Importance of Protein Denaturation to Thermochemical Ablation of Liver Tumors

2011 ◽  
Author(s):  
Shoji Mori ◽  
Rajagopal Aravalli ◽  
Jeunghwan Choi ◽  
Erik Cressman ◽  
John Bischof
Keyword(s):  
Hepatocellular Carcinoma ◽  
Total Protein ◽  
Protein Denaturation ◽  
Liver Tumors ◽  
Cellular Protein ◽  
Human Hepatoma ◽  
Single Session ◽  
Local Ablation ◽  
Chemical Ablation ◽  
Protein Denaturant

Solid tumors in the liver such as hepatocellular carcinoma, often are not amenable to chemotherapy or surgical therapies. Local “ablation” methods including thermal and chemical ablation are therefore options for treatment. Hyperthermic ablation methods (RF, microwave, HIFU and laser) can potentially accomplish treatment in a single session but are considerably more costly than chemicals. It was therefore of interest to investigate if a known protein denaturant such as urea would destroy liver tumors. Further, we wished to assess whether this destruction occurs by protein denaturation mechanisms similar to hyperthermic destruction. Specifically, Lepock showed that hyperthermic cell destruction occurs for many cells when overall protein denaturation is greater than 5% (i.e. survival drops from 95% to 5% beyond this range). In this study we report on the cytotoxicity of urea on human hepatoma HuH-7. We then quantify the amount of cellular protein denaturation associated with cytotoxicity and show that protein denaturation in excess of 5% of total protein must occur in order for significant cell killing.

scholarly journals Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Julie Pellegrinelli ◽  
Olivier Chevallier ◽  
Sylvain Manfredi ◽  
Inna Dygai-Cochet ◽  
Claire Tabouret-Viaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Risk Of Death ◽  
Transarterial Radioembolization ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

scholarly journals Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Lifeng Feng ◽  
Miaoqin Chen ◽  
Yiling Li ◽  
Muchun Li ◽  
Shiman Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cell Growth ◽  
Knockout Mice ◽  
Liver Tumors ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Conditional Knockout

Abstractp62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.

scholarly journals Recurrent hepatocellular carcinoma: comparison between repeat hepatectomy and local ablation

HPB ◽  
2016 ◽  
Vol 18 ◽  
pp. e865
Author(s):  
L. Lacaze ◽  
O. Goria ◽  
J.P. Lestrat ◽  
M. Bubenheim ◽  
M. Scotte
Keyword(s):  
Hepatocellular Carcinoma ◽  
Repeat Hepatectomy ◽  
Local Ablation ◽  
Recurrent Hepatocellular Carcinoma

Long-term outcomes after hepatectomy for recurrences after prior local ablation for hepatocellular carcinoma

2008 ◽  
Vol 34 (4) ◽  
pp. 433-438 ◽  
Author(s):  
J. Sakata ◽  
Y. Shirai ◽  
T. Wakai ◽  
K. Kaneko ◽  
K. Hatakeyama
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Local Ablation

scholarly journals Profile of hepatocellular carcinoma in the Republic of Moldova: first-hand information on the presentation, distribution and etiologies

2019 ◽  
Vol 57 (1) ◽  
pp. 37-46
Author(s):  
Adela Turcanu ◽  
Ecaterina Pitel ◽  
Vlada-Tatiana Dumbrava ◽  
Eugen Tcaciuc ◽  
Ana Donscaia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Hepatitis Virus ◽  
Primary Liver Cancer ◽  
Virus Surface ◽  
Primary Liver Tumors ◽  
B Virus ◽  
Tertiary Healthcare ◽  
Serum Alpha Fetoprotein ◽  
The Republic

Abstract Introduction. Moldova is the European country with the highest incidence of hepatocellular carcinoma (HCC) in both sexes. There is, however, no data comprehensively describing the presentation and the risk factors of HCC in the country. We decided to analyze cases of HCC recently received in a tertiary healthcare Institution from Chisinau, the Moldovian capital. Methods. A series of 148 primary liver tumors including 139 cases of HCC were retrospectively analyzed for demographic features, serological and biochemical data, and clinical presentation. Results. The mean age of patients was 59 ± 10 years (range: 19-66) with a M:F sex ratio of 1.9. Tumors appeared on full-blown liver cirrhosis in 83% of cases and were composed of multiple nodules at diagnosis in 36% of patients. Serum Alpha-fetoprotein was exceeding 10ng/mL in 76% of cases. Liver tumor and hepatitis were co-discovered in 34% of cases. More than 81% of hepatocellular carcinomas were associated with at least one hepatitis virus. Carriers of anti-hepatitis C virus were predominating (55% of cases) over patients seropositive for hepatitis B virus surface antigen (36%). Half of the latter were also infected with hepatitis Delta virus. In total, dual or triple infections were present in 24% and 7% of cases. Conclusions. The burden of infections with hepatitis viruses is particularly important in Moldova and corresponds to a situation commonly observed in countries of the Southern hemisphere. A pro-active policy of screening for persistent liver infection targeting population at risk of HCC (> 50 years) and coupled with the distribution of antivirals in positive cases should be rapidly implemented in Moldova to reduce incidence or primary liver cancer.

scholarly journals Early Exposure to Gut Microbiome Reduces Hepatocellular Carcinoma Risks in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yang-Ming Lee ◽  
Wei-Chun Chang ◽  
Fu-Ju Lei ◽  
Chew-Teng Kor ◽  
Hsueh-Chou Lai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Tumors ◽  
Male Mice ◽  
Germ Free ◽  
Housing Environment ◽  
Male Sex ◽  
Group 10 ◽  
Group 5

Aims. Liver cancer is a multietiological disease that has multiple factors contributing to the hepatocarcinogenic process, e.g., hepatitis viruses, carcinogens, male sex, or metabolic factors. Notably, emerging evidence reported that gut microbiota is crucial to the pathogenesis of hepatocellular carcinoma (HCC) via activation of innate immunity. However, the effect of time to gut microbiota exposure after birth is unknown. Using a germ-free animal housing environment, instead of antibiotics, we examined the effects of various time-to-exposure (TTE) to gut microbiota durations on HCC risk. Methods. HBV or carcinogen-mediated spontaneous HCC models were implemented in this study. The HCC incidence rates in mice either kept germ-free (GF; that is, with no exposure to gut microbiota) or exposed to gut microbiota after being moved to a specific pathogen-free (SPF) housing environment and with various time-to-exposure (TTE) durations, namely, 5 weeks after birth, 10 weeks after birth, or since conception (that is, 5-week TTE group, 10-week TTE group, and SPF group, respectively), were recorded. The mice were sacrificed at 30 or 40 weeks after birth, and macro-/microscopic observations and pathological diagnosis were performed. Results. The incidence of liver tumors among the male mice was higher than that among the female mice in the carcinogen-induced HCC mice sacrificed at 40 weeks after birth (with P=0.011, 0.035, 0.0003, and 0.012, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). Similarly, in the HBV-HCC model, the incidence of liver tumors among the male mice was significantly higher than that among the female mice (with P=0.013, 0.020, 0.012, and 0.002, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). These results suggest that gut microbiota exposure is irrelevant to the male sex preference of HCC. Surprisingly, when comparing carcinogen-induced HCC male mice in the 10-week TTE group (90%; n=10), 5-week TTE group (56%; n=9), and SPF group (30%; n=10) (P=0.020), we found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Similarly, when comparing HBV-HCC male mice in the 10-week TTE group (100%; n=11), 5-week TTE group (70%; n=10), and SPF group (33%; n=9) (P=0.080), we also found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Conclusions. Early (prepubertal) exposure to gut microbiome reduces the risk of HCC development, indicating a potentially important factor for cancer surveillance. Exploring the mechanisms by which such exposure affects HCC risk might lead to novel cancer vaccines.

scholarly journals Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

2018 ◽  
Vol 51 (1) ◽  
pp. 290-300 ◽  
Author(s):  
Chenxing Zhang ◽  
Chenyue Zhang ◽  
Jiamao Lin ◽  
Haiyong Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Critical Role ◽  
Roc Curves ◽  
Altered Expression ◽  
Qrt Pcr ◽  
Specificity And Sensitivity ◽  
Tumor Tissues ◽  
Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

scholarly journals Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors

2020 ◽  
Author(s):  
Leigh Anne Dageforde ◽  
Neeta Vachharajani ◽  
Parissa Tabrizian ◽  
Vatche Agopian ◽  
Karim Halazun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Tumors
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