A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines.

Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.

ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.

The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the enzymatic activity of TMPRSS2 in a non-catalytic manner. Furthermore, we demonstrate that ACE2 knockdown inhibits TMPRSS2-mediated cleavage of IAV hemagglutinin (HA) in Calu-3 human airway cells and suppresses virus titers 100- to 1.000-fold. Transient expression of ACE2 in ACE2-deficient cells increased TMPRSS2-mediated HA cleavage and IAV replication. ACE2 knockdown also reduced titers of MERS-CoV and prevented S cleavage by TMPRSS2 in Calu-3 cells. By contrast, proteolytic activation and multicycle replication of IAV with multibasic HA cleavage site typically cleaved by furin were not affected by ACE2 knockdown. Co-immunoprecipitation analysis revealed that ACE2-TMPRSS2 interaction requires the enzymatic activity of TMPRSS2 and the carboxypeptidase domain of ACE2. Together, our data identify ACE2 as a new co-factor or stabilizer of TMPRSS2 activity and as a novel host cell factor involved in proteolytic activation and spread of IAV in human airway cells. Furthermore, our data indicate that ACE2 is involved in the TMPRSS2-catalyzed activation of additional respiratory viruses including MERS-CoV.IMPORTANCEProteolytic cleavage of viral envelope proteins by host cell proteases is essential for the infectivity of many viruses and relevant proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of several respiratory viruses, including influenza A virus. TMPRSS2 was previously shown to interact with angiotensin-converting enzyme 2 (ACE2). Here, we report the mechanistic details of this interaction. We demonstrate that ACE2 increases or stabilizes the enzymatic activity of TMPRSS2. Furthermore, we describe ACE2 involvement in TMPRSS2-catalyzed cleavage of the influenza A virus hemagglutinin and MERS-CoV spike protein in human airway cells. These findings expand our knowledge of the activation of respiratory viruses by TMPRSS2 and the host cell factors involved. In addition, our results could help to elucidate a physiological role for TMPRSS2.

The efficacy and tolerability of latency-reversing agents in reactivating the HIV-1 reservoir in clinical studies: a systematic review.

Introduction: Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies. Methods: A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration. Results: After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed. Conclusion: This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.

Diversity in Proprotein Convertase Reactivity among Human Papillomavirus Types.

The cleavage of viral surface proteins by furin is associated with some viruses' high virulence and infectivity. The human papillomavirus (HPV) requires the proteolytic processing of its capsid proteins for activation before entry. Variability in reactivity with furin and other proprotein convertases (PCs) among HPV types was investigated. HPV16, the most prevalent and carcinogenic HPV type, reacted with PCs with the broadest selectivity compared to other types in reactions of pseudoviral particles with the recombinant PCs, furin, PC4, PC5, PACE4, and PC7. Proteolytic preactivation was assessed using a well-established entry assay into PC-inhibited cells based on the green fluorescent protein as a reporter. The inhibition of the target cell PC activity with serpin-based PC-selective inhibitors also showed a diversity of PC selectivity among HPV types. HPV16 reacted with furin at the highest rate compared to the other types in time-dependent preactivation reactions and produced the highest entry values standardized to pseudoviral particle concentration. The predominant expression of furin in keratinocytes and the high reactivity of HPV16 with this enzyme highlight the importance of selectively targeting furin as a potential antiviral therapeutic approach.

Human papillomavirus infection with anogenital warts in a patient with chronic psoriasis: A case report.

Psoriasis is a chronic inflammatory disease with characteristic skin manifestations. Several pathogens can cause flare-ups of psoriasis. The risks of skin infections are increased in patients receiving immunomodulators. A patient with chronic psoriasis presented with human papillomavirus infection and anogenital warts and was treated surgically with acceptable results.

Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases.

Trypsin-like proteases (TLPs) belong to a family of serine enzymes with primary substrate specificities for the basic residues, lysine and arginine, in the P1 position. Whilst initially perceived as soluble enzymes that are extracellularly secreted, a number of novel TLPs that are anchored in the cell membrane have since been discovered. Muco-obstructive lung diseases (MucOLDs) are characterised by the accumulation of hyper-concentrated mucus in the small airways, leading to persistent inflammation, infection and dysregulated protease activity. Although neutrophilic serine proteases, particularly neutrophil elastase, have been implicated in the propagation of inflammation and local tissue destruction, it is likely that the serine TLPs also contribute to various disease-relevant processes given the roles that a number of these enzymes play in the activation of both the epithelial sodium channel (ENaC) and protease-activated receptor 2 (PAR2). More recently, significant attention has focused on the activation of viruses such as SARS-CoV-2 by host TLPs. The purpose of this review was to highlight key TLPs linked to the activation of ENaC and PAR2 and their association with airway dehydration and inflammatory signalling pathways, respectively. The role of TLPs in viral infectivity will also be discussed in the context of the inhibition of TLP activities and the potential of these proteases as therapeutic targets.

Strategies to identify hepatitis C virus infection in patients receiving anticancer therapy: a cross-sectional study.

BACKGROUND: Optimal hepatitis C virus (HCV) screening strategies for cancer patients have not been established. We compared the performance of selective HCV screening strategies. METHODS: We surveyed patients presenting for first systemic anticancer therapy during 2013-2014 for HCV risk factors. We estimated the prevalence of positivity for HCV antibody (anti-HCV) and examined factors associated with anti-HCV status using Fisher's exact test or Student's t test. Sensitivity was calculated for screening patients born during 1945-1965, patients with ≥ 1 other risk factor, or both cohorts ("combined screening"). RESULTS: We enrolled 2122 participants. Median age was 59 years (range, 18-91); 1138 participants were women. Race/ethnicity distribution was white non-Hispanic, 76% (n = 1616); Hispanic, 11% (n = 233); black non-Hispanic, 8% (n = 160); Asian, 4% (n = 78); and other, 2% (n = 35). Primary cancer distribution was non-liver solid tumor, 78% (n = 1664); hematologic cancer, 20% (n = 422); and liver cancer, 1% (n = 28). Prevalence of anti-HCV was 1.93% (95% CI, 1.39%-2.61%). Over 28% of patients with detectable HCV RNA were unaware of infection. Factors significantly associated with anti-HCV positivity included less than a bachelor's degree, birth in 1945-1965, chronic liver disease, injection drug use, and blood transfusion or organ transplant before 1992. A total of 1315 participants (62%), including 39 of 41 with anti-HCV, reported ≥ 1 risk factor. Sensitivity was 80% (95% CI, 65-91%) for birth-cohort-based, 68% (95% CI, 52-82%) for other-risk-factor-based, and 95% (95% 83-99%) for combined screening. CONCLUSION: Combined screening still missed 5% of patients with anti-HCV. These findings favor universal HCV screening to identify all HCV-infected cancer patients.

Cytomegalovirus Reactivation in Patients with Sepsis in an Intensive Care Unit in Portugal.

INTRODUCTION: In the last few years, cytomegalovirus reactivation has been considered an aggravating factor for septic patients in Intensive Care units. The main objectives of this study were to determine cytomegalovirus reactivation in patients with a diagnosis of sepsis admitted to an intensive care unit, and whether this reactivation was related to the evolution of the patient's clinical condition. MATERIAL AND METHODS: The detection of cytomegalovirus DNA was performed by real-time polymerase chain reaction and the concentration of nine cytokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL- TNF-α, and INFγ) were determined by a Multiplex ELISA technique. RESULTS: Eight of 22 septic patients (36.3%) from the Intensive Care Unit of the Hospital da Luz had cytomegalovirus reactivation. No association was found between cytomegalovirus reactivation and gender, age, length of Intensive Care unit stay, duration of mechanical ventilation, and patient death. No significant differences were found in cytokine concentrations in patients with and without reactivation. However, patients with cytomegalovirus reactivation had a longer hospital stay from Intensive Care unit entry to hospital discharge or patient death (p = 0.025). DISCUSSION: Despite the low sampling rate, the present study suggests that reactivation is a frequent event in patients diagnosed with sepsis and may be related to prolonged hospital stay in these patients. CONCLUSION: The overall analysis of the results obtained and the literature review do not support the concept that cytomegalovirus monitoring should be implemented in routine practice, but it seems prudent to wait for further randomized trials using antiviral prophylaxis, before assuming a definitive attitude towards the role of cytomegalovirus in sepsis.

Introdução: A reativação do citomegalovírus tem sido considerada um factor de agravamento nos doentes diagnosticados com sépsis nas unidades de Cuidados Intensivos. Os principais objetivos deste estudo consistiram na determinação da reativação do Cytomegalovirus em doentes internados numa unidade de Cuidados Intensivos com diagnóstico de sépsis, e se essa reativação estaria relacionada com a evolução do quadro clínico do doente.Material e Métodos: Na presente investigação foram estudados 22 doentes, internados com o diagnóstico de sépsis na Unidade de Cuidados Intensivos do Hospital da Luz. A deteção do ácido desoxirribonucleico do citomegalovírus foi realizada por técnica de polymerase chain reaction em tempo real e as concentrações de nove citocinas (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, e INFγ) foram determinadas através de uma técnica de ELISA Multiplex.Resultados: A reativação ocorreu em oito doentes (36,3%). Não foram encontradas relações entre a reativação do citomegalovírus e o sexo, idade, tempo de permanência na unidade de Cuidados Intensivos, duração da ventilação mecânica e morte do doente. Também não foram encontradas diferenças significativas nas concentrações das citocinas nos doentes com e sem reativação. Contudo, os doentes com reativação do citomegalovírus apresentaram um maior tempo de internamento no hospital desde a entrada na unidade de Cuidados Intensivos até a alta hospitalar ou morte do doente (p = 0,025).Discussão: Apesar da amostra de pequena dimensão, o presente estudo indicia que a reativação é um evento frequente nos doentes diagnosticados com sépsis e que pode estar relacionada com o prolongamento do tempo de permanência no hospital destes doentes.Conclusão: A análise conjunta dos resultados obtidos e da revisão da literatura não apoiam o conceito de que a monitorização do citomegalovírus deva ser implementada na prática clínica, mas parece prudente aguardarem-se por mais ensaios randomizados utilizando profilaxia antiviral, antes de se assumir uma atitude definitiva relativamente ao papel do citomegalovírus na sépsis.

Hepatitis B screening rates and reactivation in solid organ malignancy patients undergoing chemotherapy in Southern Thailand.

BACKGROUND/AIMS: Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT. METHODS: Based on the Oncology unit's registration database from 2009-2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up. RESULTS: Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009-2012 (7.8-21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group. CONCLUSION: The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.

Hepatitis B screening rates and reactivation in solid organ malignancy patients undergoing chemotherapy in Southern Thailand

BACKGROUND/AIMS: Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.METHODS: Based on the Oncology unit’s registration database from 2009–2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.RESULTS: Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009–2012 (7.8–21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.CONCLUSIONS: The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.

Hepatitis B virus reactivation induced by glucocorticoids: an important issue requiring urgent attention in dermatology / 中华皮肤科杂志

There is a high incidence of hepatitis B virus (HBV) infection in China,and dermatologists often encounter patients with skin diseases complicated by HBV infection in clinic.With the widespread use of systemic glucocorticoids in dermatology,HBV reactivation has become a constant problem to face in the treatment process.Attention should be given to risk factors of HBV reactivation,including HBV DNA replication,positive hepatitis B surface antigens (HBsAg) and positive hepatitis B core antibodies (HBcAb).According to HBV serological markers,risk stratification of HBV reactivation induced by glucocorticoids needs to be grasped,and treatment measures should be taken timely to prevent HBV reactivation.In this way,liver function impairment induced by HBV reactivation during the course of glucocorticoid therapy may be avoided to the greatest extent,which is of great benefit to clinical work.

Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas.

Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA. Curcumin, a dietary spice used in Asian countries, is known for its antitumor property and therapeutic potential. Novel curcuminoids that were developed to increase efficacy and bioavailability may serve as oral CLVA adjuvants. We investigated the potential of curcumin and its analogs (curcuminoids) to trigger the EBV lytic cycle in EBVaGC and NPC cells. EBV-reactivating effects were measured by immunoblot and immunofluorescence using monoclonal antibodies specific for EBV lytic proteins. Two of the hit compounds (41, EF24) with high lytic inducing activity were further studied for their synergistic or antagonistic effects when combined with GCb+VPA and analyzed by cytotoxicity and mRNA profiling assays to measure the EBV reactivation. Curcuminoid as a single agent significantly induced EBV reactivation in recombinant GC and NPC lines. The drug effects were dose- and time-dependent. Micromolar concentration of curcuminoid EF24 enhanced the CLVA effect in all cell systems except SNU719, a naturally infected EBVaGC cell that carries a more tightly latent viral genome. These findings indicated that EF24 has potential as EBV lytic activator and may serve as an adjuvant in CLVA treatment.

Clinical issues in the diagnosis and treatment of tuberculosis patients with positive antibody to hepatitis C virus / 临床肝胆病杂志

Tuberculosis patients with positive antibody to hepatitis C virus (TB-HCV patients) are often seen in clinical practice, and these TB-HCV patients include those with HCV infection. That makes the clinical management and diagnosis/treatment of TB-HCV difficult. This article introduces the prevalence of TB-HCV around the world, and analyzes the potential issues in the diagnosis and treatment of TB-HCV patients, such as drug-drug interactions, drug-induced liver injury, HCV reactivation, and TB reactivation. Through this review, it is recommended that the management should be strengthened and the appropriate therapeutic regimen should be selected in the diagnosis and treatment of TB-HCV patients.

Management and prevention of HBV reactivation in the context of immunosuppression / 临床肝胆病杂志

HBV reactivation is commonly seen during immunosuppressive therapy and is associated with high incidence and mortality rates due to hepatitis outbreak and liver decompensation, and therefore, it should be taken seriously. However, the prevention and management of this potential complication is still a difficulty in clinical practice. This article reviews the diagnostic criteria and clinical outcomes of HBV reactivation, discusses the association of immunosuppressive therapy with the risk of HBV reactivation, and outlines the strategies for the prevention of HBV reactivation and recent advances. It is pointed out that early identification of patients with HBV infection before immunosuppressive therapy is of vital importance, and the initiation of antiviral therapy at the right moment based on risk stratification can effectively reduce the risk of HBV reactivation. We hope that this review can increase the awareness of HBV reactivation among clinicians and provide an effective reference for optimizing the management and prevention of HBV infection.

The induction, purification, whole genome sequencing and comparative genome analysis of a novel staphylococcus haemolyticus bacteriophage IME-SA4 / 中国医师杂志

Objective To induce a novel temperate bacteriophage from staphylococcus haemolyticus strain SA98,observe the morphology and size,complete the whole genome sequencing,analyse the structure of genome and evolutionary relationship.Methods The mitomycin C was used to induce the temperate phage from staphylococcushaemolyticus strain SA98,the induced phage was observed by transmission electron microscopy after be concentrated and purified.The genome DNA was extracted and high through sequenced.The feature of whole genome and evolutionary relationship was analyzed.Results A temperate phage IME-SA4 was successfully induced from staphylococcus haemolyticus strain SA98.Transmission electron microscopy analysis indicated that IME-SA4 had an isometric head and a non-contractile long tail.The whole genome of IME-SA4 was long as 41 843 bp,and the whole genome blast result indicated IME-SA4 shared only 13％ homology with most related strain phiRS7.Conclusions A novel staphylococcus haemolyticus temperate phage with low homology with other staphylococcusphages was successfully induced from staphylococcus haemolyticus strain SA98.The research of its morphology,whole genome sequencing and comparative genome analysis make the foundation for further study of staphylococcus phages' properties and practical application.

[Clinical characteristics and analysis of patients with hematological diseases and HCV-Ab positive].

Objective: To observe the biological characteristics of patients with hematological diseases and hepatitis C antibodies positive and to investigate features of HCV infection and reactivation. Methods: A total of 85 patients with seropositive HCV at the hematology ward in Henan Cancer Hospital between October 2010 and October 2015 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Original disease treatment information was obtained from the medical records. Results: The positive rate of HCV-Ab was 1.2%, which was significantly higher than that of the general population(1.2% vs 0.4%, P<0.001). Of the 25 patients who showed anti-HCV seroconversion during the period of treatment or follow-up, serum ALT level was elevated in 15 patients(60.0%)and AST level got synchronous increase in 14 patients (56.0%). Of the 85 patients with positive HCV-Ab, 13 (15.3%) patients suffered from HCV reactivation with hepatic injury in varying degrees after chemotherapy or HSCT. Conclusions: Patients with hematological diseases have high incidence of HCV infection and reactivation, and most of them have hepatic injury. Chemotherapy and HSCT are important risk factors for HCV reactivation.

Cytolytic virus activation therapy and treatment monitoring for Epstein-Barr virus associated nasopharyngeal carcinoma in a mouse tumor model.

Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV). Expression of viral proteins in the tumor cells is highly restricted. EBV reactivation by CytoLytic Virus Activation (CLVA) therapy triggers de novo expression of early viral kinases (PK and TK) and uses antiviral treatment to kill activated cells. The mechanism of tumor elimination by CLVA was analyzed in NPC mouse model using C666.1 cells. Valproic acid (VPA) was combined with gemcitabine (GCb) to stimulate EBV reactivation, followed by antiviral treatment with ganciclovir (GCV). A single cycle of CLVA treatment resulted in specific tumor cell killing as indicated by reduced tumor volume, loss of EBV-positive cells in situ, and paralleled by decreased EBV DNA levels in circulation, which was more pronounced than treatment with GCb alone. In vivo reactivation was confirmed by presence of lytic gene transcripts and proteins in tumors 6 days after GCb/VPA treatment. Virus reactivation was visualized by [124 I]-FIAU accumulation in tumors using PET-scan. This studied showed that CLVA therapy is a potent EBV-specific targeting approach for killing tumor cells. The [124 I]-FIAU appears valuable as PET tracer for studies on CLVA drug dosage and kinetics in vivo, and may find clinical application in treatment monitoring.

Correlation between TNF-α-238 gene polymorphism and hepatitis B virus reactivation in patients with malignant tumors after chemotherapy / 中华老年医学杂志

Objective To investigate the correlation between the single nucleotide polymorphism (SNP) of tumor necrosis factor (TNF-α) gene promotor-238 and hepatitis B virus (HBV) reactivation in patients with malignant tumors after chemotherapy.Methods Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to detect the SNPat TNF-α-238 site among 100 malignant tumor patients with HBV infection.HBV-DNA levels in patients were detected before and after chemotherapy.HBV reactivation was defined as that HBV-DNA level greater than 10-fold increase compared with before chemotherapy or higher than 1 × 109 logcopies/ml.Results The quantification of HBV-DNA was higher after chemotherapy than before chemotherapy [(3.02±0.68) logcopies/ml vs.(2.49±0.23) logcopies/ml,t=-7.383,P=0.000].Among the patients with malignant tumor and HBV infection,the genotype frequency of G/A was higher in HBV reactivation group than in non-reactivation group after chemotherapy [27.3％ (6/22) vs.3.8％ (3/ 78),x2 =11.499,P=0.001].Conclusions HBV reactivation is associated with TNF-α-238 gene polymorphism in malignant tumor patients with HBV infection after chemotherapy.

Varicella-zoster virus infection and stroke / 国际脑血管病杂志

The varicela-zoster virus(VZV) infection causes central vasculopathy,and then leads to stroke onset. This article review s the correlation betw een VZV infection and stroke onset in order to conduct a comprehensive assessment of patients w ith VZV infection, thereby reducing the risk of stroke after VZV infection.

Hepatitis B virus reactivation in patients with hepatocellular carcinoma undergoing anti-cancer therapy.

Patients with hepatocellular carcinoma (HCC) often experience hepatic morbidity. Hepatitis B virus (HBV) reactivation is well documented as a serious hepatic morbidity during anti-cancer therapy. Reported rates of HBV reactivation in chronic carriers with HCC undergoing chemotherapy range from 4%-67%. Apart from chemotherapy, HBV reactivation has been increasingly identified in settings of hepatectomy and local ablation therapies. The rates of HBV reactivation vary with different levels of immunosuppression and depend on treatment, viral factors, and patient characteristics. The principal concern relating to reactivation is that a substantial proportion of patients with reactivation suffer from liver dysfunction during therapy, which often leads to disruption of planned, potentially life-prolonging treatments, adversely affecting the patients' final outcome. The first step in the management of HBV reactivation is identification of patients at risk of reactivation by testing for HBV serology prior to commencing anti-cancer therapy. Although it is a serious complication, HBV reactivation is preventable with prophylactic anti-HBV drugs. Multiple publications have shown the benefit of prophylactic or preemptive antiviral therapy in this setting and justified such an approach before the start of therapy. Given the tumors and underlying cirrhosis, long-term use of antivirals with high potency and low risk of resistance is recommended in patients with HCC. This topic review will summarize the epidemiology, pathogenesis, and clinical issues related to HBV reactivation in HCC patients, and will discuss proper management against HBV reactivation during anti-cancer therapy for HCC.