Jasmina Z Cerne

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (4)14.59 Total impact

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    ABSTRACT: Purpose: Uveal melanoma (UM) tumors require large doses of radiation therapy (RT) to achieve tumor ablation, which frequently results in damage to adjacent normal tissues leading to vision-threatening complications. Approximately 50% of UM patients present with activating somatic mutations in the gene encoding for G protein αq-subunit (GNAQ), which lead to constitutive activation of downstream pathways including protein kinase C (PKC). In this study, we investigated the impact of small molecule PKC inhibitors bisindolylmaleimide I (BIM) and sotrastaurin (AEB071) combined with ionizing radiation (IR) on survival in UM cell lines. Methods: Cellular radiosensitivity was determined using a combination of proliferation, viability, and clonogenic assays. Cell cycle effects were measured by flow cytometry. Transcriptomic and proteomic profiling were performed by quantitative real-time PCR, reverse phase protein array analysis, and immunofluorescence. Results: We found that the PKC inhibitors combined with IR significantly decreased the viability, proliferation, and clonogenic potential of GNAQmt, but not GNAQwt cells, compared to IR alone. Combined treatment increased the anti-proliferative and pro-apoptotic effects of IR in GNAQmt cells through delayed DNA damage resolution and enhanced induction of proteins involved in cell cycle arrest, cell growth arrest, and apoptosis. Conclusions: Our pre-clinical results suggest that combined modality treatment may allow for reductions in the total RT dose and/or fraction size, which may lead to better functional organ preservation in the treatment of primary GNAQmt UM. These findings suggest future clinical trials combining PKC inhibitors with RT in GNAQmt UM warrant consideration.
    Investigative ophthalmology & visual science 03/2014; · 3.43 Impact Factor
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    ABSTRACT: Background:In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients.Methods:We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011.Results:A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001).Conclusions:Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.Prostate Cancer and Prostatic Disease advance online publication, 13 August 2013; doi:10.1038/pcan.2013.26.
    Prostate cancer and prostatic diseases 08/2013; · 2.10 Impact Factor
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    ABSTRACT: PURPOSE: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. METHODS AND MATERIALS: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. RESULTS: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs ≥0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. CONCLUSIONS: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level ≥0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level ≥0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.
    International journal of radiation oncology, biology, physics 10/2012; · 4.59 Impact Factor
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    ABSTRACT: The purpose of this study is to investigate whether BRCA1 promoter methylation is associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen. BRCA1 promoter methylation was determined by bisulfite pyrosequencing in two groups of sporadic breast cancer patients, systemically untreated (N = 497) and treated with adjuvant tamoxifen (N = 497). Associations of BRCA1 promoter methylation with clinopathological characteristics and the effect of BRCA1 promoter methylation on time to first recurrence (TTR) and overall survival (OS) were examined. No significant differences were observed between BRCA1 promoter methylation and clinopathological characteristics in untreated and tamoxifen-treated groups. Cut point analysis did not find any promising cut point for BRCA1 promoter methylation that would differentially influence TTR and OS in untreated and tamoxifen-treated group. Using the median (2.53 %) and an arbitrary value of 10 % as a cut point for methylation, we still found no significant effect of BRCA1 promoter methylation on TTR and OS in untreated and tamoxifen-treated group. Despite data suggesting that BRCA1 levels impact estrogen receptor response to tamoxifen, our results indicate that BRCA1 promoter methylation is not associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen.
    Breast Cancer Research and Treatment 06/2012; 135(1):135-43. · 4.47 Impact Factor