Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the epidemiology of HCV in Taiwan, anti-HCV was studied by radioimmunoassay or enzyme immunoassay in patients with chronic liver disease, healthy adults, and subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 HBsAg-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with HCC. An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV. In a prospective study of PTH, 37 or 13% patients contracted hepatitis and 22 (60%) were due to HCV, and at least 17 (77%) of them became chronic. Cloning of HCV genome in a Taiwanese patient with acute posttransfusion non-A, non-B hepatitis by using reverse transcription polymerase chain reaction was performed, and partial characterization of the nucleotide sequences showed 80% and 92% homology as compared to HCV sequences from Chiron and one of the published Japanese isolates, respectively. It is concluded that HCV infection plays a relatively minor role in HBsAg-positive liver decrease in Taiwan, but is strongly associated with HBsAg-negative chronic liver disease and HCC. It is also important in PTH, and the infection is extremely common in hemophiliacs and parenteral drug abusers. The Taiwanese strain of HCV seems more similar to that from Japan, as revealed by nucleotide sequences.
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PMID:Hepatitis C virus infection in Taiwan. 190 59

In my opinion, independent, carefully conducted scientific studies indicate that an accurate, rapid, relatively sensitive, and inexpensive laboratory test substantially reduces the major long-term risk of blood transfusion in the United States; donor ALT has emerged as one of the most effective laboratory determinants for reducing the incidence of NANB PTH. Despite its nonspecificity and limited predictive value, ALT screening may prevent up to 30 percent of cases, one-half of which would progress to chronic liver disease and then possibly to cirrhosis and hepatocellular carcinoma. Blood donors appear to understand and accept the testing rationale as a reasonable precaution. Admittedly, ALT screening is not a perfect solution. It has not been validated by prospective studies and probably never will be. Determination of the proper cutoff value remains controversial. However, the risk of PTH progresses with increasing ALT levels, so that the real issue is not whether to test, but how best to configure the test to exclude the fewest false-positive donors while detecting the most true-positive donors. It is undesirable and expensive to discard safe units of blood, but the primary responsibility of blood collectors is to ensure an adequate supply of safe components. Some still consider the ALT assay technically too demanding for routine use. However, technical concerns regarding performance and interpretation are not insurmountable, and both quality control and proficiency testing are being addressed at the national level. The assay is capable of great precision, and a system employing a national standard and single cutoff has already been described and tested with excellent results. Circumstances have changed since donor screening with ALT was widely implemented in 1986. More thorough screening and testing have eliminated many high-risk donors. Public expectations have changed as well. While it is neither reasonable nor responsible to promise the public blood transfusions without risk, neither is it prudent to propose any major change in management of the blood supply without compelling evidence that such a change will not impair transfusion safety. It is hard to defend discontinuing the ALT screen at this time, especially when the costs of retaining it are minimal and the benefits clearly greater than those of screening for HTLV-I and for Treponema pallidum (in the United States) or HIV-2 (in West Germany). A first-generation assay specific for antibody to hepatitis C will probably be available within a year.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Controversies in transfusion medicine. Alanine aminotransferase screening of blood donors: pro. 234 35

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.
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PMID:Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. 673 66

1. All available evidence for and against the concept of ectopic hyperparathyroidism, including 307 case reports of tumor hypercalcemia, was collated. 2. Of 104 combined cases of tumors of the kidney, lung, liver, head, neck and esophagus, 91 (88%) were in men. 3. The parathyroid glands were examined in 170 of 307 cases and parathyroid hyperplasia or adenoma were described in 34 cases. This high frequency may reflect higher likelihood of reporting such association. 4. Analysis of the histological pattern of tumors associated with humoral hypercalcemia revealed a marked association with certain histological types in different organs, such as clear-cell carcinoma of the kidney and ovary, hepatocarcinoma and cholangiocarcinoma, pheochromocytoma, and squamous-cell carcinoma of the lung, head, neck, esophagus, and urogenital tract. This histological correlation is not compatible with the "random derepression" hypothesis. 5. The existence of tumor humoral hypercalcemia is well documented, as 61 of 74 operated patients sustained remission of hypercalcemia following tumor removal. 6. The evidence for ectopic PTH being produced by tumor is not well documented and is based on conflicting radioimmunoassay results. We have found no case in the literature which fulfilled unequivocally criteria of ectopic production of biologically active PTH. There has been a lack of studies of tumors for the presence of biologically active hypercalcemic factors because only relatively insensitive bioassays are available at present. More information is also required on microscopic bone changes in tumor hypercalcemia as x-ray studies alone are inadequate. 7. On the basis of the present evidence, causes and mechanisms of tumor hypercalcemia are likely to be multiple.
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PMID:Tumor hypercalcemia and "ectopic hyperparathyroidism". 699 43

PTH is a mediator of skeletal development and remodeling that influences gene expression in osteoblastic cells. It is well established that PTH modulates the activity of membrane-associated second messenger signal transduction pathways. In these studies we have addressed the potential contribution of components of cell structure to the integration of PTH-related regulatory signals that influence the expression of bone cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma cells with PTH is accompanied by changes in gene expression that are at least in part transcriptionally controlled. To explore the involvement of nuclear architecture in PTH-responsive modifications in gene expression, we investigated changes in the nuclear matrix after PTH treatment. Consistent with a role for the nuclear matrix in determining spatial organization and topology of chromatin as well as in the localization and targeting of transcription factors, we observed PTH-associated changes in a 200-kilodalton nuclear matrix protein in response to PTH. A significant down-regulation of synthesis was observed when nuclear matrix proteins were resolved electrophoretically in two-dimensional gels. This protein was restricted to the nuclear matrix and was not detected in the chromatin or cytoskeletal cellular fractions. These alterations in nuclear matrix proteins that occur after PTH treatment in osteosarcoma cells were phenotype related. They did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role for the nuclear matrix in transducing PTH-mediated regulatory signals to facilitate the extent to which genes in osteoblasts are transcribed.
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PMID:Parathyroid-responsive modifications in the nuclear matrix of ROS 17/2.8 rat osteosarcoma cells. 813 38

A well differentiated human hepatoma cell line (Hep G2) was used to explore potential roles for PTH-related peptide (PTHrP) as an autocrine/paracrine growth factor. Using Northern analysis or reverse transcription-PCR, Hep G2 cells were found to express messenger RNAs for both PTHrP and the cloned PTH/PTHrP receptor, and the cells exhibited specific binding for [125I]PTHrP(1-36). Hep G2 growth medium was found to contain relatively large amounts of immunoreactive PTHrP (30 vs. 1-2 pM in medium not exposed to cells), and the PTHrP in growth medium (conditioned medium) was shown to contain N-terminal PTHrP biological activity, as assessed by the ability of the medium to stimulate cAMP production in rat osteosarcoma cells (ROS 17/2.8). Conditioned medium produced a dose-dependent severalfold increase in ROS cell cAMP that could be blocked by the PTHrP receptor antagonist [Asn10,Leu11,DTrp12]PTHrP-(7-34). PTHrP in Hep G2 cells also was detected by immunocytochemistry using antiserum to either synthetic PTHrP-(1-34) or recombinant PTHrP-(-5 to 139). Furthermore, these antisera were found to inhibit the ability of PTHrP-(1-34) to stimulate ROS cell cAMP production. When either antiserum (1:800-1:100 dilution) was added to subconfluent Hep G2 cells in medium containing 5% FBS for 3 days, a dose-related 40-50% increase in cell number occurred that could be inhibited by concurrent addition of 10 microM synthetic PTHrP-(1-36). The results show that Hep G2 cells synthesize and secrete both immunoreactive and biologically active PTHrP. As neutralization of PTHrP secreted by these cells by the addition of antiserum to PTHrP resulted in increased cell growth, the findings suggest that PTHrP can function as an autocrine or paracrine growth factor to suppress the growth of these human hepatoma cells.
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PMID:Effect of endogenously produced parathyroid hormone-related peptide on growth of a human hepatoma cell line (Hep G2). 864 Nov 88

We report a case of hepatocellular carcinoma with hypercalcemia. There was no evidence of bone metastasis or increase in parathyroid hormone-related protein. The serum level of intact parathyroid hormone (intact PTH) was very high, and the results of the hepatic venous sampling suggested that the tumor produced intact PTH. Transcatheter arterial chemoembolization effectively controlled the humoral hypercalcemia.
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PMID:Intact PTH-producing hepatocellular carcinoma treated by transcatheter arterial embolization. 1002 99

PTH and dibutyryl cAMP [(Bu)2cAMP] induced the expression of a 19-kDa protein in the conditioned media of rabbit growth plate chondrocyte cultures. The 19-kDa protein was identified as plasma retinol-binding protein (RBP) by aminoterminal sequence analysis and immunoblot analysis with an anti-RBP monoclonal antibody. Northern blot analysis showed that PTH, PTH-related peptide (PTHrP), and (Bu)2cAMP increased the RBP messenger RNA (mRNA) level in chondrocyte cultures. Further, both PTH and (Bu)2cAMP markedly induced the expression of RBP mRNA by about 10-fold at 3 h and by about 40-fold at 24 h, indicating a pretranslational regulation. The level of the mRNA expression induced by PTH, PTHrP, and (Bu)2cAMP was as high as that by retinoic acid (RA), known as a potent inducer of RBP in hepatoma cells. RBP mRNA was also detected in cartilage tissues at higher levels than in the other tissues examined except liver. Both RBP and PTH/PTHrP inhibited the dedifferentiative activity of RA on growth plate chondrocytes when added to the culture medium. These results demonstrate that chondrocytes synthesize and secrete RBP in vivo and in vitro and suggest that PTH/PTHrP modulates the effect of RA by means of RBP production in chondrocytes.
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PMID:Retinol-binding protein is produced by rabbit chondrocytes and responds to parathyroid hormone (PTH)/PTH-related peptide-cyclic adenosine monophosphate pathway. 1006 28

Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC.
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PMID:Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide. 2628 47