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)

Microcirculation and molecular biology are the hottest topics in modern surgical research. In familial adenomatous polyposis the incidence of carcinoma can be assessed by the localisation of the PAC-gene mutation. Restorative proctocolectomy with ileoanal pouch represents the procedure of choice. The optimal age for the operation varies between 20 and 35 years according to the localisation of the mutation. RT-PCR directed to recently defined surface antigens allows for the sensitive detection of intraoperative tumor cell liberation. Due to tumor cell detection in the systemic circulation the perioperative administration of monoclonal antibodies must be advocated. A preciser definition of lymphogenic tumor spread underlines the importance of systematic lymphadenectomy in resection of the colon. The understanding of microcirculatory disorders has optimized surgical decision-making intra- and perioperatively: function of renal and hepatic microcirculation is a reliable parameter to predict graft quality already intraoperatively and to monitor therapeutic approaches to ischemia/reperfusion injury. Results in the therapy of acute pancreatitis could be improved by operating less and later. Analysis of pancreatic microcirculation resulted in an improvement of ICU-therapy in the early stages of the disease. Transplantation of the liver is limited to hepatocellular carcinoma when its localisation or the residual hepatic function after resection preclude curative excision. In addition liver transplantation should not be carried out in tumors larger than 5 cm or in patients with more than 3 tumor nodules. Liver resection for colorectal metastases is a standard procedure. A second resection of recurrent metastases is advocated since an identical median survival can be achieved compared to the primary resection (32 mo). The surgical treatment of non-colorectal liver metastases is under evaluation and should be restricted to oncological centers. Special aspects of backwashileitis in ulcerative colitis will be outlined concerning timing of colectomy, pouch construction, and follow-up.
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PMID:[State of the art: gastroenterologic surgery]. 1006 3

We previously reported that in vitro hypoxic condition enhanced VEGF level and its receptor expression in hepatic cancer cell line, HepG2. Transcatheter hepatic arterial embolization (TAE) therapy is one of the vasculo-occlusive and hypoxic challenges to hepatocellular carcinoma (HCC). Therefore, we examined the level of VEGF in sera of patients with HCC who underwent TAE during the course of the treatment. Thirty-eight patients with HCC and hepatitis C virus-positive cirrhosis were studied. Peripheral blood samples were taken before and 1, 3 and 7 days after TAE with informed consent. The serum levels of VEGF as well as hepatocyte growth factor (HGF), another hepatic remodeling factor, were measured. The molar ratio (BTR) of serum branched chain amino acid (BCAA) to tyrosine (Tyr), the serum levels of AST, ALT and LDH were also examined. Although the level of AST, ALT and LDH reached the peak value within 1 day after TAE, VEGF level increased significantly 7 days later. On the other hand, there were no significant alterations in the levels of HGF and BTR during the course of TAE. Although the level of HGF was significantly correlated with the level of VEGF before TAE, this correlation was no more observed after TAE. These data collectively suggest that VEGF may be secreted in response to clinical hypoxic intervention, TAE, independent of HGF or altered amino acid metabolism. VEGF may play a role as a sensitive marker for tumor ischemia.
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PMID:Serum vascular endothelial growth factor in the course of transcatheter arterial embolization of hepatocellular carcinoma. 1033 62

Erythropoietin (Epo), the major hormone controlling the hypoxia-induced increase in the number of erythrocytes, has also a functional role in the brain. However, few data exist as to the cellular source of brain-derived Epo as well as to the molecular mechanisms that control Epo expression in the central nervous system. Using patch-clamp and RT-PCR methods, we provide direct evidence that, besides astrocytes, neurons are a source of Epo in the brain. Both the astrocytic and neuronal expression of Epo mRNA are induced not only by hypoxia, but also by desferrioxamine (DFX) and cobalt chloride (CoCl(2)), two agents known to mimic the hypoxic induction of Epo in hepatoma cells. This induction is blocked by cycloheximide suggesting that de novo protein synthesis is required. Furthermore, the addition of H(2)O(2) decreases the hypoxia-induced Epo mRNA levels. These data indicate that, following hypoxia, a common oxygen sensing and signaling pathway leads to increased Epo gene expression in both nervous and hepatoma cells; this pathway would be dependent on the redox-state of the brain. Furthermore, we show that the in vivo administration of CoCl(2) and DFX to mice induces an increased Epo mRNA level in the neocortex. As Epo protects the brain against ischemia, our in vivo experiments suggest that the use of molecules such as CoCl(2) or DFX, that provoke an increased Epo gene expression in the brain, could be useful in the development of potential therapeutic strategies for the treatment of hypoxic or ischemic brain injury.
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PMID:Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. 1075 76

Activity of neutral and acidic sphingomyelinases (N- and A-SMases) were studied in regenerating liver after partial hepatectomy (during 48 hrs after operation), in ischemic liver during 15, 30 min and 1 and 2 hrs ischemia and during following reperfusion (from 5 min up to 2 hrs), in hepatoma- 22 after 15 days of transplantation and in liver of tumor bearing animals. It was shown that activity of N-SMase is increased in hepatoma-22 and in regenerating liver and it is decreased in ischemic liver. Following reperfusion of ischemic liver area activity of enzyme was found to have returned to baseline in dependence on time of ischemia and reperfusion. Activity of A-SMase is decreased in tumor, is not changed in regenerating liver and increased after long time of ischemia. It was supposed that N-SMase is involved in cell proliferation, but A-SMase is connected with cell damage.
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PMID:[Changes in the activity of neutral and acidic isoforms of sphingomyelinase in hepatoma-22, regenerating and ischemic liver]. 1076 Dec 12

Chemoembolization has become the preferred treatment for patients with inoperable, hypervascular hepatic malignancies in the Far East, but controversial elsewhere. In vivo microscopy in addition to other experimental procedures are used in this presentation to better understand the mechanisms involved in chemoembolization. In chemoembolization Lipiodol acts as a contrast material, a vehicle for chemotherapy and an embolic agent. Although not optimal, Lipiodol injected into the hepatic artery, traverses the peribiliary plexus to the portal veins resulting in a dual embolization. Chemoembolization creates ischemia, slows arterial flow and increases the contact time between the infusate and the neoplasms, increasing the tumor cell kill. However, the vascular occlusion also produces infarction and fibrosis compounding the already existing cirrhosis frequently associated with hepatocellular carcinoma. Lipiodol/ethanol (3:1) injected into the segmental or lobar hepatic artery supplying the neoplasm also gains access to the associated portal venous branches causing focal ablation. This preoperative approach is easier to perform than direct portal vein occlusion, with less parenchymal damage and comparable hypertrophy of the remnant liver frequently necessary for adequate hepatic function following resection. Polymer-drug conjugates, e.g. PG-TXL, have considerable potential for intra-arterial delivery especially with the dramatic increase in concentration of the drug in the tumor and its efficacy. Using in vivo microscopy especially with green fluorescent protein (GFP) gene as an efficient and non-toxic tumor cell marker, the events leading to hepatic metastases can be documented which will serve to better evaluate these varied techniques of chemoembolization.
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PMID:Hepatic chemoembolization: clinical and experimental correlation. 1092 54

This study was undertaken to evaluate whether topical cooling can alleviate ischemia/reperfusion injury, after continuous inflow occlusion during hepatectomy. Using a canine model of 70% partial liver ischemia (60 min), alteration in the subcellular (cytoplasm, mitochondria, nucleus) elements calcium, sodium, potassium, and chloride, and liver functions following reperfusion were compared between control livers and livers subjected to topical cooling down to 23 degrees +/- 4.9 degrees C by seeding ice slush over the ischemic lobe. The elements were determined by X-ray microanalysis using liver biopsy specimens. A similar clinical study was undertaken examining ten patients with hepatocellular carcinoma and chronic liver disease who underwent right-sided segmentectomy under continuous right inflow occlusion, five of whom were given topical cooling and five of whom were not. In the experimental study, postreperfusion worsening of liver function tests was significantly suppressed in the cooling group, which was associated with the suppression of subcellular Ca, Na, and Cl increases and K decreases after reperfusion. In the clinical study, the occlusion time was significantly longer in the hypothermic patients than in the normothermic patients, but no significant differences in postoperative liver function or postischemic increases in Ca, Na, or Cl and decreases in K were observed. These experimental and clinical findings suggest that topical cooling alleviates ischemic insult and enhances safe prolonged inflow occlusion.
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PMID:Does topical cooling alleviate ischemia/reperfusion injury during inflow occlusion in hepatectomy? Results of an experimental and clinical study. 1103 7

Apoptosis, or programmed cell death, and the elimination of apoptotic cells are crucial factors in the maintenance of liver health Apoptosis allows hepatocytes to die without provoking a potentially harmful inflammatory response In contrast to necrosis, apoptosis is tightly controlled and regulated via several mechanisms, including Fas/Fas ligand interactions, the effects of cytokines such as tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), and the influence of pro- and antiapoptotic mitochondria-associated proteins of the B-cell lymphoma-2 (Bcl-2) family. Efficient elimination of apoptotic cells in the liver relies on Kupffer cells and endothelial cells and is thought to be regulated by the expression of certain cell surface receptors. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for other diseases, for example, hepatocellular carcinoma. Use and abuse of certain drugs, especially alcohol, chemotherapeutic agents, and acetaminophen, have been associated with increased apoptosis and liver damage. Apoptosis also plays a role in transplantation-associated liver damage, both in ischemia/reperfusion injury and graft rejection. The role of apoptosis in various liver diseases and the mechanisms by which apoptosis occurs in the liver may provide insight into these diseases and suggest possible treatments.
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PMID:Apoptosis in diseases of the liver. 1134 18

We report a 72-year-old man with hepatocellular carcinoma, which showed spontaneous regression. He was diagnosed as having chronic hepatitis type C five years before admission. In January 1998, a liver mass was found by ultrasonography. In February, computed tomography showed a low-density mass, 3.5 cm in diameter in the S5 region. Although liver biopsy was not performed, findings obtained by computed tomography and ultrasonography indicated that the tumor was hepatocellular carcinoma. The levels of alpha-fetoprotein and PIVKA (protein induced by vitamin K antagonist)-II were increased to 1000 ng/mL and 2000 mAU/mL, respectively. The patient was admitted to our hospital in March 1998. At the time, the size of liver mass was reduced to 2.5 cm in diameter on computed tomography, and the tumor markers, alpha-fetoprotein and PIVKA-II, spontaneously decreased to the normal range. We considered that hepatocellular carcinoma of this patient regressed spontaneously. Because it was hard to exclude the possibility that the mass contained residual malignant cells, we resected the mass on April 28, 1998. Microscopically, the resected mass did not contain any malignant cells. The parenchyma surrounding tumor necrosis, which is reflected by severe inflammatory infiltration with lymphocytes, indicates spontaneous regression. Although the precise mechanism regarding spontaneous regression of hepatocellular carcinoma is not fully understood, either ischemia due to rapid growth of the tumor or some inflammatory mechanism may be involved in regression of hepatocellular carcinoma.
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PMID:Spontaneous regression of hepatocellular carcinoma--a case report. 1181 13

Magnetic resonance angiography (MRA) has been used to image abdominal vessels less frequently than renal arteries. Until the use of fast contrast-enhanced (CE) techniques, an important limitation was the acquisition time of phase-contrast or time-of-flight imaging and, consequently, the creation of motion artifacts. Recent advances in MRA technology have shortened acquisition times, so it is now possible to obtain successive images in the arterial and then the portal phase. MRA can be used as an adjunct to any MR examination to assess, e.g., the arterial feeding of hepatocellular carcinoma, the encasement of arteries, and segmental portal thrombosis in pancreatic carcinoma. However, MRA has been used mainly to study chronic mesenteric ischemia, portal vein diseases, and complications from liver transplantation. The portal venous system is exquisitely portrayed with this method; MRA is as accurate as digital subtraction angiography (DSA) in the diagnosis of portal vein diseases. Acute mesenteric ischemia is an emergency in which computed tomography is the most appropriate imaging modality. Conversely, chronic mesenteric ischemia is best examined with CE-MRA, which is almost as accurate as DSA. CE-MRA is superior to DSA for the simultaneous exploration of the aorta, renal arteries, and iliac arteries, thereby providing a panoramic view of abdominal vascular involvement. MRA can be coupled with measurements of flow. With this functional approach, MRA is the only modality that can completely assess vascular diseases of the abdomen.
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PMID:MR angiography: noninvasive vascular imaging of the abdomen. 1217 87

The term bland arterial embolization refers to catheter-directed delivery of particulate material for the purpose of embolizing selected arteries. This technique is used in humans to treat a number of conditions, including arteriovenous malformations, uterine fibroids, and epistaxis. The term chemoembolization refers to selective intra-arterial delivery of chemotherapeutic agents in conjunction with particulate material for the purpose of embolizing arteries supplying blood to a tumor. Compared with traditional modes of drug delivery, chemoembolization increases local concentration and dwell time of the chemotherapeutic agent, augments tumor ischemia, and minimizes systemic toxic effects. In humans, the technique has shown encouraging results in the treatment of a variety of nonresectable tumors. The present report describes techniques for percutaneous bland arterial embolization and chemoembolization in dogs and goats and results of these techniques in 3 dogs and a goat. Bland arterial embolization was performed in 2 dogs and the goat. The goals of treatment included pain palliation, reduction of tumor growth, and control of hemorrhage, and each animal was considered to have benefited from the procedure on the basis of the preprocedural goals. Chemoembolization was performed in 1 dog for treatment of a nonresectable hepatocellular carcinoma. Unfortunately, this dog did not live long enough to identify any response to treatment. Results for animals studied illustrate the feasibility of bland arterial embolization and chemoembolization in veterinary patients and suggest that embolization may provide an alternative method of treatment for animals with inoperable lesions.
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PMID:Percutaneous arterial embolization and chemoembolization for treatment of benign and malignant tumors in three dogs and a goat. 1245 12


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