scholarly journals A Case of Well-differentiated Hepatocellular Carcinoma that Developed in a Normal Liver of a Young Woman

2014 ◽  
Vol 75 (1) ◽  
pp. 190-196
Author(s):  
Hisafumi KITAGAWA ◽  
Shouiti TSUDA ◽  
Kaori TUBOI ◽  
Ken YAGI ◽  
Akira YAMAMOTO ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Young Woman ◽  
Normal Liver ◽  
Well Differentiated

scholarly journals Diagnostic Value of Clusterin Immunostaining in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Yuan Li ◽  
Fangfang Liu ◽  
Wendi Zhou ◽  
Sharon Zhang ◽  
Peiguo Chu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Pattern ◽  
Staining Pattern ◽  
Hepatocellular Adenoma ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Tissue Samples ◽  
Regenerative Nodules ◽  
Well Differentiated ◽  
Mass Lesions

Abstract Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs.Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26% and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC.Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.

scholarly journals Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2499
Author(s):  
Lisanne Noordam ◽  
Zhouhong Ge ◽  
Hadiye Özturk ◽  
Michail Doukas ◽  
Shanta Mancham ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Occult Metastasis ◽  
Recurrence Rates ◽  
Curative Intent ◽  
Cancer Testis Antigens ◽  
Negative Prognostic Factor ◽  
Increased Risk ◽  
Hcc Recurrence ◽  
Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

scholarly journals SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 178
Author(s):  
Jiann Ruey Ong ◽  
Oluwaseun Adebayo Bamodu ◽  
Nguyen Viet Khang ◽  
Yen-Kuang Lin ◽  
Chi-Tai Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Metabolism ◽  
Interaction Analysis ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Vital Role ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Characteristic Analysis

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA−LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with ‘normal’ paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals FXYD6 overexpression in HBV-related hepatocellular carcinoma with cirrhosis

2020 ◽  
Vol 15 (1) ◽  
pp. 259-266
Author(s):  
Xiongfei Chen ◽  
Lishuang Ding ◽  
Deshuai Kong ◽  
Xiulei Zhao ◽  
Lili Liao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Early Recurrence ◽  
Tumor Diameter ◽  
Tumor Number ◽  
B Virus ◽  
Expression Rate ◽  
Polymerase Chain ◽  
And Gender ◽  
Liver Tissues

AbstractObjectiveThe aim of this study was to investigate the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) mRNA and protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues with cirrhosis, the corresponding paracancerous tissues and the normal liver tissues, and to explore the clinical significance of FXYD6 expression in HBV-related HCC with cirrhosis.MethodsThe FXYD6 mRNA and protein were examined by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively.ResultsThe FXYD6 mRNA in HBV-related HCC tissues was significantly higher than that in the cirrhosis tissues or that in the normal liver tissues. The positive expression rate of FXYD6 protein was statistically higher in HBV-related HCC tissues than that in HBV-related cirrhosis or that in normal liver tissues. There was no significant correlation between the expression of FXYD6 protein and gender, age, histological differentiation, tumor diameter, tumor number, integrity of tumor capsule or not and alpha fetoprotein (AFP) concentration in serum, but the protein expression was associated with microvascular invasion, pathological stage, and early recurrence after operation within 1 year.ConclusionFXYD6 might be involved in hepatocyte carcinogenesis and tumor progression in HBV-related HCC with cirrhosis and indicated a poor prognosis.

scholarly journals Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jian-Yao Wang ◽  
Xiang-Kun Wang ◽  
Guang-Zhi Zhu ◽  
Xin Zhou ◽  
Jun Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Tumor Tissue ◽  
Bioinformatics Analysis ◽  
Mrna Level ◽  
Normal Liver ◽  
Predictive Index ◽  
Expression Levels ◽  
Interactive Analysis ◽  
Diagnostic Values

Abstract Backgroud In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.

scholarly journals Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma

2021 ◽  
pp. 344-351
Author(s):  
Hiroki Kanno ◽  
Toshihiro Sato ◽  
Ryuta Midorikawa ◽  
Satoki Kojima ◽  
Shogo Fukutomi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carbohydrate Antigen ◽  
Epithelioid Hemangioendothelioma ◽  
Arterial Phase ◽  
Rapid Progression ◽  
Imaging Findings ◽  
Liver Segment ◽  
Contrast Enhanced ◽  
Well Differentiated ◽  
Enhanced Computed Tomography

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.

scholarly journals Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kai-Lin Yang ◽  
Mau-Shin Chi ◽  
Hui-Ling Ko ◽  
Yi-Ying Huang ◽  
Su-Chen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase I ◽  
Response Rate ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Normal Liver ◽  
Maximum Tolerated Dose ◽  
Outcome Analysis ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

Abstract Background To investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1–3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC). Methods This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local–regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS). Results Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months. Conclusions Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461

scholarly journals Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics

2021 ◽  
Vol 22 (8) ◽  
pp. 3956
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Hae June Lee ◽  
Kiwon Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Primary Liver Cancer ◽  
Atmospheric Pressure Plasma ◽  
Normal Liver ◽  
Normal Liver Cell ◽  
Ample Evidence ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.

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