Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Cancer Biother Radiopharm 2003 Aug
PMID:Assessment of hepatic toxicity from treatment with 90Y-SMT 487 (OctreoTher(TM)) in patients with diffuse somatostatin receptor positive liver metastases. 1450 53

SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery, using a carrier, lipiodol, that consists of ethyl esters of iodized poppy seed oil. We have performed a phase I clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order to investigate the maximum allowable dose and to maximize the efficacy and safety of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension was administered at doses of 6, 12 and 20 mg ml(-1) in a maximum lipiodol volume of 6 ml. An antitumour efficacy rating of complete response was achieved for one patient and a partial response rating was achieved for a second patient, giving an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia, thrombocytopenia and increases in AST, ALT and total bilirubin were observed as adverse effects, but each was transient and each patient had recovered completely by 4 weeks after drug administration. Hence, we concluded that the maximum allowable dose was not reached in this study. Overall, our results suggest that SM-11355 is effective in treating HCC and we suggest that the dose for early phase II trials should be 20 mg ml(-1).
Br J Cancer 2003 Nov 03
PMID:Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol. 1458 58

Since there has been no report on histologic subtypes of hepatocellular carcinoma (HCC) and its significance in the Thai population, the present study was conducted to elucidate the situation through appraisal of histologic and laboratory records. A total of 180 archived microscopic slides of HCC in Sonklanagarind Hospital from 1991 to 1998 were of good enough quality with sufficient tissue to be reviewed. The reclassified histologic subtypes were correlated with microscopic features and laboratory data. Of the 180 cases, 147 were males and hepatitis B was the main etiologic factor. The histologic subtypes of HCC were trabecular 63.3%, compact 15.6%, scirrhous 7.8%, pseudoglandular 5%, and fibrolamellar 0.6%. There was no correlation between histologic subtypes and morphological findings, as well as HBV, HCV, and cirrhotic status. A correlation between AFP levels and the AST/ALT ratio was evident.
Asian Pac J Cancer Prev
PMID:Histologic subtypes of hepatocellular carcinoma in the southern Thai population. 1472 87

HIV caregivers face many challenges following initiation of ART. The development of jaundice is uncommon but worrisome. In this case, two distinct and contrasting episodes of jaundice were observed. In the first instance, isolated elevation of the indirect bilirubin without elevation of the alkaline phosphatase was noted. The normal PT and serum aminotransferase levels indicate the absence of intrinsic liver dysfunction. Elevations in the indirect bilirubin may result from either impaired uptake/conjugation or excess production. The latter, usually from acquired hemolysis, may be a complication of an occult NHL. A work-up for this AIDS-related malignancy was not initiated since the caregivers recognized jaundice as a complication of IDV, which inhibits UDP-glucuronyl transferase and produces a Gilbert's-like syndrome. Physicians can expect to encounter this syndrome even more frequently with ATV. Experienced patients given RTV-boosted ATV have experienced elevations of unconjugated hyper-bilirubinemia in up to 45 percent of cases in clinical trials. However, such elevations do not reflect liver dysfunction and symptomatic jaundice requiring dosage reduction that occurred infrequently (7 to 8 percent of study patients). Counseling patients about this syndrome may promote adherence and prevent self-directed interruptions of ATV that compromise efficacy. The second case of jaundice provides a more formidable diagnostic challenge. The triad of LFT abnormalities (mild elevation of aminotransferases, normal PT, and marked cholestatic jaundice) implies an acute process that is mildly toxic to hepatocytes without affecting their synthetic function. The subacute nature of the patient's cholestatic jaundice suggests either intrahepatic infiltrative disease of the liver or extrahepatic obstruction of the biliary tree, most likely due to the patient's relatively modest level of pain and lack of fever. Despite LFT abnormalities occurring 17 months after a switch in his ART, cumulative drug-related toxicities must still be considered. Ritonavir can produce significant elevations in the AST/ALT, especially with pre-existing chronic liver disease as with hepatitis C virus coinfection. The NRTIs can produce hepatic steatosis, a result of mitochondrial toxicity and impaired fatty acid oxidation. However, jaundice and cholestasis are not typical of the latter syndrome. With a negative contrast CT that excludes parenchymal liver disease, investigation of the biliary tree to assess the presence of AIDS-related cholangitis was the next step. Performing a sphincterotomy or stent placement, and obtaining brushings or biopsy specimens to determine the extent of extrahepatic obstruction may help define a pathogen and be life-saving. The negative results of the ERCP justify the final diagnostic step, a liver biopsy to evaluate microscopic infiltrative disease that might not have been detected on contrast abdominal CT. Examples might include granulomatous disease (MAC), fungal etiologies (histoplasmosis), carcinomatosis (lymphoma, hepatoma, cholangiocarcinoma), and microvascular disease (bacillary angiomatosis). The failure to observe granulomatous inflammation in the liver does not exclude MAC infection, as MAC may involve other peri-aortic or mesenteric lymph nodes. This form of IRIS is unlikely given the abdominal CT findings, lack of systemic complaints, and extended persistence of liver aminotransferases. The nonspecific results of the liver biopsy are a common outcome in advanced AIDS patients with elevated alkaline phosphatase levels. Despite not having identified a pathogen, the biopsy establishes chronic liver disease and prompts re-evaluation and change of treatment to NFV. The subsequent normalization of the patient's aminotransferase levels suggests a prior adverse effect of LPV/r in the setting of unexplained, chronic liver disease. Most importantly, this case highlights the importance of HIV caregivers to review ART for safety when noting chronic liver dysfunction. Patients need to be counseled to minimize acetaminophen use, to consume alcohol in moderation, and to avoid behavior with risk for hepatitis C. Finally, all HIV patients should receive appropriate vaccination against hepatitis A and B if serology shows lack of protective immunity.
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PMID:Clinical vignette in antiretroviral therapy: jaundice. 1498 14

This study found a correlation between some serum markers [AST/ALT ratio, level of matrix metalloproteinase 9 (MMP9), level of viraemia and HCV serotype] and severity of liver fibrosis in HCV-infected patients. The study included 72 human cases referred to the Early Cancer Detection Unit, for liver biopsy assessment. The severity of liver fibrosis was staged using the METAVIR scoring system into 4 stages. The level of viraemia did not differ significantly in the different stages of liver fibrosis. Also, the type of HCV had no effect on the severity of liver fibrosis. However, the transaminases ratio differed significantly in the different fibrosis stages (P < 0.01). This serum test has a relatively high sensitivity and specificity (92.6% and 94.3%, respectively) in diagnosing severe fibrosis and cirrhosis. The level of MMP9 was, however, inversely correlated with the fibrosis stages and was found to have an 88.9% sensitivity and an 88.6% specificity when diagnosing severe fibrosis and cirrhosis. Although, the sensitivity of these serum markers did not reach 100%, yet their use can reduce the number of liver biopsies when diagnosing and treating HCV-infected patients.
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PMID:Non-histological assessment of liver fibrosis in HCV infection. 1528 65

We investigated the effects of a sublethal concentration of H(2)O(2) on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 microM H(2)O(2). These sublines (AST cells) showed an elongated morphology distinct from the rounded morphology of A549 cells. Notably, AST cells demonstrated telomere shortening despite displaying telomerase activity and expressing human telomerase reverse transcriptase (hTERT). This functional impairment of telomerase occurred due to perturbed subcellular localization of hTERT in AST cells. Endogenous as well as ectopically expressed hTERT was localized in the nuclei of A549 cells; however, in AST cells, the localization was mainly in the cytoplasm. Furthermore, these AST cells demonstrated decreased tumorigenic features both in vitro and in vivo. These results suggest that depletion of hTERT from nuclei not only endows cancer cells with a finite replicative life span accompanied by telomere shortening, but also decreases the tumorigenicity of cancer cells.
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PMID:Functional impairment of telomerase in sublines derived from human lung adenocarcinoma exposed to mild oxidative stress. 1600 65

Studies of release under physiological conditions provide more direct data about the identity of neuromodulatory signaling molecules than studies of tissue localization that cannot distinguish between processing precursors and biologically active neuropeptides. We have identified neuropeptides released by electrical stimulation of nerves that contain the axons of the modulatory projection neurons to the stomatogastric ganglion of the crab, Cancer borealis. Preparations were bathed in saline containing a cocktail of peptidase inhibitors to minimize peptide degradation. Both electrical stimulation of projection nerves and depolarization with high K+ saline were used to evoke release. Releasates were desalted and then identified by mass using MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-flight) mass spectrometry. Both previously known and novel peptides were detected. Subsequent to electrical stimulation proctolin, Cancer borealis tachykinin-related peptide (CabTRP), FVNSRYa, carcinustatin-8, allatostatin-3 (AST-3), red pigment concentrating hormone, NRNFLRFa, AST-5, SGFYANRYa, TNRNFLRFa, AST-9, orcomyotropin-related peptide, corazonin, Ala13-orcokinin, and Ser9-Val13-orcokinin were detected. Some of these were also detected after high K+ depolarization. Release was calcium dependent. In summary, we have shown release of the neuropeptides thought to play an important neuromodulatory role in the stomatogastric ganglion, as well as numerous other candidate neuromodulators that remain to be identified.
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PMID:Profiling of neuropeptides released at the stomatogastric ganglion of the crab, Cancer borealis with mass spectrometry. 1618 23

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. (166)Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. (166)Holmium-Chitosan complex, in which chitosan is chelated with (166)Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of (166)Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. (166)Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.
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PMID:A pilot study of trans-arterial injection of 166Holmium-Chitosan complex for treatment of small hepatocellular carcinoma. 1638 56

A 66-year-old white male presented with jaundice, pruritus, and a 30-pound weight loss over two months. Physical examination revealed scleral icterus. Laboratory evaluation revealed ALT 161 U/L, AST 290 U/L, alkaline phosphatase 2004 U/L, GGT 2,552 U/L, total bilirubin 10.2 mg/dL, and a carbohydrate antigen 19-9 (CA 19-9) level of 4,374 U/mL. Initial endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessful due to ulceration in the duodenum healed with esomeprazole therapy. Subsequent ERCP showed a possible filling defect in the common bile duct treated with sphincterotomy and balloon sweeping of the common bile duct. Symptoms and jaundice resolved five months after initial presentation with normal labs and studies. While elevated CA 19-9 levels occur in most patients with carcinoma of the pancreas, it can also be elevated in patients with extrapancreatic malignancies and acute cholangitis. This case illustrates the fact that a markedly elevated CA 19-9 can be secondary to causes other than carcinoma.
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PMID:Patient with markedly elevated CA 19-9 not associated with malignancy. 1655 91

Macroenzymes are normal enzymes complexed with an immunoglobulin (usually IgG, rarely IgA or IgM). A number of macroenzymes have been reported in the literature. Among them, macro-AST has been detected in diseases such as acute and chronic hepatitis, various malignancies and autoimmune diseases, but usually not associated with any specific disease. We report a case of elevated AST activity in serum due to marco-AST formation in a female with chronic hepatitis C which was confirmed by AST isoenzyme electrophoresis. To our knowledge, this is the first report of macro-AST occurred in chronic hepatitis patient in Korea.
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PMID:[Macro-aspartate aminotransferase in a patient with chronic hepatitis C]. 1655 78


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