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)

Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample collected in Yunnan Province, China, has been verified as a clavam peptide. Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells with multidrug resistance. The IC50 values of G0069A to KB and KB/VCR cells were 0.60 and 0.46 mumol.L-1, and to MCF-7 and MCF-7/ADM cells were 1.4 and 1.2 mumol.L-1, respectively. G0069A displayed equally potent cytotoxicity to the parent cell lines and their resistant sublines. When administered by i.v. or i.p. route at tolerable doses, G0069A exhibited markedly inhibitory effect on the growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg.kg-1, i.v., x3, sarcoma 180 and hepatoma 22 were suppressed by 87%(P < 0.01) and 72%(P < 0.01), respectively. The results indicate that G0069A is a beta-lactam antibiotic showing antitumor activity.
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PMID:[Antitumor activity of the clavam peptide antibiotic G0069A]. 1159 87

The hepatic artery-embolizing effect of degradable starch microspheres (DSM) was assessed by dynamic CT scanning soon after embolization in patients with malignant hepatic tumors. Using the Seldinger method, DSM with a mixture of contrast medium, MMC, ADM or Epi-ADM was manually injected. The subjects were 32 patients with metastatic carcinoma of the liver (62 treatments) and 15 patients with hepatocellular carcinoma(19 treatments) (47 patients received 81 treatments in all). Dynamic CT scanning was performed within 2 weeks of each embolization procedure, and the percent reduction in the area visualized (necrotic effect) was calculated to assess the efficacy of embolization. The necrotic effect of embolization was classified as CR, PR, NC, and PD after 9, 41, 10, and 2 treatments, respectively, in the patients with metastatic carcinoma of the liver and after 4, 6, 6, and 3 treatments, respectively, in the patients with hepatocellular carcinoma. Although there was no patient in whom the tumor showed 50% or more reduction, the contrast enhanced area showed 50% or more decrease in 60 out of 81 treatments. Therefore, blocking of blood flow seemed to contribute more to the response than enhancement of the efficacy of the anticancer agents. Adverse reactions were all transient and controllable. Based on our results, intra-arterial chemotherapy plus DSM embolization seems to be useful for treating malignant hepatic tumors.
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PMID:[Early effect of intra-arterial chemotherapy combined with degradable starch microspheres for malignant hepatic tumors]. 1255 9

A 74-year-old male was examined with abdominal CT scan because of general fatigue. Abdominal CT scan indicated enhanced tumors, 9x8 cm in size in subsegment 6/7 and 5 mm in size in subsegment 3. Tumor thrombus was observed in the right portal branch to the main portal vein. We diagnosed the patient with Vp3 hepatocellular carcinoma. A right hepatectomy with extraction of portal venous thrombus was performed. Unresectable tumor was treated with one shot arterial infusion (epi-ADM 40 mg) and TAE 3 times at an interval of three months. The side effect was only a fever and the QOL was good under the treatment. But a tumor in S1 had developed, and the patient died at about 12 months after the operation.
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PMID:[A case of Vp3 hepatocellular carcinoma with a good QOL after multidisciplinary treatments]. 1555 58

A case is a male in his 50's. He received hepatic resections twice for hepatocellular carcinoma. Recurrence was pointed out in the residual liver with tumor thrombus to the right branch of the portal vein. The serum level of AFP was 648 ng/ml. We performed transhepatic arterial embolization (TAE) with Epi-ADM, CDDP, Lipiodol and spongel through the right hepatic artery before re-hepatectomy. Posterior segmentectomy with an extraction of portal vein thrombus was performed. Pathological findings showed complete necrosis not only in the main tumor but in the portal vein thrombus also. He is alive for more than 5 years without recurrence after surgeries following pre-operative TAE.
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PMID:[A successful case of more than 5 years of disease free survival in hepatocellular carcinoma with tumor thrombus to the right main branch of portal vein after repeated hepatic resection following transhepatic arterial embolization (TAE)]. 1631 52

Thymosin alpha1 (Talpha1), a 28-amino acid peptide, is a well-known immune system enhancer for the treatment of various diseases. In the present investigation, the effects of Talpha1 on the proliferation and apoptosis of human leukemia cell lines (HL-60, K562 and K562/ADM) were studied. The proliferation was significantly depressed after 96 h of treatment with Talpha1, and obvious signs of apoptosis, i.e., cell morphology, nuclei condensation and Annexin V binding, were observed thereafter. Moreover, the up-regulation of Fas/Apol (CD95) and decrease in bcl-2 anti-apoptotic gene expression were observed in apoptotic cells. The expression and the function of P-glycoprotein (P-gp) can be slightly inhibited by Talpha1. It is noteworthy that K562 and K562/ADM were more sensitive than HL-60 cells when subjected to Talpha1. Furthermore, HepG-2, the human hepatoma cell line, displayed significant less sensitivity to Talpha1 than all the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine receptors (nAChRs) antagonist, significantly antagonized the inhibition effects induced by Talpha1, whereas atropine, a muscarinic acetylcholine receptor antagonist, did not exhibit such effects. All the results indicate that Talpha1 was able to significantly suppress proliferation and induce apoptosis in human leukemia cell lines.
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PMID:Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia cell lines. 1664 63

Multidrug resistance (MDR) is one of the major obstacles to successful chemotherapy of human malignancies. Although many strategies have been explored to overcome MDR, none of them have been proven to be clinically useful until now. The aim of this study was to investigate whether a novel therapeutic ultrasound (US) approach would have useful effects on the reversal of MDR in cancer cells. Wild-type and MDR phenotype (HepG2/ADM) cells of the human hepatocarcinoma cell line HepG2 were exposed to 0.8 MHz US at an intensity of 0.43 W/cm(2) for a 9s exposure (total energy density: 3.87 J/cm(2)). After US exposure, cell number and viability were counted immediately, and flow cytometry was performed to measure retention of rhodamine 123 and adriamycin in HepG2 and HepG2/MDR cells. Both cell lines were then incubated in suspension with adriamycin, vincristine, etoposide, cisplatin and 5-fluorouracil, respectively, and the MTT assay was used to determine cytotoxicity. The results showed that US exposure could significantly increase the uptake of Rh123 and ADM by HepG2/ADM tumor cells. The resistant index for the chemotherapeutic drugs was significantly lower in the US-exposed HepG2/ADM cells than in those not exposed to US. It was therefore concluded that US exposure could enhance the sensitivity of HepG2/ADM tumor cells to these chemotherapeutic agents, and the functional and structural changes induced by previous US exposure in MDR tumor cells may be responsible for it. However, further study is needed to investigate the mechanism behind US-mediated reversal of MDR.
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PMID:Cytotoxic effects and in vitro reversal of multidrug resistance by therapeutic ultrasound in human hepatocarcinoma cell line (HepG2). 1819 65

Previous studies have shown that ultrasound (US) could enhance cellular uptake and cytotoxicity of chemotherapeutic agents in drug-resistant cancer cells. The goal of this study was to investigate the optimization of physical parameters of US exposure for in vitro reversal of multidrug resistance (MDR) in human hepatocarcinoma cell line (HepG2). Using a constant total energy density (3.87 J/cm(2)) that could maintain cell viability at the 90% level, we exposed parent (HepG2) and MDR variant (HepG2/ADM) tumor cells to US in vitro to a variety of US frequency, exposure intensity and duty cycle. After US exposure, flow cytometry was performed to measure retention of rhodamine 123 (Rh123) in both HepG2 and HepG2/MDR cells. The results showed that US frequency and duty cycle (DC) could influence the intracellular retention of Rh123 in HepG2/ADM tumor cells; intensity and exposure duration appeared to be of little importance. At a constant total energy density of 3.87 J/cm(2), the optimal US parameters for in vitro reversal of MDR in HepG2/ADM tumor cells appear to be 0.8 MHz, 0.43 W/cm(2) and 60% DC, respectively. These findings support our hypothesis that varying the physical parameters would have an effect on efficiency of US-mediated reversal of MDR in cancer cells.
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PMID:Optimization of ultrasound-mediated in vitro reversal of multidrug resistance in human hepatocarcinoma cell line HepG2. 1846 74

Although great advances have been made in therapies for patients with hepatocellular carcinoma(HCC), the prognosis for advanced HCC remains poor because liver transplantation is not applicable. We report three(3)cases of HCC treated successfully by transcatheter arterial chemoembolization(TACE)using a suspension of Lipiodol and a fine powder formulation of cisplatin(DDPH). Case No. 1 was a 64-year-old man with multiple HCCs who had undergone several sessions of TACE using doxorubicin(ADM). During the course of the treatment, the HCC became intractable and residual tumors were observed repeatedly within a short period. He was then treated by TACE using DDPH instead of ADM. The tumor marker levels decreased in response to this treatment and no recurrence of HCC has been observed. Case No. 2 was a 71-year-old man who had been diagnosed with multiple HCCs in 2004. He was treated by TACE with ADM, but the procedure had to be repeated more than three(3)times due to residual tumors. Despite the treatment, the tumor grew gradually and a formation of tumor thrombus was observed in the inferior vena cava. Both the tumor and tumor thrombus reduced in size after TACE with DDPH. Case No. 3 was a 52-year-old man who had been monitored diabetes mellitus and chronic hepatitis at our hospital. Multiple HCCs were diagnosed in 2006. TACE with DDPH was performed as an initial therapy. The tumors shrank or disappeared in response to this treatment. These results propose that TACE with DDHP against advanced HCC is effective.
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PMID:[Three (3) cases of advanced hepatocellular carcinoma (HCC) treated successfully by transcatheter arterial chemoembolization (TACE) using lipiodol and a fine- powder formulated cisplatin (DH)]. 1929 76

Some membrane transporters in liver, such as P-glycoprotein, multidrug resistance-associated protein 2 (MRP2), MRP3, and MRP5 can lead to a complex multidrug resistance (MDR) to antineoplastic agents. How to inhibit these proteins is still an issue. Tetramethylpyrazine is a bioactive constituent isolated from the root of Ligusticum chuanxiong Hort, a Chinese herb. Recent studies showed that it can enhance the chemosensitivity effects of a drug on human hepatocellular carcinoma cells, acting as a multidrug resistance modulator. In this study, the reversal effect of TMP on MDR was evaluated and its activity mechanism in vitro was explored. The IC50 value shows that TMP reversed the multidrug resistance of BEL-7402/ADM cells 9.23-fold (P<0.01) at the concentration of 600 microM. The mean fluorescence intensity of ADM in BEL-7402/ADM cells with TMP was found to be 163.78+/-39.5% (P<0.01) versus in BEL-7402/ADM cells without TMP by flow cytometry and 126.73+/-28.72% in BEL-7402/ADM cells with TMP versus in BEL-7402/ADM cells without TMP (P<0.01) by high performance liquid chromatography, respectively. It was also found that the mRNA level of multidrug resistant gene MDR1, MRP2, MRP3 and MRP5 and the level of the proteins they encode were decreased after treatment with TMP, indicating that TMP can effectively reverse the MDR in BEL-7402/ADM cells, and its activity mechanism may be correlated with the down-regulation of expression in these transporters.
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PMID:Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. 1995 84

Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection.
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PMID:Alcohol and HCV chronic infection are risk cofactors of type 2 diabetes mellitus for hepatocellular carcinoma in Italy. 2061 35


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