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Etiology and early pathogenesis of malignant testicular germ cell tumors： towards possibilities for preinvasive diagnosis

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Asian Journal of Andrology 2015年第3期17卷 381-393页

作者： Jenny E Elzinga-Tinke Gert R Dohle Leendert HJ Looijenga Department of Urology Subsection of Andrology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands Department of Pathoiogy Laboratory of Experimental Patho-Oncology Erasmus MC Cancer institute University Medical Center Rotterdam Rotterdam The Netherlands

Malignant testicular germ cell tumors （TGCT） are the most frequent cancers in Caucasian males （20-40 years） with an 70% increasing incidence the last 20 years, probably due to combined action of （epi）genetic and （micro）environmental factors. It is expected that TGCT have carcinoma in situ （CIS） as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies （GWAS） have been published, reporting on single-nucleotide polymorphisms （SNPs） with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF71P, HPGDS, MAD1L1, RFWD3, TEX14, and PPMIE, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS.

关键词： carcinoma in situ etiology environmental exposure semen diagnostics single nucleotide polymorphism testicular germcell tumor pathogenesis

Meeting report on the first Sino-Dutch symposium on oncology

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Chinese Journal of cancer 2016年第4期35卷 160-162页

作者： Maikel P.Peppelenbosch erasmus Medical Center cancer institute Erasmus University of Rotterdam

On October 31,2015,the first Sino-Dutch symposium on oncology was organized in Guangzhou(China).The symposium revealed similarities between Chinese and Dutch efforts to improve the care of tumor patients and to create enhanced insight into the nature of *** particular,it became evident for some types of cancer that immunotherapy should focus on counteracting interleukin-17-associated immunity and targeting cancer *** specific cancer microenvironment and stroma also opens new therapeutic options,including the use of radio-active theranostics and live tumor imaging-guided surgeries.

关键词： Meeting report cancer care

The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

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Frontiers of Medicine 2023年第3期17卷 527-533页

作者： Kevin M.Veen Grigorios Papageorgiou Casper F.Zijderhand Mostafa M.Mokhles Jasper J.Brugts Olivier C.Manintveld Alina A.Constantinescu Jos A.Bekkers Johanna J.Makkenberg Ad J.J.CBogers Kadir Caliskan Department of Cardiothoracic Surgery Erasmus MC3000 CA RotterdamThe Netherlands Department of Biostatistics Erasmus MC3000 CA RotterdamThe Netherlands Department of Cardiology Erasmus MC3000 CA RotterdamThe Netherlands

In this study,we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation(TR),taking into account its dynamic nature,after biatrial orthotopic heart transplant(OHT).All consecutive adult patients undergoing biatrial OHT(1984−2017)with an available follow-up echocardiogram were ***-models were used to model the evolution of *** mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with *** total,572 patients were included(median age:50 years,males:74.9%).Approximately 32% of patients had moderate-to-severe TR immediately after ***,this declined to 11%on 5 years and 9% on 10 years after surgery,adjusted for survival *** mechanical support was associated with less TR during follow-up,whereas concurrent LV dysfunction was significantly associated with more TR during *** at 1,5,10,20 years was 97%±1%,88%±1%,66%±2% and 23%±2%,*** presence of moderate-to-severe TR during follow-up was associated with higher mortality(HR:1.07,95%CI(1.02–1.12),p=0.006).The course of TR was positively correlated with the course of creatinine(R=0.45).TR during follow-up is significantly associated with higher mortality and worse renal ***,probability of TR is the highest immediately after OHT and decreases ***,it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.

关键词： orthotopic heart transplant tricuspid regurgitation clinical impact biatrial heart transplantation

Management of acute nonvariceal upper gastrointestinal bleeding:Current policies and future perspectives

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World Journal of Gastroenterology 2012年第11期18卷 1202-1207页

作者： Ingrid Lisanne Holster Ernst Johan Kuipers Department of Gastroenterology and Hepatology Erasmus MC University Medical Centre Departments of Gastroenterology and Hepatology and Internal MedicineErasmus MC University Medical Centre

Acute upper gastrointestinal bleeding(UGIB) is a gastroenterological emergency with a mortality of 6%-13%.The vast majority of these bleeds are due to peptic *** anti-inflammatory drugs and Helicobacter pylori are the main risk factors for peptic ulcer *** has become the mainstay for diagnosis and treatment of acute UGIB,and is recommended within 24 h of *** pump inhibitor(PPI) administration before endoscopy can downstage the bleeding lesion and reduce the need for endoscopic therapy,but has no effect on rebleeding,mortality and need for *** therapy should be undertaken for ulcers with high-risk stigmata,to reduce the risk of *** can be done with a variety of ***-dose PPI administration after endoscopy can prevent rebleeding and reduce the need for further intervention and mortality,particularly in patients with high-risk stigmata.

关键词： Disease management Upper gastrointesti-nal bleeding Nonvariceal bleeding Peptic ulcer bleed-ing Gastrointestinal endoscopy Pharmacotherapy Endoscopic therapy

New therapeutic opportunities for Hepatitis C based on small RNA

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World Journal of Gastroenterology 2007年第33期13卷 4431-4436页

作者： Qiu-wei Pan Scot D Henry Bob J Scholte Hugo W Tilanus Harry LA Janssen Luc JW van der Laan Departments of Gastroenterology & Hepatology and Surgery Erasmus MC-University Medical Centre Rotterdam The Netherlands Department of Surgery Erasmus MC-University Medical Centre Rotterdam The Netherlands Department of Cell Biology Erasmus MC- University Medical Centre Rotterdam The Netherlands Department of Gastroenterology & Hepatology Erasmus MC-University Medical Centre Rotterdam The Netherlands

Hepatitis C virus （HCV） infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, antisense oligonucleotides （ASO）, or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA （miR-222） in viral replication and discuss its potential for HCV molecular therapy.

关键词： Hepatitis C virus therapy miR-122 RNAi Antisense oligonucleotides Viral vectors

SARS-CoV-2-specific T-cells in unexposed humans:presence of cross-reactive memory cells does not equal protective

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Signal Transduction and Targeted Therapy 2020年第1期5卷 635-636页

作者： Rory D.de Vries Department Viroscience Erasmus MCRotterdamthe Netherlands

Using human blood samples obtained from pre-pandemic donors,a recent article by Mateus et *** Science provided new evidence that SARS-CoV-2-reactive T-cells in unexposed donors are indeed HCoV-specific T-cells.1 The rapid global spread of coronavirus disease 2019(COVID-19),caused by the newly-emerged coronavirus SARS-CoV-2,has led to millions of infections with substantial morbidity and mortality.2 Different clinical manifestations of COVID-19 have been observed:asymptomatic infections,mild self-limiting disease,acute respiratory distress syndrome and *** determinants underlying disease severity currently remain elusive;since severe patients often present with immune hyperresponsiveness,it is speculated that the host’immune response could be a contributing factor to severe disease.

关键词： protective distress reactive

Comparison of long-term outcome between patients aged 〈 65 years vs. ≥ 65 years after atrial fibrillation ablation

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Journal of Geriatric Cardiology 2017年第9期14卷 569-574页

作者： Zsuzsanna Kis Anna ME Noten Mihran Martirosyan Astrid A Hendriks Rohit Bhagwandien Tamas Szili-Torok Department of Cardiology Erasmus MC University Medical Center Rotterdam the Netherlands

Background Atrial fibrillation （AF） is the most frequent arrhythmia, and its prevalence is increasing with aging. We aimed to com-pare the long-term outcome data of patients 〈 65 years vs.≥ 65 years who underwent catheter ablation （CA） for drug-refractory AF. MethodsConsecutive patients with primary pulmonary vein isolation performed between March 2001 and December 2011, and those who completeda five-year of follow-up were divided into two groups： patients aged 〈 65 years into group 1, and patients aged ≥ 65 into group 2. Long-termoutcome data concerning mortality, thromboembolic events （TE） and success rates were compared between these groups. Results A totalnumber of 390 patients were included, group 1 contained 310 patients, and 80 patients in group 2. In group 2, patients had more often impairedrenal function （P 〈 0.001） and thyroid disease （P = 0.047）. A total of fifteen patients died during the 6.63 ± 2.1 years of follow-up, with a sig-nificantly higher incidence in the older group （8/80 vs. 7/310 patients, P = 0.004）. The majority of fatal outcome was due to cancerous dis-eases in both groups. No difference was observed concerning the long-term TE rate （12/310 vs. 4/80 patients, P = 0.75）. Rhythm controlfailed in 25.9% of the patients, with no difference between the groups： 26.4% in group 1 vs. 23.7% in group 2 （P = 0,67）, ConclusionsDespite growing prevalence of AF in aging population, the elderly patients are underrepresented in CA procedures. Similar clinical successand TE complication rate are observed between the age-groups. Our data suggest more liberal criteria might be applied while selecting pa-tients for AF ablation.

关键词： Atrial fibrillation Catheter ablation Clinical outcome The elderly Thromboembolic complication

Future prospectives for the management of chronic hepatitis B

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World Journal of Gastroenterology 2007年第18期13卷 2554-2567页

作者： WF Leemans HLA Janssen RA de Man Department of Gastroenterology & Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands

Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load （HBV-DNA） plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory （interferons） and antiviral suppressants （nucleoside and nucleotide analogues） all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion： chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the susta

关键词： Hepatitis B virus Cirrhosis Treatment Interferon Nucleoside analogues Nucleotide analogues Lamivudine Adefovir Entecavir Telbivudine Tenofovir Resistance Genotype

Telaprevir/boceprevir era: From bench to bed and back

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World Journal of Gastroenterology 2012年第43期18卷 6183-6188页

作者： Maikel P Peppelenbosch Harry LA Janssen Robert J de Knegt Department of Gastroenterology and Hepatology Erasmus MC-University Medical Center 3015 CE Rotterdam The Netherlands

Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.

关键词： Telaprevir Boceprevir Mechanism-of-action Clinical efficacy Liver transplantation patient Interferon Ribavirin