Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor-1α and its significance

Yasuda, Seiichi; Arii, Shigeki; Mori, Akira; Isobe, Naoki; Yang, Weige; Oe, Hideaki; Fujimoto, Akihisa; Yonenaga, Yoshikuni; Sakashita, Hiromi; Imamura, Masayuki

doi:10.1016/s0168-8278(03)00503-8

Cited by 130 publications

(93 citation statements)

References 26 publications

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“…Thus, it is conceivable that HKII expression by HIF contributes to this. In fact, a correlation has been detected between the presence of HIF and the upregulation of HKII (Yasuda et al, 2004). This is to our knowledge so far the most direct link between the tumorigenesis scenarios enumerated above and the PTP inhibition by a specific component of the PTP.…”

Section: Subunits Of the Permeability Transition Pore Are Differentiamentioning

confidence: 65%

The permeability transition pore complex in cancer cell death

2006

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The permeability transition pore (PTP) is a multi-protein complex at contact sites of the inner with the outer mitochondrial membrane. Research over the past years has led to the concept that the PTP occupies a central role in cell death induction. Numerous apoptosis signals convert this protein aggregate into an unspecific pore, thus activating mitochondria for the cellular self-destruction process. Here, we describe the evidence for this and the various approaches being undertaken to elucidate its subunit composition and mode of regulation. In particular, we review data that indicate a role of specific PTP subunits for apoptosis inhibition during tumorigenesis.

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Section: Subunits Of the Permeability Transition Pore Are Differentiamentioning

confidence: 65%

The permeability transition pore complex in cancer cell death

2006

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“…This may be caused by increased glycolysis in residual tumors after TACE. HCCs pretreated with TACE displayed significantly higher hexokinase II messenger RNA expression, and there was a significant correlation between the expression of hypoxia-inducible factor 1a (HIF-1a) protein and hexokinase II messenger RNA (20). Furthermore, both HIF-1a and hexokinase II protein were colocalized in cancer cells near necrotic regions.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using¹⁸F-FDG PET/CT

Kim¹,

Kim²,

Shin³

et al. 2010

J Nucl Med

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This study aimed to evaluate the metabolic characteristics of lipiodolized hepatocellular carcinomas (HCCs) and the diagnostic accuracy of 18 F-FDG PET/CT in assessing the viability of lipiodolized HCCs. Methods: Thirty-six patients (age range, 32-73 y) with 38 lipiodolized HCCs who had undergone transcatheter arterial chemoembolization (TACE) with lipiodol before 18 F-FDG PET/CT (2-434 d) and 55 patients (age range, 36-77 y) with 57 treatment-naïve HCCs who had not been treated with TACE were retrospectively studied. All patients underwent hepatic lobectomy or transplantation within 1 mo after PET/CT and multiphasic contrast-enhanced CT. 18 F-FDG uptake by lipiodolized and naïve HCCs was compared and correlated with tumor size, pathologic grade, serum a-fetoprotein (AFP) concentration, and time interval between TACE and PET/CT. The diagnostic accuracy of PET/CT and contrast-enhanced CT in evaluating the viability of lipiodolized HCC was compared. Results: Histologic examination showed 30 viable and 8 nonviable lipiodolized HCCs. Of the 30 viable tumors, 19 showed increased, 10 similar, and 1 decreased 18 F-FDG uptake. Of the 8 nonviable HCCs, 3 showed increased and 5 decreased 18 F-FDG uptake. Uptake by viable lipiodolized HCCs was correlated with tumor size (P , 0.05) but not correlated with pathologic grade, AFP concentration, or interval between TACE and PET/ CT. In contrast, 18 F-FDG uptake by naïve HCCs was significantly correlated with tumor size and pathologic grade (P , 0.05 for each comparison). When lipiodolized HCCs with 18 F-FDG uptake that was greater than or similar to that in the surrounding normal liver were considered viable, the diagnostic sensitivity of PET/CT and contrast-enhanced CT in the early postembolic period (,3 mo) was 100% and 94%, respectively, and that in the late postembolic period was 93% and 79%, respectively. The specificity of 18 F-FDG PET/CT and contrastenhanced CT was 63% and 100%, respectively, in the acute period. Three viable lipiodolized HCCs with high AFP concentration were true-positives on PET/CT but false-negatives on contrast-enhanced CT images. Conclusion: After TACE, 18 F-FDG uptake in lipiodolized HCCs was not correlated with pathologic grade, in contrast to uptake in treatment-naïve HCCs. 18 F-FDG PET/CT showed a high diagnostic sensitivity in assessing the viability of lipiodolized HCCs, with moderate specificity. This method may be useful in determining the viability of lipiodolized HCCs in patients with increased serum AFP concentration or normal results on contrast-enhanced CT images.

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“…HIF1A and VEGFA are generally overexpressed in HCC and required for tumor survival under hypoxic conditions. (36) VEGF expression levels correlate with clinicopathological factors, such as proliferation, vascular invasion, and tumor multiplicity. (37) Increased expression of HIF1A and VEGFA is associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

et al. 2016

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There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT.Liver Transplantation 22 665-676 2016 AASLD.Received August 31, 2015; accepted December 9, 2015.Hepatocellular carcinoma (HCC) is the most frequent cancer of the liver and the third most common cause of cancer deaths worldwide.(1) Curative treatment is limited to hepatic resection and liver transplantation (LT). However, the overall cumulative recurrence rate after hepatic resection is approximately 80% at 5 years.(2) Among various recurrent patterns of HCC, the prognosis of extrahepatic recurrence-metastasis (M) is much poorer than that of intrahepatic metastasis and multicentric recurrence. (3)(4)(5) LT can overcome the problems of intrahepatic metastasis and multicentric recurrence theoretically. However, the recurrence of HCC after LT is a critical problem to be solved because the outcomes of patients with HCC recurrence after LT are extremely poor. (6) Abbreviations: AFP, alpha-fetoprotein; DCP, des-gamma-carboxyprothrombin; DDLT, deceased donor liver transplantation; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIF1A, hypoxia-inducible factor 1 alpha; IGF1R, insulin-like growth factor 1 receptor; IGF2, insulin-like growth factor 2; LDLT, living donor liver transplantation; LT, liver transplantation; M, recurrence-metastasis; miR-18a, microRNA-18a; miR-199a-5p, microRNA-199a-5p;...

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Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor-1α and its significance

Cited by 130 publications

References 26 publications

The permeability transition pore complex in cancer cell death

The permeability transition pore complex in cancer cell death

Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using¹⁸F-FDG PET/CT

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

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Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor-1α and its significance

Cited by 130 publications

References 26 publications

The permeability transition pore complex in cancer cell death

The permeability transition pore complex in cancer cell death

Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using18F-FDG PET/CT

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

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Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using¹⁸F-FDG PET/CT