Publications (9)61.01 Total impact
-
Article: Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes.
[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION: Signal transducer and activator of transcripton-5a (Stat5a) and its close homolog, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. METHODS: Stat5a and Stat5b protein levels were quantified in situ in a breast cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data using multivariate models. RESULTS: Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared to normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a and Stat5b-modulated genes was found. In two cohorts of therapy-naive, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with more than 4-fold risk of unfavorable outcome. CONCLUSIONS: Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer, and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.Breast cancer research: BCR 10/2012; 14(5):R130. · 5.24 Impact Factor -
Article: Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure.
[show abstract] [hide abstract]
ABSTRACT: To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). CONCLUSION Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.Journal of Clinical Oncology 06/2011; 29(18):2448-58. · 18.37 Impact Factor -
Article: Latency to first seizure after temporal lobectomy predicts long-term outcome.
[show abstract] [hide abstract]
ABSTRACT: Temporal lobectomy is a well-established treatment for refractory temporal lobe epilepsy, yet many patients experience at least one seizure postoperatively. Little is known about the prognostic significance of the time from surgery to first seizure relapse in predicting long-term outcome. In a retrospective analysis of patients who reported at least one complex partial seizure (CPS) or generalized tonic–clonic seizure (GTCS) after anterior temporal lobectomy (n = 268), we used a nominal response logistic model to predict the odds ratio (OR) of a seizure outcome based on length of the latency period from surgery to first postoperative seizure. A modified Engel outcome class scheme was used. We controlled for factors known to influence postoperative outcome, including history of tonic–clonic seizures, intelligence quotient (IQ), preoperative seizure frequency, magnetic resonance imaging (MRI) findings, and history of febrile convulsions. In the univariate analysis, the latency from surgery to the first postoperative disabling seizure was significantly associated with long-term outcome. Longer latency was associated with higher odds of being seizure-free or improved (modified Engel's classes 1, 2, and 3) relative to the unimproved state (class 4) (p < 0.001, 0.001 and 0.004, respectively). Conversely, a shorter latency increased the likelihood of achieving the worst prognosis (class 4) relative to class 1 (p < 0.001). Multivariate analysis yielded similar results. Latency to the first postoperative seizure predicts long-term outcome, with short latencies portending poor prognosis and long latencies portending a good prognosis. This information can be used for patient counseling and may influence decisions regarding reoperation.Epilepsia 10/2010; 51(10):1987-93. · 3.96 Impact Factor -
Article: Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas.
[show abstract] [hide abstract]
ABSTRACT: Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy. Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV). Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation > or = 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors. H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.Journal of Clinical Oncology 06/2010; 28(18):3048-53. · 18.37 Impact Factor -
Article: Clinical, radiographic, and audiometric predictors in conservative management of vestibular schwannoma.
[show abstract] [hide abstract]
ABSTRACT: Vestibular schwannomas (VS) can be managed by observation. The goals were to examine clinical, radiographic, and audiometric variables at presentation and during observation that may predict which patients fail conservative management. A retrospective chart review was performed of 202 patients who elected observation primarily. Data collection included presenting symptoms, symptom progression, tumor size, audiologic measures, and global clinical outcomes. Univariate and multivariate analyses were performed. Follow-up ranged from 1 month to 16 years (mean, 2.48 yr). Nineteen patients (9.4%) in the study group failed. Disequilibrium as a presenting symptom appeared more often in patients who failed observation (58% versus 32%; p = 0.039), as did new-onset disequilibrium. Presenting tumor size differed for patients who failed conservative management, with a mean of 14.0 versus 8.4 mm (p = 0.0006). Neurotologic complications compared favorably to those treated with primary surgery or radiotherapy. Patients with subjective disequilibrium at presentation and subjective disequilibrium developed during observation may be more likely to fail conservative management. Increased tumor size at presentation also may indicate the same, although no threshold could be achieved.Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 05/2009; 30(4):507-14. · 1.44 Impact Factor -
Article: Effect of percentage of positive prostate biopsy cores on biochemical outcome in low-risk PCa treated with brachytherapy or 3D-CRT.
[show abstract] [hide abstract]
ABSTRACT: To investigate the significance of the percentage of positive biopsy cores (PPBCs) in predicting the biochemical outcome in patients with low-risk prostate cancer undergoing brachytherapy or three-dimensional conformal external beam radiotherapy (3D-CRT). We retrospectively reviewed 360 patients with low-risk prostate cancer who had undergone low dose-rate brachytherapy ((125)I) or 3D-CRT from 1993 to 2006. Of the 360 patients, 189 had undergone 3D-CRT and 171 had undergone brachytherapy. The patients were stratified according to treatment modality and PPBCs (<34%, 34%-50%, >50%). Biochemical failure was defined by the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology, Phoenix Consensus Conference definition. The median follow-up in the 3D-CRT and brachytherapy groups was 51 and 37 months, respectively. The number of patients who had a PPBCs of <34%, 34%-50%, and >50% in the 3D-CRT and brachytherapy cohorts was 154, 26, and 9 and 133, 25, and 15, respectively. The 5-year freedom from biochemical failure rate for 3D-CRT and brachytherapy was 95% and 96%, respectively; the corresponding median prostate-specific antigen nadirs were 0.7 and 0.3 ng/mL (P < .001). No significant differences were found in age, stage, Gleason score, or PPBCs between the 2 cohorts. Cox regression analysis showed that the pretreatment prostate-specific antigen level, stage, PPBCs, and treatment modality did not predict for the time to biochemical failure. When stratified by PPBCs, no significant difference in FFBF for either modality was seen. In patients with low-risk prostate cancer, brachytherapy and 3D-CRT remain excellent treatment choices, regardless of the tumor volume as estimated by the PPBCs. Longer follow-up and the recruitment of men with a greater volume of disease (>50% PPBCs) are needed to confirm these preliminary findings.Urology 04/2009; 73(6):1328-34. · 2.43 Impact Factor -
Article: A randomized, controlled trial of mindfulness-based art therapy (MBAT) for women with cancer.
[show abstract] [hide abstract]
ABSTRACT: The purpose of this study was to gather data on the efficacy of a newly developed psychosocial group intervention for cancer patients, called mindfulness-based art therapy (MBAT). One hundred and eleven women with a variety of cancer diagnoses were paired by age and randomized to either an eight-week MBAT intervention group or a wait-list control group. Ninety-three participants (84%) completed both the pre- and post-study measurements. As compared to the control group, the MBAT group demonstrated a significant decrease in symptoms of distress (as measured by the Symptoms Checklist-90-Revised) and significant improvements in key aspects of health-related quality of life (as measured by the Medical Outcomes Study Short-Form Health Survey). This investigation of MBAT provides initial encouraging data that support a possible future role for the intervention as a psychosocial treatment option for cancer patients.Psycho-Oncology 06/2006; 15(5):363-73. · 3.34 Impact Factor -
Article: The fragile histidine triad/common chromosome fragile site 3B locus and repair-deficient cancers.
[show abstract] [hide abstract]
ABSTRACT: In various studies of sporadic breast cancers, 40-70% were strongly positive for fragile histidine triad (Fhit) protein expression, whereas only 18% of BRCA2 mutant breast cancers demonstrated strong Fhit expression, suggesting that the BRCA2 repair function may be necessary to retain intact fragile common chromosome fragile site 3B(FRA3B)/FHITloci. In the current study, 22 breast tumors with deleterious BRCA1 mutations were analyzed for Fhit expression by immunohistochemistry in a case-control matched pair analysis. Loss of Fhit expression was significantly more frequent in the BRCA1 cancers compared with sporadic breast tumors (9% Fhit positive versus 68% Fhit positive), suggesting that the BRCA1 pathway is also important in protecting the FRA3B/FHIT locus from damage. To investigate the relationship between repair gene deficiencies and induction of chromosome fragile sites in vitro, we have analyzed the frequency of aphidicolin induction of chromosome gaps and breaks in PMS2-, BRCA1-, MSH2-, MLH1-, FHIT-, and TP53-deficient cell lines. Each of the repair-deficient cell lines showed elevated expression of chromosome gaps and breaks, consistent with the proposal that proteins involved in mismatch and double-strand break repair are important in maintaining the integrity of common fragile regions. Correspondingly, genes at common fragile sites may sustain elevated levels of DNA damage in cells with deficient DNA repair proteins such as those mutated in several familial cancer syndromes.Cancer Research 08/2002; 62(14):4054-60. · 7.86 Impact Factor -
Article: Initial Tumor Metabolic Parameters (Maximum SUV and Metabolic Volume) Predict Death From Lung Cancer and Rapid SUV Decline is Associated with Local Control
[show abstract] [hide abstract]
ABSTRACT: Factors associated with local failure and death from lung cancer were evaluated based on post-treatment FDG-PET imaging in patients (pts) with non-small cell lung cancer (NSCLC).PET-CT scans were obtained 6-8 weeks after thoracic RT and approximately every 3 months thereafter.Department of Radiation Oncology Faculty Papers.
Top co-authors
Top Journals
- Journal of Clinical Oncology (2)
- Cancer Research (1)
- Psycho-Oncology (1)
- Breast cancer research: BCR (1)
- Urology (1)
