Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven adults with refractory leukemia treated with a combination of 6-mercaptopurine and Adriamycin developed hepatic dysfunction manifested by elevations of serum total bilirubin, alkaline phosphatase, and glutamic oxaloacetic transaminase. Liver tissue obtained at necropsy showed intrahepatic cholestasis (eight cases), hepatocellular necrosis (ten cases), leukemic infiltration (two cases), and fatty change (nine cases). Neither this frequency nor severity of hepatocellular destruction has hitherto been associated with 6-mercaptopurine at the dose levels used in this study, nor has Adriamycin previously been found to be hepatotoxic. It is postulated that Adriamycin potentiated the hepatotoxicity of 6-mercaptopurine in these patients.
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PMID:Clinico-pathologic correlation of liver damage in patients treated with 6-mercaptopurine and Adriamycin. 106 39

Sixty-nine patients with advanced gastrointestinal carcinomas were given adriamycin intravenously at a dose level of 40-75 mg/m once every 3 weeks. Toxic effects included nausea, vomiting, diarrhea, stomatitis, alopecia, leukopenia, thrombocytopenia, and minor ECG changes. There was a slight trend toward move severe leukopenia in patients with markedly abnormal liver function test (serum glutamic oxaloacteic transaminase and alkaline phosphatase). Of the 57 pateints with colorectal cancer treated with adriamycin, four (7%) showed partial objective responses. In a controlled comparison of adriamycin versus 5-fluorouracil (5-FU) in patients with previously untreated large bowel carcinoma, three of 23 patients (13%) receiving adriamycin showed partial objective responses as compared with six of 25 patients (24%) receiving 5-FU. The median duration of response with adriamycin was 3 months com pared to over 6 months with 5-FU. Four of eight patients with gastric carcinoma showed partial objective responses. No responses were noted in a small number of patients with pancreatic and gallbladder carcinomas. Adriamycin would not seem to have any role in the treatment of advanced colorectal carcinoma. Our results, however, would justify further evaluation of this agent in gastric carcinoma.
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PMID:Adriamycin (NSC-123127) therapy for advanced gastrointestinal cancer. 109 99

The Radiation Therapy Oncology Group (RTOG) conducted a Phase I/II study in hepatocellular cancer that closed on September 9, 1987 and some results presented previously. Here, 17 patient characteristics are evaluated to identify any of prognostic significance. Two hundred sixteen patients were entered and 198 (74% with metastases and/or previous chemotherapy) were evaluable. Treatment began with an induction regimen of external beam radiotherapy to the liver (21.0 Gy, 3.0 Gy/Fx, 10 MV photons, 4 days per week) with low-dose chemotherapy (5-Fluorouracil (FU), 500 mg, i.v.; Doxorubicin, 15 mg, i.v.) on treatment Days 1, 3, 5 and 7. In the later stages of these studies, 56 patients received external beam radiotherapy as hyperfractionated treatment (1.2 Gy twice daily, 4 hours separation, 5 days per week, 24.0 Gy total) with similar chemotherapy. One month following induction therapy, cycles of radiolabeled antibody therapy were given every 2 months. Each cycle was derived from a different species of animal and consisted of 30 mCi I-131 antiferritin, Day 0, and 20 mCi, Day 5. On Day -1, 5-FU, 500 mg, and Adriamycin, 15 mg, were administered. The overall median survival for the entire group, including previously treated patients, was 4.9 months. The median survival for alpha-fetoprotein (AFP) - patients not previously treated was 10.5 months. Median survival for all AFP - patients was 8.5 months and for all AFP + patients was 4.6 months (p = 0.006). Of the 17 pretreatment characteristics investigated for prognostic value Karnofsky Performance Score (KPS) (80-100 vs. less than 80) (p = 0.0001), presence/absence of ascites (p = 0.0002), bilirubin level (less than 1.5 vs. greater than or equal to 1.5) (p = 0.018), SGOT (less than or equal to 35 vs. greater than 35) (p = 0.001); alkaline phosphatase (less than or equal to 95 vs. greater than 95) (p = 0.008) were found to be significant independently using a multivariant regression model. The relative risk of dying for the unfavorable component of each of these characteristics was 2.2, 2.0, 1.5, 1.9 and 1.7, respectively. Good and poor prognostic groups were then defined and compared to a similar patient population (RTOG study 83-19) with confirmation of the validity of the model. When stratification for these overpowering clinical factors was incorporated, AFP status was again significant with a relative death rate 1.80 times higher for AFP+ patients. Our recommendations for structuring future prospective randomized trials are discussed and include stratification by AFP status.
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PMID:Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01. 184 27

Between February 1983 and February 1986, 132 patients with advanced urothelial tract tumors were treated with methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Analysis of prognostic factors for survival of the first 92 patients was undertaken using the Cox proportional hazards model. Normal alkaline phosphatase and high Karnofsky performance status (KPS) were predominant for long survival. Patients 60 years or older at initiation of therapy were likely to survive longer than younger patients, perhaps indicating physician selectivity of older patients for this therapy, and those with initial hemoglobin in the normal range were also likely to survive longer. The additional 40 patients' data were used to validate the model. Clinical implications of the prognostic factors are discussed.
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PMID:Prognostic factors for survival of patients with advanced urothelial tumors treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy. 200 40

The processes responsible for the multidrug-resistant (Mdr) phenotype in Adriamycin (doxorubicin)-resistant HL-60 leukemia cells (HL-60/AR) are not defined. Since enhanced transcription of resistance-related proteins is associated with Mdr cells, we sought to determine whether changes in the expression of specific transcription factors were a feature characteristic of the Mdr process. Nuclear extracts were prepared from wild-type and resistant cells and compared for their ability to bind DNA consensus sequences for the transcription factors Sp1 and NF kappa B contained in the 5' long terminal repeat region of human immunodeficiency virus type 1. Southwestern (DNA-protein) blots showed a family of DNA-binding proteins of 105 kilodaltons (kDa) that were present only in HL-60/AR cells. Competitive gel shift assays indicated that these factors were related to transcription factor Sp1, and immunoblotting with an Sp1 antibody identified this factor as Sp1. DNase footprinting of the promoter region in the human immunodeficiency virus type 1 5' long terminal repeat showed that protection occurred at two Sp1 sites as well as two NF kappa B sites and the trans-acting region with nuclear extracts only from resistant cells. Preliminary evidence also suggests that phosphorylation may play a negative regulatory role in the activity of Sp1, since calf intestine alkaline phosphatase stimulated the DNA-binding activity of Sp1 in vitro. These results indicate that HL-60/AR cells contain an abundance of DNA-binding proteins, particularly Sp1, which probably interact with other cis-acting regulatory proteins in a cooperative manner.
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PMID:Increased expression and DNA-binding activity of transcription factor Sp1 in doxorubicin-resistant HL-60 leukemia cells. 220 18

Weekly intravenous doses of 20 mg Adriamycin were given to 22 patients with hormone-resistant metastatic cancer of the prostate. (Median duration treatment: 8 weeks; range 3-60 weeks.) Of 21 adequately treated patients, 6 achieved a subjective response (Median duration: 4 weeks; range 4-28 weeks). In 2 patients a more than 50% size reduction of measurable lymph node metastases was observed, while the disease progressed at other sites (mixed response). The median survival from treatment start (8.5 months) was unrelated to the achievement of subjective response. In 10 of 21 patients a reduction of serum alkaline phosphatase was observed and 7 of 21 patients showed a decrease of serum prostatic acid phosphatase. These biochemical changes were not related to response. Toxicity was generally mild, but one case with severe irreversible thrombocytopenia was observed after 3 weekly doses of 20 mg Adriamycin. Weekly low-dose Adriamycin has marginal subjective efficacy in progressing hormone resistant prostatic cancer, a condition where effective and feasible chemotherapy is lacking. The combination of weekly low-dose Adriamycin with other agents, preferably hormones, should be explored.
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PMID:Weekly low-dose adriamycin in hormone-resistant metastatic cancer of the prostate. 243 53

The effect of sodium butyrate was examined on the growth and phenotypic expression of a cell line derived from the ascitic fluid of an untreated patient with ovarian carcinoma. The chemical inducer of differentiation, sodium butyrate, markedly enhances the activity of the membrane-bound glycoprotein enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase. The alkaline phosphatase corresponds to placental Regan type. Sodium butyrate (1 mM) alone has only a small inhibitory effect on cell growth. However, it was shown to potentiate the anti-proliferative effect of Adriamycin and to render the cells sensitive to cis-platinum.
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PMID:Sodium butyrate enhances the activities of membranal enzymes and increases drug sensitivity in a cell line from ascitic fluid of an ovarian carcinoma patient. 257 49

The early effects of 4'-epidoxorubicin (Epi-Adriamycin) on liver regeneration and late effects on liver function were studied after a standard partial hepatectomy in rats. 4'-epidoxorubicin was given intravenously immediately preoperatively. Neither suppression nor delay in DNA synthesis (analyzed by incorporation of 3H-thymidine) during the first 72 h postoperatively was registered after a dose of 5 mg/kg body weight. Four weeks following the dose of 5 mg/kg a slight decrease was found in liver weight (8%), body weight (8%) and plasma albumin values (9%) compared with the partial hepatectomized controls. Total protein, alkaline phosphatase, total bilirubin and alanine aminotransferase were not changed. A dose of 2 mg/kg did not alter any of the parameters. No histological signs of liver and kidney damage were seen. The results indicate that preoperative treatment with 4'-epidoxorubicin combined with partial hepatectomy may possibly be used in humans without clinically significant impairment of liver regeneration and function of the remaining liver and without histological detectable nephrotoxicity. The dosage of 4'-epidoxorubicin must, however, be adjusted according to species differences in pharmacokinetics.
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PMID:Effect of preoperative 4'-epidoxorubicin (epi-adriamycin) treatment on the regeneration and function of the liver in partially hepatectomized rats. 280 48

Adriamycin (ADR) has a broad spectrum of antitumoral activity but is ineffective against human brain tumors. However, such tumors can be sensitive to a combination of adriamycin and lipophilic antineoplastic agents such as the nitrosoureas. CCNU, a nitrosourea, induces cholestasis in the rat and ADR is predominantly excreted via the biliary route. We decided to investigate the effect of CCNU on the nephrotic syndrome induced by ADR. Female Wistar rats were injected with a single dose of 10 mg/kg ADR and 24 h later were force fed 20 mg/kg CCNU in a single dose. Animals were sacrificed 4, 8, 15, 21, 28 or 60 days after the injection of ADR. A high rate of fatality (60%) occurred after the 21st day of treatment. Biological changes (alkaline phosphatase, SGPT, bilirubin) and ultrastructural studies showed that CCNU and CCNU + ADR induced the same degree of cholestasis. With the administered dose, CCNU is not nephrotoxic, ADR induces a nephrotic syndrome and ADR + CCNU appeared more nephrotoxic. With ADR, visceral epithelial foot process fusion was seen on day 15 and tubulo-interstitial lesions and glomerulosclerosis on day 60. With ADR + CCNU fusion of the foot process was seen on day 4, glomerular vacuolation on day 8, tubulo-interstitial alterations on day 15 and glomerulosclerosis on day 60. For both ADR and ADR + CCNU wrinkling and thickening of the basement membrane of proximal tubular cells were seen on day 60. Lipid mesangial overload was seen with ADR and was more intense with ADR + CCNU on day 60. CCNU hepatoxicity modifies the excretion of ADR and the predominantly renal excretion of ADR seems to induce earlier renal alterations in ADR + CCNU-treated rats. This study supports the concept that lipid mesangial overload may play an important role in chronic progressive glomerulosclerosis and thus the ADR + CCNU combination appears to be an interesting model in which to study these relationships.
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PMID:CCNU-adriamycin association induces earlier and more severe nephropathy in rats. 337 83

Bone morphogenetic activity of osteosarcomas from 20 patients was assayed. The activity was demonstrated as ectopic bone formation on implantation of a lyophilized fraction of the tumor into athymic nude mice in 8 of 20 cases. Osteosarcomas producing bone morphogenetic protein (BMP) differed in clinical features from those not producing BMP. They were characterized radiologically by perpendicular spicules, histologically by osteoblastic type cells, and clinically by an increased serum alkaline phosphatase level, relative resistance to preoperative chemotherapy with Adriamycin (doxorubicin) plus high-dose methotrexate, and a tendency to metastasize to other bones and the lungs.
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PMID:Clinical significance of bone morphogenetic activity in osteosarcoma. A study of 20 cases. 386 Dec 32


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