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Smith B.A.,University of Notre Dame | Xiao S.,University of Notre Dame | Wolter W.,University of Notre Dame | Wheeler J.,Center for Cancer Care | And 2 more authors.
Apoptosis | Year: 2011

A synthetic, near-infrared, fluorescent probe, named PSS-794 was assessed for its ability to detect cell death in two animal models. The molecular probe contains a zinc(II)-dipicolylamine (Zn2+-DPA) affinity ligand that selectively targets exposed phosphatidylserine on the surface of dead and dying cells. The first animal model used rats that were treated with dexamethasone to induce thymic atrophy. Ex vivo fluorescence imaging and histological analysis of excised organs showed thymus uptake of PSS-794 was four times higher than a control fluorophore that lacked the Zn2+-DPA affinity ligand. In addition, the presence of PSS-794 produced a delayed and higher build up of dead and dying cells in the rat thymus. The second animal model employed focal beam radiation to induce cell death in tumor-bearing rats. Whole-body and ex vivo imaging showed that the amount of PSS-794 in a radiationtreated tumor was almost twice that in a non-treated tumor. The results indicate that PSS-794 may be useful for preclinical optical detection of tumor cell death due to therapy. © Springer Science+Business Media, LLC 2011.

Gunn S.,CombiMatrix | Gunn S.,University of Texas Health Science Center at San Antonio | Gunn S.,Center for Cancer Care | Yeh I.-T.,University of Texas Health Science Center at San Antonio | And 9 more authors.
BMC Cancer | Year: 2010

Background: HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods.Methods: In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms.Results: Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to 'ratio skewing' caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability.Conclusions: These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two probe FISH interphase analysis is inadequate and results interpreted using the HER2/CEP17 ratio should be reported 'with caution' when the presence of centromeric amplification or monosomy is suspected by FISH signal gains or losses. The presence of these pericentromeric copy number changes may result in artificial skewing of the HER2/CEP17 ratio towards false negative or false positive results in breast cancer with chromosome 17 complexity. Full genomic analysis should be considered in all cases with complex chromosome 17 aneusomy as these cases are likely to have genome-wide instability, amplifications, and a poor prognosis. © 2010 Gunn et al; licensee BioMed Central Ltd.

Sarkar V.,University of Utah | Wang B.,University of Louisville | Zhao H.,University of Utah | Lynch B.,Center for Cancer Care | And 3 more authors.
Journal of Applied Clinical Medical Physics | Year: 2015

As very small ion chambers become commercially available, medical physicists may be inclined to use them during the linear accelerator commissioning process to better characterize the beam in steep dose gradient areas. For this work, a total of eight different ion chambers (volumes from 0.007 cc to 0.6 cc) and four different scanning systems were used to scan PDDs at both +300V and -300V biases. We observed a reproducible, significant difference (overresponse with depth) in PDDs acquired when using very small ion chambers, with specific bias/water tank combinations - up to 5% at a depth of 25 cm in water. This difference was not observed when the PDDs were sampled using the ion chamber in static positions in conjunction with an external electrometer. This suggests noise/signal interference produced by the controller box and cable system assemblies, which can become relatively significant for the very small current signals collected by very small ion chambers, especially at depth as the signal level is even further reduced. Based on the results observed here, the use of very small active volume chambers under specific scanning conditions may lead to collection of erroneous data, introducing systematic errors into the treatment planning system. In case the use of such a chamber is required, we recommend determining whether such erroneous effect exists by comparing the scans with those obtained with a larger chamber.

Gulec S.A.,Florida International University | Suthar R.R.,Florida International University | Barot T.C.,Florida International University | Pennington K.,Center for Cancer Care
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2011

Purpose: Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images. These parameters could potentially have clinical value in response to treatment evaluation and disease prognostication. The objectives of this study were to investigate the relationship between functional tumor parameters (FTV and TLG) and clinical outcomes in patients with colorectal cancer liver metastases (CRCLM) undergoing 90Y-resin microsphere selective internal radiation therapy (SIRT) (SIR-Spheres®, Sirtex Medical Limited, Lane Cove, NSW, Australia). Methods: FDG PET/CT studies of 20 patients with unresectable CRCLM who underwent 90Y SIRT under a phase II clinical trial were analyzed. FTV and TLG were calculated using PET VCAR (GE Healthcare, Milwaukee, WI, USA) on pretreatment and 4-week posttreatment scans. The effects of pretreatment and posttreatment functional tumor activity on patient survival were evaluated using Kaplan-Meier survival curves. Results: The median survival in the study group was 14.8 months (range 2.0-27.7 months). The median survival for patients with pretreatment FTV values of above and below 200 cc were 11.2 and 26.9 months, respectively (p<0.05). The median survival for patients with 4-week posttreatment FTV values of above and below 30 cc were 10.9 and 26.9 months, respectively (p<0.05). The median survival for patients with pretreatment TLG values of above and below 600 g were 11.2 and 26.9 months, respectively (p<0.05). The median survival for patients with 4-week posttreatment TLG values of above and below 100 g were 10.9 and 26.9 months, respectively (p<0.05). Conclusion: Pretreatment and posttreatment FTV and TLG showed very strong association with survival. These values can be useful quantitative criteria for patient selection and disease prognostication when 90Y SIRT is contemplated in patients with CRCLM. © 2011 Springer-Verlag.

Wildes K.A.,University of Texas at San Antonio | Miller A.R.,Center for Cancer Care | De Majors S.S.M.,University of Texas at San Antonio | Otto P.M.,University of Texas Health Science Center at San Antonio | Ramirez A.G.,University of Texas at San Antonio
Journal of Women's Health | Year: 2011

Objective: The aim of this study was to evaluate the relationship of satisfaction with the cancer care doctor and health-related quality of life (HRQOL) among Latina breast cancer survivors (BCS) by (1) assessing whether satisfaction would be positively correlated with HRQOL and (2) assessing whether satisfaction would significantly influence HRQOL while controlling for covariates. Methods: The cross-sectional study used self-report data from 117 Latina BCS. Satisfaction was measured with the Hall Satisfaction Index, and HRQOL was measured with the Functional Assessment of Cancer Therapy-General (FACT-G). Analyses included calculation of descriptive statistics, t tests, bivariate correlations, analyses of variance (ANOVAs), and multivariate analyses. Results: Latina BCS had high satisfaction and generally good HRQOL. The Hall Satisfaction Index total score was positively associated with FACT-G functional well-being (r=0.265, p=0.004). Multivariate analyses showed that the Hall Satisfaction Index total score was a significant predictor of FACT-G functional well-being (p=0.012). Employment status was also a significant predictor, where being employed or retired resulted in better functional well-being than being unemployed. Conclusions: Latina BCS were quite satisfied with their cancer care doctors, and high levels of satisfaction with the cancer care doctor influenced functional well-being when confounding variables were controlled. Despite reportedly high satisfaction, Latina BCS did report barriers to satisfaction that could be considered cultural. Implications are discussed. Copyright © 2011, Mary Ann Liebert, Inc.

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