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)

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2-acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin-dependent kinase inhibitor p27(kip1) compared to the non-treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two-step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC.
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PMID:Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide. 1790 Mar 9

In digestive oncology, the most frequent indication for FDG PET, in our experience and as reported in the literature, is the localisation of recurrent colorectal cancer. This molecular imaging method has also been shown to be clinically useful in various other settings, especially for preoperative staging, for colorectal, esophageal, gastric, pancreatic, hepatic and biliary cancers. We also report on current PET practice in two particular cancers: hepatocellular carcinoma, for which other tracers, including fluoromethylcholine-(18F), are being currently evaluated, and gastrointestinal endocrine tumours, which are included in the recent French marketing authorisation of fluoroDOPA-(18F) and which are also potential targets for radiolabelled somatostatin analogues for PET imaging.
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PMID:[PET and digestive cancers]. 1795 Oct 24

Gastro-entero-pancreatic tumors (GEP) contain, in their majority, somatostatin receptors. In-111-DTPA-phenyl-pentetreotide has been proved to have high affinity for somatostatin receptors subtypes 2, 3 and 5. The aim of the present study was to evaluate the utility of (111)In-DTPA-O somatostatin receptors' scintigraphy (SRS) in the diagnosis of suspected GEP. Thirty-five consecutive patients (17 males and 18 females-mean age 57.9+/-7.6) with GEP as a possible diagnosis were enrolled in the study. The primary diagnosis was diarrheic syndrome susceptive of intestinal carcinoid tumor (24 patients), carcinoid of the rectum (2 patients), adenocarcinoma of the pancreas (2 patients), insulinoma (2 patients), gastrinoma (3 patients) and hepatocellular carcinoma (2 patients). All patients were submitted to computerized tomography (CT) of the thorax and the abdomen and pentetreotide SRS was performed 4 h (total body and SPET acquisition) and 24 h (planar views), post iv injection of 185 MBq of the radiolabeled compound. Results showed: Four of the patients were false positive diagnosed as having inflammatory intestinal disease and gallbladder dilatation. At the time of the evaluation, 14 of the remaining patients were free of disease, concerning secondary involvement. In these cases, CT and SRS studies matched each other, with no pathological lesions and no abnormal accumulation of the radiopharmaceutical respectively. Concerning pathological cases, only one SRS study in a patient with rectum carcinoid was normal, with liver lesions in the CT study. These lesions were considered as subtypes 2, 3 and 5 somatostatin receptors negative. SRS revealed three lesions more than CT. According to these results, sensitivity of SRS study was 93.8% and specificity 86.9%. The authors believe that molecular imaging of somatostatin receptors, is a sensitive method for the evaluation of patients with GEP tumors. However, in cases of intestinal disease, we should be aware of false positive results due to inflammatory processes and the presence of lymphocyte infiltration.
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PMID:[Indium-111-DTPA-phenyl-pentetreotide somatostatin receptors' scintigraphy in the evaluation of patients with suspected gastro-entero-pancreatic tumors. Comparison with computerized tomography]. 1808 69

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.
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PMID:Mechanisms of action and resistance of somatostatin analogues for the treatment of hepatocellular carcinoma: a message not well taken. 1827 5

As there is no effective systemic therapy for advanced hepatocellular carcinoma (HCC), we investigated the presence of receptors for somatostatin, bombesin and luteinizing hormone-releasing hormone (LHRH) in SK-Hep-1 human hepatic carcinoma and the effects of cytotoxic analogs of somatostatin (AN-238), bombesin (AN-215) and LHRH (AN-207) on the growth of this tumor. Nude mice bearing SK-Hep-1 HCCs were treated with AN-238, AN-215, AN-207 and their combination, or cytotoxic radical 2-pyrrolinodoxorubicin (AN-201). Tumor growth reduction was determined and cell proliferation characteristics and apoptosis were studied by histologic analysis. The expression of receptors for somatostatin, bombesin and LHRH was investigated by radioreceptor assays and immunohistochemistry. High-affinity binding sites for somatostatin, bombesin and LHRH were detected in SK-Hep-1 cancers. All three cytotoxic peptide analogs inhibited growth of SK-Hep-1 tumors and decreased the cell proliferation rate. Combination therapy with two or three cytotoxic analogs resulted in the strongest tumor inhibition. Receptors for somatostatin, bombesin and LHRH are expressed in SK-Hep-1 human HCC. Cytotoxic peptide analogs targeted to these receptors inhibit growth of this tumor. Targeting to multiple receptors enhances the efficacy of therapy. The results of our study encourage additional experimental investigations to permit the introduction of these cytotoxic analogs into clinical trials.
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PMID:Therapy of experimental hepatic cancers with cytotoxic peptide analogs targeted to receptors for luteinizing hormone-releasing hormone, somatostatin or bombesin. 1845 45

Tyr(3)-octreotide (TOC), a somatostatin analogue, is reversibly lipidized for passive delivery to the liver with the aim of increasing its association with hepatocytes. The reversibly lipidized TOC (REAL-TOC) was formed by the conjugation of the N-palmitoyl cysteinyl moiety to the cysteinyl residues of reduced TOC through disulfide linkages and characterized by matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) analysis. The measured mass of REAL-TOC (M+H)(+) is 1752.31 Da (calculated mass: 1752.78), confirming that two molecules of N-palmitoyl cysteines are linked to TOC via disulfide bonds. TOC and REAL-TOC were radioiodinated and administered to mice. Their biodistribution and intrahepatic distribution were subsequently investigated. The area under the curve (AUC) of (125)I-REAL-TOC in the liver was 3.8-fold greater than that of (125)I-TOC, with 20.5% and 5.8% of the injected dose (ID)/g of (125)I-REAL-TOC remaining in the liver at 2 and 24h post injection, respectively. Within the liver, TOC was primarily distributed to parenchymal cells (PC). Nevertheless, TOC was quickly excreted out and only 2.4% ID per 100mg protein remained in the PC at 2h post injection. (125)I-REAL-TOC was retained in PC for up to 2h with a constant concentration of around 6% ID/100mg protein. (125)I-REAL-TOC was also highly associated with nonparenchymal cells (NPC) at significantly higher levels than (125)I-TOC at 10min, 1h and 2h post injection. Since somatostatin analogues have been evaluated for treating late-stage hepatocellular carcinoma (HCC), the reversibly lipidized conjugates may possess enhanced therapeutic efficacy due to the liver-targeting effect.
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PMID:Reversible lipidization of somatostatin analogues for the liver targeting. 1861 43

Hepatocellular carcinoma (HCC) is a hypervascular tumor, and tumor progression and prognosis is associated with angiogenesis. Extracellular matrix remodeling and inflammation play important roles in hepatocarcinogenesis. Some ingredients of extracellular matrix such as endostatin and sulfated polysaccharide, some immunomodulatory agents and cox-2 inhibitor suppress the angiogenesis of HCC. Because vasculogenic mimicry is associated with high tumor grade, some differentiation agents are used to inhibit antiagiogenesis. Besides suppressing the proliferation directly, somatostatin inhibits angiogenesis to suppress growth indirectly. Copper chelator prevents copper from functioning as a cofactor in angiogenesis. The renin-angiotensin system is frequently activated in patients with chronic liver diseases. Perindopril, an angiotensin converting enzyme inhibitor, inhibits angiogenesis by reducing vascular endothelial growth factor (VEGF) production. Kinase inhibitors of VEGF and epidermal growth factor receptors are expected to be of benefit for some patients. Following transarterial embolisation and/or resection, antiangiogenic therapy could prevent the recurring and metastasis. Hypoxia enhances the proliferation, suppresses the differentiation and apoptosis, and induces multidrug resistance of HCC. Because antiangiogenic therapies induce hypoxia, it should be borne in mind the side affects of antiangiogenic therapy. Because long-acting antiangiogenent are needed to control cancer, it needs more clinical studies to confirm the drug resistance of antiangiogenetic therapy.
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PMID:New strategy of antiangiogenic therapy for hepatocellular carcinoma. 1899 74

Occurrence of second primary tumors and metastasis remains the major obstacles to prolonged survival of patients with primary hepatocellular carcinoma (HCC). A somatostatin analogue, octreotide, has been previously reported to inhibit the growth of human HCC xenografts in nude mice through its anti-angiogenic activity. It is therefore important to investigate whether octreotide could prevent second primary hepatomas or distant metastasis following resection of primary HCC. In this study, nude mice, bearing the human HCC xenografts with highly metastatic potential (LCI-D20) in the left liver lobe, underwent tumor resection, and received intraperitoneal administration of octreotide or saline as a control for 35 consecutive days. Compared with the control group, octreotide at the doses of 100 and 200 microg/kg/day significantly inhibited the growth (P < 0.001 and P < 0.001, respectively) and incidence of second primary tumors (P = 0.016 and P = 0.001, respectively), decreased lung metastasis (P < 0.001 and P < 0.001, respectively), and prolonged the life span (P = 0.029 and P = 0.006, respectively). Moreover, intratumoral angiogenesis quantified by microvessel density as well as serum and tissue vascular endothelial growth factor (VEGF) levels were considerably decreased in octreotide-treated animals compared to the control animals. These findings suggest that octreotide may prevent the occurrence of second primary hepatomas and lung metastasis after resection of primary HCC, which may be partially attributed to down-regulation of VEGF and subsequent reduction in tumor angiogenesis. Octreotide administration may be useful as an adjuvant therapy to improve survival of patients with HCC.
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PMID:A somatostatin analogue, octreotide, inhibits the occurrence of second primary tumors and lung metastasis after resection of hepatocellular carcinoma in mice. 1947 72

Hepatocellular carcinoma (HCC) is increasing worldwide and is the third cause of cancer-related death. HCC develops in a pre-neoplastic organ, the cirrhotic liver. Therefore, chemoprevention could play a role in the management of HCC. We have previously shown that lanreotide, a somatostatin analogue, inhibits the development of "foci of altered hepatocytes", which represent very early neoplastic changes in rat liver. Here we induced bona fide HCC by means of a different chemically induced model that is known to lead to significant fibrosis before HCC appearance. Lanreotide was given from the beginning of the experiment in one group and from the time when significant fibrosis was present in the second group. Lanreotide decreased the frequency of occurrence of HCC in both groups. In both groups, significant decreases in hepatocyte proliferation and inhibition of fibrosis were demonstrated. When given at the start of the experiment, lanreotide dramatically decreased levels of angiogenic factors and enhanced apoptosis. Further work on the anti-tumoral effect of lanreotide is called for to assess the mechanistic relationships of its anti-proliferative and anti-angiogenic actions on liver neoplastic cells.
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PMID:Efficacy of lanreotide in preventing the occurrence of chemically induced hepatocellular carcinoma in rats. 1987 7

To determine the variety of chemotherapy drugs administrable for malignant pancreatic neoplasm as a result of typification with endoscopic ultrasonography-fine needle aspiration (EUS-FNA). A retrospective assessment, in one center, over a period of 1 year. Only malignant pancreatic neoplasm diagnosed by EUS-FNA was recorded. Benign (serous cystic neoplasm) and potentially malignant lesions (mucinous cystic neoplasm and intraductal papillary-mucinous neoplasm) were excluded. Medical data were recorded and Oncological Pharmacy records were studied. Ductal adenocarcinoma were detected in 17 patients (N = 17/22), 2 of them with adenocarcinoma in signet ring and 1 with mucinous adenocarcinoma. The primary therapies used were as follows: Whipple pancreaticoduodenectomy (3), biliary stent by endoscopic retrograde cholangiopancreatography (3), radiological transhepatic percutaneous stent (2), intestinal bypass (2), and a gastric stent (1). The adjuvant drugs used were gemcitabine (10), erlotinib (3), and cetuximab (1), and also radiotherapy was used (1). An unresectable squamous cell carcinoma (N = 1) of the tail was detected, and gemcitabine + vinorelbine + fluorouracil + cisplatin used. Nonfunctioning neuroendocrine tumors were seen in 3 (N = 3) cases and long-acting somatostatin analogues were used (1); the remaining 2 patients showed resectable tumors and were resected accordingly. A metastasis to the pancreatic head in a hepatocellular carcinoma was found in 1 patient (N = 1), allowing specific treatment with sorafenib. Histopathologic analysis with EUS-FNA implies a variety of different treatments. Optimal management was achieved as a result of improved diagnosis, with the advent of new molecular genetic diagnostic methods facilitating the design of specific new therapy and neoadjuvant targeting strategies.
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PMID:Types of pancreatic cancer in EUS-FNA and chemotherapy. 2001 88


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