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)

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

Porfimer sodium (Photofrin II) is a photosensitizer which distributes selectively to tumor tissues, and causes tumor cell death by combination with light irradiation. Photodynamic therapy (PDT) by combination of porfimer sodium and laser was developed as a new cancer therapy. Tumor selectivity of porfimer sodium are based on the following reasons; 1) high affinity for lipoprotein, especially, low density lipoprotein (LDL), 2) elevation of LDL receptor activity in cancer tissue, and 3) lack or imcompleteness of lymphatic system in cancer tissue. Porfimer sodium is activated by laser irradiation at 630 nm, which can reacts with tissue oxygen to produce highly reactive excited siglet oxygen (1O2). This highly reactive molecule is subsequently capable of killing tumor cells through oxidation of cellular component like mitochondrial enzymes. In addition, this highly reactive intermediate causes destruction of the tumor capillaries, which accelerates tumor cell death. The growth suppression or lethal damage to tumor cells by PDT of porfimer sodium and excimer dye laser were observed in experimental tumor models. In human clinical trials, the rates of complete response (CR) for roentgenographically occult lung cancer, stage I lung cancer, superficial esophageal cancer, superficial gastric cancer and carcinoma in situ or dysplasia of the cervix were 84.8%, 50.0%, 90.0%, 87.5% and 94.4%, respectively. The major side effects were cutaneous symptoms e.g. photosensitivity, pigmentation, increasing GOT, GPT but these symptoms were not severe. PDT using porfimer sodium and excimer dye laser must be clinically useful for the treatment of inoperable early cancer or conservation of organ functions.
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PMID:[Porfimer sodium (Photofrin-II)]. 766 80

The p53 tumor-suppressor gene is the most commonly altered gene in human cancers. Here we demonstrate that transcripts of the mdm2 gene, which encodes a cellular p53 binding protein, markedly increased in the rat liver within 1 to 3 h, reached a peak at 12 h and returned to the basal level 48 h after the administration of carbon tetrachloride. However, the level of hepatic mdm2 mRNA did not significantly change after partial hepatectomy. This is in contrast to p53 gene expression which increased after either procedure. C-myc transcripts also rapidly increased after the injection of carbon tetrachloride, reaching a maximal level at 3 h. The activity of serum alanine aminotransferase was low within the first 12 h and was maximal 24 h after carbon tetrachloride. These results suggest that the transient hepatic expression of the mdm2 gene prior to the onset of cell death is more likely to reflect events associated with necrosis rather than with cell proliferation.
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PMID:Expression of the protooncogene mdm2 markedly increases in response to carbon tetrachloride but not after partial hepatectomy in contrast to p53. 766 43

74 breast tumor patients were preoperatively examined by means of colour and pulsed-wave Doppler sonography using the ultrasonic instrument ALT Ultramark 9 HDI with a broad-band linear scanner, 5-10 MHz. The Doppler flow velocity waveforms, from the vessels of the mammary lesion (affected breast) and the corresponding quadrant of the contralateral breast (non-affected breast), respectively, were compared in respect of the four parameters maximal systolic velocity, minimal diastolic velocity, pulsatility index (PI) and resistance index (RI). In 48 cases we succeeded in representing arterial vessels both inside the affected and the contralateral breast. The aim of the study was to examine whether these parameters show a significantly different degree of deviation in correlation with the tumours being either benign or malign. In cases with benign lesions (n = 24) we did not find any significant differences in all the parameters that we examined. In cases with cancer, however (n = 18), a significantly higher systolic velocity was found in the affected breast compared to the contralateral breast, but there were no differences in the other parameters. Although the quantitative Doppler measurements are angle-dependent parameters, the study showed that the maximal velocity in the affected breast compared to the contralateral breast is the most useful parameter in differential diagnosis of breast tumours.
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PMID:[Differential breast tumor diagnosis by comparing blood circulation of the tumor with the contralateral breast using color coded, pulsed Doppler ultrasound]. 770 92

As a novel method for the medical application of liposomes, we have tried hepatic artery chemoembolization using temperature-sensitive liposomes with hyperthermia for the treatment of hepatic tumors. In this study, the effect of temperature-sensitive liposomes was compared with that of Lipiodol emulsion, which has been used clinically. The temperature-sensitive liposomes, consisting of dipalmitoylphosphatidylcholine or Lipiodol emulsions entrapping doxorubicin, were administered into the hepatic artery of hepatic tumor-bearing rats via a cannula. Doxorubicin administered in a liposomal form showed a high accumulative property toward tumors, with heating, while that in the emulsion form showed a slow release property toward tumors. Not only was tumor growth inhibited, but also, an actual diminishing of the tumor was observed in each form. Side effects were also examined: an abnormal rise in GPT, or necrosis of the normal tissues in liver, which was often observed in hepatic artery chemoembolization using Lipiodol emulsion, was remarkably reduced in the liposomal chemoembolization.
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PMID:Study on hepatic artery chemoembolization using temperature-sensitive liposome or lipiodol emulsion. 774 98

Family history of hepatocellular carcinoma (HCC) has been identified as a risk factor of HCC. The pathogenesis is still uncertain. In order to evaluate the risk factors and to detect the small HCC. 721 asymptomatic family members (419 males and 302 females with a mean age of 40.21 years) of the index cases of HCC received a series of examinations including: serum GOT, GPT, alpha-fetoprotein (AFP). HBsAg, Anti-HCV, and abdominal ultrasonography (US). Of the 18 patients with liver tumor detected by US. 6 were proved to be HCC, 8 were hemangioma, and the nature of the rest was undetermined. The US found 22 with cirrhosis, 24 with chronic liver disease, 133 with fatty liver, and 14 with a liver cyst. The incidence of HCC in our study was 0.96% in males (4 of 419 cases), and 0.66% in females (2 of 302 cases) which was much higher than that in the general population of Taiwan (0.025% in males and 0.01% in females). The positive rate of HBsAg in the participants, including all the newly detected HCC patients, was 46.5% (335 cases) which was also higher than the prevalence in Taiwan (15-20%). Male, sibling and liver cirrhosis seemed to have higher risk. These results suggest that family members of patients with HCC have a high risk of developing HCC. The hepatitis B virus may be the most important link. Early diagnosis is possible by screening the family members by means of AFP and abdominal US.
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PMID:Risk factors of hepatocellular carcinoma with familial tendency. 776 61

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

The use of herbal and other "natural" health products by healthy and ill people is more common than is appreciated by many health care providers. Since most of these substances are not categorized as medicines, they are exempt from U.S. Government approval processes, and are essentially uncontrolled. In this article we describe a patient who developed painless jaundice, fatigue, and pruritus after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial liver biopsies and serum chemistries documented severe cholestasis and hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma-glutamyl transpeptidase to 35-fold. Endoscopic retrograde cholangiopancreatography showed smooth, but severely narrowed biliary ducts without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The diagnosis remained in doubt until the publication of two cases of chaparral hepatotoxicity. Because of the similarity of our patient's illness to those cases we concluded that chaparral was almost certainly the cause. Chaparral, also known as creosote or greasewood, is used by some practitioners to treat a diverse group of ailments including ethanol withdrawal. This report should heighten the awareness by primary care physicians and gastroenterologists that any chaparral herbal preparation is a potential hepatotoxin that can lead to serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. 780 38

The medical and necropsy records of 41 cats diagnosed with nonlymphomatous hepatobiliary (NLHB) masses, including neoplasia and cysts, were reviewed. Overall, benign masses (n = 27) were more common than malignant ones (n = 14). The single most common malignancy was cholangiocellular carcinoma. The median age at diagnosis was significantly lower (P < .01) for cats with malignant rather than benign disease. Clinical signs associated with hepatobiliary neoplasia were usually vague and included lethargy, vomiting, and anorexia, often present for at least 2 weeks before presentation. Benign masses were an incidental finding in significantly more (P < .01) of the cases than were malignant masses. Median values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were significantly higher (P < .05) in cats with malignant versus benign masses. The prognosis for malignant disease was poor, with 86% of the cats dying or being euthanatized during hospitalization. Cats with benign disease that underwent exploratory celiotomy were more likely to recover and warranted a more favorable prognosis than cats with malignant tumors. Factors associated with malignancy included age at presentation, presence of clinical signs at presentation, and specific serum chemistry changes.
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PMID:Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to 1991). 783 94

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.
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PMID:[The clinical phase I study of TNP-351. The TNP-351 Research Committee]. 785 2


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