Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A survival experiment is described in which 1920 Wistar rats were used. These rats were injected intravenously with different quantities and different alpha-doses of Thorotrast. The following observations were made: The distribution of Thorotrast in the liver of the experimental animals is similar to that in human livers. Liver fibrosis and liver cirrhosis are rarely seen in experimental animals. The liver cell carcinomas, intrahepatic bile duct carcinomas and haemangiosarcomas that developed in the liver of the rats showed an identical biology and morphology with those seen in corresponding Thorotrast tumours in human patients. One particular tumour type that occurred in the liver of the rats probably represents a Kupffer cell sarcoma: the tumour cells show a positive peroxidase reaction and the metastases contained Thorotrast. Unlike human Thorotrast liver tumours, rat liver tumours include benign tumours such as liver cell adenomas and intrahepatic bile duct adenomas. The animals of the control group did not develop these benign liver tumours. The total frequency of the liver and spleen tumours in the trial groups receiving 230Th enriched Thorotrast was dependent on the dose given. The relationship between dose and effect was almost linear. The volume of the injected Thorotrast quantity, given a constant dose rate, seems to have only a slight influence on the number of tumours.
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PMID:Recent results of the German Thorotrast study--pathoanatomical changes in animal experiments and comparison to human thorotrastosis. 686 8

The role of thymidine phosphorylase (TP), an angiogenic factor, in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to clarify the significance of TP in HCC. Thirty-seven patients with HCC, who underwent hepatectomy, were included. The TP activity in both cancerous and non-cancerous parts of livers were measured by an enzyme-linked immunosorbent assay. Another 11 patients without HCC were used to evaluate the TP activity in the non-cancerous parts of livers. Both the cancerous and non-cancerous TP activities were clinico-pathologically investigated with special reference to the multicentric occurrence of HCCs and the degree of liver fibrosis; consisting of normal, fibrosis and cirrhosis. The TP activity in the cancerous part was 94.6 +/- 70.2 U/mg protein, while that in non-cancerous parts of the liver was 80.9 +/- 48.8 U/mg protein. No significant difference was observed. The TP activity in the cancerous part did not correlate with any clinicopathological variables, such as tumor differentiation, portal vein invasion, intrahepatic metastases and prognosis. However, the TP activity in the non-cancerous parts of the liver correlated with the degree of fibrosis (normal/fibrosis/cirrhosis = 34:74:90 U/ mg protein, respectively). Furthermore, regarding the correlation between TP activity in the non-cancerous parts and the simultaneously multicentric occurrence of HCC, the TP activity in the multicentric group (n = 8; 121 U/mg protein) was significantly higher than that in the non-multicentric group (n = 29; 70 U/mg protein). The TP activity in the non-cancerous parts increased in proportion to the degree of liver fibrosis. Furthermore, it is suggested that the higher TP activity in the non-cancerous part is related to the multicentric occurrence of HCCs.
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PMID:The significance of thymidine phosphorylase activity in hepatocellular carcinoma and chronic diseased livers: a special reference to liver fibrosis and multicentric tumor occurrence. 1069 93

It has become more and more clear in recent decades that the plasminogen activation system, which includes urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), plasminogen activator inhibitor (PAI)-1 and PAI-2, plays a very important role in the aggressiveness of cancer. Using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), the expression of these four components of the uPA system was analyzed in 19 cases of hepatocellular carcinoma (HCC) and 18 cases of the adjacent non-cancer tissues which all had chronic active hepatitis with liver fibrosis or liver cirrhosis. Four cases of normal liver tissues, as controls for immunohistochemical stains, were obtained from the hepatectomized liver of patients with metastatic cancer in the liver. The positive rates of uPA, uPAR, PAI-1 and PAI-2 for immunohistochemical stains in cancer tissues were 78.9, 68.4, 57.9 and 31.6%, respectively. Positive signals were mainly distributed in the cytoplasm of the cancer and in stromal cells. Moreover, the strong stains were chiefly located in the invasive front of the cancer cells. No specific stain was detected in four cases of normal liver tissues. In ELISA, there were significant differences between cancer and non-cancer tissues in concentration of uPA, uPAR and PAI-1 (P < 0.0003, 0.0024 and 0.01, respectively), but there was no significant difference in that of PAI-2 (P = 0.37). These results suggest that uPA, uPAR and PAI-1 are related to invasion of HCC.
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PMID:Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 and -2 in hepatocellular carcinoma. 1084 28

Authors describe in the case report a development of the primary hemochromatosis. At the time of the diagnosis in 1979 from organ complication the liver fibrosis and secondary diabetes mellitus were presented. Patient was treated with the venepunctions and with desferoxamine. In the 1998 the primary hepatocellular tumor was found and resected. Instead of the chemotherapy occurred the progression of the disease with multiple metastases and liver insufficiency and 66-years old patient died 19 months after surgery in the 20th year of the disease.
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PMID:[Primary hemochromatosis]. 1257 61

The liver produces a large amount of lymph, which is estimated to be 25 to 50 % of lymph flowing through the thoracic duct. The hepatic lymphatic system falls into three categories depending on their locations: portal, sublobular, and superficial lymphatic vessels. It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains through sublobular and capsular lymphatic vessels. The hepatic lymph primarily comes from the hepatic sinusoids. Our tracer studies, together with electron microscopy, show many channels with collagen fibers traversing through the limiting plate and connecting the space of Disse with the interstitial space either in the portal tracts, or around the sublobular veins. Fluid filtered out of the sinusoids into the space of Disse flows through the channels traversing the limiting plate either independently of blood vessels or along blood vessels and enters the interstitial space of either portal tract or sublobular veins. Fluid in the space of Disse also flows through similar channels traversing the hepatocytes intervening between the space of Disse and the hepatic capsule and drains into the interstitial space of the capsule. Fluid and migrating cells in the interstitial space pass through prelymphatic vessels to finally enter the lymphatic vessels. The area of the portal lymphatic vessels increases in liver fibrosis and cirrhosis and in idiopathic portal hypertension. Lymphatic vessels are abundant in the immediate vicinity of the hepatocellular carcinoma (HCC) and liver metastasis. HCCs expressing vascular endothelial growth factor-C are more liable to metastasize, indicating that lymphangiogenesis is associated with their enhanced metastasis.
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PMID:Lymph circulation in the liver. 1848 10

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.
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PMID:[Diagnosis and treatment of colorectal liver metastases - workflow]. 1856 94

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further evaluated in a clinical study of prostate-, lung- and breast-cancer patients stratified according to skeletal metastases. A technically robust ELISA assay specific for a MMP-2, -9 and -13 neo-epitope was produced and seen to be statistically elevated in BDL rats compared to baseline levels as well as significantly elevated in CCL4 rats stratified according to the amount of total collagen in the livers. CO1-764 levels also correlated significantly with total liver collagen and type I collagen mRNA expression in the livers. Finally, the CO1-764 marker was not correlated with skeletal involvement or number of bone metastases. This ELISA has the potential to assess the degree of liver fibrosis in a non-invasive manner.
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PMID:A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M). 2198 80

The lymphatic system is part of the circulatory system and plays a key role in normal vascular function. Its failure plays a crucial role in the development and maintenance of various diseases including liver diseases. Lymphangiogenesis (the growth of lymphatic vessels) and changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. Therefore, how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases are largely unknown. This article summarizes: 1) the lymphatic vascular system; 2) its role in liver tumors, liver fibrosis/cirrhosis and portal hypertension; and 3) its role in ascites formation.
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PMID:The lymphatic vascular system in liver diseases: its role in ascites formation. 2383 33

Excessive ethanol consumption is one of the main causes of liver fibrosis. However, direct effects of ethanol exposure on endothelial cells and their contribution to fibrogenesis and metastasis were not investigated. Therefore we analysed whether ethanol directly affects endothelial cells and if this plays a role during fibrogenesis and metastasis in the liver. Murine and human endothelial cells were exposed to ethanol for up to 72 hours. In vitro, effects on VEGF, HIF-1alpha, PECAM-1, and endothelial cell functions were analysed. In vivo, effects of continuous liver damage on blood vessel formation and metastasis were analysed by PECAM-1 immunohistochemistry. Ethanol increased HIF-1alpha and VEGF levels in murine and human endothelial cells. This resulted in enhanced intracellular signal transduction, and PECAM-1 expression as well as tube formation and wound healing. In vivo, toxic liver damage increased angiogenesis during fibrogenesis. Metastasis was also enhanced in fibrotic livers and located to PECAM-1 positive blood vessels compared to nonfibrotic mice. In conclusion, ethanol had strong effects on endothelial cells, which--at least in part--led to a profibrotic and prometastatic environment mediated by PECAM-1. Blockade of increased PECAM-1 expression could be a promising tool to inhibit fibrogenesis and metastasis in the liver.
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PMID:Toxic damage increases angiogenesis and metastasis in fibrotic livers via PECAM-1. 2473 40

An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors.
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PMID:Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis. 2684 53


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