Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous antiangiogenic reagents discovered to date. Its antiangiogenic potential in neoplastic disease remains unclear. In this study, we investigated antiangiogenic property of PEDF in hepatocellular carcinoma (HCC), a typical hypervascular tumor. In HCC cell lines, constitutive messenger RNA and protein expression of PEDF varied. Genomic DNA encoding the PEDF gene was the same in the cell lines examined by Southern blotting. In chemically induced hypoxic conditions, secreted PEDF protein was suppressed in contrast to elevation of vascular endothelial growth factor protein. When PEDF was overexpressed by gene transfer, proliferation and migration of endothelial cells were inhibited in conditioned media derived from all HCC cell lines. However, the serum concentration of PEDF, as measured by enzyme-linked immunosorbent assay, was decreased in patients with cirrhosis or HCC complicated by cirrhosis compared to healthy volunteers and patients with chronic hepatitis. According to the endothelial cell proliferation assay, the serum PEDF of patients with HCC had antiangiogenic activity. Moreover, intratumoral injection of a PEDF-expressing plasmid in athymic mouse models caused significant inhibition of preestablished tumor growth. In conclusion, PEDF plays a role in the angiogenic properties of HCC. Reduction of serum PEDF concentration associated with the development of chronic liver diseases may contribute to the progression of HCC. In addition, gene therapy using PEDF may provide an efficient treatment for HCC.
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PMID:Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma. 1523 9

Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.
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PMID:[Endoscopic mucosal resection for early esophageal cancer with esophageal varices]. 1524 10

A few years ago surgical resection was the only treatment modality for primary and metastatic liver tumors. However, most of the liver tumors are diagnosed at advanced stage and are unresectable. Criteria for unresectability are: uncontrolled extrahepatic disease, extensive intrahepatic tumor growth, insufficient remnant liver volume and severe co-morbid disease. Several therapeutic strategies have been developed to deal with primarily unresectable tumors. A downstaging ("downsizing") of hepatocellular carcinoma (HCC) can be reached by transarterial chemoembolisation (TACE) or local tumor ablation using ethanol injection, cryosurgery and radiofrequency. Preoperative unilateral portal vein embolization resulting in hypertrophy of the remnant liver volume permits to resect some patients with former unresectable liver tumors. Furthermore, liver transplantation is an option for patients with early stage HCC and liver cirrhosis. Preoperative downstaging of colorectal metastases can be achieved with neoadjuvant chemotherapy, whereas TACE, ethanol injection and liver transplantation are no established options for these patients. So far, there are no standardized guidelines for the treatment of patients with unresectable primary or metastatic liver tumors. In this review we aim to describe the different approaches suggested in the literature and to present our algorithms for the management of patients with liver tumors.
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PMID:[Surgical therapy of liver tumors: resection vs. ablation]. 1613 70

The X protein (HBx) of hepatitis B virus (HBV) plays important roles in hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) during viral infection. In this study, we demonstrated that co-transfection of mouse embryo fibroblasts (STO) with HBx and activated Ras triggered apoptotic cell death, while HBx or activated Ras individually failed to induce apoptosis. In addition, STO cells were able to form colonies on soft agar after transfected with HBx or Ras, and cells co-transfected with both genes failed to transform. Moreover, nude mice injected with STO cells carrying either HBx or Ras could develop tumor, but tumor growth was inhibited by the injection of both STO cells harboring HBx and carrying Ras. These results suggested that HBx plays a role as a tumor inducer and stimulates neoplastic transformation of normal cells, but shifts its function to the induction of apoptosis in association with Ras.
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PMID:Functional switch of viral protein HBx on cell apoptosis, transformation, and tumorigenesis in association with oncoprotein Ras. 1656 76

The Authors take a hint from recent observation of two patients with hepatocellular carcinoma presenting with obstructive jaundice to analyse the litterature and their clinical cases. They conclude that in the evolution of hepatocellular carcinoma can be found "early" or "late" jaundice. The latest is hepatocellular and/or obstructive jaundice and it is harbinger of fatal prognosis because of a big hepatocelluar carcinoma that has invaded biliary tree and/or liver failure by concomitant cirrhosis. The "early" jaundice appears when the tumor is still small and it is always obstructive due to intrabile duct tumor growth. This kind of jaundice has a good prognostic meaning because, together with imaging techniques, permits an early diagnosis of the hepatocellular carcinoma necessary for satisfactory palliation or occasional cure.
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PMID:[Obstructive jaundice caused by hepatocellular carcinoma]. 1682 15

Hepatocellular carcinoma (HCC) recurs in 10% to 60% of the patients after liver transplantation (OLT) and is associated with increased mortality. The average time to recurrence ranges from 1 to 2 years following OLT, and the median survival from the time of diagnosis is about 1 year. We report a case of a 69-year-old man who underwent OLT for hepatitis C virus-related cirrhosis with HCC, and was diagnosed with recurrent HCC 6.5 years after OLT. Biopsies from the initial and recurrent tumors showed a well-differentiated HCC with foci of clear cell pattern. The patient was still alive and asymptomatic 32 months after the diagnosis despite extensive tumor burden. He expired 9 years, 9 months after OLT and 3 years, 2 months after the detection of recurrence. In conclusion, HCC may recur more than 6 years after OLT and may exhibit an indolent course. This case illustrates the highly variable rate of tumor growth and progression post-OLT. The impact of this information on the need for long-term surveillance for recurrent HCC post-OLT remains to be determined.
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PMID:Very late recurrence of hepatocellular carcinoma after liver transplantation: case report and literature review. 1711 21

Hepatocellular carcinoma (HCC) accounts for more than 80% of all primary liver cancers and is one of the most common malignancies worldwide. Most patients with HCC also suffer from concomitant cirrhosis, which is the major clinical risk factor for hepatic cancer and results from alcoholism, infection with the hepatitis B or hepatitis C virus, and other causes. HCC is often diagnosed at an advanced stage, when established treatment options provide limited benefit. Effective treatment for HCC includes liver resection and liver transplantation. Under most clinical circumstances, those options provide a high rate of complete response and are thought to improve survival. Partial hepatectomy is the therapy of choice in patients with HCC and a noncirrhotic liver. Usually, liver transplantation is not indicated for such patients, although in individual cases, transplantation may be considered. For most cirrhotic patients who fulfill the Milan criteria, liver transplantation is the ultimate treatment option. Liver transplantation restores liver function and ensures the removal of all hepatic foci of tumor as well as tissue with a high oncogenic potential for early tumor recurrence. Because of the present lack of available organs, living-donor liver transplantation (LDLT) is an increasingly popular alternative. LDLT enables recipients to avoid a long pretransplantation waiting time and increases the number of livers available for transplantation. It is also the most effective approach to reducing the dropout rate. Strategies to reduce tumor growth in patients who are awaiting liver transplantation are important to ensure that those individuals continue to fulfill the Milan criteria for transplantation. For that purpose, using ablative techniques or chemoembolization to control local tumor growth is useful.
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PMID:Liver resection and transplantation in the management of hepatocellular carcinoma: a review. 1723 57

Liver transplantation has emerged as an optimal treatment for stage I and II hepatocellular carcinoma for patients with underlying cirrhosis as it provides a treatment for the underlying liver disease as well as a reduced incidence of recurrent cancer. The current system of organ allocation in the United States allows an opportunity for liver transplantation for patients with tumor burden within the Milan criteria (a single tumor 2-5 cm or up to 3 lesions with none >3 cm). Outcomes of patients receiving transplants within these criteria approach outcomes for patients receiving transplants for all indications (85.9%, 74.8%, and 64.1% actuarial survival at 1, 3, and 5 years, respectively, for those with HCC receiving transplants compared with 82%, 73%, and 67% for the entire cohort). Transarterial chemoembolization, radiofrequency ablation, and other pretransplant treatment modalities aimed to slowing tumor growth for patients on a transplant waiting list are commonly used, although the impact on pretransplant disease progression or posttransplant survival remains uncertain. There is continued controversy over expanding patient selection criteria, in particular for those who have undergone downstaging of tumors. In addition, the role of certain immunosuppressive agents such as sirolimus in the reducing HCC recurrence posttransplant remains unclear.
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PMID:Liver transplantation for hepatocellular carcinoma. 1839 14

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-alpha signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-beta signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial-mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.
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PMID:Role of platelet-derived growth factors in physiology and medicine. 1848 17

Human hepatocellular carcinoma (HCC) often arises from a background of liver cirrhosis. Therefore, in order to develop therapeutic strategies for HCC, an animal model bearing multifocal liver tumors accompanied by liver cirrhosis is a preferred experimental setting. In this study, we developed a rapid and reproducible method for generating such a model in rats by weekly administration of diethylnitrosamine (DEN) at doses based on body weight (BW). By adjusting the duration of administration of DEN, the animals could be induced to develop HCC alone, or HCC and liver cirrhosis simultaneously. The latter model was used for evaluating the therapeutic effects of adenoviral delivery of interferon-alpha (IFN-alpha). Our results demonstrated that targeting of IFN-alpha expression to the liver significantly reduced liver tumor volume and ameliorated liver cirrhosis. Mechanistic studies revealed that IFN-alpha gene therapy induced immunomodulatory, antiproliferative, and proapoptotic activities that were effective in the control of tumor growth, and reduced the expressions of transforming growth factor-beta (TGF-beta) and tissue inhibitor of metalloproteinase-1 (TIMP-1), leading to amelioration of liver cirrhosis. These results suggest that IFN-alpha gene therapy is a promising strategy to treat HCC patients who have concomitant liver cirrhosis.
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PMID:Dual therapeutic effects of interferon-alpha gene therapy in a rat hepatocellular carcinoma model with liver cirrhosis. 1866 56


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