08 febrero 2018

Yondelis . Leucemia Linfocítica Crónica (Chronic Lymphocytic Leukemia, CLL) . Building on This Very Encouraging in Vitro Data and the Well-Known Clinical Features of Trabectedin, We Performed in Vivo Experiments with this Agent in Mouse Models of CLL.

Resultado de imagen de cllNucleotide Excision Repair as a Targetable Vulnerability in Leukemia .


Gregor Lohmann, Björn Schumacher, and Marco Herling .

... In systems of syngeneic transfers of leukemic splenocytes from Eμ-TCL1 initi-ated strains, their fludarabine-refractory subclones, and their engineered TP53-deficient variants, trabectedin was active at well-tolerated dosages. It delayed the outgrowth of the engrafted leukemic clone and prolonged the survival of animals.

In conclusion, because of the positive efficacy/toxicity profiles of our ‘TC-NER-active’ agents, we suggest the implementation of targeting of (TC)-NER as a salvage strategy in high-risk and refractory CLL patients or those in Richter’s transformation. As a pilot substance the well-known trabectedin appears attractive, particularly given its multi-effect profile that even goes beyond targeting NER-coupled DNA damage. [7] Its modulatory impact on the local microenvironment, particularly targeting the immunosuppressive and pro-angiogenic effects of polarized tumor-associated mac-rophages [8], is appealing with respect to ongoing efforts to convert the milieu of CLL towards a more immunogenic state.


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Scheme of postulated synergistic mechanisms of (TC)-NER-targeting
a “normal scenario”: Transcription-coupled nucleotide excision repair (TC-NER) specific DNA lesions are processed by the protective NER machinery mostly re-sulting in adequate DNA repair and cell survival. b “scenario of ‘TC-NER-active’ compounds in synergy with fludarabine in leuke-mia”: ‘TC-NER-active‘ compounds (illudinM, ferrocen-IM or trabectedin) induce enhanced rates of TC-NER specific lesions, while nucleotide excision repair mechanisms are simultaneously blocked by trabectedin. Fludarabine poisons the final gap-filling step of the NER cascade. The ‘TC-NER-active’ agents syn-ergistically cooperate with fludarabine. This induces mainly ATM/p53 independ-ent programmed cell death and can overcome therapeutic resistance.

Saber si harás o no metástasis, en qué parte del cuerpo... y, ahora, cuándo . Post by Celtia .



 El investigador del IRB que ha liderado el último descubrimiento en torno a la metástasis lo explica y resume la historia de la investigación de este efecto del cáncer para  contextualizarlo.

PAULA CLEMENTE // 7 FEB. 2018 .

Cáncer. Esa palabra. Seis letras que esconden la tremenda preocupación médica de un gran conglomerado de generaciones. La enfermedad en la que se han volcado científicos, investigadores y fondos financieros. Los mismos que descubrieron, cuando parecía aminorar el terror que despertaba la misma, que el gran problema se escondía tras ella. Que el gran problema era la metástasis. La culpable del 90% de las muertes relacionadas con la enfermedad.

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