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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.

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 3 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.

Du L.,Harold mmons Comprehensive Cancer Center | Pertsemlidis A.,Harold mmons Comprehensive Cancer Center | Pertsemlidis A.,Eugene rmott Center for Human Growth and Development | 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.

Bishop W.P.,Southwestern Medical Center | Bishop W.P.,Harold mmons Comprehensive Cancer Center | Craddock Lee S.J.,Southwestern Medical Center | Craddock Lee S.J.,Harold mmons Comprehensive Cancer Center | And 6 more authors.
American Journal of Public Health | Year: 2016

Objectives. To evaluate 3 single-item screening measures for limited health literacy in a community-based population of English and Spanish speakers. Methods. We recruited 324 English and 314 Spanish speakers from a community research registry in Dallas, Texas, enrolled between 2009 and 2012.We used 3 screening measures: (1) How would you rate your ability to read?; (2) How confident are you filling out medical forms by yourself?; and (3) How often do you have someone help you read hospital materials? In analyses stratified by language, we used area under the receiver operating characteristic (AUROC) curves to compare each item with the validated 40-item Short Test of Functional Health Literacy in Adults. Results. For English speakers, no difference was seen among the items. For Spanish speakers, "ability to read" identified inadequate literacy better than "help reading hospital materials" (AUROC curve = 0.76 vs 0.65; P = .019). Conclusions. The "ability to read" item performed the best, supporting use as a screening tool in safety-net systems caring for diverse populations. Future studies should investigate how to implement brief measures in safety-net settings and whether highlighting health literacy level influences providers' communication practices and patient outcomes.

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