Francis Levi

..This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also in tumor promotion or growth...

..Thus, the optimal circadian timing of chemotherapy requires precise determination according to sex, and should involve the noninvasive monitoring of circadian biomarkers...

..We hypothesized that EGFR blockade with cetuximab would enhance the activity of chronotherapy as a result of improved circadian coordination...

..The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy...

..The goal was to evaluate its incidence and impact on the outcome of patients resected for colorectal liver metastases (CLM)...

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..In this article, the authors report their experience with chronomodulated HAI chemotherapy as rescue therapy in heavily pretreated patients who had metastatic colorectal cancer...

..Targeting circadian clocks represents a novel potential challenge for cancer therapeutics...

..Here, we investigate whether circadian changes in local abcc2 expression participate in the circadian rhythm of irinotecan toxicity for ileum mucosa, and further assess whether genetic background or sex modify this relation...

..We report the first case of multiple KRAS mutations acquired during the metastatic phase of CRC, and retrospectively reviewed all patients with CRC, in whom KRAS was analyzed in at least two tumor samples from distinct lesions...

..Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments...

..CONCLUSIONS: Altered light-dark or feeding schedules modified the expression of molecular clock genes and genes involved in carcinogenesis and tumor progression...

..This shows that disruption of circadian coordination accelerates malignant growth in mice, suggesting that the host circadian clock controls tumor progression...

..CONCLUSIONS: Disruption of circadian rhythms in mice was associated with accelerated growth of malignant tumors of two types, suggesting that the host circadian clock may play an important role in endogenous control of tumor progression...

..Here, we investigate the role of CJL as a tumor promoter in mice exposed to the hepatic carcinogen, diethylnitrosamine (DEN)...

..It is conducting currently six trials and preparing four new studies. The 19 contributions in this special issue reflect the current status and perspectives of the several components of cancer chronotherapeutics...

..These results support the role of the CTS in cancer progression and call for the development of therapeutic strategies aimed at preventing or treating circadian clock dysfunctions...

..Conversely, a molecular circadian clock likely regulated BCL-2 and BAX expression in the bone marrow, increasing cellular protection against apoptosis during the rest span...

..CONCLUSIONS: ChronoIFLO safely and durably halted tumor progression in most extensively pretreated MCRC patients...

..The circadian timing system constitutes a novel therapeutic target. Interventions that normalize circadian timing system dysfunction may affect quality of life and survival in cancer patients...

..This knowledge can in turn be used in improving or designing chronotherapeutics for the patients who suffer from many of the major human diseases...

..The models showed that additional therapeutic strategy further sets the constraints for the identification of the most effective chronomodulated schedules...

..The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient's molecular clock...

..The results support the administration of CPT-11 to cancer patients in the second half of the night, during sleep, in order to improve drug tolerability...

..Results of laboratory animal studies have been extrapolated to the design of clinical cancer therapy trials involving a chronobiological approach...

..Modifications of cell cycle gene expression in the liver likely involve other mechanisms. Circadian clocks represent relevant targets to consider for optimization of therapeutic schedules of CDK inhibitors...

..Conclusions:These results indicate that circadian system could play an important role in malignant growth control. This should be taken into consideration in cancer prevention and therapy...

..The coordination of clock gene expression patterns in tumor cells was associated with best antitumor activity of Seliciclib. The circadian clock and its upstream regulators represent relevant targets for CDKIs...

..The risk for other postoperative complications is related to the duration of preoperative chemotherapy administration...

..The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure...

..Our findings demonstrate that VRL can transiently, yet profoundly, alter circadian clock function. Vinorelbine-induced circadian dysfunction may contribute to the toxicokinetics of this and possibly other anticancer drugs...

..Such 24h rhythm alterations appeared to be independent of conventional clinical factors...

..BCL-2 acrophase coincided with the time of highest docetaxel tolerability and efficacy in this model. This suggests that BCL-2 protects the bone marrow from the drug toxicity, especially during the light phase...

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..Intelligent drug delivery systems could then integrate the critical rhythmic information stemming from the individual patient and achieve a critical leap forward in the safe administration of potentially toxic therapeutic agents...

..This study suggests that the clinical relevance of cortisol circadian rhythm for patient outcome may differ according to the hormonal dependency of the tumor...