Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the best route of administration of TNP-470, an angiogenesis inhibitor, by comparing the anti-tumour effects and toxicity following injection via the hepatic artery, the portal vein, or the jugular vein in a rabbit model of liver metastases. Following the injections of 1 x 10(6) VX2 carcinoma cells into the portal vein of rabbits, 50 mg of TNP-470 was injected continuously into the hepatic artery, portal vein, or jugular vein for 7 days. The number of tumours on the surface of the liver was counted 14 days following the start of the infusion, and the serum glutamic-oxaloacetic transamine (GOT), glutamic-pyruvic transaminase (GPT) and total bilirubin concentrations were examined. In addition, a coloured silicon rubber was injected into the vessels of the liver to visualise the capillary networks around the tumours and assess the degree of suppression of angiogenesis by TNP-470. The mean number of tumours following intra-arterial injection (17.5 +/- 2.9) was significantly less than the control (237.0 +/- 34.0) (P < 0.05). The mean numbers of the tumours following intraportal (89.1 +/- 16.0) and intravenous (140.6 +/- 31.2) injection were both less than the controls (215.3 +/- 45.5, 284.8 +/- 55.4 respectively), but the differences were not significant. We conclude that intra-arterial injection of TNP-470 is the most effective method for preventing liver metastases in this model.
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PMID:Intra-arterial administration of the angiogenesis inhibitor TNP-470 blocks liver metastasis in a rabbit model. 754 15

The patient was a 53-year-old woman who underwent a standard radical mastectomy for right breast cancer five years ago and was recently referred to our hospital with a complaint of abdominal fullness. Systemic chemotherapy (CMFS) was performed based on the diagnosis of multiple liver metastases of the breast cancer, but its effect was unsatisfactory. In this case, we gave her high-dose intraarterial chemotherapy under HVI.CHP for metastatic liver tumors. Although slight elevation of serum GOT and GPT levels and leucopenia (1,800/mm3) were observed, alopecia did not occur throughout the posttreatment course. The levels of tumor markers including CEA, NCC-ST439 and CA15-3 showed remarkable reductions; CEA (ng/ml): 18.4-->3.0, NCC-ST439 (U/ml): 33.0-->2.4, CA15-3(U/ml): 137.9-->26.3. Abdominal CT scan after the treatment demonstrated remarkable regression of liver metastases, showing a partial response (volume reduction: 61%). In conclusion, HVI.CHP achieved a significant reduction in systemic drug exposure and allowed dose intensification of adriamycin during intraarterial chemotherapy. Therefore, we consider that high-dose intraarterial chemotherapy under HVI.CHP offers an effective therapeutic option for multiple liver metastases of the breast cancer.
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PMID:[A case of multiple liver metastases of breast cancer treated successfully with high-dose intraarterial chemotherapy under hepatic venous isolation and charcoal hemoperfusion (HVI-CHP)]. 757

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.
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PMID:Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. 778 9

Plachitin formed of both poly-N-acetyl-D-glucosamine (chitin) and cis-diamminedichloroplatinum (CDDP), was used as an arterial chemoembolization therapy against unresectable liver cancer. One gram of Plachitin contained 300 mg of CDDP. The Plachitin particle was 50-100 microns in diameter. Plachitin particles (50-100 mg) were injected via hepatic artery once or twice every week, and the total amount of 300 mg was considered one course of this therapy. The size and number of tumors were measured by computer tomography (CT). Pharmacokinetics of this drug was also assessed by serum and urine platinum (Pt) concentration. Three patients underwent the chemoembolization therapy using plachitin particles. Case 1 had multiple hepatocellular carcinomas. The tumor regression rate was 39% after two courses of this therapy. Serum alpha-fetoprotein (AFP) level decreased from 1,182 ng/ml to 300 ng/ml. Case 2 suffered from bile duct cystadenocarcinoma. After three courses of the therapy, the tumor regression rate was 84.4%. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 731 U/ml to 75 U/ml. Case 3 had synchronous multiple liver metastases from sigmoid colon cancer. The tumor regression rate was 77% after one course of the therapy. Carcinoembryonic antigen (CEA) and CA19-9 decreased from 406 ng/ml to 65 ng/ml and from 4,800 U/ml to 790 ng/ml, respectively. The response rate of the 3 cases was 66.7%. The peak levels of the serum Pt concentration of three patients were 0-0.4 microgram/g throughout the therapy, but peak urine Pt concentrations were observed during one course of the therapy of three patients ranging from 0.5 microgram/g to 3.2 micrograms/g, and decreased gradually for three weeks after the first course. Adverse effects of Plachitin particles for arterial chemoembolization were epigastralgia, nausea, fever, and elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. These adverse effects were observed in all patients, but were transient. Catheter obstruction occurred in one patient (case 2). Cholecystitis, pancreatic pseudocyst, and duodenal ulcer were noticed in case 3. No renal hypofunction was observed. Plachitin might be a useful agent for arterial chemoembolization therapy for primary and secondary liver cancer.
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PMID:[Intraarterial chemoembolization therapy for unresectable liver cancer using plachitin particles]. 794 46

The pathogenetic mechanism underlying glucose intolerance in pancreatic cancer is still unclear. We studied the pattern of three glucose regulating hormones (C-peptide, glucagon and GH) in pancreatic cancer patients with (N = 34) and without (N = 8) hyperglycemia, and compared the findings made with those from subjects with other hyperglycemic conditions of well-known origin [type I diabetes mellitus (8 cases) and diabetes mellitus secondary to chronic pancreatitis (13 cases) or liver cirrhosis (4 cases)]. In hyperglycemic pancreatic cancer patients, C-peptide was absent in 26% of the cases, reduced in 24%, elevated in 29% and within the normal range in the remaining 21%. In normoglycemic pancreatic cancer this hormone was reduced in two cases (25%) and within the normal range in all the others. GH was within the normal range in all cases: glucagon was below the normal range in some hyperglycemic pancreatic cancer patients (41%) or within the normal range in all the remaining patients. No correlations were found between the three hormones when findings from subjects were considered all together. However, in pancreatic cancer C-peptide and glucagon presented consensual variations. C-peptide, glucagon and GH levels were not related to tumor volume; glucagon was found to be associated with liver metastases. C-peptide was correlated with serum ALT and ALP. We may conclude that hyperglycemia associated with pancreatic cancer may be caused by different mechanisms. In some cases a reduced secretion of both insulin and glucagon was observed, as occurs in chronic pancreatitis. In the majority of patients, beta cell function appears normal, and the hyperglycemic state may depend on an altered peripheral sensitivity to insulin due to the pancreatic pathology itself or to consensual liver involvement.
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PMID:C-peptide pattern in patients with pancreatic cancer. 813 97

The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg(-1)) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug-light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours.
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PMID:Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model. 1057 44

The purpose of this study was to clarify the safety of hepatic arterial infusion of degradable starch microspheres (DSM).adriamycin (ADM).mitomycin C (MMC) on aged patients with liver metastases of colorectal cancer. A total of 19 patients who received this therapy (DSM: 600 mg or less, ADM: 30 mg, and MMC: 10 mg) three times or more every three weeks were included. Changes in laboratory data and frequency of the occurrence of the adverse effects were compared between patients aged 75 (n = 5) or more and those aged 74 or less (n = 14). There were no significant differences in changes in the leukocyte counts, AST, ALT, and c-reactive protein levels between the groups. The frequency of adverse effects also was not different between the groups. These results suggests that this therapy is feasible with acceptable safety even in patients aged 75 years or more.
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PMID:[Audit of the safety of hepatic arterial infusion of degradable starch microspheres (DSM). Adriamycin (ADM).mitomycin C (MMC) on aged patients with liver metastases of colorectal cancer]. 1248 78

The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with (90)Y-SMT487 ((90)Y-DOTA-tyr3-octreotide, OctreoTher(TM)) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of (90)Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of (90)Y-SMT487. (111)In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi (90)Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury.
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PMID:Assessment of hepatic toxicity from treatment with 90Y-SMT 487 (OctreoTher(TM)) in patients with diffuse somatostatin receptor positive liver metastases. 1450 53

The present work is a continuation of studies on arginase as a marker in the diagnosis of colorectal cancer liver metastases (CRCLM). The purpose of the study was the evaluation of the arginase test in comparison with other colorectal cancer tests such as CEA, CA 19-9 and biochemical markers of liver function such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The studies were conducted on blood serum from 85 patients with CRCLM obtained one to two days before tumor resection. The control group comprised 140 healthy blood donors and 81 patients with various non-malignant gastrointestinal diseases. Raised arginase activity was observed in serum of 85% of CRCLM patients, whereas elevated levels of CEA and CA 19-9 were found in 63% and 42% of patients, respectively. The combination of CEA or CA 19-9 with the arginase assay improved their sensitivity, but the sensitivity of the combined parameters was not higher than that of the arginase test itself. AST and ALT activities were increased in about 30% of CRCLM patients. The specificity of the arginase test calculated for 221 control subjects was 76%. It can thus be concluded that the determination of serum arginase activity can be helpful in the diagnosis of patients with colorectal cancer liver metastases.
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PMID:Arginase as a useful factor for the diagnosis of colorectal cancer liver metastases. 1671 12

Liver dysfunction in a patient with anthracycline-resistant breast cancer and liver metastases with poor performance status (PS) represents a serious situation. Taxanes are the drugs of choice, but once the transaminase enzyme levels are raised more than 10-times the upper limit of normal (>10 ULN), paclitaxel administration is contraindicated. We present the report of one such case who had a gratifying response to escalating doses of weekly paclitaxel thus suggesting that even patients with severe liver dysfunction can derive benefits from such a strategy. The patient, a 54-year-old lady with breast cancer metastatic to the liver and bones and previous receipt of anthracycline-based therapy, presented to us with a PS of 3. Her liver functions (LFT) were: serum bilirubin 2.2 mg% (0.3-1.1 mg%), aspartate aminotransferase 375 IU/L (0-25 IU/L), alanine aminotransferase 369 IU/L (0-35 IU/L) and alkaline phosphatase 363 IU/L (38-126 IU/L). She was started on weekly paclitaxel 20 mg/m(2) and zoledronate. After the first dose, the LFTs rose marginally but the skin lesions stabilized. Dose was subsequently escalated to 40 mg/m(2). At the end of the 10th week, her PS improved to 1 and the disease showed a partial response. LFTs improved markedly. However, 5 days after the administration of the 13(th) dose, the disease progressed and paclitaxel had to be discontinued. It is possible to derive maximum palliative benefit with escalating doses of weekly paclitaxel even in patients whose liver functions are deranged with transaminase levels (>10 ULN) and in whom conventional administration of paclitaxel is contraindicated.
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PMID:Weekly paclitaxel in escalating doses in a patient with anthracycline-resistant, triple-negative, metastatic breast cancer with severe liver dysfunction. 2324 24


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