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Vergunst CE Gerlag DM Lopatinskaya L Klareskog L Smith MD van den Bosch F Dinant HJ Lee Y Wyant T Jacobson EW Baeten D Tak PP 《Arthritis and rheumatism》2008,58(7):1931-1939
OBJECTIVE: CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2-mediated chemotaxis in vitro and modulates arthritis in animal models of RA. In this study we examined the effects of CCR2 blockade on synovial inflammation in RA. METHODS: The study was designed as a phase IIa clinical trial with a human CCR2 blocking antibody (MLN1202) in patients with active RA. Thirty-two patients received 3 infusions, over a period of 6 weeks, with either placebo (n = 9) or anti-CCR2 monoclonal antibody at 0.5 mg/kg (n = 7), 1.5 mg/kg (n = 7), or 4.0 mg/kg (n = 9). Safety was monitored with laboratory tests, immunotoxicity assessments, and documenting of adverse events, and European League Against Rheumatism and American College of Rheumatology response criteria were used to assess clinical improvement. Synovial tissue was obtained at baseline and after 43 days of treatment, for pharmacodynamic analysis using immunohistochemistry and digital image analysis. The Kruskal-Wallis test was used to compare groups, and the Wilcoxon signed rank test was used to assess changes within the groups. RESULTS: All patients completed the study. Treatment with CCR2 blocking antibody reduced the levels of free CCR2 on CD14+ monocytes by at least 57% and up to 94% (P < 0.001), demonstrating the biologic activity of the compound. However, there was no reduction in the levels or expression of any of the synovial biomarkers. Accordingly, no clinical improvement was observed. CONCLUSION: Treatment with anti-CCR2 blocking antibody did not result in amelioration of synovial inflammation in active RA. The results do not support the notion that blockade of CCR2 may be sufficient to induce clinical improvement in RA. 相似文献
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Kees Hendricksen Antoine G. van der Heijden Erik B. Cornel Henk Vergunst Theo M. de Reijke Erika van Boven Geert A. H. J. Smits Rajiv Puri Sigrid Gruijs J. Alfred Witjes 《World journal of urology》2009,27(3):337-342
Objectives To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete
ablative response after intravesical apaziquone instillations.
Methods Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma
(UCC) of the bladder, with the exception of one marker lesion of 0.5–1.0 cm. Intravesical apaziquone was administered at weekly
intervals for six consecutive weeks, without maintenance instillations. A histological confirmed response was obtained 2–4 weeks
after the last instillation. Routine follow-up (FU) was carried out at 6, 9, 12, 18 and 24 months from the first apaziquone
instillation.
Results At 3 months FU 31 of 46 patients (67.4%) had a complete response (CR) to ablative treatment. Side-effects on the long-term
were only mild. Two CR patients dropped out during FU. On intention-to-treat (ITT) analysis 49.5% of the CR patients were
recurrence-free at 24 months FU, with a median duration of response of 18 months. Of 15 no response (NR) patients, only two
received additional prophylactic instillations after TURBT. On ITT-analysis 26.7% of the NR patients were recurrence-free
(log rank test, P = 0.155). The overall recurrence-free survival was 39% (18 of 46 patients) at 24 months FU.
Conclusions The CR of the marker lesion in 67% of patients was followed by a recurrence-free rate of 56.5% at 1-year FU, and 49.5% at
2-year FU. These long-term results are good in comparison with the results of other ablative studies. 相似文献
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A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells 下载免费PDF全文
Schulein R Guye P Rhomberg TA Schmid MC Schröder G Vergunst AC Carena I Dehio C 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(3):856-861
Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells. 相似文献
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Sinecatechins ointment 10% (Veregen®) for genital warts: percutaneous penetration of epigallocatechin gallate concentrations in the stratum corneum collected by adhesive tape stripping method 下载免费PDF全文
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Vergunst Francis Chadi Nicholas Orri Massimiliano Brousseau-Paradis Camille Castellanos-Ryan Natalie Séguin Jean R. Vitaro Frank Nagin Daniel Tremblay Richard E. Côté Sylvana M. 《European child & adolescent psychiatry》2022,31(11):1729-1738
European Child & Adolescent Psychiatry - Substance abuse is a significant public health concern that disproportionately burdens males and low-income communities. This study examined (1)... 相似文献
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Ruben G.H.M. Cremers Emile N.J.T. van Lin Wieneke L.J. Gerrits Lambertus A.L.M. Kiemeney Henk Vergunst Johannes H.A.M. Kaanders 《Radiotherapy and oncology》2010,97(3):467-473
Background and purpose
Goals of this study are to report the outcomes and tolerance of salvage radiotherapy (SRT) after prostatectomy, to identify risk factors for failure after SRT and to evaluate how these results compare with published results of immediate post-operative adjuvant radiotherapy (ART).Material and methods
Men receiving SRT for elevated PSA levels after radical prostatectomy (RP) were included. Biochemical progression-free survival (bPFS), overall survival (OS) and disease-specific survival (DSS) were estimated. Risk factors for biochemical failure and death were evaluated. Late toxicity and quality of life were evaluated. Secondary bPFS (defined as bPFS from prostatectomy until progression after radiotherapy) was calculated for high-risk patients (pT3 and/or positive surgical margins) in order to compare SRT outcomes with ART.Results
197 Men were included. Five-year bPFS after SRT was 59% (95% CI 49-69%). Five-year OS and DSS were 90% (85-96%) and 97% (93-100%), respectively. Capsular perforation (pT ? T3), negative surgical margins and serum PSA > 1 ng/ml at the start of RT were significant predictors of lower bPFS. Patients without any negative factors had a 5-year bPFS of 89%. No severe late toxicity was reported. Five-year secondary bPFS for SRT in high-risk patients was 78% and comparable with published results for ART.Conclusions
Salvage radiotherapy for patients with organ-confined prostate cancer was effective and well tolerated. SRT outcomes were comparable with published ART results for high-risk patients. Initially monitoring serum PSA and considering early SRT for these patients are not harmful and might be a valuable alternative for immediate ART. 相似文献9.
Context
Cryosurgery is an evolving treatment for localized prostate cancer in European centers. Modern cryotechnology is associated with a low complication rate, but its definitive role in the spectrum of different treatment modalities remains to be determined.Objective
The primary objective of this review is to analyze the oncological results and complication rates of modern cryosurgery for prostate cancer. Secondarily, the impact of patient selection and the criteria for treatment success are discussed.Evidence acquisition
A structured literature review was performed by an online Pubmed search for data of primary and salvage cryosurgery of the prostate. Papers with relevant information on clinical outcome and complication rates were selected.Evidence synthesis
The introduction of gas-based third-generation cryotechnology has significantly decreased side effects with similar oncological results compared to older techniques. The occurrence of severe complications like rectourethral fistulas (<1%) has almost been eradicated, but the rates of erectile dysfunction remain high (90%). With salvage cryosurgery more side effects can be expected with an average incontinence rate of 8% and fistulas up to 3.4%. Nevertheless, this minimal invasive treatment remains an option for radiorecurrent prostate cancer. Focal cryosurgery is considered experimental, but is an interesting new development in cryosurgery. The intermediate-term biochemical disease free survival rates of 60%–90% are comparable to the results of other treatment modalities. However, the current data of cryosurgery in literature are of low-level evidence which should be discussed when counselling patients.Conclusions
Modern cryosurgery is reliable and results are promising with minimal morbidity. Focal cryosurgery in selected patients aims to reduce side effects, but is currently experimental treatment. Randomized trials comparing the outcomes of the different treatment modalities and long-term follow-up data are needed to define the ultimate role of cryosurgery in the treatment of localized prostate cancer. 相似文献10.
OBJECTIVE: In sacral as well as tibial nerve stimulation test stimulation is the main prognostic factor for success. In our study we tried to identify prognostic patient characteristics to improve patient selection for neuromodulation therapy. METHODS: PTNS was applied to 132 patients in 8 study centers (51 men, 81 women, mean age of 53 years (range: 21-82)). 83 patients were treated for overactive bladder, 16 for non-obstructive urinary retention and 33 for chronic pelvic pain. All patients had to fill out micturition or pain diaries, as well as quality of life questionnaires before and after treatment. Patient characteristics were evaluated for their prognostic value for successful outcome of neuromodulation therapy with use of logistic regression. RESULTS: Objective success was seen in 32.6% of patients, subjective success in 51.5%. Most evaluated clinical parameters proved not to be of prognostic value. A history of sexual and/or physical abuse was found in 12 of 103 interviewed patients, but did not alter PTNS treatment outcome. However, a low total score at baseline in the SF-36 questionnaire proved to be predictive for not obtaining objective (OR 0.444 [95% CI: 0.198-0.996], p = 0.04) or subjective success (OR 0.424 [CI: 0.203-0.887], p = 0.02). Especially patients with a low SF-36 Mental Component Summary were prone to fail neuromodulation therapy: OR 0.123 (95% CI: 0.273-0.552), p = 0.006 for objective success. These patients also scored worse on disease-specific quality of life questionnaires, although they had no different disease severity compared to patients with good mental health. CONCLUSION: Bad mental health as measured with the SF-36 Mental Component Summary does not depend on symptom severity and is a negative predictive factor for success of percutaneous tibial nerve stimulation. It therefore might be used as a tool for better patient selection in neuromodulation therapy. 相似文献