Association Between Adjuvant Chemotherapy and Nephrotoxicity and Kidney Function Monitoring in Elderly Breast Cancer Patients

University of Minnesota Ph.D. dissertation. May 2013. Major: Epidemiology. Advisor: Aaron Folsom. 1 computer file (PDF); viii, 130 pages.Background: Chronic kidney disease (CKD) and cancer are major public health problems in the elderly population. In elderly cancer patients, little is known about chemotherapy-related nephrotoxicity or patterns of CKD screening. The purpose of this dissertation was to evaluate the association between adjuvant chemotherapy (CHEMO) and risks of acute kidney injury (AKI) and CKD and rate of CKD screening in elderly women diagnosed with stages I-III breast cancer. Methods: The study was a 1:1 individually matched, retrospective cohort design using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Matching was performed at the day of CHEMO initiation based on propensity score. The assembled matched cohorts were used in the analyses for all three objectives with different follow-up periods and statistical methods for each objective. HASH(0x307f974) Results: A total of 28,048 patients were included. CHEMO was associated with a 2.7-fold increased risk of AKI within 6 months after initiation (HR 2.7, 95% CI 1.8-4.1). To find a possible explanation to this association, the distribution of other diseases coded on hospital claims for AKI was examined and showed that septicemia occurred in 40% of CHEMO treated patients with AKI and in only 17% of untreated patients with AKI. No significant association was found between CHEMO and risk of CKD in the maximum 18 years follow-up (HR 1.00, 95% CI 0.93-1.07). The rate of CKD screening after treatment completion was low regardless of CHEMO status. HASH(0x2faf9d4) Conclusion: CHEMO is associated with increased risk of AKI. This association may be partially explained by septicemia caused by infection/neutropenia due to use of myelosuppressive chemotherapeutic agents, which highlights the importance of preventing serious complications of CHEMO in preventing AKI. The finding of no association between CHEMO and risk of CKD may not suggest a late nephrotoxic effect of chemotherapeutic agents commonly used to treat breast cancer in the adjuvant setting, or provide evidence to recommend a clinical practice guideline for CKD screening specifically in elderly breast cancer patients treated with CHEMO. Future studies of CKD as a late effect of cancer treatment for other solid tumors commonly treated with known or potential nephrotoxic agents are warranted

Restriction of subapical proteins during cellularization depends on the onset of zygotic transcription and the formin Dia

Cortical domains are characterized by spatially restricted polarity proteins. The pattern of cortical domains is dynamic and changes during cell differentiation and development. Although there is a good understanding for how the cortical pattern is maintained, e. g. by mutual antagonism, less is known about how the initial pattern is established, and its dynamics coordinated with developmental progression. Here we investigate the initial restriction of subapical marker proteins during the syncytial-cellular transition in Drosophila embryos. The subapical markers Canoe/Afadin, the complex ELMO-Sponge, Baz and Arm become initially restricted between apical and lateral domains during cellularization. We define the role of zygotic genome activation as a timer for subapical domain formation. Subapical markers remained widely spread in embryos treated with α-amanitin and became precociously restricted in mutant embryos with premature zygotic transcription. In contrast, remodeling of the nuclear division cycle without cytokinesis to a full cell cycle is not a prerequisite for subapical domain formation, since we observed timely subapical restriction in embryos undergoing an extra nuclear cycle. We provide evidence that earliest subapical markers ELMO-Sponge and Canoe are required for subapical accumulation of Baz. Supporting an important role of cortical F-actin in subapical restriction, we found that the formin Dia was required for Baz restriction, and its distribution depended on the onset of zygotic gene expression. In summary, we define zygotic transcription as a timer, to which subapical markers respond in a dia-dependent mechanism

A sensitive and rapid HPLC-DAD method for the determination of 3-hydroxy-1,2-dimethyl-4-pyridone and its distribution in rats

Purpose: To establish a sensitive and rapid method for the determination of the tissue distribution of 3-hydroxy-1,2-dimethyl-4-pyridone (L1) in vivo, and its plasma protein binding capacity.Methods: This study optimized a reverse-phase HPLC method for specific and sensitive determination of L1 as well as its plasma and tissue  distributions. The optimized method was used to determine the plasma protein-binding capacity of L1 in Wistar rats.Results: A rapid, sensitive and simple HPLC-DAD method was established for studying the plasma and tissue distribution of L1. Following TI  administration, its liver concentrations peaked at 60 min and 360min, followed 360 min later with peak level in the kidney (second highest). The L1 concentration was significantly lower after 360 min than after 60 min, and values of its mean binding to plasma proteins was 5.2 % at different L1 concentrations.Conclusion: These results indicate that L1 is a drug with rapid-absorption and rapid-elimination thath is distributed widely in vivo in rats. Moreover, the drug has a weak plasma protein-binding capacity. Keywords: 3-Hydroxy-1,2-dimethyl-4-pyridone, Distribution, Alzheimer’s disease, Therap

Opportunistic Wireless Control Over State-Dependent Fading Channels

The heterogeneous system consisting of the wireless control system (WCS) and mobile agent system (MAS) is ubiquitous in Industrial Internet of Things (IIoT) systems. Within this system, the positions of mobile agents may lead to shadow fading on the wireless channel that the WCS is controlled over and can significantly compromise the WCS's performance. This paper focuses on the controller design for the MAS to ensure the performance of WCS in the presence of WCS and MAS coupling. Firstly, the constrained finite field network (FFN) with profile-dependent switching topology is adopted to proceed the operational control for the MAS. By virtue of the algebraic state space representation (ASSR) method, an equivalent form is obtained for the WCS and MAS coupling. A necessary and sufficient condition in terms of constrained set stabilization is then established to ensure the Lyapunov-like performance with expected decay rate. Finally, a graphical method together with the breath-first searching is provided to design state feedback controllers for the MAS. With this method, it is easy to check the constrained set stabilization of MAS and to ensure the performance requirements of WCS in the presence of WCS and MAS coupling. The study of an illustrative example shows the effectiveness of the proposed method

An atlas of DNA methylomes in porcine adipose and muscle tissues

It is evident that epigenetic factors, especially DNA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DNA methylation and obesity. We sample eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generate 1,381 Gb of sequence data from 180 methylated DNA immunoprecipitation libraries, and provide a genome-wide DNA methylation map as well as a gene expression map for adipose and muscle studies. The analysis shows global similarity and difference among breeds, sexes and anatomic locations, and identifies the differentially methylated regions. The differentially methylated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth

Corrigendum to “Restriction of subapical proteins during cellularization depends on the onset of zygotic transcription and the formin Dia” [Dev. Biol. 487 (2022) 110–121]

Corrigendum to “Restriction of subapical proteins during cellularization depends on the onset of zygotic transcription and the formin Dia”