Harold mmons Comprehensive Cancer Center

Dallas, TX, United States

Harold mmons Comprehensive Cancer Center

Dallas, TX, United States
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Pruitt S.L.,University of Texas Southwestern Medical Center | Pruitt S.L.,Harold mmons Comprehensive Cancer Center | Leonard T.,University of Texas at Dallas | Zhang S.,University of Texas Southwestern Medical Center | And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

Background:We(i) described variability in colorectal cancer (CRC) test use across multiple levels, including physician, clinic, and neighborhood; and (ii) compared the performance of novel cross-classified models versus traditional hierarchical models. Methods:Weexamined multilevel variation inCRCtest use among patients not up-to-date with screening in a large, urban safety net health system (2011-2012). Outcomes included: (i) fecal occult blood test (FOBT) or (ii) colonoscopy and were ascertained using claims data during a 1-year follow-up. We compared Bayesian (i) cross-classified four-level logistic models nesting patients within separate, nonoverlapping -levels- (physicians, clinics, and census tracts) versus (ii) three hierarchical two-level models using deviance information criterion. Models were adjusted for covariates (patient sociodemographic factors, driving time to clinic, and census tract poverty rate). Results: Of 3,195 patients, 157 (4.9%) completed FOBT and 292 (9.1%) completed colonoscopy during the study year. Patients attended 19 clinics, saw 177 physicians, and resided in 332 census tracts. Significant variability was observed across all levels in both hierarchical and cross-classified models that was unexplained by measured covariates. For colonoscopy, variance was similar across all levels. For FOBT, physicians, followed by clinics, demonstrated the largest variability. Model fit using cross-classified models was superior or similar to 2-level hierarchical models. Conclusions: Significant and substantial variability was observed across neighborhood, physician, and clinic levels in CRC test use, suggesting the importance of factors at each of these levels on CRC testing. Impact: Future multilevel research and intervention should consider the simultaneous influences of multiple levels, including clinic, physician, and neighborhood. © 2014 American Association for Cancer Research.

Pruitt S.L.,University of Texas Southwestern Medical Center | Pruitt S.L.,Harold mmons Comprehensive Cancer Center | Harzke A.J.,University of Texas Medical Branch
Cancer Causes and Control | Year: 2013

Background Using 1998-2005 SEER-Medicare data, we examined the effect of diagnostic and treatment delays on all-cause and colorectal cancer (CRC)-specific death among US adults aged ≥ 66 years with invasive colon or rectal cancer. We hypothesized that longer delays would be associated with a greater risk of death. Methods We defined diagnostic and treatment delays, respectively, as days between (1) initial medical consult for CRC symptoms and pathologically confirmed diagnosis (maximum: 365 days) and (2) pathologically confirmed diagnosis and treatment (maximum: 120 days).Cases(CRCdeaths) and controls (deaths due to other causes or censored) were matched on survival time. Logistic regression analyses adjusted for sociodemographic, tumor, and treatment factors. Results Median diagnostic delays were 60 (colon) and 40 (rectal) days and treatment delays were 13 (colon) and 16 (rectal) days in 10,663 patients. Colon cancer patients with the longest diagnostic delays (8-12 months vs. 14-59 days) had higher odds of all-cause (aOR: 1.31 CI: 1.08-1.58), but not CRC-specific death. Colon cancer patients with the shortest treatment delays (<1 vs. 1-2 weeks) had higher odds of all-cause (aOR: 1.23 CI: 1.01-1.49), but not CRCspecific death. Among rectal cancer patients, delays were not associated with risk of all-cause or CRC-specific death. Conclusions Longer delays of up to 1 year after symptom onset and 120 days for treatment did not increase odds of CRC-specific death. There may be little clinical benefit in detecting and treating existing symptomatic disease earlier. Screening prior to symptom onset must remain the primary goal to reduce CRC incidence, morbidity, and mortality. © Springer Science+Business Media Dordrecht 2013.

Zheng N.,Peking University | Dai W.,Peking University | Du W.,Peking University | Zhang H.,Peking University | And 6 more authors.
Molecular Pharmaceutics | Year: 2012

Many tumor cells specifically overexpress somatostatin receptors, in particular, subtype 2 (SSTR2). Lanreotide, a somatostatin analogue with high affinity for SSTR2, can be exploited as a ligand for tumor targeted therapy. In this study, lanreotide was first conjugated to poly(ethylene glycol)-b-poly(μ-caprolactone) (PEG-b-PCL) copolymer, and the active targeting micelles with paclitaxel (lanreotide-PM-PTX) or fluorescent agent were constructed and characterized with various analytical methods. Lanreotide-PM-PTX micelles were spherical in shape with a hydrodynamic diameter of 43.2 ± 0.4 nm, high drug encapsulation (87.1 ± 2.8%) and slow drug release rate. Two cancer cell lines (human lung cancer H446 and human breast cancer MCF-7 cells) with different expression levels of SSTR2 were used in this study. As observed by flow cytometry, confocal microscopy and cytotoxicity studies, lanreotide-encoded PEG-b-PCL micelles demonstrated more specific cell uptake and cytotoxicity in SSTR2-positive tumor cells via a receptor-mediated mechanism over the passive targeting micelles. The active targeting micelles showed higher accumulation in tumor tissue and tumor cells in tumor-bearing mice in vivo by near-infrared fluorescence (NIRF) imaging, high-performance liquid chromatography and confocal microscopy, respectively. Furthermore, treatment with lanreotide-PM-PTX micelles resulted in stronger tumor inhibition, increased life span and enhanced tumor cell apoptosis in SSTR2-overexpressing tumor model in athymic nude mice. The in vivo efficacy test with both H446 and MCF-7 tumor models further demonstrated the involvement of receptor-mediated interaction. Finally, the active targeting micelles exhibited less body weight loss, lower hemolysis and lower myelosuppression, as compared with the control groups. In conclusion, lanreotide can serve as an effective homing peptide, and the lanreotide-modified PEG-b-PCL micelles hold considerable promise in the treatment of SSTR2-overexpressing solid tumors. © 2012 American Chemical Society.

Togao O.,Advanced Imaging Research Center | Kessinger C.W.,Harold mmons Comprehensive Cancer Center | Huang G.,Harold mmons Comprehensive Cancer Center | Soesbe T.C.,Advanced Imaging Research Center | And 5 more authors.
PLoS ONE | Year: 2013

Amide proton transfer (APT) imaging is one of the chemical exchange saturation transfer (CEST) imaging methods which images the exchange between protons of free tissue water and the amide groups (-NH) of endogenous mobile proteins and peptides. Previous work suggested the ability of APT imaging for characterization of the tumoral grade in the brain tumor. In this study, we tested the feasibility of in-vivo APT imaging of lung tumor and investigated whether the method could differentiate the tumoral types on orthotopic tumor xenografts from two malignant lung cancer cell lines. The results revealed that APT imaging is feasible to quantify lung tumors in the moving lung. The measured APT effect was higher in the tumor which exhibited more active proliferation than the other. The present study demonstrates that APT imaging has the potential to provide a characterization test to differentiate types or grade of lung cancer noninvasively, which may eventually reduce the need invasive needle biopsy or resection for lung cancer. © 2013 Togao et al.

PubMed | Southwestern Medical Center, Health Outcomes Sciences and Harold mmons Comprehensive Cancer Center
Type: | Journal: The American journal of hospice & palliative care | Year: 2016

Studies have identified racial differences in advance care planning and use of hospice for care at the end of life. Multiple reasons for underuse among African American patients and their families have been proposed and deserve further exploration.The goal of this study was to examine perceptions of advance care planning, palliative care, and hospice among a diverse sample of African Americans with varying degrees of personal and professional experience with end-of-life care and use these responses to inform a culturally sensitive intervention to promote awareness of these options.Semistructured interviews and focus groups were conducted with African Americans who had varying degrees of experience and exposure to end-of-life care both personally and professionally. We conducted in-depth qualitative analyses of these interviews and focus group transcripts and determined that thematic saturation had been achieved.Several themes emerged. Participants felt that advance care planning, palliative care, and hospice can be beneficial to African American patients and their families but identified specific barriers to completion of advance directives and hospice enrollment, including lack of knowledge, fear that these measures may hasten death or cause providers to deliver inadequate care, and perceived conflict with patients faith and religious beliefs. Providers described approaches they use to address these barriers in their practices.Findings, which are consistent with and further elucidate those identified from previous research, will inform design of a culturally sensitive intervention to increase awareness and understanding of advance care planning, palliative care, and hospice among members of the African American community.

Chakrabarti G.,Southwestern Medical Center | Chakrabarti G.,Harold mmons Comprehensive Cancer Center | Gerber D.E.,Southwestern Medical Center | Gerber D.E.,Harold mmons Comprehensive Cancer Center | And 2 more authors.
Clinical Pharmacology: Advances and Applications | Year: 2015

Nicotinamide adenine dinucleotide phosphate (NADPH) biogenesis is an essential mechanism by which both normal and cancer cells maintain redox balance. While antitumor approaches to treat cancers through elevated reactive oxygen species (ROS) are not new ideas, depleting specific NADPH-biogenesis pathways that control recovery and repair pathways are novel, viable approaches to enhance cancer therapy. However, to elicit efficacious therapies exploiting NADPH-biogenic pathways, it is crucial to understand and specifically define the roles of NADPH-biogenesis pathways used by cancer cells for survival or recovery from cell stress. It is equally important to select NADPH-biogenic pathways that are expendable or not utilized in normal tissue to avoid unwanted toxicity. Here, we address recent literature that demonstrates specific tumor-selective NADPH-biogenesis pathways that can be exploited using agents that target specific cancer cell pathways normally not utilized in normal cells. Defining NADPH-biogenesis profiles of specific cancer-types should enable novel strategies to exploit these therapeutic windows for increased efficacy against recalcitrant neoplastic disease, such as pancreatic cancers. Accomplishing the goal of using ROS as a weapon against cancer cells will also require agents, such as NQO1 bioactivatable drugs, that selectively induce elevated ROS levels in cancer cells, while normal cells are protected. © 2015 Chakrabarti et al.

Du L.,Harold mmons Comprehensive Cancer Center | Pertsemlidis A.,Harold mmons Comprehensive Cancer Center | Pertsemlidis A.,Southwestern Medical Center
Journal of Molecular Cell Biology | Year: 2011

Although cancer and neurodegenerative disease are two distinct pathological disorders, emerging evidence indicates that these two types of disease share common mechanisms of genetic and molecular abnormalities. Recent studies show that individual microRNAs (miRNAs) could be involved in the pathology of both diseases, indicating that the mechanisms of these two seemingly dichotomous diseases converge in the dysregulation of gene expression at the post-transcriptional level. Given the increasing evidence showing that miRNA-based therapeutic strategies that modulate the activity of one or more miRNAs are potentially effective for a wide range of pathological conditions, the involvement of miRNAs in the common pathways of leading both diseases suggests a bright future for developing common therapeutic approaches for both diseases. Moreover, the miRNAs that are dysregulated in both diseases may hold promise as uniquely informative diagnostic markers. Here, we review recent studies on the miRNAs that have been implicated in both cancer and neurodegenerative diseases. © 2011 The Author. Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Huang X.,Harold mmons Comprehensive Cancer Center | Huang G.,Harold mmons Comprehensive Cancer Center | Zhang S.,ADVANCE Medical | Sagiyama K.,ADVANCE Medical | And 9 more authors.
Angewandte Chemie - International Edition | Year: 2013

Imaging all the people: Using ionizable diblock copolymers a series of nanoprobes encoded with different 19F reporters for specific pH transitions is prepared for use in MRI. The pH response of the nanoprobes is extremely sharp (ΔpHON/OFF≈0.25 pH), and results from the disassembly of polymer micelles (see scheme). A collection of three nanoprobes provides the proof of concept and allows for a qualitative measurement of environmental pH values. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Li Y.,Harold mmons Comprehensive Cancer Center | Wang Y.,Harold mmons Comprehensive Cancer Center | Huang G.,Harold mmons Comprehensive Cancer Center | Ma X.,Harold mmons Comprehensive Cancer Center | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2014

Traditional micelle self-assembly is driven by the association of hydrophobic segments of amphiphilic molecules forming distinctive core-shell nanostructures in water. Here we report a surprising chaotropic-anion-induced micellization of cationic ammonium-containing block copolymers. The resulting micelle nanoparticle consists of a large number of ion pairs (≈60 000) in each hydrophobic core. Unlike chaotropic anions (e.g. ClO4 -), kosmotropic anions (e.g. SO4 2-) were not able to induce micelle formation. A positive cooperativity was observed during micellization, for which only a three-fold increase in ClO4 - concentration was necessary for micelle formation, similar to our previously reported ultra-pH-responsive behavior. This unique ion-pair-containing micelle provides a useful model system to study the complex interplay of noncovalent interactions (e.g. electrostatic, van der Waals, and hydrophobic forces) during micelle self-assembly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed | Harold mmons Comprehensive Cancer Center
Type: | Journal: Angewandte Chemie (International ed. in English) | Year: 2016

Efficient delivery of biomacromolecules (e.g., proteins, nucleic acids) into cell cytosol remains a critical challenge for the development of macromolecular therapeutics or diagnostics. To date, most common approaches to assess cytosolic delivery rely on fluorescent labeling of macromolecules with an always on reporter and subcellular imaging of endolysosomal escape by confocal microscopy. This strategy is limited by poor signal-to-noise ratio and only offers low throughput, qualitative information. Herein we describe a quantitative redox-activatable sensor (qRAS) for the real-time monitoring of cytosolic delivery of macromolecules. qRAS-labeled macromolecules are silent (off) inside the intact endocytic organelles, but can be turned on by redox activation after endolysosomal disruption and delivery into the cytosol, thereby greatly improving the detection accuracy. In addition to confocal microscopy, this quantitative sensing technology allowed for a high-throughput screening of a panel of polymer carriers toward efficient cytosolic delivery of model proteins on a plate reader. The simple and versatile qRAS design offers a useful tool for the investigation of new strategies for endolysosomal escape of biomacromolecules to facilitate the development of macromolecular therapeutics for a variety of disease indications.

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