19 research outputs found

    Sulforaphane induces apoptosis in rhabdomyosarcoma and restores TRAIL-sensitivity in the aggressive alveolar subtype leading to tumor elimination in mice.

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    Rhadbomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and is subdivided in the embryonal (ERMS) and alveolar (ARMS) subtypes, the latter being associated with the worst prognosis. We report that sulforaphane (SFN), a broccoli-derived anticancer isothiocyanate, causes dose- and time-dependent growth inhibition and apoptosis in both ERMS and ARMS cells. In ARMS, SFN induced the modulation of expression of crucial genes and proteins: mRNA and protein levels of PAX3-FKHR, MYCN, and MET decreased, while those of p21 and TRAIL-receptor DR5 (but not DR4) increased. Since DR5 expression increased specifically in ARMS, we treated ARMS cells with TRAIL, SFN, or their combination. While ARMS cells (RH30 and RH4) proved to be TRAIL-resistant, SFN restored their sensitivity to TRAIL-induced cell-growth inhibition, leading to a stronger effect in combination with TRAIL. ARMS cells transfected with siDR5 showed that SFN-induced DR5 acts as a key regulator, being directly related to the TRAIL-induced cell-growth inhibition. The in vivo anti-tumor activity of SFN and TRAIL was evaluated in a xenograft murine model of ARMS through microPET. The results showed that the systemic treatment (3 wk) of mice with SFN or TRAIL as single agents only delayed tumor evolution, while the combined treatment of SFN and TRAIL led to tumor elimination. These findings indicate that SFN triggers the apoptotic pathway in both alveolar and embryonal rhabdomyosarcomas and that combined treatment with SFN and TRAIL might be a promising therapy for the aggressive alveolar subtype

    Image-guided robotic radiosurgery as salvage therapy for locally recurrent prostate cancer after external beam irradiation : retrospective feasibility study on six cases

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    Aims and background. Technological advances in treatment planning and execution are providing new potential opportunities in the treatment of recurrent prostate cancer. This studywas conducted to evaluate the feasibility and safety of reirradiationwith image-guided radiosurgery using CyberKnife, a robotic arm-driven compact linear accelerator, for intraprostatic recurrence after external beam radiotherapy (EBRT). Methods. Between September 2007 and May 2008, 6 patients diagnosed with locally recurrent prostate cancer after EBRT were treated using the CyberKnife system. The total reirradiation dose was 30 Gy in five fractions. Prior to radiosurgery four patients were treated with androgen-deprivation therapy. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and the Houston-Phoenix definition (PSA nadir + 2 ng/mL) were used for toxicity and biochemical failure evaluation, respectively. Results. After a median follow-up of 11.2 months (range, 9.6-18.6 months), all patients are alive with no evidence of severe urinary or rectal acute morbidity. Local control cannot be exactly determined due to the short follow-up and the bias of the use of androgen ablation. Four patients had biochemical failure, three of them with clinical failure evidence (lymph node, bone and lung metastasis, respectively): none of these patients had clinical evidence of tumor persistence in the prostate. Conclusions. Salvage radiosurgery with CyberKnife after irradiation is feasible with low urinary and rectal morbidity. A longer follow-up and a larger number of patients are necessary to evaluate its effectiveness and optimal patient selection criteria. Free full text available at www.tumorionline.it

    Cross-Coupling of 5,11-Dibromotetracene Catalyzed by a Triethylammonium Ion Tagged Diphenylphosphine Palladium Complex in Ionic Liquids

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    Suzuki-Miyaura cross-coupling reactions of 5,11-dibromotetracene with arylboronic acids, using a triethylammonium-tagged palladium(II) diphenylphosphine complex as catalyst in a pyrrolidinium-based ionic liquid (IL), allowed the preparation of new 5,11-diaryl-substituted tetracenes in good to excellent yields. The synthesis of the new 5,11-diboronic-tetracene bis-pinacolate ester and its use in Suzuki-Miyaura cross-coupling reaction with aryl bromides in IL are also reported
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