Post-transplant malignancy:Focusing on virus-associated etiologies,pathogenesis,evidence-based management algorithms,present status of adoptive immunotherapy and future directions

Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and associated cancers by impairing immune response against viruses and cancer immunoediting.This review reflects the magnitude,etiology and immunological characteristics of various virus-related post-transplant malignancies,emphasizing the need for future research.A multidisciplinary and strategic approach may serve best but overall literature evidence targeting it is sparse.However,the authors attempted to provide a more detailed update of the literature consensus for the prevention,diagnosis,management and surveillance of post-transplant viral infections and associated malignancies,with a focus on the current role of adoptive immunotherapy and the way forward.In order to achieve long-term patient and graft survival as well as superior post-transplant outcomes,collaborative research on holistic care of organ recipients is imperative.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal

AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by immunohistochemistry.RESULTS The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

Development of Epstein-Barr virus-associated gastric cancer:Infection,inflammation,and oncogenesis

Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.

Protective effects of curcumin against human immunodeficiency virus 1 gp120 V3 loop-induced neuronal injury in rats

Curcumin improves the learning and memory deficits in rats induced by the gp120 V3 loop. The present study cultured rat hippocampal neurons with 1 nM gp120 V3 loop and 1 μM curcumin for 24 hours. The results showed that curcumin inhibited the gp120 V3 loop-induced mitochondrial membrane potential decrease, reduced the mRNA expression of the pro-apoptotic gene caspase-3, and attenuated hippocampal neuronal injury.

Fatty liver is associated with an increased risk of diabetes and cardiovascular disease- Evidence from three different disease models: NAFLD, HCV and HIV

Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

Gastric submucosa-invasive carcinoma associated with EpsteinBarr virus and endoscopic submucosal dissection: A case report

BACKGROUND Epstein-Barr virus(EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma(GCLS).Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas.Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.CASE SUMMARY We present two GCLS cases subjected to endoscopic submucosal dissection(ESD)for a definitive diagnosis.A protruded gastric lesion was identified by routine endoscopic examination,but forceps biopsy showed no atypical cells before ESD.The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa.The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma.Accordingly,additional gastrectomy was recommended to obtain a complete cure.One patient underwent additional distal gastrectomy with lymph node dissection,but the other was refused because of cardiovascular complications.Both patients remained in remission for more than half a year.EBV positivity was determined by EBV-encoded RNA in situ hybridization.We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.CONCLUSION Submucosa-invasive GCLS could be dissected using ESD,and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required.Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.

Hepatitis B virus molecular biology and pathogenesis

As obligate intracellular parasites,viruses need a host cell to provide a milieu favorable to viral replication.Consequently,viruses often adopt mechanisms to subvert host cellular signaling processes.While beneficial for the viral replication cycle,virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis,including,for oncogenic viruses,cell transformation and cancer progression.Included among these oncogenic viruses is the hepatitis B virus(HBV).Despite the availability of an HBV vaccine,350-500 million people worldwide are chronically infected with HBV,and a significant number of these chronically infected individuals will develop hepatocellular carcinoma(HCC).Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC.Globally,HCC is the second highest cause of cancer-associated deaths,underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC.HBV is the prototype member of the Hepadnaviridae family;members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts.The extremely small and compact hepadnaviral genome,the unique arrangement of open reading frames,and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae.In this review,the authors provide a comprehensive description of HBV biology,summarize the model systems used for studying HBV infections,and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC.For example,the HBV X protein(HBx),a key regulatory HBV protein that is important for HBV replication,is thought to play a cofactor role in the development of HBV-induced HCC,and the authors highlight the functions of HBx that may contribute to the development of HBV-associated HCC.

The 150 most important questions in cancer research and clinical oncology series: questions 86-93

Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which spark diverse thoughts,interesting communications,and potential collabora-tions among researchers all over the world.In this article,8 more questions are presented as follows.Question 86.In which circumstances is good supportive care associated with a survival advantage in patients with cancer?Question 87.Can we develop animal models to mimic immunotherapy response of cancer patients?Question 88.What are the mechanisms underlying hepatitis B virus-associated non-hepatocellular cancers?Question 89.Can we more pre-cisely target tumor metabolism by identifying individual patients who would benefit from the treatment?Question 90.What type of cranial irradiation-based prophylactic therapy combination can dramatically improve the survival of patients with extensive small-cell lung cancer?Question 91.How can postoperative radiotherapy prolong overall survival of the patients with resected pIIIA-N2 non-small cell lung cancer?Question 92.What are the key molecular events that drive oral leukoplakia or erythroplakia into oral cancer?Question 93.How could we track the chemothera-peutics-driven evolution of tumor genome in non-small cell lung cancer for more effective treatment?