Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

Correction to"Liu LP,Sheng XP,Shuai TK,Zhao YX,Li B,Li YM.Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.World J Gastroenterol 2018;24:4565-4577[PMID:30386106 DOI:10.3748/wjg.v24.i40.4565]."In this article,we have identified some of the images in Figure 2A,C,E,G,and I are identical to the images in Figures 1B,2A,3B,3E,and 3G of another paper entitled"Liu L,Zhao Y,Fan G,Shuai T,Li B,Li Y.Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.",which was published by us in the Molecular Medicine Reports in December,2018[PMID:30320396 DOI:10.3892/mmr.2018.9558].The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology(WJG)and Molecular Medicine Reports,we uploaded the wrong pictures to the WJG,which were same as those submitted to the Molecular Medicine Reports.We apologize for this negligence and any inconvenience that this may cause.We would be grateful if you could replace the wrong pictures with the correct ones attached.

Combined treatment for solid pseudopapillary tumor of the pancreas with liver metastasis

Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic disease. Generally, it is considered a benign or low-grade malignant tumor. SPT of the pancreas with liver metastasis or invasion to adjacent organs is usually uncommon.

Cyclooxygenase-2 promoter polymorphism -899G/C is associated with hepatitis B-related liver cancer in a Chinese population of Gansu province

Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. Cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B （CHB） patients, liver cirrhosis patients, and hepatocellular carcinoma （HCC） patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. Methods Patients were divided into four groups： 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. Results The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups （0R=2.835, 95%C/： 1.751-4.589）; HCC and CHB groups （OR=1.933, 95%C/： 1.248-2.994）; and HCC and liver cirrhosis groups （OR=1. 175, 95%C/： 1.119-2.628）. Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. Conclusion COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Accumulating evidence has suggested that the gap junction plays an important role in the determination of cerebral ischemia, but the underlying mechanisms remain to be elucidated. In this study, we assessed the effect of a gap-junction blocker, carbenoxolone （CBX）, on ischemia/reperfusion-induced brain injury and the possible mechanisms. By using the transient cerebral ischemia model induced by occlusion of the middle cerebral artery for 30 min followed by reperfusion for 24 h, we found that pre-administration of CBX （25 mg/kg, intracerebroventricular injection, 30 min before cerebral ischemic surgery） diminished the infarction size in rats. And this was associated with a decrease of reactive oxygen species generation and inhibition of the activation of astrocytes and microglia. In PC12 cells, H202 treatment induced more coupling and apoptosis, while CBX partly inhibited the opening of gap junctions and improved the cell viability. These results suggest that cerebral ischemia enhances the opening of gap junctions. Blocking the gap junction with CBX may attenuate the brain injury after cerebral ischemia/reperfusion by partially contributing to amelioration of the oxidative stress and apoptosis.

Identification of two novel mutations in the ATP7B gene that cause Wilson's disease

Background:Wilson's disease is an autosomal recessive disorder characterized by liver disease and/or neurologic deficits due to copper accumulation and is caused by pathogenic mutations in the ATP7B gene.Methods:Two unrelated Chinese patients born to nonconsanguineous parents who were diagnosed with earlyonset Wiison's disease.DNA sequencing and bioinformation analysis were conducted.Results:We have identified four mutations in two family trios,of which two were novel,namely,c.3028A>G(p.K1010E) and c3992T>G (p.Y1331X),in each patient.Conclusions:Gene testing is playing an important role in diagnosis of Wilson's disease.The early-onset of Wilson's disease is apparently not associated with P-ATPase domain in the ATP7B protein.Our findings further widen the spectrum of mutations involving the ATP7B gene.

The advances in immunotherapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the malignant tumors with higher incidence and mortality worldwide.Recently,significant progress has been made in uncovering immunotherapy in HCC,for instance programmed death-1,cytotoxic T-lymphocyte antigen 4,chimeric antigen receptor T-cell therapy,T cell receptor T cell therapy,dendritic cell vaccine,and cytokine-induced killer cells.This paper reviews the advances in immunotherapy and focuses on the results of many of preclinical studies and clinical trials in the field,as well as some of the promising therapeutic strategies for HCC in the future.