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Articles by W Zhou
Total Records ( 5 ) for W Zhou
  X Gong , W Ye , H Zhou , X Ren , Z Li , W Zhou , J Wu , Y Gong , Q Ouyang , X Zhao and X. Zhang

Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.

  G Venkatraman , D. S Likosky , W Zhou , S. R. G Finlayson and D. C. Goodman

Objective  To examine the trends in rates of endoscopic sinus surgery, open sinus procedures (open sinus surgery), and the prevalence of diagnosis of chronic rhinosinusitis in the Medicare population from 1998 to 2006.

Design  Retrospective cohort analysis.

Patients  Twenty-percent sample of Medicare beneficiaries aged 65 to 99 years for the years 1998 to 2006.

Main Outcome Measures  Change in per capita annual rates of endoscopic sinus surgery, open sinus surgery, and chronic rhinosinusitis diagnosis among Medicare beneficiaries.

Results  From 1998 to 2006, the rate of patients undergoing endoscopic sinus surgery per 1000 Medicare beneficiaries increased by 20%, from 0.72 (95% confidence interval [CI], 0.70-0.74) to 0.92 (95% CI, 0.89-0.95). Over the same period, the rate of open sinus surgery declined 40%, from 0.20 (95% CI, 0.19-0.21) to 0.11 (95% CI, 0.10-0.12). However, the per capita rate of beneficiaries diagnosed as having chronic rhinosinusitis declined by 1.4% over the study period. Further analysis by age cohort revealed significantly higher rates of surgery and diagnosis rates in the 65- to 69-year-old beneficiaries relative to older age groups. Over the study period, the per capita rate of diagnosis of chronic rhinosinusitis declined or remained stable across age groups. Despite this, all age groups showed increases in endoscopic sinus surgery rates.

Conclusions  Our findings indicate that endoscopic sinus surgery is increasingly becoming the mainstay of chronic rhinosinusitis management in the Medicare population. Because of the uncertainty regarding the outcomes of surgical vs medical management, the root causes of the observed increase in endoscopic sinus surgery rates need to be investigated. Given that sinusitis is a common diagnosis necessitating physician visits, comparative effectiveness studies examining medical vs surgical management would be warranted.

  W Zhou , J Longmate , S. F Lacey , J. M Palmer , G Gallez Hawkins , L Thao , R Spielberger , R Nakamura , S. J Forman , J. A Zaia and D. J. Diamond

Reconstitution of cytomegalovirus (CMV)–specific CD8+ T cells is essential to the control of CMV infection in CMV-positive recipients (R+) after allogeneic hematopoietic stem cell transplantation (HCT). Six-color flow cytometry was used to assess the functional profile of CMV-specific CD8+ T cells in 62 of 178 R+ HCT recipients followed virologically for CMV reactivation. R+ recipients receiving grafts from CMV-negative donors (D; D/R+) reconstituted fewer multifunctional CD8+ T cells expressing tumor necrosis factor- (TNF-), macrophage inflammatory protein-1β (MIP-1β), and CD107 in addition to interferon- (IFN-), compared with D+/R+ recipients. Unlike monofunctional CD8+ T cells secreting IFN-, which were abundantly generated during CMV reactivation in D/R+ recipients, the relative lack of multifunctional CD8+ T cells persisted until at least 1 year post-HCT. D/R+ recipients were more likely to require recurrent and prolonged use of antivirals. These findings were robust to statistical adjustment for pretransplant factors, as well as for posttransplant factors including graft-versus-host disease (GVHD) and its treatment by steroids. These analyses suggest that D+/R+ transplants, on average, generate higher levels of multifunctional CMV-specific T cells and require less antiviral therapy compared with D/R+ HCT recipients. These results highlight the benefit of D+ donors in improving outcomes of R+ HCT recipients by reducing the duration and recurrent need of antiviral treatment, aided by increased levels of multifunctional CMV-specific T cells.

  E Yao , W Zhou , S. T Lee Hoeflich , T Truong , P. M Haverty , J Eastham Anderson , N Lewin Koh , B Gunter , M Belvin , L. J Murray , L. S Friedman , M. X Sliwkowski and K. P. Hoeflich

Purpose: Oncogenic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is prevalent in breast cancer and has been associated with resistance to HER2 inhibitors in the clinic. We therefore investigated the combinatorial activity of GDC-0941, a novel class I PI3K inhibitor, with standard-of-care therapies for HER2-amplified breast cancer.

Experimental Design: Three-dimensional laminin-rich extracellular matrix cultures of human breast cancer cells were utilized to provide a physiologically relevant approach to analyze the efficacy and molecular mechanism of combination therapies ex vivo. Combination studies were done using GDC-0941 with trastuzumab (Herceptin), pertuzumab, lapatinib (Tykerb), and docetaxel, the principal therapeutic agents that are either approved or being evaluated for treatment of early HER2-positive breast cancer.

Results: Significant GDC-0941 activity (EC50 <1 µmol/L) was observed for >70% of breast cancer cell lines that were examined in three-dimensional laminin-rich extracellular matrix culture. Differential responsiveness to GDC-0941 as a single agent was observed for luminal breast cancer cells upon stimulation with the HER3 ligand, heregulin. Combined treatment of GDC-0941, trastuzumab, and pertuzumab resulted in growth inhibition, altered acinar morphology, and suppression of AKT mitogen-activated protein kinase (MAPK) / extracellular signed-regulated kinase (ERK) kinase and MEK effector signaling pathways for HER2-amplified cells in both normal and heregulin-supplemented media. The GDC-0941 and lapatinib combination further showed that inhibition of HER2 activity was essential for maximum combinatorial efficacy. PI3K inhibition also rendered HER2-amplified BT-474M1 cells and tumor xenografts more sensitive to docetaxel.

Conclusions: GDC-0941 is efficacious in preclinical models of breast cancer. The addition of GDC-0941 to HER2-directed treatment could augment clinical benefit in breast cancer patients.

  J. C Umhau , W Zhou , R. E Carson , S. I Rapoport , A Polozova , J Demar , N Hussein , A. K Bhattacharjee , K Ma , G Esposito , S Majchrzak , P Herscovitch , W. C Eckelman , K. A Kurdziel and N. Salem

Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-11C]DHA mostly entered nonbrain organs, with ~0.5% entering the brain. Then, using PET and intravenous [1-11C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [15O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate Jin, the product of K*, and the unesterified plasma DHA concentration equaled 3.8 ± 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease.

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