Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

保留肾单位手术治疗早期小肾癌21例临床分析

OBJECTIVE: To evaluate the clinical effects of nephron-sparing surgery in patients with early-stage small renal cell carcinoma. METHODS: Nephron-sparing surgery was performed in 21 patients with renal cell carcinoma including 1 with solitary kidney, 3 with unilateral tumor and contralateral renal compromise, and 17 with unilateral tumor and normal contralateral kidney. The diameter of the tumors ranged from 1.5 to 6.0 cm, with a mean of 2.8 cm. The tumor diameter in 17 patients with normal contralateral kidney was less than 4 cm (mean 2.5 cm) and the average diameter in 4 patients with contralateral renal compromise was 4.2 cm. Sixteen cases were in stage T(1), 4 in stage T(2), and 1 in stage T(3). Of the 21 patients, 4 underwent tumor enucleation, 10 polar nephrectomy and 7 wedge resection. RESULTS: All patients were followed up for an average of 40.8 months (7 to 66 months). One patient suffered a right lung and mediastinum metastasis 3 years after the surgery later and 1 with chronic glomerulonephritis required dialysis 27 months after the operation. No surgical complication or local recurrence were found in other patients. CONCLUSION: As a safe and effective therapy for early-stage small renal cell carcinoma, nephron-sparing surgery can be considered as the gold-standard therapy for patients with lesions less than 4 cm in T(1) and T(2) stages of localized unilateral tumor with normal contralateral kidney.     

Indications and limitations of locked plating

The goal of fracture fixation is to achieve bone healing and restore the function of the injured limb in the shortest possible time without compromising safety. Newer technologies such as the locking compression plate (LCP) and its derivatives are valuable additions to the orthopaedic traumatologist's armamentarium. As with any emerging technology, the indications will be extended until a threshold is reached and the limitations of the technology are seen. It is vital that surgeons involved in fracture care are aware of when locked plating is superior to other methods and also when they should use another treatment modality.This paper reviews the use of locked plating as a fixation method. Five topics covered in this review are: a historical perspective on locked plating, general indications, specific modes and techniques, patterns of failure, and an anatomical overview of current indications for locked plating.     

新型纳米根管充填材料对成骨细胞生长的影响

通过体外培养的成骨细胞,采用二甲基噻唑二苯基四唑溴盐比色法和流式细胞术对新型纳米根管充填材料(nHA-PA66)作用下的成骨细胞生长情况的变化进行研究,评价其对成骨细胞生长的影响。以该材料的细胞培养基浸提液作用于实验组细胞,对照组采用培养基本身。实验组和对照组成骨细胞的生长情况和细胞周期无显著性差异,表明该新型纳米材料对成骨细胞的生长和细胞周期无不良影响。提示新型纳米根管充填材料的成骨细胞相容性较好,具有用作根充材料的基础。     

甲氧苄氨嘧啶—PVP共沉淀物的研究

本工作用差示扫描量热法(DSC)研究甲氧苄氨嘧啶与PVP溶剂法制备的共沉淀物,表明已不存在甲氧苄氨嘧啶晶体。用x射线衍射法研究了1:12共沉淀物,证明无甲氧苄氨嘧啶的晶体衍射峰。经分光光度法测定结果,1:12共沉淀物比原药的溶解度大28.3倍。     

A central mechanism of acute baroreflex resetting in the conscious dog

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses.

A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.     

Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.