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
The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.
Patients and Methods
Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.
Results
A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.
Conclusion
Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial. 相似文献
Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of... 相似文献
The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.
Objectives
The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.
Methods
PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.
Results
Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).
Conclusions
In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) 相似文献
Our objectives were to study the prevalence, risk factors for carriage, and transmission dynamics of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBLPE) in a national survey of cattle. This was a point prevalence study conducted from July to October 2013 in Israel. Stool samples were collected from 1,226 cows in 123 sections on 40 farms of all production types. ESBLPE were identified in 291 samples (23.7%): 287 contained Escherichia coli and 4 contained Klebsiella pneumoniae. The number of ESBLPE-positive cows was the highest in quarantine stations and on fattening farms and was the lowest on pasture farms (P = 0.03). The number of ESBLPE-positive cows was the lowest in sections containing adult cows (age, >25 months) and highest in sections containing calves (age, <4 months) (P < 0.001). Infrastructure variables that were significant risk factors for ESBLPE carriage included crowding, a lack of manure cleaning, and a lack of a cooling (P < 0.001 for each), all of which were more common in sections containing calves. Antimicrobial prophylaxis was given almost exclusively to calves and was associated with a high number of ESBLPE carriers (P < 0.001). The 287 E. coli isolates were typed into 106 repetitive extragenic palindromic (REP)-PCR types and mostly harbored blaCTX-M-1 or blaCTX-M-9 group genes. The isolates on the six farms with ≥15 isolates of ESBLPE were of 4 to 7 different REP-PCR types, with one dominant type being harbored by about half of the isolates. Fourteen types were identified on more than one farm, with only six of the farms being adjacent to each other. The prevalence of ESBLPE carriage is high in calves in cowsheds where the use of antimicrobial prophylaxis is common. ESBLPE disseminate within cowsheds mainly by clonal spread, with limited intercowshed transmission occurring. 相似文献
This study deals with a series of operations to isolate the micro-cellulose from the palm tree spathe sheath by using a modified chemical method to take into account the low cost and the completion speed and its characterization using X-ray diffraction technique (XRD), infrared spectroscopy (FTIR) and scanning electron microscope coupled with element analyzer (SEM/EDX). The results showed that the extraction method succeeded in obtaining very pure microscopic fibers with a width of 2–10 μm with a crystallinity index equal to 79.21%, containing the two cellulose features Iβ and II, that, the conversion ratio of the first to the second was estimated at 32, 87%. 相似文献
Herbal medicine has been widely utilized by pregnant women despite the limited available evidence regarding the safety and efficacy of that practice. The current available studies, from different countries, estimated that the use of herbal medicine during pregnancy range from 7% up to 96%. The aim of this study is to determine the prevalence, attitude, source of information, and reasoning behind the use of herbal medicine among pregnant women in Saudia Arabia.
Methods
A cross-sectional study conducted using a convenience sample including pregnant women who visited the obstetric clinics at King Abdulaziz Medical City in Riyadh, Saudi Arabia. A survey was administered in order to evaluate the prevalence and perception toward herbal medicine use among pregnant women in Saudi Arabia.
Results
A total of 297 pregnant women completed the survey. The results showed that 56% of the respondents have used some type of herbal medicine during their pregnancy. Olive oil was utilized in 26% of the respondents followed by cumin 20% and garlic 15%. In addition, 37% of the respondents used herbal medicine by their own initiative, while 33% and 12% used herbal medicine based on recommendations from their families and friends, respectively. Furthermore, 19% of the respondents reported a positive attitude toward herbal medicine use during pregnancy. In addition, the percentage of women with positive attitude was marginally higher among respondents with lower educational level.
Conclusion
The prevalence of using herbal medicine is considerably high among pregnant women in Saudi Arabia. Unfortunately, the majority of the users relied on informal sources to use herbal medicine during pregnancy. 相似文献