Mark Conaway

Publications (39)168.02 Total impact

• Article: Factors Associated With Neonatal Intensive Care Follow-up Appointment Compliance.

  Sara L Harmon, Mark Conaway, Robert A Sinkin, James A Blackman
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  ABSTRACT: Background and methods. Our goal was to identify factors that affect neonatal intensive care unit (NICU) follow-up appointment compliance. Compliant and noncompliant infants discharged from the NICU over 1 year and scheduled for follow-up (133) were compared retrospectively; a prospective telephone survey of noncompliant families was also undertaken. Results. Maternal drug use (odds ratio [OR] = 0.049, 95% confidence interval [CI] = 0.005-0.506), multiple gestation pregnancy (OR = 0.163, 95% CI = 0.050-0.533), male sex (OR = 0.308, 95% CI = 0.112-0.850), and greater distance from the hospital (OR = 0.987, 95% CI = 0.976-0.999) were independently associated with lower appointment compliance. A greater number of days on oxygen was associated with greater odds of compliance (OR = 1.057, 95% CI = 0.976-0.999). Shorter NICU stays (P = .047) and less chronic lung disease (P = .026) were significantly associated with noncompliance by bivariate analysis only. Distance from the hospital and travel expense were the most often self-cited reasons for appointment noncompliance. Conclusion. Understanding factors associated with NICU follow-up noncompliance is a starting point for providing targeted intervention.
  Clinical Pediatrics 02/2013; · 1.15 Impact Factor
• Source

  Available from: pnas.org

  Article: CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

  Jonathan B. Overdevest, Kristina H. Knubel, Jason E. Duex, Shibu Thomas, Matthew D. Nitz, Michael A. Harding, Steven C. Smith, Henry F. Frierson, Mark Conaway, Dan Theodorescu
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  ABSTRACT: Overexpression of CD24, a glycosyl phosphatidylinositol-linked sialoglycoprotein, is associated with poor outcome in urothelial carcinoma and contributes to experimental tumor growth and metastasis. However, the requirement for CD24 (Cd24a in mice) in tumorigenesis and spontaneous metastasis from the orthotopic site remains uncharacterized. Using N-butyl-N-(4-hydroxybutyl) nitrosamine induction of invasive and metastatic bladder cancer, we show that Cd24a-deficient male mice developed fewer bladder tumors than C57BL/6 control male mice. Evaluating only mice with evidence of primary tumors, we observed that Cd24a-deficient male mice also had fewer metastases than wild-type counterparts. In parallel observations, stratification of patients based on CD24 immunohistochemical expression in their tumors revealed that high levels of CD24 are associated with poor prognosis in males. In female patients and mice the above observations were not present. Given the significant role of CD24 in males, we sought to assess the relationship between androgen and CD24 regulation. We discovered that androgen receptor knockdown in UM-UC-3 and TCCSUP human urothelial carcinoma cell lines resulted in suppression of CD24 expression and cell proliferation. Androgen treatment also led to increased CD24 promoter activity, dependent on the presence of androgen receptor. In vivo, androgen deprivation resulted in reduced growth and CD24 expression of UM-UC-3 xenografts, and the latter was rescued by exogenous CD24 overexpression. These findings demonstrate an important role for CD24 in urothelial tumorigenesis and metastasis in male mice and indicate that CD24 is androgen regulated, providing the foundation for urothelial bladder cancer therapy with antiandrogens.
  Proceedings of the National Academy of Sciences 09/2012; · 9.68 Impact Factor
• Article: Psychometric evaluation of the myasthenia gravis composite using Rasch analysis.

  Reza Sadjadi, Mark Conaway, Gary Cutter, Donald B Sanders, Ted M Burns
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  ABSTRACT: The MG Composite (MGC) is a validated outcome measure of the clinical manifestations of myasthenia gravis. We performed Rasch analyses of the MGC to investigate additional properties, including its unidimensionality and the appropriateness of the weights assigned to the response categories for the MGC items. The fit statistics indicated that the 10 items belong together and can be summated for a total score. There was an overall absence of item order distortion between response categories. The Rasch model's expected category response values were compatible with item weights previously assigned. Our analysis suggests that: (1) the score can be summated to estimate an overall disease severity score; (2) the response options of the 10 items are not significantly distorted; and (3) the assigned weights of the response options are appropriate.
  Muscle & Nerve 06/2012; 45(6):820-5. · 2.37 Impact Factor
• Article: MG-ADL: still a relevant outcome measure.

  Srikanth Muppidi, Gil I Wolfe, Mark Conaway, Ted M Burns
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  ABSTRACT: The aim of this analysis was to examine the performance of the Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) during a multicenter scale validation study. Consecutive MG patients were assessed with several MG outcome measures, including the MG-ADL. Statistical tests included descriptive analysis, Pearson correlation, and sensitivity/specificity. Eighty-seven patients completed the MG-ADL, MG Composite (MGC), and MG 15-item Quality of Life scale (MG-QOL15) on the first visit, and 76 returned for the second visit. At the first visit, there was a strong positive correlation between MG-ADL and MGC (r = 0.85, P < 0.0001) and MG-QOL15 (r = 0.76, P < 0.0001). Correlation of the delta MG-ADL score and physician impression of change between the visits was strong (r = 0.70, P < 0.0001). A 2-point improvement in the MG-ADL best predicted clinical improvement. Test-retest analysis demonstrated a high reliability coefficient. The MG-ADL correlates strongly with newer, validated MG outcome measures. A 2-point improvement in the MG-ADL indicates clinical improvement. The MG-ADL is useful as a research tool and in routine clinical management.
  Muscle & Nerve 11/2011; 44(5):727-31. · 2.37 Impact Factor
• Article: Factors associated with the level of backrest elevation in a thoracic cardiovascular intensive care unit.

  Carole Ballew, Marie V Buffmire, Charles Fisher, Paula Schmidt, Beth Quatrara, Mark Conaway, Suzanne Burns
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  ABSTRACT: Ventilator-associated pneumonia is a complication of mechanical ventilation that is associated with increased length of stay, morbidity, mortality, and costs. Evidence-based guidelines to reduce the risk of ventilator-associated pneumonia recommend use of 30º to 45º backrest elevation. Despite recommendations, patients continue to be cared for in positions with a lower backrest elevation. Hemodynamic stability may be a factor in the lack of adherence, yet few data exist to confirm this hypothesis. To determine the relationship between backrest elevation and hemodynamic instability among patients in a thoracic cardiovascular intensive care unit. A sample of 100 patients was studied. Patients were randomly selected by time of day. A protractor was used to measure patients' backrest elevation. Mean blood pressure, time of day, and fluid and vasopressor use also were recorded. Lower backrest elevation was associated with use of vasopressors (P = .001). Patients who received hemodynamic support also had a lower backrest elevation than did patients not receiving these therapies (mean, 19º vs 26º ; P = .01). Patients with a mean blood pressure of 64 mm Hg or less had a mean backrest elevation of 17º versus 24º for patients with a mean blood pressure greater than 65 mm Hg (P = .01). Back-rest elevations did not differ between shifts. That backrest elevation is associated with lower mean blood pressure and vasopressor use suggests that nurses are not adhering to recommended levels of backrest elevation so as to maintain hemodynamic stability. Further studies are needed to elucidate reasons for lack of adherence to recommended levels of backrest elevation.
  American Journal of Critical Care 09/2011; 20(5):395-9. · 1.66 Impact Factor
• Article: RalBP1 is necessary for metastasis of human cancer cell lines.

  Zhong Wu, Charles Owens, Nidhi Chandra, Kay Popovic, Mark Conaway, Dan Theodorescu
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  ABSTRACT: RalA expression in human prostate cancer is associated with cell migration and is necessary for bone metastasis. However, the downstream effectors of RalA that mediate these functions remain unclear. Here we examined cell migration after small interfering RNA-mediated depletion of Ral effectors Ral binding protein 1 (RalBP1/RLIP), exocyst complex component 2 (Sec5), and phospholipase D1 (PLD1) and found that RalBP1 and RalA depletion inhibited cell migration to a similar extent. Stable lentivirus short hairpin interfering RNA-mediated depletion of RalA and RalBP1 in PC3 human prostate cancer cells inhibited bone metastasis after intracardiac inoculation. Depletion of RalBP1 diminished orthotopic tumor growth of PC3 cells and inhibited spontaneous metastasis from this site. Interestingly, the expression of wild-type or RalA mutants deficient in RalBP1 binding was effective at rescuing the reduced metastatic capacity of RalA-depleted PC3 cells, suggesting that RalA depletion does not reduce this solely by diminished interaction with RalBP1. To determine whether the role of RalBP1 in metastasis is relevant beyond prostate cancer, we studied the requirement of RalBP1 expression in an experimental metastasis model of human bladder cancer, a tumor type with high RalBP1 expression. Depletion of RalBP1 in UMUC3 cells resulted in decreased lung colonization while having a minimal effect on subcutaneous tumor growth. Our studies are the first to suggest that the expression of RalBP1 is necessary for human cancer cell metastasis. Furthermore, we show that the requirement for RalA expression for manifestation of this phenotype is not entirely dependent on a RalA-RalBP1 interaction.
  Neoplasia (New York, N.Y.) 12/2010; 12(12):1003-12. · 5.48 Impact Factor
• Source

  Available from: Wei Yue

  Article: Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms.

  Wei Yue, Ji-Ping Wang, Yuebai Li, Ping Fan, Guijian Liu, Nan Zhang, Mark Conaway, Hongkun Wang, Kenneth S Korach, Wayne Bocchinfuso, Richard Santen
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  ABSTRACT: Development of breast cancer involves genetic factors as well as lifetime exposure to estrogen. The precise molecular mechanisms whereby estrogens influence breast tumor formation are poorly understood. While estrogen receptor alpha (ERalpha) is certainly involved, nonreceptor mediated effects of estradiol (E(2)) may also play an important role in facilitating breast tumor development. A "reductionist" strategy allowed us to examine the role of ERalpha independent effects of E(2) on mammary tumor development in ERalpha knockout (ERKO) mice bearing the Wnt-1 oncogene. Exogenous E(2) "clamped" at early follicular and midluteal phase levels (i.e., 80 and 240 pg/ml) accelerated tumor formation in a dose-related fashion in ERKO/Wnt-1 animals (p = 0.0002). Reduction of endogenous E(2) by oophorectomy (p < 0.001) or an aromatase inhibitor (AI) (p = 0.055) in intact ERKO/Wnt-1 animals delayed tumorigenesis as further evidence for an ER-independent effect. The effects of residual ERalpha or beta were not involved since enhancement of tumor formation could not be blocked by the antiestrogen fulvestrant. 17alpha-OH-E(2), a metabolizable but ER-impeded analogue of E(2) stimulated tumor development without measurable uterine stimulatory effects. Taken together, our results suggest that ER-independent actions of E(2) can influence breast tumor development in concert with ER dependent effects. These observations suggest 1 mechanism whereby AIs, which block E(2) synthesis, would be more effective for breast cancer prevention than use of antiestrogens, which only block ER-mediated effects.
  International Journal of Cancer 10/2010; 127(8):1748-57. · 5.44 Impact Factor
• Article: Recognizing the needs of family members of neuroscience patients in an intensive care setting.

  Tanya Lynn Prachar, Dea Mahanes, Amy Arceneaux, Bridget L Moss, Sue Jones, Mark Conaway, Suzanne M Burns
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  ABSTRACT: This quantitative study was designed to identify the needs of family members of neuroscience patients. An adaptation of the Critical Care Family Needs Inventory was used to identify the top 10 needs of neuroscience families. Results were compared on the basis of whether the admission was planned or emergent. Needs were further examined on the basis of a family's perception of patient prognosis and communication with physicians and nurses. Most needs were recognized as being either important or very important with the need for information about the patient's care receiving the highest rating. Significant differences were noted between family members who expected their loved one to return to normal or with a slight decrease in activity versus those who expected their loved one to have a moderate to complete inability to perform normal activities. Communication with nurses was rated excellent or good significantly more often than communication with physicians.
  Journal of Neuroscience Nursing 10/2010; 42(5):274-9. · 0.81 Impact Factor
• Article: The MG Composite: A valid and reliable outcome measure for myasthenia gravis.

  Ted M Burns, Mark Conaway, Donald B Sanders
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  ABSTRACT: To study the concurrent and construct validity and test-retest reliability in the practice setting of an outcome measure for myasthenia gravis (MG). Eleven centers participated in the validation study of the Myasthenia Gravis Composite (MGC) scale. Patients with MG were evaluated at 2 consecutive visits. Concurrent and construct validities of the MGC were assessed by evaluating MGC scores in the context of other MG-specific outcome measures. We used numerous potential indicators of clinical improvement to assess the sensitivity and specificity of the MGC for detecting clinical improvement. Test-retest reliability was performed on patients at the University of Virginia. A total of 175 patients with MG were enrolled at 11 sites from July 1, 2008, to January 31, 2009. A total of 151 patients were seen in follow-up. Total MGC scores showed excellent concurrent validity with other MG-specific scales. Analyses of sensitivities and specificities of the MGC revealed that a 3-point improvement in total MGC score was optimal for signifying clinical improvement. A 3-point improvement in the MGC also appears to represent a meaningful improvement to most patients, as indicated by improved 15-item myasthenia gravis quality of life scale (MG-QOL15) scores. The psychometric properties were no better for an individualized subscore made up of the 2 functional domains that the patient identified as most important to treat. The test-retest reliability coefficient of the MGC was 98%, with a lower 95% confidence interval of 97%, indicating excellent test-retest reliability. The Myasthenia Gravis Composite is a reliable and valid instrument for measuring clinical status of patients with myasthenia gravis in the practice setting and in clinical trials.
  Neurology 05/2010; 74(18):1434-40. · 8.31 Impact Factor
• Article: PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma.

  Mary T Galgano, Mark Conaway, Adam M Spencer, Bryce M Paschal, Henry F Frierson
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  ABSTRACT: Protein kinase C-related kinases are regulated by phosphatidylinositol-3-kinase and Rho family GTPases. The isoform PRK1 has been characterized in detail in prostate cancer, but not in other carcinomas. We analyzed our prior microarray data for PRK1 gene expression in 175 carcinomas and evaluated tissue microarrays for protein expression in 251 carcinomas and a comprehensive group of normal tissues. We also used immunoblotting to determine the levels and phosphoactivation status of PRK1, PRK2, and PDK1 in 12 ovarian serous carcinomas, SKOV3 cells, and 3 samples of normal ovarian surface epithelium (OSE). The highest average level of PRK1 messenger RNA was observed in ovarian serous carcinomas compared with all other carcinomas, including those of the prostate, bladder/ureter, breast, colon, stomach/esophagus, kidney, liver, pancreas, and lung (P = .05). By immunohistochemistry, PRK1 was observed in selected normal cells, including epithelium from the gynecologic tract and hematolymphoid elements. All serous ovarian and endometrial endometrioid adenocarcinomas and mesotheliomas were immunoreactive for PRK1. The findings in nonserous ovarian and most carcinomas from the prostate, breast, and pancreas were also positive but less consistently so. In comparison with OSE, the serous carcinomas typically had greater pPRK1/total PRK1 (P = .02) as well as greater pPDK/total PDK (P = .01). The relative phosphorylation status of these 2 kinases correlated within each sample. In summary, PRK1 is present in various malignancies, but especially in serous carcinomas, where the increased activation status of PRK1 and its upstream regulator, PDK, as compared with normal OSE suggests a role in ovarian cancer development or progression.
  Human pathology 06/2009; 40(10):1434-40. · 3.03 Impact Factor
• Article: Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis.

  Jill K Slack-Davis, Kristen A Atkins, Christine Harrer, E Daniel Hershey, Mark Conaway
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  ABSTRACT: Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5-year survival <25%). Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface receptor that mediates leukocyte attachment and extravasation across endothelial and mesothelial monolayers at sites of inflammation. Membranous VCAM-1 expression was observed on the mesothelium of 13 of 14 women with ovarian cancer compared with 6 of 15 who were cancer-free. Using a cell culture model system of mesothelial invasion, highly tumorigenic SKOV-3 and ES-2 cells were 2.5 to 3 times more efficient in transmigration through the mesothelial monolayer compared with poorly tumorigenic OVCAR-3 cells. Blocking antibodies to, or small interfering RNA knockdown of, VCAM-1 or its ligand alpha(4)beta(1) integrin significantly decreased, but did not completely inhibit, transmigration of SKOV-3 cells through mesothelial monolayers. Furthermore, using a mouse model of ovarian cancer metastasis, treatment with VCAM-1 function-blocking antibodies decreased tumor burden and increased survival. Together, these observations implicate VCAM-1-alpha(4)beta(1) integrin interactions in the regulation of ovarian cancer cell mesothelial invasion and metastatic progression and offer the possibility of novel therapeutic targets.
  Cancer Research 02/2009; 69(4):1469-76. · 7.86 Impact Factor
• Article: Measuring blood pressure accurately in an ambulatory cardiology clinic setting: do patient position and timing really matter?

  Melly Turner, Suzanne M Burns, Cherie Chaney, Mark Conaway, Margaret Dame, Cherie Parks, Sandra Staggers, Melissa Stell, Melynda Zarzyski
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  ABSTRACT: The American Heart Association (AH) guidelines for assuring accuracy in blood pressure measurement stress the importance of timing and positioning. Investigators in an ambulatory cardiology setting studied the relationship and their findings supported the recommendations. The AHA recommendations are reviewed along with results of a study in an ambulatory cardiology setting.
  Medsurg nursing: official journal of the Academy of Medical-Surgical Nurses 05/2008; 17(2):93-8.
• Article: Depletion of major vault protein increases doxorubicin sensitivity and nuclear accumulation and disrupts its sequestration in lysosomes.

  Mikael Herlevsen, Gary Oxford, Charles R Owens, Mark Conaway, Dan Theodorescu
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  ABSTRACT: The major vault protein (MVP) is the major constituent of the vault particle, the largest known ribonuclear protein complex. To date, vaults have no clear function, although their low expression levels in de novo chemosensitive and curable tumors, such as testicular cancer, make them attractive candidates as contributors to intrinsic drug resistance. Here, we show that MVP knockdown in human bladder cancer cells via small interfering RNA results in sensitization toward doxorubicin in two distinct exposure protocols. The drug was detected in the nucleus immediately following addition and was subsequently sequestered to lysosomes, predominantly located adjacent to the nucleus. MVP knockdown leads to increased sensitivity toward doxorubicin and an enhanced nuclear accumulation of the drug as well as a loss of its perinuclear sequestration. Not only doxorubicin subcellular distribution was perturbed by MVP knockdown but lysosomal markers, such as pH-sensitive LysoSensor, pinocytosed dextran conjugates after 24-h chase period, and the lysosomal specific antigen Lamp-1, also showed a markedly different staining compared with controls. Lysosomes appeared dispersed through the cytoplasm without a clear organization adjacent to the nucleus. Microtubules, however, appeared unperturbed in cells with reduced MVP expression. Based on these data, we hypothesize that MVP and, by extension, vault complexes are important for lysosomal function and may influence cellular drug resistance by virtue of this role.
  Molecular Cancer Therapeutics 07/2007; 6(6):1804-13. · 5.23 Impact Factor
• Article: The effect of respiratory rate and ingestion of hot and cold beverages on the accuracy of oral temperatures measured by electronic thermometers.

  Beth Quatrara, Julie Coffman, Tricia Jenkins, Kristi Mann, Kathryn McGough, Mark Conaway, Suzanne Burns
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  ABSTRACT: Researchers examined hot and cold beverage consumption, tachypnea, and bradypnea effects on oral electronic thermometer readings. Results indicate that waiting at least 30 minutes after drinking yields a more accurate reading. Outcomes also suggest that bradypnea may create false temperature elevations.
  Medsurg nursing: official journal of the Academy of Medical-Surgical Nurses 05/2007; 16(2):105-8, 100.
• Article: The level of carcinoembryonic antigen and the presence of mucin as predictors of cystic pancreatic mucinous neoplasia.

  Vanessa M Shami, Vinay Sundaram, Edward B Stelow, Mark Conaway, Christopher A Moskaluk, Grace E White, Reid B Adams, Paul Yeaton, Michel Kahaleh
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  ABSTRACT: Characterization of pancreatic cysts using endoscopic ultrasound-guided fine-needle aspiration includes cytological interpretation and chemical analysis. We prospectively analyzed the contribution of carcinoembryonic antigen (CEA) and cytological identification of extracellular mucin as predictors of mucinous neoplasia and malignancy. From January 2003 to October 2005, all patients referred to the University of Virginia with cystic lesions of the pancreas underwent endoscopic ultrasound-guided fine-needle aspiration with cytological evaluation and CEA level analysis. Data were collected prospectively and confirmed by resection or tissue biopsy. Univariate and multivariate analyses were performed on the following variables with regard to their ability to predict mucinous neoplasia: age (<55 or >55 years), sex, CEA level (<300 or >300 ng/mL), and cytological appreciation of extracellular mucin (positive or negative). P values less than 0.05 were considered significant. A total of 43 patients were included in this study. There were 19 men and 24 women with a mean age of 63 +/- 14 years. The only complication was pancreatitis secondary to cyst leak in one patient. Multivariate analysis confirmed CEA level greater than 300 ng/mL (P= 0.007) and the identification of mucin (P < 0.001) as significant predictors. With pancreatic cyst fluid analysis, the strongest predictor of mucinous neoplasia is the presence of identifiable mucin, followed by a CEA level greater than 300 ng/mL. The workup of cystic lesions of the pancreas should include chemical analysis for the CEA level and cytological examination with particular attention to extracellular mucin.
  Pancreas 05/2007; 34(4):466-9. · 2.39 Impact Factor
• Article: Growth assessment of children with cerebral palsy: the clinician's conundrum.

  Richard D Stevenson, Mark Conaway
  Developmental Medicine & Child Neurology 04/2007; 49(3):164. · 2.92 Impact Factor
• Article: The prevalence and severity of burnout among academic orthopaedic departmental leaders.

  Khaled J Saleh, James Campbell Quick, Mark Conaway, Wesley E Sime, Wayne Martin, Shepard Hurwitz, Thomas A Einhorn
  The Journal of Bone and Joint Surgery 04/2007; 89(4):896-903. · 3.27 Impact Factor
• Article: Prediction of drug combination chemosensitivity in human bladder cancer.

  Dmytro M Havaleshko, HyungJun Cho, Mark Conaway, Charles R Owens, Garret Hampton, Jae K Lee, Dan Theodorescu
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  ABSTRACT: The choice of therapy for metastatic cancer is largely empirical because of a lack of chemosensitivity prediction for available combination chemotherapeutic regimens. Here, we identify molecular models of bladder carcinoma chemosensitivity based on gene expression for three widely used chemotherapeutic agents: cisplatin, paclitaxel, and gemcitabine. We measured the growth inhibition elicited by these three agents in a series of 40 human urothelial cancer cell lines and correlated the GI(50) (50% of growth inhibition) values with quantitative measures of global gene expression to derive models of chemosensitivity using a misclassification-penalized posterior approach. The misclassification-penalized posterior-derived models predicted the growth response of human bladder cancer cell lines to each of the three agents with sensitivities of between 0.93 and 0.96. We then developed an in silico approach to predict the cellular growth responses for each of these agents in the clinically relevant two-agent combinations. These predictions were prospectively evaluated on a series of 15 randomly chosen bladder carcinoma cell lines. Overall, 80% of the predicted combinations were correct (P = 0.0002). Together, our results suggest that chemosensitivity to drug combinations can be predicted based on molecular models and provide the framework for evaluation of such models in patients undergoing combination chemotherapy for cancer. If validated in vivo, such predictive models have the potential to guide therapeutic choice at the level of an individual's tumor.
  Molecular Cancer Therapeutics 03/2007; 6(2):578-86. · 5.23 Impact Factor
• Article: A novel model to identify interaction partners of the PTEN tumor suppressor gene in human bladder cancer.

  Mikael Herlevsen, Gary Oxford, Celeste Ptak, Jeffrey Shabanowitz, Donald F Hunt, Mark Conaway, Dan Theodorescu
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  ABSTRACT: Phosphatase and tensin homolog (PTEN), deleted on chromosome 10, is a potent tumor suppressor. PTEN expression is reduced in advanced bladder cancer and reduction correlates with disease stage. To gain insights into the function of PTEN in human bladder cancer by identifying its binding partners, we developed a novel IPTG inducible PTEN expression system and evaluated this system in the PTEN null UMUC-3 human bladder cancer xenograft model. In this model, induction of PTEN in vivo resulted in reduced tumor growth. We used mass spectrometry to identify PTEN interaction partners in these cells, which identified known interaction partners major vault protein (MVP) and paxillin as well as a novel interaction partner, TRK fused gene (TFG). In conclusion, using a biologically relevant model system to dissect PTEN tumor suppressor function in human bladder cancer, we identified three molecules important for many cellular functions in complex with PTEN.
  Biochemical and Biophysical Research Communications 02/2007; 352(2):549-55. · 2.48 Impact Factor
• Article: Clinical proteomics: A need to define the field and to begin to set adequate standards

  Harald Mischak Dr, Rolf Apweiler, Rosamonde E. Banks, Mark Conaway, Joshua Coon, Anna Dominiczak, Jochen H. H. Ehrich, Danilo Fliser, Mark Girolami, Henning Hermjakob, [......], Jan Novak, Karlheinz Peter, Kasper Rossing, Joost Schanstra, O. John Semmes, Dan Theodorescu, Visith Thongboonkerd, Eva M. Weissinger, Jennifer E. Van Eyk, Tadashi Yamamoto
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  ABSTRACT: The aim of this manuscript is to initiate a constructive discussion about the definition of clinical proteomics, study requirements, pitfalls and (potential) use. Furthermore, we hope to stimulate proposals for the optimal use of future opportunities and seek unification of the approaches in clinical proteomic studies. We have outlined our collective views about the basic principles that should be considered in clinical proteomic studies, including sample selection, choice of technology and appropriate quality control, and the need for collaborative interdisciplinary efforts involving clinicians and scientists. Furthermore, we propose guidelines for the critical aspects that should be included in published reports. Our hope is that, as a result of stimulating discussion, a consensus will be reached amongst the scientific community leading to guidelines for the studies, similar to those already published for mass spectrometric sequencing data. We contend that clinical proteomics is not just a collection of studies dealing with analysis of clinical samples. Rather, the essence of clinical proteomics should be to address clinically relevant questions and to improve the state-of-the-art, both in diagnosis and in therapy of diseases.
  PROTEOMICS - CLINICAL APPLICATIONS 01/2007; 1(2):148 - 156. · 1.81 Impact Factor