UMLS:C0019204 - FACTA Search

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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is often a considerable lapse of time between the definition of what causes a disease in the laboratory and the development of successful therapy. However, the history of medicine teaches us that the need to understand the scientific basis of disease before the discovery of new treatments is both essential and inevitable. During the middle of the 19th century, the work of the great German pathologist, Rudolf Virchow, defined disease as having an anatomic or histologic basis. In the clinic, this scientific perspective would lead to increasingly effective and, often, increasingly aggressive surgical approaches to disease. Later in the 19th century, Koch's discovery of the tubercle bacillus (a discovery Virchow disbelieved and publication of which he thwarted, since he hypothesized that cancer, not microbes, caused consumption!), would define a microbiological basis for disease. With bacteria defined as a major cause of human suffering, the stage was set for the development of the discovery of effective antibiotics. In the early 20th century, the pioneering work of Banting, Best and others would show that disease can also have an endocrine or metabolic basis. This new body of scientific knowledge would lead not only to the specific discovery of insulin as an effective treatment for diabetes but also to a more general understanding of the role of hormones, vitamins and co-factors in human health and disease. Basic medical research and its successful translation into effective treatments has fundamentally altered the cause of human death. In the developed world, where access to the benefit of this work is available, infectious disease is not the problem it was in the days of Pasteur, Metchnikoff and Ehrlich. As we approach the millennium, science is now teaching us that diseases, particularly cancer, can have a molecular or genetic basis. Can successful application of this new knowledge be far behind? We are already seeing the application of this new knowledge in cancer drug screening and cancer drug development. At the NCI, for example, the old in vivo mouse screen using mouse lymphomas has been shelved; it discovered compounds with some activity in lymphomas, but not the common solid tumors of adulthood. It has been replaced with an initial in vitro screen of some sixty cell lines, representing the common solid tumors-ovary, G.I., lung, breast, CNS, melanoma and others. The idea was to not only discover new drugs with specific anti-tumor activity but also to use the small volumes required for in vitro screening as a medium to screen for new natural product compounds, one of the richest sources of effective chemotherapy. The cell line project had an unexpected dividend. The pattern of sensitivity in the panel predicted the mechanism of action of unknown compounds. An antifolate suppressed cell growth of the different lines like other antifolates, anti-tubulin compounds suppressed like other anti-tubulins, and so on. It now became possible, at a very early stage of cancer drug screening, to select for drugs with unknown-and potentially novel-mechanisms of action. The idea was taken to the next logical step, and that was to characterize the entire panel for important molecular properties of human malignancy: mutations in the tumor suppressor gene p53, expression of important oncogenes like ras or myc, the gp170 gene which confers multiple drug resistance, protein-specific kinases, and others. It now became possible to use the cell line panel as a tool to detect new drugs which targeted a specific genetic property of the tumor cell. Researchers can now ask whether a given drug is likely to inhibit multiple drug resistance or kill cells which over-express specific oncogenes at the earliest phase of drug discovery. In this issue of The Oncologist, Tom Connors celebrates the fiftieth anniversary of cancer chemotherapy. His focus is on the importance of international collaboration in clinical trials and the negative impact of unnecessary bureaucracy and regulation. As a student of Tom's in the 1970s in London, working on hepatoma-specific alkylating agents at Charing Cross Hospital in collaboration with his lab on the other side of town, I can attest to the fact that the regulatory hurdles to cancer drug development just twenty years later have added immeasurably to the effort and cost of cancer drug development. However, I look with optimism to the future of cancer diagnosis, prevention and treatment. It is a future where what we are learning now about the molecular and genetic basis of cancer will find their clinical outlet just as surely as the anatomic, microbial, metabolic and endocrine basis for disease has in the past. This new knowledge will provide new techniques in molecular diagnosis, which will allow us to predict which in situ cancers are destined for malignant behavior, and which can be safely watched without the need for intervention. Individual patient risk for particular cancers will be accurately predictable, so that patients can alter lifestyle habits or begin other prevention strategies. Oncogenes and growth suppressor genes give us new targets to inhibit or replace. Tumor-specific kinases will meet their inhibitors. The oncologist will play a leading role in understanding, applying and interpreting this new information in the clinic-an exciting and challenging future!
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PMID:Cancer Drug Development: New Targets for Cancer Treatment. 1038 87

We report a 66-year-old man with hepatocellular carcinoma who was positive for hepatitis B surface antigen, and was hospitalized because of hypoglycemia and hypertension. His plasma renin activity was normal (2.3 ng/ml per h), but concentrations of angiotensin I (>2500 pg/ml) and II (86 pg/ml) were high. Increased angiotensin I level at sites proximal and distal from the confluence of the hepatic vein and the inferior vena cava indicated that the hypertension was provoked by overproduction of angiotensin I from the hepatocellular carcinoma. Previous reports of patients with hepatocellular carcinoma with hypertension due to abnormality of renin-angiotensin system are reviewed.
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PMID:Hypertension as a paraneoplastic syndrome in hepatocellular carcinoma. 1045 90

A 64-year old man was admitted to our hospital with multiple hepatocellular carcinoma (HCC) lesions in the liver, lung and bone. Three weeks after admission, the patient became complicated with right upper chest pain. A chest radiograph showed a marked increase in right pleural effusion. Thoracentesis demonstrated a hemothorax. Despite treatment with a continuous pleural tap and blood transfusions, the patient's clinical status worsened and he developed severe dyspnea. His right pleural effusion might be considered to be caused by a rupture of the HCC metastasis in the right 2nd rib. The patient died due to respiratory and hepatic failure 26 hours after his occurring the pleural effusion. An autopsy revealed moderately differentiated HCC in the liver, lung and bone. The HCC metastasis of the right 2nd rib was found to have torn the nearby pleura. We described a rare case in which hemothorax was caused by a ruptured rib-based HCC.
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PMID:Hepatocellular carcinoma with metastasis to the rib complicated by hemothorax. An autopsy case. 1049 47

The structure of hepatitis B virus (HBV) nucleocapsids has been revealed in great detail by cryoelectron microscopy. How nucleocapsids interact with surface antigens to form enveloped virions remains unknown. In this study, core mutants with N-terminal additions were created to address two questions: (1) can these mutant core proteins still form nucleocapsids and (2) if so, can the mutant nucleocapsids interact with surface antigens to form virion-like particles. One plasmid encoding an extra stretch of 23 aa, including six histidine residues, fused to the N terminus of the core protein (designated HisC183) was expressed in Escherichia coli and detected by Western blot. CsCl gradient and electron microscopy analyses indicated that HisC183 could self-assemble into nucleocapsids. When HisC183 or another similar N-terminal fusion core protein (designated FlagC183) was co-expressed with a core-negative plasmid in human hepatoma cells, both mutant core proteins self-assembled into nucleocapsids. These particles also retained kinase activity. Using an endogenous polymerase assay, a fill-in HBV DNA labelled with isotope was obtained from intracellular nucleocapsids formed by mutant cores. In contrast, no such signal was detected from the transfection medium, which was consistent with PCR and Southern blot analyses. Results indicate that core mutants with N-terminal extensions can form nucleocapsids, but are blocked during the envelopment process and cannot form secreted virions. The mutant nucleocapsids generated from this work should facilitate further study on how nucleocapsids interact with surface antigens.
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PMID:Hepatitis B viral core proteins with an N-terminal extension can assemble into core-like particles but cannot be enveloped. 1057 58

Two cases of intraperitoneal hemorrhage, which is one of the major complications of percutaneous ethanol injection therapy for hepatocellular carcinoma, are reported. A 70-year-old man was hospitalized for treatment of a small recurrent hepatocellular carcinoma located on the surface of the left lobe of the liver. Acute hemoperitoneum developed after percutaneous ethanol injection therapy, but he was treated conservatively with blood transfusion, and recovered. The other patient was a 72-year-old man who was admitted for treatment of a solitary superficial hepatocellular carcinoma on the dome of the liver. Immediately after percutaneous ethanol injection, he suffered the sudden onset of severe abdominal pain with shock and massive hemoperitoneum. His bleeding was successfully controlled by emergency transcatheter arterial embolization. Our experience suggests that care must be taken when using percutaneous ethanol injection to treat patients with superficial hepatocellular carcinomas located on the surface of the liver. Moreover, transcatheter arterial embolization should be considered the treatment of choice for the management of uncontrollable intraperitoneal hemorrhage after percutaneous ethanol injection therapy.
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PMID:Intraperitoneal hemorrhage as a major complication of percutaneous ethanol injection therapy for hepatocellular carcinoma. 1110 Mar 10

Hepatoma cells show alterations in the response to oxidative stress (decreased lipid peroxidation) and in xenobiotic metabolism enzymes (decreased P450, increased GST and ALDH3). This study examined the effect of lipid peroxidation on the expression of the above enzymes in two rat hepatoma cell lines (MH(1)C(1) and 7777). To induce oxidative stress, cells were exposed to arachidonic acid (to increase lipid peroxidation substrate) and/or to beta-naphthoflavone (to increase CYP450), and treated with one dose of iron/histidine. The cells, that were still viable after the challenge, were refed with the culture medium and CYP1A1, GST, and ALDH3 enzymes monitored for 1, 6, 12, and 24 h. Treatments that increased markers indicative of lipid peroxidation are associated with a decrease in enzyme activities, which was permanent for CYP1A1 and transient for the other enzymes. We speculate from these data that aldehydic byproducts of lipid peroxidation may be responsible for these effects. Thus, restoration of lipid peroxidation in hepatoma cells seems to induce a rapid adaptation to oxidative stress, which is achieved by a simultaneous decrease of reactive oxygen species production and an increase in the two main enzymes involved in the removal of the aldehydic products of lipid peroxidation.
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PMID:Changes of CYP1A1, GST, and ALDH3 enzymes in hepatoma cell lines undergoing enhanced lipid peroxidation. 1112 27

A conjugate of doxorubicin and glutathione via glutaraldehyde (GSH-DXR) inhibited glutathione S-transferase (GST) activity of rat hepatoma AH66 cells, and treatment of the cells with GSH-DXR induced caspase-3 activation and DNA fragmentation. After treatment of AH66 cells with 0.1 microM GSH-DXR, GST-P (placental type of rat GST isozymes) mRNA and its protein increased transiently and then decreased thereafter compared with the levels in nontreated cells. Caspase-3 activation and DNA fragmentation were induced following the suppression of GST-P expression by treatment with GSH-DXR. When the cells were treated with 100 microM ethacrynic acid (ECA), an inhibitor of GST, DNA fragmentation and caspase-3 activation were observed. In contrast, treatment of AH66 cells with a low concentration of ECA (1 microM) that showed little inhibition of GST activity induced slight, but significantly enhanced expression and activity of GST-P, and consequent prevention of DXR- and GSH-DXR-induced DNA fragmentation. Overexpression of GST-pi (placental type of human GST isozymes) by transfection of GST-pi sense cDNA into AH66 cells decreased sensitivities to DXR and GSH-DXR, and the suppression of GST-P by transfection of the antisense cDNA into the cells increased drug sensitivity. On the other hand, there was little change in drug sensitivity caused by overexpression of site-directedly mutated GST-P in which the active-site residue Tyr39 was replaced with His (W39H) or the substrate-binding site residue Cys48 was replaced with Ser (C48S) by transfection of those cDNAs into AH66 cells. These results suggested that the suppression of GST-P in AH66 cells treated with GSH-DXR must play an important role in the induction of apoptosis.
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PMID:Suppression of GST-P by treatment with glutathione-doxorubicin conjugate induces potent apoptosis in rat hepatoma cells. 1166 94

A 74-year-old man had multiple liver recurrence of hepatocellular carcinoma (HCC) after extended left hepatectomy. He was treated by continuous hepatic arterial infusion (HAI) chemotherapy with low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) via an implanted reservoir. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. The patient was administered 10 mg of CDDP on day 1 and 500 mg/day of 5-FU for 4 days as one course. Four courses were administered and the PIVKA-II level decreased from 427 to 216 mAU/ml. However, infusion port problems led to interruption of chemotherapy and PIVKA-II increased to 798 mAU/ml. His chemotherapy was changed to 10 mg of CDDP on day 1 and 750 mg/day of 5-FU for 2 days. After five courses were administered, PIVKA-II decreased to 540 mAU/ml. This patient is still alive 15 months after the start of therapy. This case suggests that HAI with low-dose CDDP and 5-FU might be useful for prolonging the survival of HCC patients with a good quality of life.
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PMID:[A case of hepatocellular carcinoma responding to hepatic arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil]. 1170 16

To explore the possibility of prokaryotic expression of human hepatic stimulator substance (hHSS), hHSS gene was inserted in the downstream of glutathion S-transferase (GST) in a pET-42a expression vector and recombinant GST-hHSS fusion protein was expressed under IPTG induction in BL-21(DE3) cells. The recombinant HSS was purified with His.Tag affinity chromatography, and its bioactivity was analyzed. The results showed that GST-hHSS fusion protein was expressed both as a soluble or a inclusive body in bacterial cytosol. The soluble GST-hHSS expression reached up to 30% of the whole soluble protein of bacteria as determined by densitometry. The cleavage of GST-hHSS fusion protein with Factor Xa produced two fragments of the protein, which sized 33 and 15 kD, respectively. The molecular weight of recombinant HSS protein was identical to theoretical deduction based on the DNA sequences. The protein homology of 15 kD hHSS could be efficiently eluted out after Factor Xa cleavage. It is further indicated that the recombinant hHSS is able to proliferate hepatoma cells of BEL-7402 in the preliminary experiments.
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PMID:[Prokaryotic expression and purification of human hepatic stimulator substance]. 1193 Feb 36

Ochratoxin A (OTA) is a widespread mycotoxin that occurs in many commodities from grains to coffee beans all over the world. Evidence is accumulating that OTA may cause cancer in humans. The compound was tested in micronucleus (MN) and single-cell gel electrophoresis (SCGE) assays in human-derived hepatoma (HepG2) cells and caused pronounced dose-dependent effects at exposure concentrations of 5 microg/ml and greater. On the contrary, no induction of His(+) revertants was found in Salmonella microsome assays with strains TA98 and TA100 with HepG2-derived enzyme (S9) mix in liquid incubation assays under identical exposure concentrations. Taken together, our results indicate that OTA is clastogenic in the human-derived cells. These findings support the assumption that this mycotoxin may cause genotoxic effects in hepatic tissue of humans.
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PMID:Genotoxic effects of ochratoxin A in human-derived hepatoma (HepG2) cells. 1206 68

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