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)

Synthesis of the iron-storage protein ferritin is thought to be regulated at the translational level by the cytosolic content of chelatable iron. This response to iron is regulated by the iron-modulated binding to ferritin mRNAs of a repressor protein, the iron regulatory element-binding protein. From measurements made in a cell-free system, regulation of the iron regulatory element-binding protein has been recently suggested to involve direct interaction with hemin. The following observations on the synthesis of ferritin and of heme oxygenase (HO), the heme-degrading enzyme, in rat fibroblasts or hepatoma cells lead us to conclude that chelatable iron is a direct physiological regulator of ferritin synthesis in intact cells: (i) the inhibitor of heme degradation, tin mesoporphyrin IX, reduces the ability of exogenous hemin to induce ferritin synthesis but enhances HO synthesis; (ii) the iron chelator desferal suppresses the ability of hemin to induce synthesis of ferritin but not of HO; (iii) the heme synthesis inhibitor succinylacetone does not block iron induction of ferritin synthesis; (iv) there is no apparent relationship between the ability of various metalloporphyrins to inactivate the iron regulatory element-binding protein in cell-free extracts and their capacity to induce ferritin synthesis in intact cells; (v) administered inorganic iron significantly induces the synthesis of ferritin but not of HO; (vi) addition of delta-aminolevulinic acid to stimulate heme synthesis represses the ability of inorganic iron to induce ferritin synthesis while activating HO synthesis. Taken together, our results demonstrate that (i) release of iron by HO plays an essential role in the induction of ferritin synthesis by heme and (ii) chelatable iron can regulate ferritin synthesis independently of heme formation.
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PMID:Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. 199 60

Liver scanning with radiocolloids is an important method to determine the presence, the position and the size of space-occupying lesions in the liver. Unfortunately, this information is nonspecific and it is not possible to distinguish between tumours, abscesses or cysts. Thirty-six patients in whom a definite diagnosis of hepatoma, amoebic liver abscess or echinococcus cyst had been made were examined with technetium-99m tin colloid and indium-113m chloride. The amoebic liver abscesses were avascular, showed a hyperaemic area surrounding the abscess and appeared smaller on the indium than on the technetium scan. The hepatomas showed greater vascularity and absence of the hyperaemic area. Cysts were avascular, did not show a hyperaemic rim and the size was equal on both scans. The experience of the observers had an influence on the accuracy of interpretation of the scans; experienced observers made a correct diagnosis in 73% of cases. It is suggested that simultaneous 99mTc tin colloid and 113mIn-chloride scans provide additional specificity in the differential diagnosis between hepatoma, amoebic liver abscess and echinococcus cysts.
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PMID:[Study of space-occupying lesions in the liver using technetium-99m tin colloid and indium-113m chloride]. 298 17

Sn-protoporphyrin IX (SnPP), an inhibitor of heme oxygenase and a potential therapeutic agent for neonatal hyperbilirubinemia, is bound tightly by hemopexin. The apparent dissociation constant (Kd) at pH 7.4 is 0.25 +/- 0.15 microM, but estimation of the Kd for the SnPP-hemopexin complex is hampered by the fact that at physiological pH SnPP exists as monomers and dimers, both of which are bound by hemopexin. SnPP is readily displaced from hemopexin by heme (Kd less than 1 pM). The hemopexin-SnPP interaction, like that of heme-hemopexin, is dependent on the histidine residues of hemopexin. However, as expected from the differences in the coordination chemistries of tin and iron, the stability of the histidyl-metalloporphyrin complex is lower for SnPP-hemopexin than for mesoheme-hemopexin. Nevertheless, when SnPP binds to hemopexin, certain of the ligand-induced changes in the conformation of hemopexin which increase the affinity of the protein for its receptor are produced. Binding of SnPP produces the conformational change in hemopexin which protects the hinge region of hemopexin from proteolysis, but SnPP does not produce the characteristic increase in the ellipticity of hemopexin at 231 nm that heme does. Competition experiments confirmed that human serum albumin (apparent Kd = 4 +/- 2 microM) has a significantly lower affinity for SnPP than does hemopexin. Appreciable amounts of SnPP (up to 35% in adults and 20% in neonates) would be bound by hemopexin in the circulation, and the remainder of SnPP would be associated with albumin due to the latter's high concentration in serum. Essentially no non-protein-bound SnPP is present. Importantly, SnPP-hemopexin binds to the hemopexin receptor on mouse hepatoma cells with an affinity comparable to that of heme-hemopexin and treatment of the hepatoma cells with SnPP-hemopexin causes a rapid increase in the steady state level of heme oxygenase messenger RNA. These results show that hemopexin participates in the transport of SnPP to heme oxygenase and in its regulation by SnPP.
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PMID:Interaction of hemopexin with Sn-protoporphyrin IX, an inhibitor of heme oxygenase. Role for hemopexin in hepatic uptake of Sn-protoporphyrin IX and induction of mRNA for heme oxygenase. 337 22

Concentration of Tc-99m(Sn)-N-pyridoxyl-5-methyltryptophan (Tc-99m PMT), a biliary agent, in hepatic tumors was studied with delayed hepatobiliary imaging in 23 patients with histologically verified hepatocellular carcinomas. All 23 showed filling defects on liver images obtained with Tc-99m tin colloid. In the images taken 5 hr after Tc-99m PMT injection, ten cases showed increased uptake in the carcinoma, six nearly normal uptake, and seven decreased uptake. In those showing the increased uptake of Tc-99m PMT in the tumor, the ratio of the radioactivity in the lesion to that in the adjacent liver parenchyma (T/L ratio) increased progressively with time for 5 hr after injection. These results indicate that delayed Tc-99m PMT images, obtained 5 hr after injection, are useful in assessment of uptake of the radioactivity by hepatocellular carcinoma.
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PMID:The importance of delayed imaging in the study of hepatoma with a new hepatobiliary agent. 609 Jun 18

Uptake of Tc-99m di-isopropyliminodiacetic acid (DISIDA) by hepatocellular carcinoma was assessed in 30 patients showing obvious liver defects on a Tc-99m tin colloid image. In none of these patients was there complete "filling in" of the defects, and even partial "filling in" occurred in only 11 (36.7%). There was no uptake of Tc-99m DISIDA by the primary tumor in the remaining 19 patients (63.3%). In 19 of the 30 patients an attempt was made to correlate the degree of histologic differentiation of the tumor with the uptake of DISIDA by the tumor. No difference in uptake could be demonstrated between well, moderately, and poorly differentiated tumors. Tc-99m DISIDA was not taken up by pulmonary metastases in the only two patients tested. We conclude that imaging with Tc-99m DISIDA in conjunction with Tc-99m colloid is of no value in the specific diagnosis of hepatocellular carcinoma.
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PMID:Uptake of Tc-99m di-isopropyliminodiacetic acid by hepatocellular carcinoma: concise communication. 631 2

Two quantitative cytotoxicity assay methods (cytoplasmic retention of carboxyfluorescein and mitochondrial cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)) have been used to evaluate the response of two cultured human cell lines; HepG2 (hepatoma) and W138va13 (transformed lung fibroblasts) to extracts of a range of poly(vinyl chloride) (PVC) formulations. Two plasticizers; di(2-ethylhexyl)phthalate (DEHP) and di-isooctyl phthalate and a range of tin and non-tin stabilizers were incorporated in the study. Only those formulations containing both a plasticizer and a tin-based stabilizer produced extracts which were toxic. Extracts of those formulations which contained both plasticizer and dibutyl tin dimaleate stabilizer were toxic to both cell lines in both assay methods. Extracts of a formulation containing plasticizer and a dioctyl tin mercaptide were toxic to both cell lines in the carboxyfluorescein assay but were only toxic to the WI38va13 cells in the MTT assay. The WI38va13 cells were generally more sensitive to the extracts than the HepG2 cells. When serial dilutions of the extracts were evaluated, the carboxyfluorescein assay proved to be the more sensitive of the two. The acute toxicity of extracts of these PVC formulations cannot be directly attributed to the plasticizers or to the tin stabilizers. It is likely that a synergistic mechanism, such as plasticizer facilitated extraction of the tin stabilizer, exists.
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PMID:Poly(vinyl chloride) formulations: acute toxicity to cultured human cell lines. 856 22

Both toxic exposure to cadmium and cancer therapy with cisplatin (CDDP) can induce anemia in patients owing to the insufficient production of erythropoietin (EPO). Therefore, the effects of cadmium chloride (Cd) and CDDP in the Hep3B human hepatoma cell line, which up-regulates EPO expression in response to hypoxia and cobalt (Co), were investigated. The induction of binding activity of the HIF-1 transcription factor and EPO mRNA expression and protein production were suppressed by Cd and CDDP in a dose-dependent manner with no apparent cell damage. Mercuric chloride also suppressed hypoxia- and Co-induced EPO production, mRNA expression, and HIF-1 binding in a manner similar to Cd and CDDP, whereas zinc chloride suppressed Co-induced EPO production, mRNA expression, and HIF-1 binding but did not affect hypoxia induction or that observed after simultaneous exposure to hypoxia and Co. In contrast, lead and tin salts had no effect on HIF-1 activation or EPO expression. These results indicate that Cd and CDDP have a strong and specific inhibitory effect on hypoxia- and Co-induced signaling and EPO induction in hepatic cells. It is likely that these agents cause anemia by directly impacting EPO production in the kidney. (Blood. 2000;96:3743-3747)
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PMID:Cadmium and platinum suppression of erythropoietin production in cell culture: clinical implications. 1109 55

Ursodeoxycholic acid (UDCA) protects cells from the apoptotic effects of hydrophobic bile acids and some other cytotoxic agents. We observed the opposite result when assessing the effects of UDCA on the apoptotic response to mitochondrial photodamage induced by photodynamic therapy (PDT). Two photosensitizers with predominantly mitochondrial specificity were used: a porphycene we have designated CPO; and the tin etiopurpurin SnET2. UDCA potentiated the loss of mitochondrial potential, release of cytochrome c into the cytosol, activation of caspase-3, and apoptotic cell death after irradiation of photosensitized murine leukemia L1210 or hepatoma 1c1c7 cells. These effects were not observed when UDCA was added after irradiation. Glyco-UDCA and tauro-UDCA, conjugated forms of UDCA that are formed in vivo, were as effective as UDCA in promoting PDT phototoxicity. Because UDCA does not act by enhancing intracellular accumulation of the photosensitizing agents used in this study, we propose that the mode of action of UDCA involves the sensitization of mitochondrial membranes to photodamage. UDCA is used currently in gastroenterology for several indications. The drug may offer a means for promoting the efficacy of PDT with minimal adverse effects.
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PMID:Potentiation of photodynamic therapy by ursodeoxycholic acid. 1115

Induction of haem oxygenase-1 (HO-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HO-1 in solid tumour with a focus on the antiapoptotic activity of HO-1. Treatment of rat hepatoma AH136B cells with the HO inhibitor zinc protoporphyrin IX (ZnPP IX) or tin protoporphyrin IX resulted in extensive apoptotic changes of tumour cells both in vivo and in vitro. Caspase-3 activity of the ZnPP IX-treated hepatoma cells increased significantly. Moreover, ZnPP IX-induced apoptosis was completely inhibited by simultaneous incubation with a specific caspase-3 inhibitor and was partially abrogated by bilirubin, a reaction product of HO. In vivo ZnPP IX treatment did not affect nitric oxide (NO) production and tumour blood flow. Western blot analyses showed that HO-1 expression in AH136B cells was strongly upregulated by NO donors, for example, S-nitroso-N-acetyl penicillamine and propylamine NONOate in vitro; conversely, it was remarkably reduced in vivo by pharmacological blockade of NOS. We conclude that HO-1 may function in antiapoptotic defense of the tumour, and thus it may have important protective and beneficial effects for tumour cells against oxidative stress induced by NO, which is produced in excess during solid tumour growth in vivo.
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PMID:Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour. 1264 28

Electrochemical impedance spectroscopy (EIS) was used to monitor the growth of mammalian cancer cells and evaluate the cytotoxicity of chemicals using Fe(CN)6(3-/4-) as a redox probe. Cancer cells, the human hepatocarcinoma cell line (BEL7404), were grown on optically transparent indium tin oxide (ITO) semiconductor slides, which were used as the working electrodes in electrochemical experiments. Attachment and proliferation of cancer cells on ITO surfaces resulted in increase of electron-transfer resistance (R(et)) between the redox probe of Fe(CN)6(3-/4-) in electrolyte solution and ITO electrode surface. For cytotoxicity assessment, cells grown on ITO substrates were further cultured in the presence of different cytotoxicants and electrochemical impedance measurements were carried out at different time intervals. Gemcitabine, a promising antineoplastic drug showing activity against a wide spectrum of human solid tumors, was selected as a model for long-term cytotoxicity effect study, whereas mercury chloride represented a model for acute toxicants. The inhibitions of gemcitabine and mercury chloride on the viability and proliferation of BEL7404 cells were observed from the electrochemical impedance experiments, and the different action modes were discriminated. Additionally, microscope images were also used to observe the effects of these two chemicals on the morphology of the cells. General consistency has been found between the electrochemical impedance response and the morphological observation. Such an impedance method provides a simple and inexpensive way for in vitro assessment of chemical cytotoxicity.
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PMID:Monitoring of cell growth and assessment of cytotoxicity using electrochemical impedance spectroscopy. 1638 5


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