Deciphering cellular states of innate tumor drug responses

BACKGROUND: The molecular mechanisms underlying innate tumor drug resistance, a major obstacle to successful cancer therapy, remain poorly understood. In colorectal cancer (CRC), molecular studies have focused on drug-selected tumor cell lines or individual candidate genes using samples derived from patients already treated with drugs, so that very little data are available prior to drug treatment. RESULTS: Transcriptional profiles of clinical samples collected from CRC patients prior to their exposure to a combined chemotherapy of folinic acid, 5-fluorouracil and irinotecan were established using microarrays. Vigilant experimental design, power simulations and robust statistics were used to restrain the rates of false negative and false positive hybridizations, allowing successful discrimination between drug resistance and sensitivity states with restricted sampling. A list of 679 genes was established that intrinsically differentiates, for the first time prior to drug exposure, subsequently diagnosed chemo-sensitive and resistant patients. Independent biological validation performed through quantitative PCR confirmed the expression pattern on two additional patients. Careful annotation of interconnected functional networks provided a unique representation of the cellular states underlying drug responses. CONCLUSION: Molecular interaction networks are described that provide a solid foundation on which to anchor working hypotheses about mechanisms underlying in vivo innate tumor drug responses. These broad-spectrum cellular signatures represent a starting point from which by-pass chemotherapy schemes, targeting simultaneously several of the molecular mechanisms involved, may be developed for critical therapeutic intervention in CRC patients. The demonstrated power of this research strategy makes it generally applicable to other physiological and pathological situations

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

« Die erinnerung an de AlgerienKrieg in den Medien »,

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« L'argent des médias » Dossier de la revue Le Temps des Médias, Revue d'histoire, n°7, printemps 2006, 320 p.

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Jean d’Arcy et l’information

Jean d’Arcy est un homme de programmes et de technique, il est un organisateur et un gestionnaire, il réfléchit à la communication et à sa mondialisation, mais il s’occupe peu de l’information. Même dans ses fonctions internationales, après qu’il a quitté la télévision française, il se contente de grands principes et d’énoncés théoriques sur la communication sans jamais entrer dans la réflexion sur l’information elle-même. Manifestement, il ne sait pas ce qu’est le journalisme ni quelles sont..

La prensa en Francia ante un futuro incierto: secuencia histórica de un sector en crisis

Desde que en 2004 Philip Meyer, antiguo periodista y profesor de periodismo en la Universidad de Carolina del Norte, publicó The Vanishing Newspaper (Meyer, 2004: 296), donde anunciaba que el último de los diarios americanos dejaría de publicarse en 2043, las malas noticias no han parado de difundirse por todo el mundo: la quiebra de numerosos periódicos el despido masivo de periodistas, la lista es larga y seguirá aumentando con el tiempo. Internet parece acaparar el mercado de la información que era, hasta hace poco, propiedad exclusiva de los diarios. La competencia de la información en línea ha acarreado una crisis de la prensa escrita, acentuada desde hace algunos meses por los efectos de la grave recesión del mercado publicitario, ocasionada por la crisis económica. La prensa francesa no ha escapado a este desastre. Es más, ésta se deja sentir de forma aún más violenta que en otros países, ya que la crisis estructural de la prensa diaria nacional es más vieja y profunda en Francia. ¿Van a desaparecer los diarios nacionales