Research progress and prospects of markers for liver cancer stem cells

Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell(CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells(LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.

Risk factors of poor prognosis and portal vein tumor thrombosis after curative resection of solitary hepatocellular carcinoma

BACKGROUND:Predictors of poor prognosis of solitary hepatocellular carcinoma(SHCC),a subgroup encompassing most patients with the malignancy,are still controversial.Hence,risk factors for portal vein tumor thrombosis(PVTT) in SHCC are obscure.The present study was designed to address this issue.METHOD:Clinicopathological and follow-up data for 156 consecutive patients with SHCC following curative hepatic resection were analyzed using uni-and multi-variate analyses.RESULTS:Univariate analysis showed that PVTT,tumornode-metastasis(TNM) stage,Edmondson-Steiner grade and preoperative serum alpha-fetoprotein(AFP) level were associated with the overall and disease-free survival,whereas tumor size only influenced the overall survival.In multivariate Cox regression tests,Edmondson-Steiner grade and TNM stage were independent prognostic markers for both overall and diseasefree survival.In addition,the Chi-square test showed that AFP level and Edmondson-Steiner grade were correlated with PVTT.Among them,only Edmondson-Steiner grade was shown to be of independent significance for PVTT in multi-variate logistic regression analysis.Additionally,AFP,the sole preoperative factor for PVTT,was not adequately sensitive and specific.CONCLUSIONS:Factors relating to post-surgical prognosis and PVTT in SHCC are all tumor-related.Of these,EdmondsonSteiner grade and TNM stage might be of particular importance in survival analysis.In addition,accurate prediction of PVTT by clinicopathological parameters before surgery remains difficult.

Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma

AIM: To investigate the relationship between ARID1 A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma(IHCC).METHODS: We assessed ARID1 A protein and m RNA expression in IHCC tissues and paracarcinomatous(PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ2 tests to analyze relationships between clinicopathological parameters and ARID1 A expression. The Kaplan-Meier method and Cox regression were used to analyze survival.RESULTS: The mean ARID1 A protein level in IHCC tissues was 1.16 ± 0.36 relative units(RU), which was significantly lower than that in PC tissues(1.26 ± 0.21 RU, P < 0.01) and NL tissues(1.11 ± 0.31, P < 0.001).The mean ARID1 A m RNA level in IHCC tissues(1.20 ± 0.18) was also lower than that in PC tissues(1.27 ± 0.15, P < 0.001) and normal liver tissues(1.15 ± 0.34, P < 0.001). Low ARID1 A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival(OS) and disease-free survival(DFS) for the low ARID1 A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1 A expression group at 25.0 and 22.0 mo(OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1 A expression was significantly associated with worse OS(HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses.CONCLUSION: Low expression of ARID1 A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.

Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis

AIM: To compare kinesin family member 1B(KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma(HCC) patients.METHODS: KIF1 B protein and m RNA expression was assessed in HCC and paracarcinomatous(PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1 B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups.RESULTS: Mean protein and m RNA levels of KIF1 B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1 B protein levels compared to those without vein invasions(2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1 B protein levels in HCC tissues from patients with recurrence during the followup period were significantly lower than those without recurrence(2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1 B protein and m RNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1 B m RNA expression in HCC tissues to those in PC tissues were correlated with overall survival(13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival(11.5 mo vs 19.5 mo, P < 0.05).CONCLUSION: Downregulation of KIF1 B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1 B can serve as a prognostic marker.

Serial therapies oriented by surgery for large primary liver carcinoma

Objective: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of pri- mary large liver cancers. Methods: From January 1993 to June 1999, 191 pa- tients with large liver carcinoma were treated surgi- cally. The size of tumors varied from 5.2 to 19.7 cm (mean 9.4 cm). Several types of liver resections were made in 121 patients and as a supplement, cry- osurgery was carried out for the remaining 70 pa- tients. Importable drug delivery system was institu- ted intraoperatively. Transcatheter arterial chemo- embolization (THP 30-60 mg, E-ADM 20-40 mg, CDDP 40-80 mg, MMC 10-20 mg, iodin oil 5-30 ml), percutaneous ethanol injection, bioimmunother- apy and traditional Chinese medicine were used pre- and post-operatively. CT angiography and CT dur- ing arterial portography were used to find satellite nodules. Early stage recurrences were predicted by AFPmRNA in peripheral blood. Child-Pugh's classi- fication plus branch chain amino acid/aromatic ami- no acid ratio (BCAA/AAA) was adopted in evalua- ting pre-operative liver functions. Results: Marked results were observed after serial treatments oriented by surgery. The 1-, 3- and 5- year survival rates in resection group were 75.8 %, 45.6% and 30.4%. respectively. The 1- and 3-year survival rates in cryosurgery group were 63.2 % and 37.0 %. The operative mortality was 1.57 %. Recur- rence rates were 69.2 % in AFPmRNA positive group and 33.3% in AFPmRNA negative group (P< 0.05). The BCAA/AAA ratio was lower than 1.5 in two patients who died of hepatic failure after resec- tion. Conclusions: Serial treatments with surgery as the chief modality gives satisfactory results in patients with large primary liver carcinoma. This regimen should be regarded as a main strategy to deal with large liver carcinoma. AFPmRNA in the peripheral blood, signifying a recurrence, may become a new clinical parameter. The BCAA/AAA ratio plus Child-Pugh's classification is able to evaluate more accurately liver function reserve before surgery.

Hepatic trisegmentectomy for 29 patients with huge liver neoplasms

Objective: To evaluate retrospectively the feasibility and effect of hepatic trisegmentectomy in therapy of huge neoplasms of the liver. Methods: From July 1993 to October 1999, 29 pa- tients with huge hepatic neoplasms underwent hepatic trisegmentectomy. Of these, 23 patients suffered from primary liver cancer, 1 hepatic infiltration of gallbladder cancer, 1 metastasis of colon cancer, 1 hepatic angiosarcoma, 1 hepatic neurofibroma, and 2 huge liver cysts. Twenty-six patients were subjected to right trisegmentectomy and the rest 3 left triseg- mentectomy. All trisegmentectomies were performed under normothermic interruption of the porta hepatis at single time and these interruptions lasted 15 to 40 minutes. Results: The relatively good effect was seen in our se- ries. The 1-, 3-, 5-year survival rates for primary liver cancer patients were 63.6%, 36.4% and 27.3 %, respectively. The survival period for the pa- tients with hepatic infiltration of gallbladder cancer and liver metastasis of colon cancer was 6 months. Those with hepatic angiosarcoma, hepatic neurofi- broma and huge liver cysts have been surviving 35, 26, 25 and 40 months, respectively. Major complica- tions were noted in 5 patients, and one (3.4%, 1/29) died. Conclusion: Hepatic trisegmentectomy is safe and ef- fective in treatment of huge hepatic neoplasms if its indications and operative techniques are properly mastered.

Both the 5th and 6th Editions of TNM Staging System Fail to Independently Predict Long-term Prognosis after Radical Hepatectomy in Hepatocellular Carcinoma Sized > or = 5cm

Objective To validate the predictive power of the 5th and 6th editions of TNM staging system(TNM-5,TNM-6) in a Chinese patient cohort with hepatocellular carcinoma(HCC) sized > or = 5 cm after radical hepatectomy.Methods Consecutive 121 patients with HCC sized > or = 5 cm undergoing radical hepatectomy between January 1995 and December 2002 were included.The impact of clinicopathological variables on prognosis was determined by univariate and multivariate analyses,after excluding 2 perioperative deaths.Results In univariate analysis,TNM-5 stage did not show prognostic significance for overall or disease-free survival,as opposed to TNM-6 stage,Edmondson-Steiner grade,portal vein tumor thrombosis(PVTT),vascular invasion,satellite nodule,Child-Pugh grade,and hepatitis B surface antigen(HBsAg) positivity.When these significant variables were entered in multivariate analysis,Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival,whereas Child-Pugh grade independently influenced disease-free survival.However,TNM-6 stage lost its predictive potential in multivariate analysis.Conclusions Neither TNM-5 nor TNM-6 staging system is revealed to be independently prognostic in patients with HCC sized > or = 5 cm after radical hepatectomy.Therefore,TNM-6 calls for more support in many subsets of HCC patients.

Highly anti-corrosive NiFe LDHs–NiFe alloy hybrid enables long-term stable alkaline seawater electrolysis

Owing to the significant potential of alkalin seawater electrolysis for converting surplus power into eco friendly hydrogen fuel,we developed bifunctional elec trodes that integrate low-crystalline NiFe LDHs and amorphous NiFe alloy on a Ni foam(NF)substrate to enhance this process.Driven by the battery-like charac teristics of NiFe LDHs,an anti-corrosive and active oute layer of NiFe^(vac)OOH continuously forms over time in th hybrid on the anode for the oxygen evolution reaction(OER),effectively mitigating powder shedding caused by corrosion induced by multiple anions in seawater.Mean while,the strong bond between the hybrid and the NF substrate maintains intact hybrid coatings to ensure a rel atively high overall conductivity of the electrodes,signif icantly reducing the negative effects of structura degradation during the OER and hydrogen evolution reaction(HER),as well as the accumulation of contami nants on the electrode surfaces.In long-term tests,thes bifunctionalhybridelectrodesmaintained stable performance,even at a high current density o500 mA·cm^(-2).The cell voltage increased by only 88 m V over 1000 h to 1.970 V during saline electrolysis and by103 mV over 500 h to 2.062 V during seawater electroly sis.Hence,this study provides valuable insights into efficient and stable seawater electrolysis using NiFe LDHs–NiFe alloy hybrids.

Constructing robust NiFe LDHs-NiFe alloy gradient hybrid bifunctional catalyst for overall water splitting:one-step electrodeposition and surface reconstruction

NiFe layered double hydroxides(NiFe LDHs)have been intensively developed for the oxygen evolution reaction(OER)in alkaline media;however,their unsatisfactory hydrogen evolution reaction(HER)performance limits their practical application in overall water splitting.Herein,a simple and efficient one-step electrodeposition method is used to accomplish in situ growth of NiFe LDHsNiFe alloy gradient hybrid coatings on a carbon cloth(CC).Within the binder-free electrode,NiFe LDHs nanosheets with a low-crystalline nature exhibit highly active bifunctional OER/HER activities,and the NiFe alloy acts as a stable electron highway and strong skeleton bridge between NiFe LDHs and the CC.When the electrodes are simultaneously employed as the cathode and anode for overall water splitting,they require low cell potentials of 1.441 V at10 mA·cm^(-2)and 1.703 V at 100 mA·cm^(-2),respectively,and they demonstrate outstanding stability at a current density greater than 100 mA·cm^(-2)for more than 100 h.This is one of the best bifunctional OER and HER catalysts for overall water splitting.Both lattice defects and surface reconstructions crucially contribute to the bifunctional OER/HER activities of NiFe LDHs.This simple and scalable synthesis approach presents an intriguing paradigm for industrial production,and the fabricated electrode has potential application in high-current-density water splitting.