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The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit ( hTERT ) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen (ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G 0 –G 1 phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST–PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene in human tumorigenesis.

A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo( a )pyrene, aflatoxin B 1 , N -methyl- N ′-nitro- N -nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3′-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4–PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.

Keratin-associated protein is one of the major structural proteins of the hair, whose content in hair has important effect on the quality of cashmere. In order to study the relationship between HGTKAP gene expression and cashmere fineness, the quantitative real-time RT-PCR (qRT-PCR) was firstly used to detect the levels of KAP7.1, KAP8.2 gene expression in the primary and secondary hair follicles; semi-quantitative RT-PCR was used to detect whether KAP7.1, KAP8.2 gene are expressed in heart, liver, spleen, lung, kidney tissues; and in situ hybridization(ISH) to detect KAP7.1 gene expression location. qRT-PCR result showed that the expression of both KAP7.1 and KAP8.2 gene in the secondary hair follicles are significantly higher than that in the primary follicles, relative quantitative analysis obtained that KAP7.1 was 2.28 times, while KAP8.2 was 2.71 times. Semi-quantitative RT-PCR results revealed that KAP 7.1 and KAP8.2 mRNA were not detected in the heart, liver, spleen, lung and kidney tissues, demonstrating that KAP7.1 and KAP8.2 were specially expressed in hair follicles, participating in hair formation. Moreover, KAP7.1 gene has a strong expression in the cortical layer, inner root sheath of the primary follicles and the cortical layer, inner root sheath and hair matrix of the secondary hair follicles by ISH analysis. Taken together, the evidence presented here indicated that in the formation of cashmere and wool, differential expression of these two genes in the primary and secondary hair follicles may have an important role in regulating the fiber diameter.

The objective of this study was to investigate the effects of different sources and levels of zinc (Zn) on nutrient digestibility, plasma metabolites, and relative Zn bioavailability in male mink. Animals in the control group were fed a basal diet, consisting mainly of corn, soybean oil, meat and bone meal, and fish meal, with no Zn supplementation. Mink in the other 9 treatments were fed the basal diet supplemented with Zn from grade Zn sulfate (ZnSO4. 7H2O), Zn glycinate (ZnGly), or Zn pectin oligosaccharides (ZnPOS) chelate at concentrations of either 100, 300, or 900 mg Zn/kg dry matter. The results showed that zinc levels increased the AD of fat linearly (P < 0.05). The AD of fat in Zn-900 was higher (P < 0.05) than that of the control. Fecal Zn and urinary Zn were affected by dietary Zn addition (P < 0.01). Moreover, Zn supplementation increased Zn retention compared with the control group (P < 0.05). The N retention in ZnPOS was higher (P < 0.05) than that of the control. The effect of Zn level was linear (P < 0.01) for N retention. In addition, the activity of alkaline phosphatase was higher in groups supplemented with 900 mg/kg Zn (P < 0.05) compared with the control group. There were significant interactions (P < 0.05) among Zn sources on the activity of Cu-Zn superoxide dismutase (Cu-ZnSOD). Compared with ZnSO4, relative bioavailability values were 148% and 173% for ZnGly and ZnPOS, respectively, based on Cu-ZnSOD activity. In conclusion, our data show that the relative bioavailability of ZnPOS was greater than that of ZnSO4. 7H2O and ZnGly and Zn supplementation can enhance the Cu-ZnSOD of male mink, and mink can efficiently utilize ZnGly and ZnPOS.

A regulator of the protein phosphatase 2A (PP2A), alpha 4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of alpha 4 in human cell transformation and tumorigenesis, we show that alpha 4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B sub(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of alpha 4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that alpha 4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated alpha 4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of alpha 4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed alpha 4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of alpha 4 through specific binding to the 3'-untranslated region of alpha 4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that alpha 4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced alpha 4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.

A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B 1 , N-methyl-N[variant prime]-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3[variant prime]-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis. [PUBLICATION ABSTRACT]

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu -overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

Objective To explore the operative method and therapeutic efficacy of surgical resection of large invasive pituitary adenomas with individualized approach under neuronavigator guidance. Methods Seventeen patients (10 males and 7 females, aged from 22 to 78 years with a mean of 39.2 plus or minus 9.2 years) suffering from large invasive pituitary adenoma of higher than Hardy IV grade hospitalized from 2004 to 2009 were involved in the present study. All procedures were performed with the assistance of neuronavigator via individualized pterion approach, subfrontal extradural approach, trans-sphenoidal approach, or combined approach. The dispersedly invasive pituitary adenomas were resected under the guidance of neuronavigator by fully utilizing the natural anatomical cleavages. All the patients received follow-up CT scanning 3 days after operation, MRI scanning 1 to 3 months after operation, and clinical follow-up ranged from 6 to 72 months. The resection extent and outcome were assessed by imaging examination

Objective To explore the therapeutic efficacy of a new type sapphire contact laser using wavelength-shifting technique on microsurgery of brain stem tumors.Methods The clinical data were retrospectively analyzed of 23 patients(13 males and 10 females,aged 6 to 69 years with an average of 38 years,and the duration of disease was 14 to 36 months with average of 22 months) with brain stem tumor admitted from Mar.2006 to May 2010.The major symptoms of the patients were cranial nerve impairment,cerebellum function impairment or paralysis.All patients received microsurgical resection of brain stem tumor using sapphire contact laser through median suboccipital incision and posterior brain stem approach,and the tumors were resected with precision operation and vaporization and ablation.Results Of the 23 patients,4 were with glioma,15 with cavernous angioma,2 with angioreticuloma and 2 with metastatic tumor.Total resection was achieved in 15 cases,while subtotal resection(more than 80%) in 6 cases.Intraoperative hemor

Objective To explore the technique and precautions of microsurgical treatment of temporal lobe arachnoid cysts complicated with spilepsy.Methods The clinical data of 32 patients with temporal lobe arachnoid cysts complicated with epilepsy,admitted from Nov.2007 to Apr.2010,were analyzed retrospectively.The diagnosis of temporal lobe arachnoid cysts was confirmed before surgical operation by cranial MRI or CT.Continual video-electroencephalogram monitoring with sphenoidal electrodes were employed in all patients,and spike-wave,polyspike-wave and/or sharp-slow-wave was detected at arachnoid cyst side.Craniotomy was performed under general anesthesia,the temporal lobe arachnoid cysts were treated by microsurgical excision.Besides,partial anterior temporal lobectomy,hippocampectomy,amygdalotomy and bipolar electrogulation on functional cortex were conducted in all cases.Intraoperative electroencephalography(EEG) monitoring was used in all patients.And an one year follow-up after surgery was carried out.Results No