Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.
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PMID:AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma. 170 5

64 patients with various malignant neoplasms (6 primary and 18 secondary liver cancers, 40 tumors without evidence of hepatic involvement) entered a comparative study measuring serum levels of 5'nucleotidase, AFP, TPA, CEA, CA 19-9. In primary liver cancer, 5'nucleotidase true positive rate was 100% (vs 67% of AFP, TPA, CA 19-9 and 33% of CEA); in secondary liver tumors it was 67% (vs 11% of AFP, 44% of CEA, 55% of CA 19-9 100% of TPA). Diagnostic sensitivity was 75% and specificity 90.5%.
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PMID:[Diagnostic value of 5'nucleotidase in primary and secondary neoplasms of the liver]. 245 52

Tumour markers are often circulating tumour-associated indicators of tumour development. As such they are not suitable for tumour screening and localization, but valuable as adjuncts for medical follow-up care of tumour patients, where their serum level alterations may anticipate the clinical detection of tumour behaviour by a lead time of 1 to 6 months before other methods. The following tumour may be controlled by established markers: endocrine tumours by NSE, calcitonin, parathormone, 5-HIAA, catecholamines/metabolites etc.; head-neck tumours: SCC, CEA; thyroid carcinoma: TG, calcitonin; lung cancer: CEA, NSE, SCC; liver cancer: AFP (PLC), CA 19-9 (cholangiocell.), CEA (secondary): biliary tract and pancreatic cancer: CA 19-9; colorectal carcinoma: CEA, CA 19-9; squamous cell carcinoma (ENT, oesophagus, anal): SCC; breast cancer: CEA and CA 15-3; ovarian cancer: CA 125 (epithelial), CA 19-9 (mucinous); germ cell tumours (ovary including trophoblastic tumours/testes): AFP and HCG; prostatic cancer: PAP and PSA; bladder cancer: TPA.
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PMID:[Clinical relevance of tumor markers]. 267 6

Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci or hepatic cancer were determined. The doses ranged from 1 ng (TCDD) to 400 mg (chloroform). In mouse skin, 10 dose-response studies of 4 promoters (12-O-tetradecanoylphorbol-13-acetate [TPA], anthralin, chrysarobin, and 2,6-di-tert-butyl-4-hydroperoxyl-2,5-cyclohexadienone [BHTOOH]) were selected. In these mouse skin studies the doses ranged from 0.425 nmole (TPA) to 20,000 nmole (BHTOOH) per mouse. The length of time promoters were applied to the skin varied between 15 and 60 weeks. Either skin papillomas or carcinomas were determined. The dose-response relationships are presented on the basis of moles of promoter, percentage of the fully effective promoting dose, or percentage of the acute oral rat LD50. The degree of concavity of the dose-response curves was determined. The available dose-response data are critiqued and discussed on the basis of future research needs for biologically based cancer risk assessment models.
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PMID:Dose-response relationship in multistage carcinogenesis: promoters. 818 17

In 6 HCC cell lines, clear expressions of EGFR and TGF-alpha were found in flow cytometry, while expressions of EGF, HB-EGF and AR were quite low. TGF-alpha secretion into culture supernatants became measurable when TPA 0.5 microM was added. TPA accelerated the proliferation of KYN-3 cells, and anti-TGF-alpha neutralizing antibody suppressed this proliferation in a dose-dependent manner. Addition of exogenous TGF-alpha, EGF, AR, or HB-EGF with heparin accelerated cell proliferation. In non-stimulated cultures, cell proliferation was suppressed by anti-EGFR neutralizing antibody, but not by the antibodies for EGF, TGF-alpha, AR and HB-EGF. HCC may possess a paracrine system regulated by these 4 ligands, and an autocrine system, under a certain condition, via TGF-alpha and EGFR.
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PMID:Expressions of epidermal growth factor family and its receptor in hepatocellular carcinoma cell lines: relationship to cell proliferation. 1002 77

Various antioxidants in foods, such as phenolic compounds and carotenoids, were proven to have anticarcinogenic activity. In the case of carotenoids, the mixture of them was found to be very effective. In fact, the development of hepatoma in the high risk group of liver cancer, was significantly suppressed by the treatment with natural carotenoids mixture. The role of nitric oxide (NO) in carcinogenesis has been pointed out, since large quantity of NO has been detected in cancer tissues, and the expression of inducible NO synthase (iNOS) was found to correlate with tumor growth and metastasis. Recently, we found that NO possessed tumor initiating activity in mouse skin carcinogenesis. It has been suggested that some parts of pathological effects induced by NO may depend on peroxynitrite, an active metabolite of NO. Thus, we accessed the tumor initiating activity of peroxynitrite, and found that treatment with peroxynitrite (initiator) plus TPA (promoter) resulted in the formation of skin tumors. Under this experimental condition, it has been proven that natural antioxidants, such as curcumin and nobiletin, showed anti-tumor initiating effect. In the case of nobiletin, suppressive effect on iNOS induction has also been demonstrated. It is of interest that suppression of iNOS induction was also observed in phytoene synthase transgenic mouse. After administration of glycerol (a lung tumor promoter), lower induction of iNOS gene was observed in lung of the phytoene producing mice, comparing with that of control mice. Combinational use of various kinds of antioxidants distributed in foods, e.g., mixture of carotenoids and flavonoids, seems to be effective methods for cancer prevention.
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PMID:Cancer prevention by antioxidants. 1563 Feb 52

During the period of 1990-2005, 701 patients with the hepatocellular carcinoma were treated with intra-arterial infusion of 5-FU and epi-adriamycin with or without Lipiodol chemoembolization employing an implantable infusion port system. In 70% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (AFP and PIVKA-II). Also 1,091 patients with the metastatic liver cancer of colon, rectum, stomach and pancreas were treated with the same procedure employing 5-FU, mitomycin C, adriamycin, or epi-adriamycin. In more than 80% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (CEA, CA19-9, TPA, DUPAN-2, SPan-1). Intra-arterial infusion chemotherapy employing an implantable port system also proved to be a promising treatment modality for most of the intractable head and neck cancer, breast cancer and a few of the pancreas cancer.
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PMID:[Intra-arterial infusion chemotherapy for advanced cancer--40 years of experience]. 1631 88

TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes. In sum, TPA has been established as an anti-tumorigenic drug in liver cancer cells via YAP and AMOT.
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PMID:12-O-Tetradecanoylphorbol-13-acetate (TPA) is anti-tumorigenic in liver cancer cells via inhibiting YAP through AMOT. 2832 18

A proton beam therapy is considered the next generation radio-therapeutic tool for liver cancer treatments. However, its effect on metastasis has not been fully elucidated. Herein, we assessed the effects of a proton beam on the metastatic potential in HepG2, Hep3B and SK-Hep1 hepatocellular carcinomas. The result showed that a proton beam suppressed TPA-induced cell migration and invasion in HepG2 cells, but not in Hep3B and SK-Hep1 cells. In addition, matrix metalloproteinase-9 (MMP-9) activity and mRNA expressions were reversed by proton beam irradiation in TPA-treated HepG2 cells only. Furthermore, a proton beam suppressed TPA-induced gene expressions of urokinase plasminogen activator (uPA), uPA receptor (uPAR), Snail-1 and vascular endothelial growth factor (VEGF) in HepG2 cells in a dose-dependent manner. Moreover, we found that proton beam irradiation restrained p38 MAPK phosphorylation and c-Fos expression. Therefore, the result demonstrates that the anti-metastatic effects of a proton beam in TPA-treated HepG2 cells are associated with the inhibition of MMP-9 activity and the down-regulations of MMP-9, uPA, uPAR, Snail-1 and VEGF gene expression via the p38 MAPK/c-Fos signaling pathway. Taken together, this investigation suggests that the establishment of a customized proton beam therapeutic strategy for each liver cancer type is necessary to improve therapeutic efficiency.
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PMID:Anti-metastatic potential of a proton beam is regulated by p38 MAPK/c-Fos signaling pathway in TPA-treated HepG2 human hepatocellular carcinoma. 2971 Apr 90