Imaging Androgen Receptors in Breast Cancer with (18)F-fluoro-5α-dihydrotestosterone-PET: A Pilot Study

Most breast cancers express androgen receptors (AR). This prospective imaging sub-study explored imaging AR with (18)F-fluoro-5α-dihydrotestosterone (FDHT)-PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024, GTx, Inc). Methods: 11 post-menopausal women with estrogen receptor positive MBC underwent FDHT-PET/CT at baseline, 6, and 12 weeks after starting SARM therapy. Abnormal tumor FDHT uptake was quantified using maximum SUV (SUVmax). AR status was determined from tumor biopsy specimens. FDHT-SUVmax percent change between scans was calculated. Best overall response was categorized as clinical benefit (CB: non-progressive disease [PD]), or PD using RECIST 1.1. Results: Median baseline FDHT-SUVmax was 4.1 (range 1.4-5.9) for AR+ tumors versus 2.3 (range 1.5-3.2) for AR- tumors (p=0.22). Quantitative AR expression and baseline FDHT uptake were weakly correlated (Pearson rho=0.39, p=0.30). Seven participants with CB at 12 weeks tended to have larger declines in FDHT uptake compared to those with PD at both 6 (median decline, range: -26.8%, -42.9 to -14.1% vs. -3.7%, -31% to +29%, respectively, p=0.11) and 12 weeks (median decline, range: -35.7%, -69.5 to -7.7% vs. -20.1%, -26.6% to +56.5%, respectively, p=0.17) after starting GTx-024. Conclusion: This hypothesis-generating data suggests that FDHT-PET/CT is worth further study as an imaging biomarker for evaluating response of MBC to SARM therapy and reiterates the feasibility of including molecular imaging in multidisciplinary therapeutic trials

Hydrokinetic turbine power converter and controller system design and implementation

Due to environmental considerations and decline of fossil fuels, searching for the viable energy alternatives is a pressing need. In order to meet the energy demand globally, research into the renewable energy technologies must be pursued. Wind energy has emerged as the leader of new energy source, while other types of energy sources continue to be investigated. Hydrokinetic power as a potential opportunity to harvest energy is being explored recently. Because the hydrokinetic turbines are still in an early stage of development, study on the hydrokinetic system is an active topic of academic research. Although water speed is instable and unpredictable, the hydrokinetic system can still operate at the peak power point. For this reason, the power converter and rotor speed controller are the most important components in this study. In the first two chapters some background studies and some system components are introduced. In this project, the maximum power point tracking is realized by the hill-climb searching method and the lookup table method, plus the analysis and comparison of these two methods are presented. In terms of rotor speed controller design, the Field Oriented Control strategy is applied and discussed. The presented hydrokinetic system is a stand-alone system which throws excessive energy to a load resistor. In order to demonstrate the feasibility of the system, the hydrokinetic system model is simulated in the PSIM software. A number of cases are simulated with the PSIM model to validate the feasibility of this hydrokinetic system. Finally, the project objectives are achieved and some of the hardware is tested. Future work is still required, such as the bench testing with a real PMSG, a variable frequency drive, and the optimization of the maximum power point tracking method and rotor speed controller with the hardware test results.Applied Science, Faculty ofElectrical and Computer Engineering, Department ofGraduat

MAFB mediates the therapeutic effect of sleeve gastrectomy for obese diabetes mellitus by activation of FXR expression

Farnesoid X receptor (FXR) and related pathways are involved in the therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus. This study aimed to investigate the mechanism of FXR expression regulation during the surgical treatment of obese diabetes mellitus by sleeve gastrectomy. Diabetic rats were established by combined streptozotocin and high-fat diet induction. Data collection included body weight, chemical indexes of glucose and lipid metabolism, liver function, and the expression levels of musculoaponeurotic fibrosarcoma oncogene family B (MAFB), FXR, and related genes induced by sleeve gastrectomy. Chang liver cells overexpressing MAFB gene were established to confirm the expression of related genes. The binding and activation of FXR gene by MAFB were tested by Chip and luciferase reporter gene assays. Vertical sleeve gastrectomy induced significant weight loss and decreased blood glucose and lipids in diabetic rat livers, as well as decreased lipid deposition and recovered lipid function. The expression of MAFB, FXR, and FXR-regulated genes in diabetic rat livers were also restored by sleeve gastrectomy. Overexpression of MAFB in Chang liver cells led to FXR gene expression activation and the alteration of multiple FXR-regulated genes. Chip assay showed that MAFB could directly bind with FXR promoter, and the activation of FXR expression was confirmed by luciferase reporter gene analysis. The therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus was mediated by activation of FXR expression through the binding of MAFB transcription factor

Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism

Purpose. To explore the changes in FSP27 expression and fat metabolism in adipose tissue and their relationship after bariatric surgery in rats. Method. Food intake, body weight, triglyceride content, fat distribution, and fat cell morphology were evaluated in rats grouped into control, sham, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) groups. Immunohistochemistry and western blotting were used to detect protein expression and real-time PCR was used to detect mRNA expression. Mouse 3T3-L1 preadipocytes were used to assess the effects of different energy levels and nutrient factors on FSP27 in adipocytes. Result. Food intake, body weight, and triglyceride levels were reduced in RYGB and SG rats within 28 days after surgery, with a more pronounced effect in the RYGB group. Weight loss was mainly due to loss of fat mass rather than loss of lean mass, with the most pronounced decrease in trunk fat. FSP27 expression increased in lean rat adipocytes accompanied by increased lipid droplets (LDs). In SG and RYGB rats, the FSP27 protein concentration gradually increased in white adipose tissue (WAT) after operation. Hormone-sensitive lipase (HSL), p-HSL/HSL, Adipose Triglyceride Lipase (ATGL), and Comparative Gene Identification-58 (CGI-58) gradually decreased in SG and RYGB rats, but they were always higher than in control and sham animals. FSP27 was also decreased in 3T3-L1 adipocytes of animals with a high-energy diet. Conclusion. FSP27 is associated with rat lipid metabolism and its expression varies with energy and nutrient supply. It can inhibit excessive hydrolysis and fat accumulation by regulating HSL and ATGL expression and by mediating LDs formation

Photothermally responsive icariin and carbon nanofiber modified hydrogels for the treatment of periodontitis

Introduction: Periodontitis is a chronic inflammatory disease brought on by various bacteria, and effective antibacterial, anti-inflammatory and alveolar bone regeneration are the main goals of treating periodontal disease.Methods: In the current work, we employed Icariin (ICA) into a hydrogel modified with carbon nanofiber (CNF) to create a multifunctional composite nanoplatform. The composite was activated in the near infrared (NIR) to treat periodontitis.Results: The antibacterial results showed that the ICA+CNF@H showed 94.2% and 91.7% clearance of S. aureus and E. coli, respectively, under NIR irradiation. In vitro experiments showed that NIR-irradiated composites suppressed inflammatory factor (IL-6) and ROS expression and up-regulated the performance of anti-inflammatory factor (IL-10) in RAW264.7 cells. At the same time, the composites promoted the production of osteogenic factors in BMSCs, with an approximately 3-fold increase in alkaline phosphatase activity after 7 days and an approximately 2-fold increase in the rate of extracellular matrix mineralization after 21 days. In vivo tests showed that the alveolar bone height was clearly greater in the ICA+CNF@H (NIR) group compared to the periodontitis group.Discussion: In conclusion, ICA+CNF@H under NIR irradiation achieved a synergistic effect of antibacterial, anti-inflammatory, reduction of reactive oxygen species and promotion of osteogenesis, offering a novel approach for treating periodontitis

Report on the PET/CT Image-Based Radiation Dosimetry of [(18)F]FDHT in Women, a Validated Imaging Agent with New Applications for Evaluation of Androgen Receptor Status in Women with Metastatic Breast Cancer

In a prospective clinical trial, [(18)F]fluoro-5α-dihydrotestosterone ([(18)F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [(18)F]FDHT in women. Methods: [(18)F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [(18)F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of (18)F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [(18)F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [(18)F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P \u3c 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P \u3c 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P \u3c 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [(18)F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq