Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7

The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.
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PMID:Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas. 774 36

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

Hepatic and renal subacute toxicity induced by the antineoplastic drugs chlorambucil, cisplatin, epirubicin and methotrexate and the steroid alkylating agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam (p-[bis(2-chloroethyl) amino] phenyl) acetate was investigated in rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of dose regimens of the agents that were previously shown to be effective in suppressing malignant tumor growth or to prolong survival in tumor bearing animals. Hepatic and renal subacute toxicity was evaluated by measuring enzyme activity or concentrations of: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total cholesterol, gamma-glutamyltransferase, glucose, potassium, sodium, blood urea nitrogen and uric acid. The use of the above serum biochemical parameters indicated that the overall toxicity impact of the antitumor drugs was methotrexate < cisplatin < epirubicin < chlorambucil. The homo-azasteroid ester only transiently affected the biochemical parameters associated with renal toxicity, while it affected some of the biochemical parameters associated with hepatic toxicity, though to a significantly lower extent than the antitumor drugs.
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PMID:Evaluation of kidney and liver subacute toxicity of antitumor agents using serum biochemical parameters in rats. 790 82

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

Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo, sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.
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PMID:Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. 796 Nov 5

Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. The mechanism of cytotoxicity in vivo is unknown; in vitro it has been shown to inhibit macromolecular synthesis, interact with the reduced folate carrier system, and inhibit topoisomerase II. Phase I testing of fostriecin in a daily for 5 days schedule has begun in cancer patients. A high-pressure liquid chromatographic method to measure fostriecin in plasma samples was developed using sulfaquinoxaline as an internal standard and ultraviolet detection (268 nm). The extraction efficiency is 70% and the sensitivity limit is 100 ng/ml. The pharmacokinetics of fostriecin were determined in six rabbits following intravenous injection of 12 mg/m2. The mean distribution space was 4.44 L/m2 and the mean plasma clearance was 302 ml/min/m2. The elimination half-life was 11.95 +/- 8.55 min. All rabbits exhibited a 10-60-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that resolved within 48 h of drug administration.
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PMID:Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay. 800 68

Clinical and morphological findings in 91 patients with infantile hemangioendothelioma of the liver are reported. The study comprised 56 girls and 35 boys ranging in age from premature infant to 3 yr; one outlier patient was 18 yr old. Most patients with infantile hemangioendothelioma (87%) were first seen before the age of 6 mo. Congestive heart failure was evident in 15%. Skin hemangiomas were noted in 11%. Anemia, hyperbilirubinemia and increased AST level were present. Solitary lesions were more common than multiple ones (3:2). Immunohistochemical staining of tumor cells for factor VIII was positive in 20 of 21 cases tested; testing for blood group antigen was positive in 8 of 28 cases. Cytokeratin staining verified the presence of bile ducts, some of which appeared to be the result of transformation of injured liver. No pericytes were identified on electron microscopy. The 6-mo survival rate, based on 71 cases, was 70%. Average time of follow-up for the survivors was 7.7 yr. All deaths occurred during the initial presentation/hospitalization of infants, with the exception of two patients who died 3 mo and 7 mo after diagnosis. More recent analytic methods, including immunohistochemical stains and flow cytometric studies, do not contribute to the practical assessment of this tumor. Covariates with significant value in predicting death 6 mo after diagnosis included presence of congestive heart failure, jaundice, multiple tumor nodules and absence of cavernous differentiation.
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PMID:Infantile hemangioendothelioma of the liver. 802 Sep 3

Etoposide is a schedule-dependent cytotoxic drug with high single agent activity in small-cell lung cancer and lymphoma. Despite its clear dose-dependent myelosuppressive activity, dose-dependent evidence of its anti-tumour activity is harder to demonstrate. A number of reports have correlated haematological toxicity with pharmacokinetic and physiological parameters, which explains some of the variability in dynamic effects that exists between patients. Recent reports have also suggested that anti-tumour response may be related to plasma etoposide concentration. In our own studies we have investigated factors that influence the pharmacodynamic effects of etoposide, principally with regard to haematological toxicity, and these studies have highlighted a number of patient groups who are at risk. Impaired renal function causes a reduction in clearance of etoposide, resulting in increased systemic exposure and more profound myelotoxicity. A 30% dose reduction in this group is recommended to normalise the area under the plasma concentration-time curve (AUC). Patients with low serum albumin concentrations (< 35 g/l) also showed significantly worse haematological toxicity, but with no apparent change in total drug pharmacokinetics. There was, however, an increase in the free drug fraction in this group due to decreased protein binding, such that the free drug AUC was similar to that found in patients with renal dysfunction. This would also indicate that a dose reduction of around 30%-40% is required in this patient group. Patients with normal albumin levels but liver enzyme values (aspartate transaminase or gamma-glutamyl transpeptidase) more than 3 times the upper limit of normal also had a less marked but significant increase in neutropenia. In patients with normal organ function, age was the only significant factor in predicting the degree of leukopenia/neutropenia, and increasing age was also associated with decreasing drug clearance and an increase in drug AUC. A small dose reduction and/or careful monitoring is required in this patient group. Further studies are required to elucidate further the relationship between the pharmacokinetics of etoposide and its pharmacodynamics, particularly with regard to anti-tumor activity, and to determine the role of individualised therapy, based on a pharmacokinetic parameter, in reducing the dynamic variability and optimising the use of this drug.
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PMID:Etoposide dosage and pharmacodynamics. 807 31


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