen peroxide may be involved in the cytotoxicity of dithranol and that a culture system of rat keratinocytes may be useful in evaluating the mechanism of toxicity of dermatotoxicants.
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PMID:Dithranol-induced cytotoxicity in primary cultures of rat epidermal keratinocytes. I. The role of reactive oxygen species. 184 45

Tumor bearing hosts and animals treated with endotoxin commonly show a decrease in the catalase activity of the liver and kidney. Since tumor necrosis factor (TNF)/cachectin may play a significant role in these conditions, we investigated its effects on the catalatic and peroxidatic activity of catalase in the liver and kidney of the rat. The activities of glucose-6-phosphate dehydrogenase and lactate dehydrogenase were measured simultaneously to monitor the pentose phosphate and glycolytic pathways, respectively. Injection i.p. of 100 micrograms/kg/day human recombinant TNF-alpha for 5 days resulted in a significant (P less than 0.01) decrease in the catalatic activity of the liver when compared to rats fed ad libitum. The decrease in four experiments ranged from 21 to 56%. A significant decrease (18%; P = 0.01) in liver catalatic and peroxidatic activity was also observed in another experiment using pair fed rats as controls. The peroxidatic activity of catalase with ethanol as hydrogen donor closely paralleled the catalatic activity. TNF treatment had no detectable effect on the catalatic or peroxidatic activity of catalase in the kidney. The activity of glucose-6-phosphate dehydrogenase increased (31-80%) significantly (P less than or equal to 0.02) in the liver and, to a lesser extent, in the kidney (5-27%, P = 0.05). Lactate dehydrogenase activity decreased (14-19%) significantly (P less than or equal to 0.05) in the liver and kidney but mainly in rats treated with TNF and additionally fasted for 24 h. Electron microscopic examination of liver sections showed that the hepatocytes of TNF-treated rats were undamaged but contained fewer and smaller peroxisomes than those of the control rats.
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PMID:Tumor necrosis factor/cachectin decreases catalase activity of rat liver. 185 14

Three new human pancreatic adenocarcinomas of ductal origin, covering the spectrum of well differentiated to poorly differentiated neoplasms, have been established as xenotransplants in the nude mouse. Histopathological and ultrastructural features confirmed the neoplasms' ductal origin and were consistently reproduced through serial transplant generations. Carcinoembryonic antigen was only elaborated by the well differentiated neoplasms and production of lactate dehydrogenase isoenzymes was characteristic of each tumor. The morphological and biological features of these tumors make them a valuable addition to the very small number of available pancreatic tumor lines in studies aiming at clarifying many aspects of the biology of this type of neoplasia.
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PMID:Morphologic, biologic and biochemical characteristics of three human pancreatic ductal adenocarcinomas established as xenotransplants in the nude mouse. 196 87

The lysosomal enzyme beta-hexosaminidase and the melanocyte specific enzyme tyrosinase were examined in human melanoma cell cultures. The beta-hexosaminidase activity of the medium was approximately 40% of the total cellular activity after 24 h, while after 48 h the activity in the medium was twice that of the cells. The tyrosinase activity in the medium was 5% and 19% of the total cellular activity after the 24 h and 48 h incubation, respectively. The low level of lactate dehydrogenase activity in the medium after 24 as well as 48 h of incubation indicated that the release of beta-hexosaminidase and tyrosinase was not due to membrane injury. The data suggest, that 1) beta-hexosaminidase may be a candidate for tumor markers in malignant melanoma, and 2) the tyrosinase activity found in sera of melanoma patients may be due, at least partly, to enzyme release by living cancer cells.
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PMID:Enzyme release from cultured human melanoma cells. 197 50

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.
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PMID:Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse. 198 71

Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.
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PMID:Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation. 199 11

The clinical significance of pleural effusion was assessed in 24 children with unresectable abdominal small non-cleaved cell lymphoma (St. Jude Stage III). Patients were consecutively enrolled and treated on a regimen including high dose fractionated cyclophosphamide and co-ordinated high dose methotrexate and cytarabine. The overall results were excellent, with 20 of 24 patients alive and event-free at a median follow-up of 4 years. Only one of the patients who lacked pleural effusion has relapsed (testicular), even though many had massive disease. In contrast, three of seven patients with pleural effusion have failed treatment (p = 0.02) and subsequently died. Two measures of tumor burden, serum lactic dehydrogenase and, in a subset of patients, interleukin-2-receptor levels, were significantly higher in patients with pleural effusion (p = 0.002 and p = 0.05, respectively). These findings suggest that unresectable abdominal small non-cleaved cell lymphoma associated with pleural effusion should be up-staged and that these patients should receive more intensive chemotherapy.
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PMID:Pleural effusion is associated with a poor treatment outcome in stage III small non-cleaved cell lymphoma. 199 58

Calcium channel blocking drugs have been reported to reduce survival rate of laboratory animals treated with cardiotoxic antitumor anthracyclines. In order to elucidate the mechanisms of this drug interaction, cell toxicity of the anthracyclines, doxorubicin and daunorubicin, was evaluated in primary cultures of cardiac myocytes isolated from neonatal rats. Low concentrations of extracellular calcium ([Ca2+]0) and addition of calcium entry blockers (nifedipine or flunarizine) potentiated myocardial toxicity of anthracyclines as assessed by the release of lactate dehydrogenase from the cells. Accumulation of anthracyclines in the cardiomyocytes was increased by calcium entry blockers (nifedipine, flunarizine, and verapamil) and by low [Ca2+]0; efflux of [3H]daunorubicin from myocardial cells was inhibited by nifedipine. At a dose that exerts only modest calcium channel activity, R-verapamil failed to affect doxorubicin accumulation in cardiomyocytes, whereas the calcium channel activator, (+/-)-Bay K-8644, reduced the retention of anthracyclines; the calcium channel activity is thus required in order to increase the accumulation of anthracyclines in myocardial cells. Calcium channel blockers are also known to increase intracellular retention and toxicity of chemotherapeutic drugs in multidrug resistant tumor cells by inhibiting the efflux of cytotoxic agents from cells; however, the ability of the interacting drugs to inhibit the efflux of chemotherapeutic agents from tumor cells is not dependent on the calcium channel blocking activity. Therefore, the mechanism(s) by which calcium channel blocking drugs increase the accumulation of anthracyclines in resistant tumor cells and myocardial cells may be different. In accordance with previous investigations, the present in vitro study confirmed that anthracycline-induced cardiotoxicity may be potentiated by calcium channel blocking drugs. This indicates that, in the association of antineoplastic drugs with agents that reverse multidrug resistance, the potential exists for enhanced damage of normal cells and tissues; further studies are needed to evaluate the relevance of this adverse interaction.
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PMID:Increased toxicity of anthracycline antibiotics induced by calcium entry blockers in cultured cardiomyocytes. 200 1


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