Publications by authors named "G Paul Wright"

2,767 Publications

  • Page 1 of 1

Impact of Choosing Wisely Recommendations on Sentinel Lymph Node Biopsy and Postoperative Radiation Rates in Women Over Age 70 Years with Hormone-Positive Breast Cancer.

Ann Surg Oncol 2021 Jul 31. Epub 2021 Jul 31.

Spectrum Health/Michigan State University General Surgery Residency, Grand Rapids, MI, USA.

Background: In 2016, the Society of Surgical Oncology released a Choosing Wisely guideline recommending sentinel lymph node biopsy (SLNB) omission in females ≥70 years of age with early-stage, hormone-positive, clinically node-negative invasive breast cancer. This study investigated the impact of this guideline on SLNB and radiotherapy rates, in addition to assessing temporal trends of nodal biopsy and factors associated with recurrence.

Methods: The study involved a retrospective review of women who met the guideline criteria and underwent partial mastectomy at a single institution between 2009 and 2018. Using the same inclusion criteria, the National Cancer Database was queried to obtain a separate dataset. Statistical analyses included univariate comparisons, and multivariate logistic regression modeling to predict radiotherapy delivery.

Results: In our institutional series, 487 patients were included, 274 (56.3%) of whom received radiotherapy. There were 414 patients (85.0%) who underwent SLNB, with a nodal positivity rate of 11%. SLNB correlated with higher rates of radiotherapy (63.5% vs. 15.1%, p < 0.001). Age <80 years was an independent predictor of radiotherapy receipt (odds ratio 3.0, 95% confidence interval 0.22-0.52). SLNB performance decreased after 2016 (88.4% vs. 78.4%, p = 0.003). Median follow-up was 4.8 years, with 19 (3.9%) documented recurrences. SLNB performance was not associated with recurrence (2.9% vs. 5.5%, p = 0.279), whereas radiotherapy resulted in reduced recurrence (1.1% vs. 6.1%, p = 0.002). One (0.2%) disease-related mortality was observed.

Conclusion: Recurrence rates and disease-related mortality remain low in this demographic regardless of treatment rendered. Omission of SLNB and radiotherapy should remain a consideration, and efforts in both patient and physician education should continue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10460-wDOI Listing
July 2021

Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer.

Int J Mol Sci 2021 Jul 12;22(14). Epub 2021 Jul 12.

Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA.

Background: Doxorubicin (Dox) is a first-line treatment for triple negative breast cancer (TNBC), but its use may be limited by its cardiotoxicity mediated by the production of reactive oxygen species. We evaluated whether vitamin D may prevent Dox-induced cardiotoxicity in a mouse TNBC model.

Methods: Female Balb/c mice received rodent chow with vitamin D (1500 IU/kg; vehicle) or chow supplemented with additional vitamin D (total, 11,500 IU/kg). the mice were inoculated with TNBC tumors and treated with intraperitoneal Dox (6 or 10 mg/kg). Cardiac function was evaluated with transthoracic echocardiography. The cardiac tissue was evaluated with immunohistochemistry and immunoblot for levels of 4-hydroxynonenal, NAD(P)H quinone oxidoreductase (NQO1), C-MYC, and dynamin-related protein 1 (DRP1) phosphorylation.

Results: At 15 to 18 days, the mean ejection fraction, stroke volume, and fractional shortening were similar between the mice treated with vitamin D + Dox (10 mg/kg) vs. vehicle but significantly greater in mice treated with vitamin D + Dox (10 mg/kg) vs. Dox (10 mg/kg). Dox (10 mg/kg) increased the cardiac tissue levels of 4-hydroxynonenal, NQO1, C-MYC, and DRP1 phosphorylation at serine 616, but these increases were not observed with vitamin D + Dox (10 mg/kg). A decreased tumor volume was observed with Dox (10 mg/kg) and vitamin D + Dox (10 mg/kg).

Conclusions: Vitamin D supplementation decreased Dox-induced cardiotoxicity by decreasing the reactive oxygen species and mitochondrial damage, and did not decrease the anticancer efficacy of Dox against TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22147439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305038PMC
July 2021

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

NPJ Precis Oncol 2021 Jul 14;5(1):64. Epub 2021 Jul 14.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-021-00178-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280110PMC
July 2021

A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy.

Arch Womens Ment Health 2021 Jul 7. Epub 2021 Jul 7.

Departments of Psychiatry, University of British Columbia (UBC), 938 W28th Ave, Vancouver, BC, V5Z 4H4, Canada.

Depression during pregnancy affects 10-15% of women, and 5% of women take antidepressants during pregnancy. Clinical guidelines provide recommendations for selective serotonin reuptake inhibitor (SSRI) drug choice and dose based on CYP2D6 and CYP2C19 genotype; however, they are based on evidence from non-pregnant cohorts. This study aimed to test the hypothesis that women with function-altering variants (increased, decreased, or no function) in these pharmacogenes, taking SSRIs prenatally, would have more depression symptoms than women whose pharmacogenetic variants are associated with normal SSRI metabolism. Comprehensive CYP2D6 and CYP2C19 genotyping using a range of methods, including gene copy number analysis, was performed as secondary analyses on two longitudinal cohorts of pregnant women (N = 83) taking the SSRIs paroxetine, citalopram, escitalopram, or sertraline. The Kruskal-Wallis test compared mean depression scores across four predicted metabolizer groups: poor (n = 5), intermediate (n = 10), normal (n = 53), and ultrarapid (n = 15). There were no significant differences between mean depression scores across the four metabolizer groups (H(3) = .73, p = .87, eta-squared = .029, epsilon-squared = .0089). This is the first study of the relationship in pregnancy between CYP2C19 pharmacogenetic variations and depression symptoms in the context of SSRI use. Findings from this initial study do not support the clinical use of pharmacogenetic testing for SSRI use during the second or third trimesters of pregnancy, but these findings should be confirmed in larger cohorts. There is an urgent need for further research to clarify the utility of pharmacogenetic testing for pregnant women, especially as companies offering direct-to-consumer genetic testing expand their marketing efforts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00737-021-01149-wDOI Listing
July 2021

QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.

J Microsc 2021 Jul 2. Epub 2021 Jul 2.

Department of Cell Biology (route 283), Radboud Institute for Molecular Life Sciences, Nijmegen, 6525GA, Netherlands.

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated, quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments . One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique . Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g., DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE ), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility . In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models , and tools , including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper 1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; 2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists , bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers, and observers of such; 3) outlines the current actions of the QUAREP-LiMi initiative, and 4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jmi.13041DOI Listing
July 2021
-->