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Pelletier F.,University of Franche Comte | Pelletier F.,Center Hospitalier University | Pelletier F.,Center dInvestigation Clinique en Biotherapie | Parratte B.,Center Hospitalier University | And 8 more authors.
British Journal of Dermatology | Year: 2011

Background Provoked vestibulodynia is difficult to treat. The beneficial effects of botulinum toxin A are being considered because of the muscular anomalies observed in this pathology. Objective To evaluate the efficacy of botulinum toxin A in the treatment of provoked vestibulodynia. Methods Patients aged between 18 and 60 years presenting with provoked vestibulodynia (according to the 2003 International Society for the Study of Vulvar Disease classification) received 50 U of botulinum toxin A bilaterally in the bulbospongiosus muscle under electromyographic monitoring. Pain was evaluated by a visual analogue scale (VAS), quality of life was evaluated by the Dermatology Life Quality Index and sexual function by the Female Sexual Function Index. Results Twenty patients received the injections. Sixteen patients presented with a muscular hyperactivity on electromyography. After 3 months, 80% of the patients improved in terms of pain. Mean ± SD VAS values significantly decreased from 8·37 ± 1·22 (range 4·5-10) to 2·57 ± 2·67 (0-9; P < 0·0001) at month 3 and to 3·90 ± 2·92 (0-9; P < 0·001) at month 6. Quality of life and sexual function improved significantly during the first 6 months (P < 0·0001). After 3 months, 13 patients (out of 18 for whom intercourse was not possible before the injections; 72%) were able to have sexual intercourse. Conclusion Botulinum toxin A seems to be an effective and safe treatment for provoked vestibulodynia; 100 U botulinum toxin A significantly reduced pain 3 and 6 months after injections without side-effects. The treatment also improved quality of life and sexual function of patients. Botulinum toxin A appears to be a promising option for managing sexual pain disorder. © 2011 The Authors. BJD © 2011 British Association of Dermatologists. Source


Sistigu A.,French Institute of Health and Medical Research | Sistigu A.,Institute Gustave Roussy | Sistigu A.,University Paris - Sud | Viaud S.,French Institute of Health and Medical Research | And 10 more authors.
Seminars in Immunopathology | Year: 2011

Drug repositioning refers to the utilization of a known compound in a novel indication underscoring a new mode of action that predicts innovative therapeutic options. Since 1959, alkylating agents, such as the lead compound cyclophosphamide (CTX), have always been conceived, at high dosages, as potent cytotoxic and lymphoablative drugs, indispensable for dose intensity and immunosuppressive regimen in the oncological and internal medicine armamentarium. However, more recent work highlighted the immunostimulatory and/or antiangiogenic effects of low dosing CTX (also called "metronomic CTX") opening up novel indications in the field of cancer immunotherapy. CTX markedly influences dendritic cell homeostasis and promotes IFN type I secretion, contributing to the induction of antitumor cytotoxic T lymphocytes and/or the proliferation of adoptively transferred T cells, to the polarization of CD4+ T cells into TH1 and/or TH17 lymphocytes eventually affecting the Treg/Teffector ratio in favor of tumor regression. Moreover, CTX has intrinsic "pro-immunogenic" activities on tumor cells, inducing the hallmarks of immunogenic cell death on a variety of tumor types. Fifty years after its Food and Drug Administration approval, CTX remains a safe and affordable compound endowed with multifaceted properties and plethora of clinical indications. Here we review its immunomodulatory effects and advocate why low dosing CTX could be successfully combined to new-generation cancer vaccines. © 2011 Springer-Verlag. Source


Viaud S.,French Institute of Health and Medical Research | Viaud S.,Institute Gustave Roussy | Thery C.,Institute Curie | Thery C.,French Institute of Health and Medical Research | And 16 more authors.
Cancer Research | Year: 2010

Exosomes are nanovesicles originating from late endosomal compartments and secreted by most living cells in ex vivo cell culture conditions. The interest in exosomes was rekindled when B-cell and dendritic cell-derived exosomes were shown to mediate MHC-dependent immune responses. Despite limited understanding of exosome biogenesis and physiological relevance, accumulating evidence points to their bioactivity culminating in clinical applications in cancer. This review focuses on the preclinical studies exploiting the immunogenicity of dendritic cell-derived exosomes (Dex) and will elaborate on the past and future vaccination trials conducted using Dex strategy in melanoma and non-small cell lung cancer patients. ©2010 AACR. Source

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