Immunohistochemical studies on the expression of P-glycoprotein and p53 in relation to histological differentiation and cell proliferation in hepatocellular carcinoma

Nakano, Atsushi; Watanabe, Norihito; Nishizaki, Yasuhiro; Takashimizu, Shinji; Matsuzaki, Shinya

doi:10.1016/s1386-6346(02)00207-3

Cited by 22 publications

(22 citation statements)

References 24 publications

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“…This capacity of P-gp leads to strong resistance to chemotherapy. 18,22,28 In this study, P-gp was more highly expressed in HCC than in cirrhotic liver, which is consistent with the known resistance of HCC to chemotherapy. In accordance with previous human studies, the overexpression of P-gp was demonstrated in all canine HCC specimens.…”

Section: Discussionsupporting

confidence: 88%

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Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

et al. 2007

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Abstract. P-glycoprotein (P-gp), which is encoded by the multidrug resistance gene (MDR-1); alpha fetoprotein (AFP); and vascular endothelium-associated antigens are well-known markers for human and canine hepatic diseases. We obtained liver tissues from 5 dogs with hepatocellular carcinoma (HCC) and 12 dogs with cirrhosis, and we performed histopathologic and immunohistochemical evaluations using anti-P-gp, anti-AFP, anti-CD31, and anti-CD34 antibodies. P-gp was expressed at higher levels in HCC than in cirrhotic livers (P , .01), and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC (P , .01) and in a few cases of cirrhosis. In both HCC and cirrhosis, the AFP-positive cells were morphologically similar to normal hepatocytes and showed an even cytoplasmic distribution of AFP. The endothelial markers CD31 and CD34 were used to investigate vascular distribution. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. This study constitutes the first comprehensive study of P-gp, AFP, and endothelial markers in canine HCC and cirrhosis. The importance of these markers in HCC and cirrhosis in dogs was demonstrated and provides a more accurate basis for a definitive diagnosis of HCC and cirrhosis in dogs.

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Section: Discussionsupporting

confidence: 88%

“…9,18,19,21,23 This protein is also present in normal tissues, including the jejunum, liver, kidney, colon, and adrenal glands. 3,21,27 High levels of P-gp are expressed in tumor cells derived from organs normally expressing P-gp.…”

Section: Introductionmentioning

confidence: 99%

Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

et al. 2007

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“…The expression of P-glycoprotein and COX-2 in cancerous tissues varies according to several factors, decreasing with the increase of anaplasia (4,15). This observation suggests that P-glycoprotein and COX-2 can play a role in early stage of carcinogenesis and in malignity in many organs, liver included, although very few links have been shown between P-glycoprotein and COX-2 pathways.…”

Section: Introductionmentioning

confidence: 99%

P-Glycoprotein Mediates Celecoxib-Induced Apoptosis in Multiple Drug-Resistant Cell Lines

Fantappiè

Solazzo²,

Lasagna³

et al. 2007

Cancer Research

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In several neoplastic diseases, including hepatocellular carcinoma, the expression of P-glycoprotein and cyclooxygenase-2 (COX-2) are often increased and involved in drug resistance and poor prognosis. P-glycoprotein, in addition to drug resistance, blocks cytochrome c release, preventing apoptosis in tumor cells. Because COX-2 induces P-glycoprotein expression, we evaluated the effect of celecoxib, a specific inhibitor of COX-2 activity, on P-glycoprotein-mediated resistance to apoptosis in cell lines expressing multidrug resistant (MDR) phenotype. Experiments were done using MDR-positive and parental cell lines at basal conditions and after exposure to 10 or 50 Mmol/L celecoxib. We found that 10 Mmol/L celecoxib reduced P-glycoprotein, Bcl-x L , and Bcl-2 expression, and induced translocation of Bax from cytosol to mitochondria and cytochrome c release into cytosol in MDR-positive hepatocellular carcinoma cells. This causes the activation of caspase-3 and increases the number of cells going into apoptosis. No effect was shown on parental drug-sensitive or on MDR-positive hepatocellular carcinoma cells after transfection with MDR1 small interfering RNA. Interestingly, although inhibiting COX-2 activity, 50 Mmol/L celecoxib weakly increased the expression of COX-2 and P-glycoprotein and did not alter Bcl-x L and Bcl-2 expression. In conclusion, these results show that relatively low concentrations of celecoxib induce cell apoptosis in MDR cell lines. This effect is mediated by P-glycoprotein and suggests that the efficacy of celecoxib in the treatment of different types of cancer may depend on celecoxib concentration and P-glycoprotein expression. [Cancer Res 2007;67(10):4915-23]

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“…Wang et al (2005) reported that the silent MDR1 C3435T polymorphism leads to an unstable mRNA molecule and consequently, lower P-glycoprotein activity in the target tissues (Wang et al, (2005). The MDR1/ABCB1 gene seems to play a role in early carcinogenesis by preventing apoptosis in tumor (Renal, Breast) The meta-analysis 47 cells as suggested by researchers (Johnstone et al, 2000;Nakano et al, 2003;Fantappie et al, 2007). The MDR1 C3435T polymorphism in exon 26 has been extensively investigated in the variability in cancer risk and therapeutic outcome (Andersen et al, 2009;Jasim et al, 2011;Lu et al, 2011;Manduz et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Possible Roles of the Xenobiotic Transporter P-glycoproteins Encoded by the MDR1 3435 C＞T Gene Polymorphism in Differentiated Thyroid Cancers

Özdemir¹,

Uludağ²,

Sılan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Immunohistochemical studies on the expression of P-glycoprotein and p53 in relation to histological differentiation and cell proliferation in hepatocellular carcinoma

Cited by 22 publications

References 24 publications

Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

P-Glycoprotein Mediates Celecoxib-Induced Apoptosis in Multiple Drug-Resistant Cell Lines

Possible Roles of the Xenobiotic Transporter P-glycoproteins Encoded by the MDR1 3435 C＞T Gene Polymorphism in Differentiated Thyroid Cancers

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