Repeatability of quantitative18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five18F-FLT repeatability cohorts in solid tumors.18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak(RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied

Professional Seminar: Valuing a One-Credit Course Through the Lens of Doctoral Students

Professional seminar for doctoral students at a Research I University is a 1-credit course, 2 below the conventional courses. However, the course content covers at least 3 years’ worth of experiences, knowledge, and processes compressed into a single school year. The course typically extends over 16 weeks and 24 actual contact hours with 1 professor to 7 students on average. Assignments expose students to professional jobs in academia, resources available on campus, grant writing procedures, and facilitate the trajectory and purpose of the doctoral process. The purpose of this study is to investigate doctoral students’ narratives on the value they hold for seminar. Findings indicate an overarching theme of value among 5 categories: opportunities, cohort, departmental support, overcoming obstacles, and vested interest

Albumin Protein Impact on Early-Stage In Vitro Biodegradation of Magnesium Alloy (WE43)

Mg and its alloys are promising biodegradable materials for orthopedic implants and cardiovascular stents. The first interactions of protein molecules with Mg alloy surfaces have a substantial impact on their biocompatibility and biodegradation. We investigate the early-stage electrochemical, chemical, morphological, and electrical surface potential changes of alloy WE43 in either 154 mM NaCl or Hanks’ simulated physiological solutions in the absence or presence of bovine serum albumin (BSA) protein. WE43 had the lowest electrochemical current noise (ECN) fluctuations, the highest noise resistance (Zn = 1774 Ω·cm2), and the highest total impedance (|Z| = 332 Ω·cm2) when immersed for 30 min in Hanks’ solution. The highest ECN, lowest Zn (1430 Ω·cm2), and |Z| (49 Ω·cm2) were observed in the NaCl solution. In the solutions containing BSA, a unique dual-mode biodegradation was observed. Adding BSA to a NaCl solution increased |Z| from 49 to 97 Ω·cm2 and decreased the ECN signal of the alloy, i.e., the BSA inhibited corrosion. On the other hand, the presence of BSA in Hanks’ solution increased the rate of biodegradation by decreasing both Zn and |Z| while increasing ECN. Finally, using scanning Kelvin probe force microscopy (SKPFM), we observed an adsorbed nanolayer of BSA with aggregated and fibrillar morphology only in Hanks’ solution, where the electrical surface potential was 52 mV lower than that of the Mg oxide layer

Ovarian steroid hormones: what's hot in the stem cell pool?

The vital role of ovarian hormones in the development of the normal breast foreshadowed their importance in mammary stem cell regulation. Two recent papers reveal that 17β-estradiol and progesterone control the size and repopulating ability of the mammary stem cell compartment. This likely occurs via paracrine signaling from steroid receptor-positive luminal cells to steroid receptor-negative stem cells. These findings illuminate roles for the female sex steroids in mobilizing the stem cell pool in the normal breast, and also provide a crucial link between the known hormonal risks of breast cancer and the potential stem cell origin of this disease

Challenges and Strategies for Optimizing Corrosion and Biodegradation Stability of Biomedical Micro- and Nanoswimmers: A Review

The last two decades have witnessed the emergence of micro- and nanoswimmers (MNSs). Researchers have invested significant efforts in engineering motile micro- and nanodevices to address current limitations in minimally invasive medicine. MNSs can move through complex fluid media by using chemical fuels or external energy sources such as magnetic fields, ultrasound, or light. Despite significant advancements in their locomotion and functionalities, the gradual deterioration of MNSs in human physiological media is often overlooked. Corrosion and biodegradation caused by chemical reactions with surrounding medium and the activity of biological agents can significantly affect their chemical stability and functional properties during their lifetime performance. It is therefore essential to understand the degradation mechanisms and factors that influence them to design ideal biomedical MNSs that are affordable, highly efficient, and sufficiently resistant to degradation (at least during their service time). This review summarizes recent studies that delve into the physicochemical characteristics and complex environmental factors affecting the corrosion and biodegradation of MNSs, with a focus on metal-based devices. Additionally, different strategies are discussed to enhance and/or optimize their stability. Conversely, controlled degradation of non-toxic MNSs can be highly advantageous for numerous biomedical applications, allowing for less invasive, safer, and more efficient treatments

Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage

Estrogen-mediated proliferation is fundamental to normal mammary gland development. Recent studies have demonstrated that amphiregulin is a critical paracrine regulator of estrogen action during ductal morphogenesis. These studies implicate a critical role for amphiregulin in mammary stem cell differentiation as well as breast cancer initiation and progression

Identification of murine mammary stem cells: implications for studies of mammary development and carcinogenesis

The epithelial components of the mammary gland are thought to arise from a stem cell capable of both self-renewal and multi-lineage differentiation. Furthermore, there is increasing evidence that mammary carcinomas originate in these cells or their immediate progeny. The recent identification of murine mammary stem cells should facilitate their molecular characterization and help to elucidate their role in mammary carcinogenesis. In addition, an understanding of the biology of these cells including the pathways that regulate their self-renewal and differentiation may suggest new approaches for the prevention and treatment of breast cancer

Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: a potential regulator of involution

Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the involution process is initiated by fresh media withdrawal, and is characterized by cellular oxidative stress, expression of activated macrophage marker CD68 and finally complete clearing of the luminal but not basal epithelial layer. This process can be simulated by ectopic addition of reactive oxygen species (ROS) in cultures without media withdrawal. Cells isolated from post-involution alveoli were enriched for the CD49f+ mammary stem cell (MaSC) phenotype and were able to reproduce a complete alveolar structure in subcultures without any significant loss in viability. We propose that the ROS produced by accumulated milk breakdown post-weaning may be the mechanism underlying the selective involution of secretory alveolar luminal cells, and that our culture model represents an useful means to investigate this and other mechanisms further