Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD44, a widely distributed integral membrane protein, has been implicated in tumor invasion and metastatic spread in some human carcinomas and lymphomas. In this study, 35 cases of hepatocellular carcinoma from 32 patients (11 cholangiocarcinomas, 9 hepatic adenomas, and 5 cases of focal nodular hyperplasia, a non-neoplastic lesion) were examined by immunohistochemical methods for expression of CD44. The mouse monoclonal antibody A3D8 was used on formalin-fixed, paraffin-embedded tissue; this antibody does not distinguish between standard CD44 and splice variants. Positive membrane staining was seen in 13 of 35 cases of hepatocellular carcinoma (12 of 32 patients), 8 of 11 cases of cholangiocarcinoma, and 1 of 9 cases of hepatic adenoma. The strongest staining for CD44 was seen in two cases of fibrolamellar carcinoma, but CD44 expression was otherwise not related to degree of tumor differentiation. All five cases of focal nodular hyperplasia were negative for CD44. In non-neoplastic liver, hepatocytes were negative; sinusoidal lining cells and portal lymphocytes were positive; bile ducts and proliferating bile ductules were focally positive in some cases. Anatomic stage at time of presentation was similar in both groups of patients, with most patients presenting with stage III or IV disease. A trend towards slightly longer survival in patients whose hepatocellular carcinomas were CD44 negative was noted. These results show that aberrant CD44 expression is present in a subset of hepatocellular carcinomas and in most cholangio-carcinomas. The relationship between CD44 expression and tumor spread is unclear in this group of tumors, but is unlikely to be a simple association between CD44 expression and metastatic potential.
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PMID:Expression of cell adhesion molecule CD44 in primary tumors of the liver: an immunohistochemical study. 906 75

One of the most important processes controlling cellular detoxification is carried out in the endoplasmic reticulum by glucuronidation, and most likely plays an important role in the defense mechanism against chemical-induced carcinogenesis. The human UDP-glucuronosyltransferase UGT1A locus encodes up to 12 unique transferases that are transcribed through selective exon sharing. Little is known about how this locus is regulated in human tissues. We present evidence that the UGT1A gene products are differentially expressed in normal liver tissue, which is composed of hepatocellular and biliary tissue, as well as in malignant and premalignant tumor tissue. In liver, UGT1A1, UGT1A3, UGT1A4, and UGT1A9 are expressed, and are all significantly down-regulated in malignant hepatocellular carcinoma and its premalignant precursor, hepatic adenoma, but not in benign focal nodular hyperplasia. UGT1A6, which is expressed abundantly in liver, is not significantly regulated in liver tumors. UGT1A10, a newly discovered UGT1A gene product, is expressed only in biliary and not hepatocellular tissue and is also significantly down-regulated in cholangiocellular carcinoma. Differential regulation between normal biliary tissue and tumor is also observed with UGT1A4. These findings implicate the regulation of the UGT1A locus as a putative early event in hepatocarcinogenesis that discriminates between benign and malignant hepatotumorigenesis and indicates that a complex mode of cellular control underlies the regulation of this locus.
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PMID:Differential down-regulation of the UDP-glucuronosyltransferase 1A locus is an early event in human liver and biliary cancer. 923 Feb 12

The long-term use of oral contraceptives (OCs) may be associated with an increased, though quite small, risk of certain types of liver disease: acute intrahepatic canalicular idiosyncratic cholestasis, benign hepatic tumors (hepatic adenoma, focal nodular hyperplasia, hemangiomas), hepatocellular carcinoma, peliosis hepatis, hepatic vein thrombosis, and portal vein thrombosis. Estrogens have lithogenic properties, as shown by a rise in biliary cholesterol secretion and cholesterol saturation index, yet no substantial increase in the risk of gallstones among estrogen users has been found. Hormone replacement therapy (HRT), given after oophorectomy or menopause, is not associated with clinically significant liver injury. Generally speaking, synthetic sex hormones should not be used in patients with acute and chronic liver disease. A trial of a low-dose estrogen can be instituted under close monitoring for adverse reactions and HRT preparations are not contraindicated in patients with chronic liver disease. Moreover, OCs and HRT can be prescribed quite safely following successful liver transplantation. The incidence of hepatic abnormalities in patients taking androgen hormones is very high. Liver adenomas, cholestasis, peliosis, nodular regenerative hyperplasia and, particularly, hepatocellular carcinoma may complicate long-term use of C17-substituted testosterone and anabolic steroids.
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PMID:Sex hormonal preparations and the liver. 967 67

Molecular cytogenetic approaches have been applied only rarely in the characterization of hepatocellular carcinoma (HCC). The aim in this study was to evaluate aberrations, particularly deletions, of specific chromosomal regions in HCC. Dual-color fluorescence in situ hybridization (FISH) was performed on intact nuclei from touch preparations of 17 HCCs and 1 hepatic adenoma. Each touch preparation was hybridized with a digoxigenin-labeled centromere probe and a biotin-labeled unique sequence probe from the same chromosome. This approach permitted the simultaneous evaluation of ploidy changes and chromosome arm deletions. Eight noncentromeric chromosome regions, 3p14, 4q21, 6q14, 6q21, 8p12, 8p22, 9p21, and 9p24 were selected for study on the basis of their having been implicated as tumor suppressor regions in HCC or other common types of carcinoma. Together with the 5 corresponding centromeric probes on chromosomes 3, 4, 6, 8, and 9, a total of 13 chromosome loci were evaluated. All cases of hepatocellular carcinoma showed at least one deletion or aneuploidy. The hepatic adenoma was all diploid. Chromosome 4q21 showed the highest rate of deletion (76.5%) and aneusomy (88%). The second and the third were chromosome 8p22 and 6q14, which showed 59% and 47% of deletion, respectively. A 4q21 deletion is also the most frequent single chromosome aberration. Prominent tumor heterogeneity and variable deletion patterns were noted. Interphase FISH was an efficient means for evaluating numerical and structural chromosome aberrations in HCCs. Most HCCs contained deletions of known tumor suppressor regions (4q and 8p), and a novel deletion hotspot was demonstrated on chromosome band 6q14.
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PMID:Investigation of chromosomal aberrations in hepatocellular carcinoma by fluorescence in situ hybridization. 1032 86

Primary hepatic tumours in children represent an heterogeneous group of neoplasms. Malignant tumours are more common (60% of primary liver tumours), but account for only 1.2-5% of all paediatric neoplasms. There are two main types of malignant tumour, those of epithelial origin, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), and the rarer mesenchymal tumours, e.g. rhabdomyosarcoma and undifferentiated sarcoma, (Weinberg AG, Finegold, MJ. Primary hepatic tumours of childhood. Hum Pathol 1983, 14, 512-532). Vascular tumours e.g. haemangioendotheliomas are the most common of the benign tumours followed by mesenchymal hamartoma and the rare hepatic adenoma and focal nodular hyperplasia. This article will concentrate on the malignant epithelial tumours.
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PMID:Liver tumours. 1053 78

Spontaneous hepatic bleeding is a rare condition. In the absence of trauma or anticoagulant therapy, hepatic hemorrhage may be due to underlying liver disease. The most common causes of nontraumatic hepatic hemorrhage are hepatocellular carcinoma and hepatic adenoma. Such hemorrhage can also occur in patients with other liver tumors, such as focal nodular hyperplasia, hemangiomas, and metastases. Other conditions associated with this entity include HELLP syndrome, amyloidosis, and miscellaneous causes. Imaging plays a significant role in the diagnosis and management of this potentially lethal entity. In the appropriate clinical setting, the diagnosis of a hemorrhagic liver lesion is suggested when a hyperechoic mass or a mass with hyperechoic areas is seen at ultrasonography, a hyperattenuating mass is seen at computed tomography (CT), or a mass with high-signal-intensity areas is seen at T1-weighted magnetic resonance (MR) imaging. The signal intensity of blood can be increased or decreased on MR images depending on when the hemorrhage is imaged. The presence and extent of commonly associated subcapsular hematomas and hemoperitoneum can be easily ascertained with CT. During the first 24-72 hours, acute hematomas are hyperattenuating on nonenhanced CT scans; later, they decrease in attenuation and sometimes develop a pseudocapsule.
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PMID:Imaging of nontraumatic hemorrhagic hepatic lesions. 1071 37

Hepatic steatosis is a common finding encountered during cross-sectional imaging examinations. This article reviews the imaging findings of hepatic steatosis as revealed by sonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy. Focal fatty sparing and focal hepatic steatosis are conditions that can create potential diagnostic challenges for the radiologist. The typical findings, distribution, and etiology of these focal processes are presented. In the setting of diffuse hepatic steatosis, hepatic mass lesions can be difficult to discern on both computed tomography and sonography, with reported decreased sensitivity and specificity of lesion detection. In such cases, magnetic resonance imaging may be the imaging procedure of choice for the detection and characterization of both hepatic steatosis and coexistent hepatic masses. Some hepatocellular neoplasms, particularly hepatic adenoma and well-differentiated hepatocellular carcinoma, can have intratumoral lipid. By demonstrating the lipid content of these masses, imaging can add specificity in characterizing them as hepatocellular in origin because nonhepatocellular neoplasms in general do not contain intracellular lipid.
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PMID:Imaging of hepatic steatosis. 1129 98

Hepatic adenoma (HA) and focal nodular hyperplasia (FNH) are two common non-malignant tumors of the liver. Genomic analysis on these benign lesions may shed light on the genetic mechanism underlying liver carcinogenesis. We used comparative genomic hybridization (CGH) to evaluate genomic changes in eight cases of HA and six cases of FNH, obtained by surgical procedures; the resulting chromosomal aberration profiles were analyzed together with their pathological and clinical manifestations. We found consistent chromosomal lesions associated with both non-malignant hepatic tumors. The overall genomic abnormalities in HA and FNH were much less obvious than those in hepatocellular carcinoma (HCC). Among these limited changes, frequent gains were located on chromosomal arms 1q (50%), 17q (50%), 1p (38%), and 11q (38%) in HA, and on 11q (50%), 9q (33%), 17q (33%), and 22q (33%) in FNH. Gains outnumbered losses, and HA contained more CGH abnormalities than did FNH. Interestingly, CGH alteration hotspots found in HA, but not in FNH, appeared largely to coincide with common genomic lesions of cancerous HCC, suggesting an interesting relationship along the tumorigenesis pathway of HA and HCC.
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PMID:Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. 1220 77

P-Glycoprotein and C-MOAT are important hepatic transport proteins which play a role in handling anticancer drugs. Hepatocellular carcinoma is a common hepatic malignancy that is relatively resistant to chemotherapeutic drugs. We therefore studied the expression of these two transport proteins in liver sections from hepatocellular carcinoma by immunohistochemistry and compared the reactivity to that in other liver conditions, including cirrhosis and dysplasia. We studied 53 sections from 17 liver specimens and found that the majority of samples stained positively for both P-glycoprotein and C-MOAT; however, the degree of staining was less in HCC and hepatic adenoma than in liver adjacent to HCC or in cirrhosis or dysplastic nodules. HCC with a compact pattern had less staining than those with acinar, scirrhous, or trabecular patterns. The location of both P-glycoprotein and C-MOAT staining was a function of the liver lesion present. Thus, most tissues without hepatocellular carcinoma showed foci of globular canalicular staining, whereas a delicate linear pattern of canalicular staining was most common overall. We conclude that expression of P-glycoprotein and C-MOAT, as detected by qualitative immunohistochemical evaluation are little affected by the development of HCC and therefore are probably of little clinical significance for management of malignancy.
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PMID:Expression of P-glycoprotein and C-MOAT in human hepatocellular carcinoma: detection by immunostaining. 1245 78

Color Doppler sonography (CDS--spectral, color and power), harmonic imaging techniques (THI, PHI), possibility of 3D analysis of picture, usage of contrast agents, have raised the values of ultrasound as a diagnostic method to a very high level. THI--non-linear gray scale modality, is based on the processing of higher reflected frequencies, that has improved a picture resolution, which is presented with less artifacts and limiting effects of obesity and gases. Ultrasound contrast agents improve analysis of micro and macro circulation of the examined area, and with the assessment of velocity of supply in ROI (wash in), distribution and time of signal weakening (wash out), are significantly increasing diagnostic value of ultrasound. Besides the anatomical and topographic presentation of examined region (color, power), Color Doppler sonography gives us haemodynamic-functional information on vascularisation of that region, as well as on pathologic vascularisation if present. Avascular aspect of a focal pathologic lesion corresponds to a cyst or haematoma, while coloration and positive spectral curve discover that anechogenic lesions actually represents aneurysms, pseudoaneurysms or AVF. In local inflammatory lesion, abscess in an acute phase, CDS shows first increased, and then decreased central perfusion, while in a chronic phase, a pericapsular vascularisation is present. Contribution of CDS in differentiation of hepatic tumors (hemangioma, HCC and metastasis) is very significant. Central color dots along the peripheral blood vessels and the blush phenomenon are characteristics of capillary hemangioma, peritumoral vascular ring "basket" of HCC, and "detour" sign of metastasis. The central artery, RI from 0.45 to 0.60 and radial spreading characterize FNH. Hepatic adenoma is characterized by an intratumoral vein, and rarely by a vascular hallo. Further on, blood velocity in tumor defined by Color Doppler, distinguishes malignant from benign lesion, where 40 cm/s is a rough border value. Values of DPI (Doppler perfusion index) over 0.3 and tumor index over 1.0 characterize primary, and lower values characterize secondary liver malignancies. In differentiation of benign and malign tumors of kidneys, besides the aspect of vascularisation, the maximal frequency altitude in tumor artery (the limit around 2.5 kHz) is very important. However, peripheral and penetrating blood vessels are most usually seen in RCC, less often in AML and bigger oncocytomas. CDS with contrast agent is very useful in making differential diagnosis of the focal lesions with 95% specificity for some lesions.
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PMID:[Color Doppler sonography of focal abdominal lesions]. 1513 25


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