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Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.  相似文献   

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Objectives

Expedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.

Methods

Records from 39,812 patients undergoing coronary artery bypass grafting or valve operations (2008-2016) and extubated within 24 hours were stratified according to extubation time between 06:00 and 18:00 (day) or between 18:00 and 6:00 (overnight). Outcomes including reintubation, mortality, and composite morbidity-mortality were evaluated using hierarchical regression models adjusted for Society of Thoracic Surgeons predictive risk scores. To further analyze extubation during the night, a subanalysis stratified patients into 3 groups: 06:00 to 18:00, 18:00 to 24:00, and 24:00 to 06:00.

Results

A total of 20,758 patients were extubated overnight (52.1%) and were slightly older (median age 66 vs 65 years, P < .001) with a longer duration of ventilation (4 vs 7 hours, P < .001). Day and overnight extubation were associated with equivalent operative mortality (1.7% vs 1.7%, P = .880), reintubation (3.7% vs 3.4%, P = .141), and composite morbidity-mortality (8.2% vs 8.0%, P = .314). After risk adjustment, overnight extubation was not associated with any difference in reintubation, mortality, or composite morbidity-mortality. On subanalysis, those extubated between 24:00 and 06:00 exhibited increased composite morbidity-mortality (odds ratio, 1.18; P = .001) but no difference in reintubation or mortality.

Conclusions

Extubation overnight was not associated with increased mortality or reintubation. These results suggest that in the appropriate clinical setting, it is safe to routinely extubate cardiac surgery patients overnight.  相似文献   
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Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day''s more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.  相似文献   
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