Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the aim of establishing bio-indices for the development of multistep hepatotumorigenesis, rats were fed water containing 0.01% diethylnitrosamine (DEN) ad libitum for 13 weeks. This treatment with DEN only made it possible to induce hepatic tumors in 100%. After the DEN administration, several clinical symptoms were observed including minor behavioral changes, brittleness of hair and a decrease in water and food intake. The concentration of total serum protein and albumin in all treated groups was significantly lower than in non-treated controls (P<0.05). Increase of specific enzyme (AST, ALT and GGT) activity (P<0.05), variable tumor size and hepatomegaly of the liver was observed in all rats treated with DEN for 10 weeks. Both hepatocellular carcinoma and cholangiocarcinoma were found in the same livers at the same time, and were prominently developed after 12 weeks. In case of carcinoma, some of the livers showed more or less advanced states over the 12-15 weeks period. In the present study, hepatocellular carcinoma was developed by treating DEN in only the drinking water, without any other carcinogens or without partial hepatectomy. These results indicate that DEN is a new carcinogen that acts directly on it the liver, moreover, it might be very useful for investigating hepatotumorigenesis.
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PMID:Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis. 1461 95

Cervical carcinoma is the second most common cancer worldwide. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant defense mechanisms. Low levels of essential antioxidants in the circulation have been found to be associated with an increased risk of cancer. The aim of our study was to assess the extent of oxidative stress, the levels of antioxidants like superoxide dismutase (SOD), catalase (CAT), ceruloplasmin and to evaluate tumor markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and total sialic acid (TSA) levels in circulation of women with cervical carcinoma and to compare our findings with age matched controls. Low levels of SOD and CAT observed in the circulation of cervical cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as sequestration by tumor cells. Higher levels of TSA, AST, ALT and ALP, in the circulation of cervical cancer patients may be used in the diagnosis and treatment monitoring of patients with cervical carcinoma.
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PMID:Oxidative stress and tumor markers in cervical cancer patients. 1497 92

Eight cases of feline pancreatic adenocarcinoma and two cases of pancreatic adenoma were reviewed. The adenomas were incidental findings. Most cats with adenocarcinomas had anorexia (75%) and vomiting (63%), while 38% had abdominal pain, a palpable abdominal mass, and/or jaundice. Diagnostic abnormalities included leukocytosis, hyperglycemia, increased alanine aminotransferase activity, poor serosal detail on abdominal radiography, and an abdominal mass effect on ultrasonography. The majority of cats with carcinomas had metastases (mostly to liver, lung, and small intestine), and all were euthanized or died within 7 days of diagnosis. Clinically, feline pancreatic carcinoma may be difficult to distinguish from feline pancreatitis.
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PMID:Exocrine pancreatic neoplasia in the cat: a case series. 1513 Nov 6

To elucidate the potential factors modulating exposure to aflatoxin B1 (AFB1) in three Chinese populations, an epidemiologic study was conducted in Fusui County and Nanning City of Guangxi Province and Chengdu City of Sichuan Province. The incidence rates of hepatocelluar carcinoma (HCC) for males in these three regions were 92-97 per 100,000, 32-47 per 100,000, and 21 per 100,000, respectively. Eighty-nine residents from Fusui, 196 residents from Nanning, and 118 residents from Chengdu were screened for AFB1-albumin adduct (AAA) levels and hepatitis virus (HBV, HCV, HDV, HEV, and HGV) infections, as well as liver biochemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], y-glutamyl transpeptidase [GGT], 5'-nucleotidase, globulin [GLO], direct bilirubin, indirect bilirubin, and bile acid levels). At least one marker of hepatitis virus (HV) infection was present in 47.2% (42/89) of subjects from Fusui, while in Nanning and Chengdu the values were 15.8% (31/196) and 22.0% (26/118), respectively. In contrast to females, a higher level of AAA was observed in males; the difference was statistically significant in both the Nanning (P = 0.023) and the Chengdu (P = 0.026) subjects. In the Chengdu group, there was a significantly higher level of AAA in cases with HV infection (P = 0.041). There was a close association between AAA level and BMI in the adults without HV infection (r = 0.148, P = 0.044). Also, AAA was closely associated with DBIL and GGT in non-HV-infected minors (P < 0.05), closely associated with ALB, GLO, and GGT in HV-infected minors (P < 0.05), and closely associated with IBIL, GLO, TBA, and AST in non-HV-infected adults (P < 0.01). The co-effect of HV infection and AFB1 exposure may be responsible for the high risk of HCC in the Fusui region, whereas age, gender, BMI, and HV infection may modify individual aflatoxin levels. The relationship between AAA level and liver biochemistry indicates injury induced by aflatoxin to both hepatic parenchyma and biliary tract. But the associations vary with age and HV infection status.
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PMID:Associated factors in modulating aflatoxin B1-albumin adduct level in three Chinese populations. 1581 Jun 36

Hepatitis B viral (HBV) infection in early childhood is one of the leading causes of chronic hepatitis and liver cirrhosis that eventually lead to hepatic carcinoma. Despite the nationwide immunization programs to curtail the vertical transmission of HBV, childhood HBV infection through mothers is still occurring in Korea. As one of the efforts to understand the childhood HBV infection in Korea, four HBV promoter sequences in the sera of the chronically infected children were analyzed. Children harbored diverse viral variants as most of the chronically infected adult patients, but the deletion mutations were rare. The dominant viral sequences in the children were highly similar to the ones in the respective mothers, indicating that the maternal viruses were most likely transmitted to the children. The mutations in X, S1, S2/S promoters did not seem to show any correlation to the severity of the disease nor ages of the children. The mutations that showed some correlation to the severity of the disease were the mutations in C promoter, but the mutations did not seem to be vertically transmitted. Finally, the children with the elevated ALT/AST levels tended to have more child-specific variants suggesting that the accumulation of host-specific mutations might be associated with the development of clinical symptoms.
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PMID:Mutation analysis of hepatitis B virus promoters in chronically infected children. 1584 41

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

A 40-year-old Chinese-American woman with breast carcinoma metastatic to her lungs presented with a 3-month history of erosions on her inner thighs (Figure 1) and medial left shoulder. Faint livedo reticularis was evident on her legs as well. She had difficulty in walking and raising her shoulders. Her cutaneous examination was also notable for cuticular erythema (Figure 2) and mild periorbital erythema and edema. She had no systemic or rheumatologic complaints other than some difficulty in swallowing. Her blood chemistry values were notable for a creatinine kinase of 564 IU/L (5-200 IU/L), alanine aminotransferase 161 U/L (0-40 U/L) and aspartate aminotransferase 93 U/L (0-40 U/L), and an antinuclear antibody titer of 1:2560. Other blood chemistries and antibody serologies (anti-Jo-1, anti-Mi-2 and other anti-tRNA synthetase, anti-Ro/SSA, anti-U1RNP, anti-PM/Scl, and anti-Ku) were within normal limits. A biopsy specimen was obtained from an area of intact skin close to a right thigh ulceration that showed subtle vacuolar alteration at the dermo-epidermal junction with occasional necrotic keratinocyte (Figure 3). Melanophages and telangiectases were present. Within the subcutis there was fibrin deposition and neutrophils. A diagnosis of dermatomyositis was made. The patient received oral prednisone 20 mg three times a day, and her ulcerations resolved. Her creatinine kinase, alanine aminotransferase, and aspartate aminotransferase values returned to normal over the course of 3 weeks, but her antinuclear antibody was unchanged. Radiographic studies concurrently noted that her breast cancer had recurred in her lungs; plans were made to treat her with chemotherapy. The patient was lost to close follow-up, but it was learned that her erosions had reoccurred while her prednisone was tapered and resolved when her dosage of prednisone was increased.
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PMID:Ulcerative paraneoplastic dermatomyositis secondary to metastatic breast cancer. 1660 44

Acute cholecystitis associated with gallbladder carcinoma is very rare in young patients (younger than 30 years of age). Moreover, a definitive preoperative diagnosis is difficult. A 26-year-old man was referred to our hospital with a 5-day history of right upper quadrant pain. Computed tomography and ultrasonography demonstrated an enlarged gallbladder with a diffuse thick wall and a 2-cm gallstone obstructing the cystic duct. Magnetic resonance cholangiopancreatography showed no evidence of an anomalous pancreaticobiliary junction. The patient showed an elevation in the white blood cell count, serum C-reactive protein, and alkaline phosphate; however, total bilirubin, alanine aminotransferase, and tumor markers including carcinoembryonic antigen and carbohydrate antigen 19-9 were all within the normal ranges. The preoperative diagnosis of gallstone-induced acute cholecystitis was made and an open cholecystectomy was thus performed 2 days after admission. The macroscopic findings showed a necrotic enlarged gallbladder with a thick wall and a gallstone, but no intraluminal nodular lesion. Histologic examinations revealed well-differentiated focal adenocarcinoma in the gallbladder mucosa, but no venous, lymphatic, or perineural invasion. The postoperative course has been uneventful with no recurrence 18 months postoperatively.
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PMID:Latent gallbladder carcinoma in a young adult patient with acute cholecystitis: report of a case. 1764 22

In recent studies, the cytotoxic activity of NO has been investigated for its potential use in anticancer therapies. Nitrosated human serum albumin (NO-HSA) may act as a reservoir of NO in vivo. However, there are no published reports regarding the effects of NO-HSA on cancer. Therefore, the present study investigated the antitumor activity of NO-HSA. NO-HSA was prepared by incubating HSA, which had been sulfhydrylated using iminothiolane, with isopentyl nitrite (6.64 mol NO/mol HSA). Antitumor activity was examined in vitro using murine colon 26 carcinoma (C26) cells and in vivo using C26 tumor-bearing mice. Exposure to NO-HSA increased the production of reactive oxygen species in C26 cells. Flow cytometric analysis using rhodamine 123 showed that NO-HSA caused mitochondrial depolarization. Activation of caspase-3 and DNA fragmentation were observed in C26 cells after incubation with 100 muM NO-HSA for 24 h, and NO-HSA inhibited the growth of C26 cells in a concentration-dependent manner. The growth of C26 tumors in mice was significantly inhibited by administration of NO-HSA compared with saline and HSA treatment. Immunohistochemical analysis of tumor tissues demonstrated an increase in terminal deoxynucleotidyl transferase dUTP nickend labeling-positive cells in NO-HSA-treated mice, suggesting that inhibition of tumor growth by NO-HSA was mediated through induction of apoptosis. Biochemical parameters (such as serum creatinine, blood urea nitrogen, aspartate aminotransferase, and alanine aminotransferase) showed no significant differences among the three treatment groups, indicating that NO-HSA did not cause hepatic or renal damage. These results suggest that NO-HSA has the potential for chemopreventive and/or chemotherapeutic activity with few side effects.
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PMID:Design and evaluation of S-nitrosylated human serum albumin as a novel anticancer drug. 1821 31

Abstract Bicalutamide is a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We describe a 59-year-old man with metastatic prostate carcinoma treated with bicalutamide as part of androgen deprivation therapy before starting chemotherapy. At baseline, his liver function test results and serum creatinine concentration were within normal limits, and an abdominal computed tomographic scan did not demonstrate liver metastasis. After 4 days of bicalutamide therapy, the patient came to the emergency department with complaints of abdominal pain, distension, and tenderness. His liver function tests were abnormal, and bicalutamide was discontinued. After 2 days of increasing liver function tests and symptoms of hepatotoxicity, the patient developed tachycardia and hypotension that was resistant to fluid resuscitation. Multiorgan damage was manifested by an alanine aminotransferase level greater than 40 times the upper limit of normal, serum creatinine concentration of 4.2 mg/dl, and troponin I level of 18 ng/ml. The patient died 8 days after bicalutamide therapy was begun secondary to multiorgan failure, most likely as a result of fulminant hepatotoxicity. The Naranjo adverse drug reaction probability scale showed a probable (score of 5) causal relationship between bicalutamide and fulminant hepatotoxicity. Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide. Liver function tests should be monitored before and during bicalutamide therapy, even for patients who have previously completed a course of this therapy with no signs or symptoms of toxicity.
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PMID:Bicalutamide-associated fulminant hepatotoxicity. 1865 23


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