Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors

Stefano, Giuseppina Di; Fiume, L.; Bolondi, Luigi; Lanza, Marcella; Pariali, M.; Chieco, Pasquale

doi:10.1111/j.1478-3231.2005.1118.x

Cited by 20 publications

(11 citation statements)

References 36 publications

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“…The results of the Two-dimensional echocardiography was performed on all groups 14 weeks after injection of DENA. Data obtained from these images show increased % ejection fraction (a) and % fractional area change (b) in rats treated with resveratrol; however, changes were not significant [63]. Our histological study also shows significant pathological changes, indicating frequent occurrence of preneoplastic lesions in the livers of DENAinitiated rats.…”

Section: Discussionmentioning

confidence: 54%

Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma

et al. 2009

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Hepatocellular carcinoma (HCC), one of the most lethal cancers, results in more than one million fatalities worldwide every year. In view of the limited therapeutic alternatives and poor prognosis of liver cancer, preventive control approaches, notably chemoprevention, have been considered to be the best strategy in lowering the present prevalence of the disease. Resveratrol, a naturally occurring antioxidant and antiinflammatory agent found in grapes and red wine, inhibits carcinogenesis with a pleiotropic mode of action. Recently, we have reported that dietary resveratrol significantly prevents chemically-induced liver tumorigenesis in rats. One of the mechanisms of resveratrol-mediated chemoprevention of hepatocarcinogenesis could be related to its antiinflammatory action through hepatic cyclooxygenase (COX-2) inhibition. Although several COX-2 inhibitors are known to exert chemopreventive efficacy, not all are considered ideal candidates for chemoprevention due to the risk of adverse cardiovascular events. Accordingly, the objective of the present study was to evaluate the role of resveratrol on cardiac performance during experimental hepatocarcinogenesis initiated with diethylnitrosamine and promoted by phenobarbital. Rats had free access to diet supplemented with resveratrol four weeks before the carcinogen injection and 14 weeks thereafter. The cardiotoxicity of resveratrol was assessed by monitoring the cardiac function using transthoracic echocardiography as well as Western blot analysis of cardiac tissue. Long-term dietary administration of resveratrol dose-dependently suppressed hepatic tumor multiplicity, the principal endpoint for evaluating the chemopreventive potential of a candidate agent. The chemopreventive effects of resveratrol were also reflected in histopathological assessment of hepatic tissues. Resveratrol did not exhibit any cardiotoxicity but rather improved the cardiac function in a dose-responsive fashion. Our results indicate that resveratrol-mediated chemoprevention of rat liver carcinogenesis is devoid of any adverse cardiovascular events. Resveratrol may be developed as a chemopreventive as well as therapeutic drug for human HCC.

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Section: Discussionmentioning

confidence: 54%

Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma

et al. 2009

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“…9 Highly proliferative tumor cells were shown to present intracytoplasmic albumin deposits. 10 Another study confirmed that malign tumors are able to internalize albumin through endocytosis which is further processed in lysosomes. 11 The resulting amino acids are further used for the synthesis of various substrates needed for tumor growth.…”

Section: Introductionmentioning

confidence: 88%

Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

Mocan

Tabaran²,

Mocan³

et al. 2011

IJN

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The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called “nanophotothermolysis”. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.

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“…As experimental model of human HCC, we used rats treated with DEN which induces poor, moderate and well differentiated forms of HCCs with histological features similar to those of the human tumors [6].…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma

Dhanasekaran¹,

Arul²,

Ignacimuthu³

et al. 2008

Invest New Drugs

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Medicinal plants are a promising source for identification of lead molecules for cancer therapy. In our continuous search to discover bioactive compounds from natural products, we isolated (5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone (ECD), a diterpenoid from Tinospora cordifolia and studied its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) rats. Fifty male Wistar rats were divided into five groups. Group I served as normal control. Group II-IV were given DEN (0.01% in drinking water) for twenty weeks. In addition, Group III (preventive treatment) received ECD (10 mg/kg body weight) throughout the study. Group IV (curative treatment) received ECD (10 mg/kg body weight) for the last 8 weeks. Group V received ECD alone (10 mg/kg body weight) throughout the experimental period. At the end of the experimental period all the animals were sacrificed and analyzed for biochemical end points to assess the effect of ECD treatment in DEN induced HCC. The animals treated with DEN showed a decrease in the activities of antioxidant (SOD, CAT) and detoxification enzymes (GSH, GPx) with increase in the activities of the hepatic markers (SGOT, SGPT, LDH). Treatment of ECD in both preventive and curative DEN induced animals increased the level of antioxidants and detoxification enzymes, and decreased serum transaminase level and hepatic marker enzymes to near normal. Histopathological and nodular incidence also confirmed that ECD remarkably reduced tumor incidence and reversed damaged hepatocytes to normal. Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC.

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Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors

Abstract: The present results suggest that in the chemotherapy of HCCs expressing the ASGP-R the extra-hepatic toxicity of anticancer agents can be reduced by conjugation to L-HSA.

Cited by 20 publications

References 36 publications

Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma

Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma

Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma

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