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
BackgroundThe optimal management of community acquired pneumonia (CAP) depends on the clinical and microbiological profile in the locality.ObjectivesTo determine the clinical and microbiological profile of patients admitted with CAP in Ilorin, Nigeria.MethodsOne hundred and two consenting consecutively selected patients with clinical and radiologic confirmation of CAP were recruited in 12 months. The socio-demographic, physical examination and laboratory/radiologic parameters were documented in a questionnaire. Microbiological evaluation of their sputum was done and blood samples were taken for complete blood count, culture, serum urea and serological evaluation for atypical bacteria and some viral pathogens.ResultsCAP constituted 5.9% of the total medical admissions during the one-year study period. The mean age of the patients was 49 ± 22 years with the largest frequency in those aged 65 years and above. The commonest symptoms were shortness of breath (96.1%) and cough (94.1%), with a median duration of 3 days from symptom onset to admission. Systemic hypertension was the commonest comorbid illness (25/102; 24.5%). Klebsiella pneumoniae was the predominant pathogen isolated (20/102; 28.1%). The susceptible antibiotics were Imipenem, Ceftazidime and Ceftriaxone. Intra-hospital mortality was 17.6%. CURB – 65 score of ≥ 2 and the presence of complications of CAP were the independent predictors of mortality.ConclusionCAP constitutes a significant disease burden in Ilorin, Nigeria. Typical bacteria accounted for over half of the pathogens isolated from the patients with gram negative agents predominating. This highlights a possible shift in the microbiological profile which could guide empirical treatment. 相似文献
Objective:The present study evaluates a training program for fitting different hearing protection devices (HPDs) based on personal attenuation rating (PAR) before, immediately after, and six months after training.Methods:A total of 67 workers from a public university in the city of São Paulo, Brazil, were invited to participate in the measurement of PARs for foam and silicone protectors through the 3M™ E-A-Rfit Validation System. Two evaluations were performed for each protector at each sampling date: one after reading printed material (the package instructions) and another after being trained by an audiologist. The same procedures were repeated after six months. The final sample consisted of 30 individuals. ANOVA was used for statistical analysis.Results:Larger PAR values were observed after training by the audiologist, and smaller values were observed after six months. Then, after re-training, the values increased again. There were no statistically significant differences in PAR among the HPDs tested. Even after the two training sessions, 23 to 27% of the subjects did not obtain adequate PAR values.Conclusion:These findings emphasize the need for continual worker training in the correct fit of earplug HPDs and the importance of longitudinal PAR monitoring. In addition, some workers, despite the training provided, did not adapt to the HPDs used. Therefore, it is essential that other protection methods and/or other HPD types are made available to these individuals.Key words: Hearing, noise-induced hearing loss, occupational health, personal protective equipment, hearing protection devices相似文献
The spatial distribution of enteroparasitosis in an indigenous village from Paraná was evaluated to identify areas of risk for these infections. A cross-sectional study (from November 2010 to June 2011) was performed using Three Faecal Test® and Kato &; Katz method and a questionnaire on housing and hygiene conditions was administered. Local geostatistical analyses were performed to determine the spatial distribution of intestinal parasitic infections. The overall prevalence of enteroparasites was 67.2?% (457/680), and the most prevalent taxa were Ascaris lumbricoides (48.8?%) and Trichuris trichiura (44.7?%). The prevalence of heavy infection by soil-transmitted helminths was 3.6?% and the families lived in houses with an average of 5.1 residents and < 2 bedrooms per household. The average number of species per individual present spatial heterogeneity with the highest values (≥0.8) in areas with high clustering of residences. The visualization of the spatial distribution of intestinal parasites in this indigenous village is an important contribution to determining health risk areas and planning decisions and services. 相似文献
Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy. 相似文献
Maternal and Child Health Journal - Background Prenatal substance use screening is recommended. The 4 P’s Plus screener includes questions on perceived problematic substance use in parents... 相似文献