Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

Laparoscopic total extraperitoneal inguinal hernia repair is safe and feasible in patients with continuation of antithrombotics.

AIMS: We aimed to evaluate the safety and feasibility of laparoscopic total extraperitoneal (TEP) inguinal hernia repair in patients with the continuation of their antithrombotic agents. SETTINGS AND DESIGN: This was prospective cohort study. MATERIALS AND METHODS: A total of 115 patients who underwent TEP inguinal hernia repair between January 2015 and September 2016 were included in the analysis. Seventeen patients continued their antithrombotics (antithrombotic group); the other 98 had not been on antithrombotics (control group). STATISTICAL ANALYSIS USED: The analysis was performed by using Mann-Whitney U-test, Chi-square or Fisher's exact test. RESULTS: The antithrombotic group had a greater mean age (65.9 ± 8.0 vs. 57.7 ± 13.6,P= 0.002) and higher prevalence of hypertension (64.7% vs. 33.7%,P= 0.015), cardiovascular diseases (64.7% vs. 7.1%,P < 0.001), atrial fibrillation (23.5% vs. 0,P < 0.001), ischaemic heart disease (35.3% vs. 0,P < 0.001) and the American Society of Anaesthesiologists ≥2 (94.1% vs. 81.6%,P= 0.005). The operation time for the antithrombotic group was longer than that of the control group (92.06 ± 32.81 min vs. 72.33 ± 20.99 min,P= 0.015). None experienced conversion to open surgery in either group. There was no difference in the post-operative complications (29.4% vs. 28.6%) and sero-haematoma formation (23.5% vs. 11.1%). The analgesic requirement, hospital stays (23.72 ± 7.74 vs. 22.35 ± 10.33 h) and the time for return to normal daily activity (3.56 ± 1.74 vs. 3.63 ± 1.90) were not statistically different between the two groups. None in either group experienced major cardiovascular events within 30 days. CONCLUSIONS: Laparoscopic TEP inguinal hernia repair can be safely performed in patients with the continuation of their antithrombotic agents in experienced hands.

Is vegetarian diet associated with a lower risk of breast cancer in Taiwanese women?

BACKGROUND: Studies on the relationship between vegetarian diet and breast cancer in Asian populations are limited. This study aimed to investigate the relationship between vegetarian diet, dietary patterns, and breast cancer in Taiwanese women. METHODS: This case-control study compared the dietary patterns of 233 breast cancer patients and 236 age-matched controls. A questionnaire about vegetarian diets and 28 frequently-consumed food items was administered to these 469 patients in the surgical department of Taipei Tzu Chi Hospital. Serum biochemical status was also examined. RESULTS: There were no significant differences between the two groups for age, education, family history, oral contraceptive usage, or regular exercise. However, the cancer group presented with both a higher body mass index and an older age of primiparity (P < 0.05). Two food items (shellfish and seafood) were highly correlated (correlation coefficient = 0.77), so shellfish was excluded to avoid multicollinearity. A factor analysis of 27 food items produced five dietary patterns: meat, processed meat, fruit/vegetable/soybean, dessert/sugar, and fermented food. Multivariate logistic regression showed that meat/fat and processed meat dietary patterns were associated with breast cancer risk (odds ratio (OR): 2.22, 95% CI 1.67-2.94, P < 0.001; OR: 1.49, 95% CI 1.09-2.04, P = 0.013, respectively). Vegetarian diet, high isoflavone intake, and high albumin levels were inversely associated with breast cancer risk (P < 0.05). Vegetarians had a higher daily soy isoflavone intake than non-vegetarians (25.9 ± 25.6 mg vs. 18.1 ± 15.6 mg, P < 0.001). CONCLUSIONS: Vegetarian diets show as protective role against breast cancer risk, while meat and processed meat dietary patterns are associated with a higher breast cancer risk.

Efficacy and Safety of Sorafenib or Lenvatinib for Advanced Hepatocellular Carcinoma after Failure of First-Line Atezolizumab Plus Bevacizumab: A Systematic Review and Meta-Analysis.

BACKGROUND: Although atezolizumab plus bevacizumab (hereinafter, atezolizumab-bevacizumab) is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. This study evaluated the efficacy and safety of sorafenib and lenvatinib in patients with advanced HCC that progressed under atezolizumab-bevacizumab treatment. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and the Cochrane Library for articles published before November 2023. Random-effects meta-analysis was performed to determine the pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), comparing patients who received sorafenib versus lenvatinib. RESULTS: Seven studies involving 387 patients were included. The pooled ORR, DCR, OS, and PFS for sorafenib and lenvatinib together were 26% (95% CI: 14-43%), 63% (95% CI: 47-77%), 11.45 months (95% CI: 7.12-15.77, I2 = 92%, p < 0.01), and 3.78 months (95% CI: 2.34-5.23, I2 = 67%, p = 0.02), respectively. Although lenvatinib users had a longer median OS (12.42 vs. 10.75 months) and PFS (5.15 vs. 2.58 months) than sorafenib users, the pooled ORR, DCR, median OS, and PFS for these medications were comparable. Additionally, the distributions of all-grade and grade ≥ 3 adverse events for sorafenib and lenvatinib were comparable to those for these two medications when used as first-line therapies. CONCLUSIONS: Sorafenib or lenvatinib can provide effective treatment with manageable toxicity in patients with advanced HCC after disease progression under atezolizumab-bevacizumab.

Antioxidants cause rapid expansion of human adipose-derived mesenchymal stem cells via CDK and CDK inhibitor regulation.

BACKGROUND: Antioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs) in vitro, although the detailed mechanism(s) and potential side effects are not fully understood. RESULTS: During log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions. CONCLUSION: Antioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.

Synchronous but separate neuroendocrine tumor and high-grade dysplasia/adenoma of the gall bladder: A case report.

BACKGROUND: Gall bladder neuroendocrine tumors (GB-NETs) are rare, accounting for less than 0.5% of all NETs. They usually lack specific symptoms and are difficult to diagnose preoperatively. In most cases, GB-NETs are incidentally found after cholecystectomy for large polyps or cholelithiasis, causing acute or chronic cholecystitis. The coexistence of GB-NET and GB adenocarcinoma is very rare. CASE SUMMARY: We report a case of synchronous but separate GB-NET and adenoma with high-grade dysplasia in a patient who had undergone surgery for a progressively growing GB polypoid lesion. To the best of our knowledge, simultaneous separation of NETs and cancer in the GB has not been reported. CONCLUSION: Coexistent GB carcinoid tumor and adenocarcinoma is rare. A surveillance program is needed for these large GB polyps.

Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Transarterial chemoembolization with or without sorafenib for hepatocellular carcinoma: A real-world propensity score-matched study.

Objectives: Transarterial chemoembolization (TACE) or sorafenib may prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, whether their combination prolongs survival than TACE alone remains controversial. We aimed to compare the overall survival (OS) of patients with unresectable HCC treated with TACE plus sorafenib (TACE-S) versus TACE alone. Materials and Methods: All patients with unresectable HCC who received TACE as the initial therapy between January 2006 and January 2017 at Taipei Tzu Chi Hospital were enrolled. We matched patients treated with TACE-S and those treated with TACE alone (TACE) by performing propensity score matching at a 1:2 ratio. Our primary outcome was OS during a 10-year follow-up period, and represented as a hazard ratio calculated using Cox proportional hazard regression models. Results: Among 515 patients with unresectable HCC were treated initially with TACE, 56 receiving TACE-S group and 112 receiving TACE alone (TACE group) were included in the primary outcome analysis. The TACE-S group had significantly longer median OS than did the TACE group (1.55 vs. 0.32, years; P < 0.001), and the 5-year OS rates was 10.7% in the TACE-S group and 0.9% in the TACE group (P < 0.001). In multivariate analyses, patients with a lower Child-Pugh score, tumor size ≤5 cm, and no extrahepatic metastasis before treatment and those receiving antiviral agents and receiving TACE-S had longer OS (all P < 0.001). Conclusion: Antiviral agents and the combination of TACE with sorafenib may improve the OS of patients with unresectable HCC.

Evaluating the benefit of adjuvant radiotherapy after extensive lymph node dissection for gastric cancer: a single-institute retrospective study.

OBJECTIVE: This study aimed to evaluate whether adjuvant radiotherapy (RT) can improve the treatment outcome of patients with locally advanced gastric cancer who underwent extensive lymph node dissection (ELND). MATERIALS AND METHODS: This retrospective study included patients with gastric cancer pathological stages IIA-IIIC at Taipei Tzu Chi Hospital between 2008 and 2015. Patients (a) aged >80 years, (b) with distant metastasis at diagnosis, (c) with coexisting malignancies, (d) who did not complete the prescribed RT course, and (e) who died 1 month after surgery were excluded. Among 420 patients diagnosed with gastric cancer, 98 were included. RESULTS: The median follow-up was 24.5 months. Of 39 patients who underwent adjuvant RT, 38 also received adjuvant chemotherapy (CT). Of 59 patients who did not receive adjuvant RT, only 34 received adjuvant CT. ELND was performed in 67.3% of the patients. The 5-year overall survival (OS) rate was 40%. In the univariate analyses, adjuvant CT regimen, 5-fluorouracil + leucovorin, was associated with worst outcome, while TS-1 was associated with better survival outcome (P = 0.018). The number of involved lymph nodes was strongly related to the OS and disease-free survival (DFS) (P < 0.001). We tried using different numbers of involved lymph nodes as a cutoff point and found that adjuvant RT significantly improved both OS and DFS in patients whose involved lymph nodes were ≥4 (OS, P = 0.017; DFS, P = 0.015). In multivariate analyses, better DFS was associated with negative surgical margin (P = 0.04), earlier disease stage (P = 0.001), adjuvant radiotherapy (P = 0.045), and adjuvant CT regimen TS-1 (P = 0.001). CONCLUSION: Adjuvant RT could improve DFS of patients with locally advanced gastric cancer with or without ELND. When the number of involved lymph nodes is ≥4, adjuvant RT is strongly suggested.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

Open versus minilaparoscopic herniorrhaphy for children: a prospective comparative trial with midterm follow-up evaluation.

BACKGROUND: A prospective clinical trial was designed to compare the midterm surgical and functional results between open (OR) and minilaparoscopic (MR) herniorrhaphy repairs for pediatric inguinal hernia. METHODS: Between May 2005 and May 2008, 174 children with inguinal hernias were prospectively enrolled for either open or minilaparoscopic hernia repair. Of these children, 65 underwent open herniorrhaphy and 109 underwent minilaparoscopic herniorrhaphy. The postoperative functional status, pain, complications, and overall satisfaction were documented at outpatient clinic visits for analysis. RESULTS: During the study period, 35 patients were lost to follow-up evaluation and thus excluded. The mean follow-up period was about 2 years, and the baseline characteristics were matched between the two groups. The patients in the MR group had recurrence rates, postoperative pain, complications, and functional recovery comparable with those in the OR group. None in the MR patients experienced a contralateral metachronous inguinal hernia compared with 9.7% of the OR patients (p = 0.02). The MR patients had a higher rate of overall satisfaction than the OR patients (p = 0.03). CONCLUSIONS: Minilaparoscopic herniorrhaphy was superior to open repair with regard to prevention of contralateral hernia occurrence and overall satisfaction.

Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion.

BACKGROUND/AIM: Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) has been identified as a tumor suppressor in human cancers. Present study, we assessed biological role of LITAF in human gastric cancer. MATERIALS AND METHODS: The clinical impacts of LITAF expression were assessed in gastric cancer using public databases. The biological role of LITAF was assessed in gastric cancer cells using siLITAF transfection. RESULTS: High LITAF expression was correlated well with worse prognosis, including pathological stage (p=0.034) and pathological T stage (p=0.047), as well as with shorter survival. Herein, we present a novel finding that miR-1-3p could inhibit LITAF expression by directly binding to the 3'-untranslated region of LITAF mRNA. Cell functional assays revealed that LITAF knockdown could significantly suppress gastric cancer growth and motility. CONCLUSION: High LITAF expression resulting from low miR-1-3p expression is a biomarker for poor prognosis or therapeutic targets in gastric cancer.

Feasibility and safety of elective laparoscopic total extraperitoneal preperitoneal groin hernia repair in the elderly: a propensity score-matched comparison.

BACKGROUND: Several studies of hernia registries have revealed that elderly patients have higher perioperative complication rates compared with younger patients. However, the incidence of hernia increases with the aging process. To evaluate the feasibility and safety of laparoscopic hernia repair in elderly patients (≥75 years), we conducted a prospective case-matched control study to compare perioperative outcomes between patients older and younger than 75 years. METHODS: Between September 2008 and July 2015, 572 consecutive patients undergoing endoscopic hernia repair were included in this prospective study. This case-matched control study was matched based on sex, American Society of Anesthesiologists score, and body mass index between patients younger and ≥75 years. The propensity-score matching of two groups was carried out on a 1:1 basis. Perioperative data were prospectively recorded for all patients including demographic data, operation time, length of hospital stay, narcotic dose, and complications. RESULTS: In the final analysis, 54 patients who were <75 years were extracted to match the 54 patients ≥75 years. These two groups had similar baseline characteristics excluding age. They also had similar perioperative outcomes in hernia recurrence, metachronous contralateral hernia occurrence, complication rate and chronic pain. The patients ≥75 years of age had lower requirements for analgesics than those who were <75 years of age (p=0.047). CONCLUSION: This is the first comparative cohort study investigating the impact of aging in an Asian hernia population. Laparoscopic inguinal hernia repair is feasible and safe for older patients, with comparable perioperative outcomes to patients <75 years.

Is contralateral exploration justified in endoscopic total extraperitoneal repair of clinical unilateral groin hernias - A Prospective cohort study.

BACKGROUND: Laparoscopic adult hernia repair has the clinical advantage of allowing the surgeon to explore asymptomatic contralateral inguinal hernia. We conduct a retrospective study to compare the occurrence of contralateral metachronous inguinal hernia (CMIH) after laparoscopic total extraperitoneal (TEP) repair with or without contralateral exploration. METHODS: One hundred and fifty-one consecutive patients undergoing unilateral laparoscopic TEP repair during November 2007 to November 2012 were enrolled into groups with contralateral or no contralateral exploration. Preoperative, intraoperative, and postoperative factors were recorded then reviewed for analysis. The primary end-point was the occurrence of contralateral inguinal hernia. The patients were regularly interviewed postoperatively at outpatient clinics. RESULTS: Finally, 68 patients in the exploration group and 46 in the non-exploration group were eligible for analysis. All demographic data, except age, was comparable between the two groups. Twenty-three of 68 (33.8%) in the exploration cohort had at least one occult contralateral inguinal hernia detected and repaired at the time of primary repair. In contrast to the high incidence (6/46, 13%) of CMIH in the non-exploration cohort, there was only one metachronous occurrence (1/68, 1.4%) after negative contralateral exploration at a median follow-up of longer than 3 yrs (p = 0.02). The peri-operative results were comparable between groups regarding operative time, analgesic requirements, complications, and chronic pain. CONCLUSIONS: Simultaneous exploration and repair of the incidental defects on the contralateral inguinal region during laparoscopic TEP repair of unilateral inguinal hernia is recommended in selected patients based on its high safety and clinical effectiveness in preventing later CMIH.

The Tail Associated Protein of Acinetobacter baumannii Phage ΦAB6 Is the Host Specificity Determinant Possessing Exopolysaccharide Depolymerase Activity.

Acinetobacter baumannii is a non-fermenting, gram-negative bacterium. In recent years, the frequency of A. baumannii infections has continued to increase, and multidrug-resistant strains are emerging in hospitalized patients. Therefore, as therapeutic options become limited, the potential of phages as natural antimicrobial agents to control infections is worth reconsidering. In our previous study, we isolated ten virulent double-stranded DNA A. baumannii phages, ϕAB1-9 and ϕAB11, and found that each has a narrow host range. Many reports indicate that receptor-binding protein of phage mediates host recognition; however, understanding of the specific interactions between A. baumannii and phages remains very limited. In this study, host determinants of A. baumannii phages were investigated. Sequence comparison of ϕAB6 and ϕAB1 revealed high degrees of conservation among their genes except the tail fiber protein (ORF41 in ϕAB1 and ORF40 in ϕAB6). Furthermore, we found that ORF40ϕAB6 has polysaccharide depolymerase activity capable of hydrolyzing the A. baumannii exopolysaccharide and is a component of the phage tail apparatus determining host specificity. Thus, the lytic phages and their associated depolymerase not only have potential as alternative therapeutic agents for treating A. baumannii infections but also provide useful and highly specific tools for studying host strain exopolysaccharides and producing glycoconjugate vaccines.

Left paraduodenal hernia presenting as recurrent small bowel obstruction.

Internal herniation of the small bowel is a relatively rare cause of intestinal obstruction. Left paraduodenal hernia resulting from abnormal rotation of the midgut during embryonic development is the most common form of congenital internal hernia. We report our experience in the diagnosis and management of a young male with left paraduodenal hernia presenting as recurrent intestinal obstruction. Correct preoperative diagnosis of left paraduodenal hernia had been difficult due to non-specific clinical presentations, but the advent of modern imaging technology makes early and correct diagnosis possible. Due to the risk of obstruction and strangulation, surgical treatment is indicated; however, timely intervention increases the likelihood of a favorable outcome.

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.

One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression.