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
This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics. 相似文献
Background: Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions. Methods: We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis. Results: Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells. Conclusion: An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma. 相似文献
In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method. 相似文献
The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060) 相似文献
OBJECTIVE: Patients with multilevel aortic disease represent a small subgroup with the need for extensive surgical treatment at considerable risk. We present our experience of endovascular exclusion for simultaneous thoracic and abdominal aortic disease in four patients. METHODS: Between January 2002 and January 2005, four patients underwent endovascular repair for simultaneous thoracic and abdominal aortic disease. Mean age was 69+/-10 years (range, 60-81). Thoracic lesions included penetrating aortic ulcer (n=2, ruptured=1), atherosclerotic aneurysm (n=1), and chronic type B dissection (n=1). Abdominal aortic disease included atherosclerotic infrarenal (n=3) and juxtarenal (n=1) aortic aneurysms. Thoracic aortic stent-grafts had been the following: Excluder/TAG (n=3) or Talent (n=1) straight tube devices. Abdominal aortic stent-grafts used were as following: Excluder (n=3) or Zenith (n=1). All patients were followed-up with CT-angiography and chest X-rays 1, 4, 12 months after the procedure, and once per year thereafter. RESULTS: Stent-graft deployment was technically successful in all cases. Intraoperative mortality was not observed. Mean procedure time was 94+/-34 min (range, 70-145). Early postoperative complications occurred in one patient that developed acute renal failure but dialysis was not required. Mean hospitalisation was 8+/-5 days (range, 4-15). Late death occurred in one patient for an undetected ruptured thoracic type 1 endoleak. All three survivors are currently well 16.5 months (range, 3-36) after surgery. No neurological complications developed. CONCLUSION: Simultaneous abdominal and thoracic endovascular repair for multilevel aortic disease is feasible and could be a viable alternative in high-risk patients, who otherwise may not be suitable candidates for conventional repair. 相似文献
OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients with unstable angina (UA) undergoing non-elective myocardial revascularization. METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12 years, underwent non-elective coronary artery bypass grafting (CABG) for unstable angina. Two hundred and five (27%) were operated emergently and 503 (73%) urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M). RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow-up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P = 0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35% (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non-elective CABG for UA is safe and effective. Mid-term outcome, however, are superior with improved freedom from cardiac death, from coronary reintervention and from myocardial infarction. 相似文献
BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response. 相似文献
Background: Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane.
Methods: Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 [degree sign] Celsius) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min.
Results: The time-course of Delta SVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time. 相似文献