MADRID, 1 Nov. (EDIZIONES) -
Empieza noviembre y, como cada año, llega Movember (Moustache+November = Movember), el movimiento internacional surgido hace ya algunos años en las culturas angloamericanas que propone dejarse bigote durante este mes para concienciar sobre los cánceres eminentemente masculinos, es decir, el de próstata y de testículos, así como la salud mental masculina y contra el sedentarismo.
Un grupo de estudiantes de Medicina de la Universidad de Navarra ha querido hacer "algo grande" dentro de esta iniciativa solidaria. "En nuestro caso, lo vamos a centrar en el cáncer de próstata por su elevada repercusión en nuestra sociedad", explican. ...
01 noviembre 2018
Sylentis . La Fase III se dividió en dos ensayos . El primero acabará en Primer Cuatrimestre 2019 ... Si los resultados son Positivos se iniciará el segundo ensayo de Fase III ... Si el segundo ensayo también sale positivo es cuando se elaborará y Presentará el Dossier para intentar salir con el Fármaco al Mercado . Oir a partir del Minuto 5,20 del vídeo .
Y luego pasa lo que pasa ...
Yondelis . Según Oncólogos Italianos lo Proponen para Tratar las Recurrencias del Cáncer de Ovario Epitelial Humano ( COE ) .
Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model .
Rossella Canese Gianmauro Palombelli Mattea Chirico Paola Sestili … See all authors .
First published: 30 October 2018 .
Abstract
Although several drugs are available to treat recurrences of human epithelial ovarian cancer (EOC), clinical responses often remain short lived and lead to only marginal improvements in patients' survival.
One of the new drugs proposed for recurrent platinum‐resistant EOC patients is trabectedin (Trab), a marine‐derived antitumor agent initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically.
Predictive biomarkers of therapy response to this drug and the potential use of non‐invasive functional MRI and MRS approaches for an early assessment of Trab efficacy have not yet been evaluated, although they might be relevant for improving the clinical management of EOC patients.
In the present work we combined functional and spectroscopic magnetic resonance technologies, such as in vivo diffusion‐weighted MRI and 1H MRS, with ex vivo high resolution MRS (HR‐MRS) metabolomic analyses, with the aim of identifying new pharmacodynamic markers of Trab effectiveness on well characterized, highly aggressive human SKOV3.ip (a HER2‐enriched cell variant derived from SKOV3 cells) EOC xenografts.
In vivo treatment with Trab (three consecutive weekly 0.2 mg/kg i.v. injections) resulted in the following: (1) a significant reduction of in vivo tumor growth, along with the formation in cancer lesions of diffuse hyper‐intense areas detected by T2‐weighted MRI and attributed to necrosis, in agreement with histopathology findings; (2) significant increases in the apparent diffusion coefficient mean and median values versus saline‐treated control tumors; and (3) a significant reduction in the choline‐containing metabolites' signal detected by quantitative in vivo MRS.
Multivariate and quantitative HR‐MRS analyses on ex vivo tissue samples revealed Trab‐induced alterations in phospholipid and glucose metabolism identified as a decrease in phosphocholine and an increase in lactate.
Collectively, these data identify Trab‐induced functional MRI and MRS alterations in EOC models as a possible basis for further developments of these non‐invasive imaging methods to improve the clinical management of EOC patients.
YONDELIS INHIBE EL CRECIMIENTO DEL LINFOMA CLÁSICO DE HODGKIN, MONOCYTES IMMUNOSUPPRESSIVE POLARIZATION BY TUMOR CELLS AND SYNERGIZES WITH THE CCR5-ANTAGONIST MARAVIROC .
Department of Molecular Oncology, CRO Aviano National Cancer Institute, Aviano, PN, Italy
*CB and NC contributed equally.
The adverse prognostic impact of the immunosuppressive tumor-associated macrophages (TAMs) in classical Hodgkin Lymphoma (cHL) is now well established and the depletion of TAMs is a key mechanism of the antitumor efficacy of trabectedin, a DNA damaging agent of marin origin.
Our studies demonstrated that trabectedin: had a potent antitumor activity in cHL cells, with IC50 ranging from 0.17 to 0.5 nM; induced DNA damage resulting in G2/M cell cycle arrest; induced necroptosis and increased the generation of reactive oxygen species. Trabectedin was active also in the presence of mesenchymal stromal cells (MSCs), which have been shown to play a role in chemotherapy resistance.
Treatment of cHL cells with subtoxic concentrations of trabectedin decreased: NF-kB activity; CCL5, CCL17/TARC, IL-6, IL-13, M-CSF and TGF-β secretion; the capability of cHL-conditioned medium (CM) to induce the migration of monocytes, MSCs, and lymphocytes; the reprogramming/tumor-education of monocytes (E-monocytes) towards immunosuppressive macrophages, characterized by increased IDO and PD-L1 expression, the secretion of IL-10, TGF-β, and TARC, and the inhibition of the proliferation of activated lymphocytes.
Trabectedin exerted a moderate synergistic activity with gemcitabine, but not with cisplatin, doxorubicin or vinorelbine. The combination with the CCR5-antagonist Maraviroc, found to increase cell killing mediated by DNA-damaging chemotherapeutic agents as doxorubicin, enhanced the cytotoxic effects of trabectedin in cHL, especially in L-540 cells, decreasing the IC50 of trabectedin-mediated cell killing by up to 2-fold.
In vivo, trabectedin (50 μg/Kg) led to a more than 40% tumor growth reduction of L-540-derived tumor xenograft and inhibited monocytes tumor infiltration, without weight loss.
In conclusion, since the present challenges are to find new drugs or less toxic drug combinations, as well as counteract the formation of an immunosuppressive tumor microenvironment, this study offers a preclinical rationale for the use of trabectedin in the treatment of refractory/relapsed cHL.
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