Coevolution of Prostate Cancer and Bone Stroma in Three-Dimensional Coculture: Implications for Cancer Growth and Metastasis

[[abstract]]Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes with reactive oxygen species serving as mediators. The evolved stromal cells are highly inductive of human PCa growth in mice, and expressed increased levels of extracellular matrix (versican and tenascin) and chemokine (BDFN, CCL5, CXCL5, and CXCL16) genes. These genes were validated in clinical tissue and/or serum specimens and could be the predictors for invasive and bone metastatic PCa. These results, combined with our previous observations, support the concept of permanent genetic and behavioral changes of PCa epithelial cells after being either cocultured with prostate or bone stromal cells as three-dimensional prostate organoids or grown as tumor xenografts in mice. These observations collectively suggest coevolution of cancer and stromal cells occurred under three-dimensional growth condition, which ultimately accelerates cancer growth and metastasis

Effects of a simulation-based blended training model on nurses’ treatment decision-related knowledge about oral cancer in Taiwan: a pilot survey

The present study aimed to evaluate the effects of virtual reality (VR) simulations combined with bedside assignments on nurses’ self-efficacy in providing pre-treatment educational services. Between March 2019 and November 2020, we conducted a study of VR educational materials that were developed to cover information about the treatment of oral cancers. The effects of the VR simulation, the thinking-path tracking map method, and bedside assignments on the nurses’ treatment decision-related knowledge were evaluated in a ward for oral cancer patients at Taipei Veterans General Hospital, Taipei, Taiwan. The blended training model significantly increased nurses’ familiarity (P<0.01) and confidence (P<0.03) regarding their knowledge of treatments and treatment decision-related knowledge. This model also significantly increased their confidence in their skills in bedside pre-treatment education for admitted oral cancer patients (P<0.002). Oral cancer-specific VR materials enhanced the effectiveness of skills training among nurses in the oral cancer ward

Dreyfus scale-based feedback increased medical students’ satisfaction with the complex cluster part of a interviewing and physical examination course and improved skills readiness in Taiwan

Purpose In contrast to the core part of the clinical interviewing and physical examination (PE) skills course, corresponding to the basic, head-to-toe, and thoracic systems, learners need structured feedback in the cluster part of the course, which includes the gastrointestinal, neuromuscular, and musculoskeletal systems. This study evaluated the effects of using Dreyfus scale-based feedback, which has elements of continuous professional development, instead of Likert scale-based feedback in the cluster part of training in Taiwan. Methods Instructors and final-year medical students in the 2015–2016 classes of National Yang-Ming University, Taiwan comprised the regular cohort, whereas those in the 2017–2018 classes formed the intervention cohort. In the intervention cohort, Dreyfus scale-based feedback, rather than Likert scale-based feedback, was used in the cluster part of the course. Results In the cluster part of the course in the regular cohort, pre-trained standardized patients rated the class climate as poor, and students expressed low satisfaction with the instructors and course and low self-assessed readiness. In comparison with the regular cohort, improved end-of-course group objective structured clinical examination scores after the cluster part were noted in the intervention cohort. In other words, the implementation of Dreyfus scale-based feedback in the intervention cohort for the cluster part improved the deficit in this section of the course. Conclusion The implementation of Dreyfus scale-based feedback helped instructors to create a good class climate in the cluster part of the clinical interviewing and PE skills course. Simultaneously, this new intervention achieved the goal of promoting medical students’ readiness for interviewing, PE, and self-directed learning

Involvement of the nuclear high mobility group B1 peptides released from injured hepatocytes in murine hepatic fibrogenesis

AbstractThis study investigated the pro-fibrogenic role of high mobility group box 1 (HMGB1) peptides in liver fibrogenesis. An animal model of carbon tetrachloride (CCl4)-induced liver fibrosis was used to examine the serum HMGB1 levels and its intrahepatic distribution. The increased serum HMGB1 levels were positively correlated with elevation of transforming growth factor-β1 (TGF-β1) and collagen deposition during fibrogenesis. The cytoplasmic distribution of HMGB1 was noted in the parenchymal hepatocytes of fibrotic livers. In vitro studies confirmed that exposure to hydrogen peroxide and CCl4 induced an intracellular mobilization and extracellular release of nuclear HMGB1 peptides in clone-9 and primary hepatocytes, respectively. An uptake of exogenous HMGB1 by hepatic stellate cells (HSCs) T6 cells indicated a possible paracrine action of hepatocytes on HSCs. Moreover, HMGB1 dose-dependently stimulated HSC proliferation, up-regulated de novo synthesis of collagen type I and α-smooth muscle actin (α-SMA), and triggered Smad2 phosphorylation and its nuclear translocation through a TGF-β1-independent mechanism. Blockade with neutralizing antibodies and gene silencing demonstrated the involvement of the receptor for advanced glycation end-products (RAGE), but not toll-like receptor 4, in cellular uptake of HMGB1 and the HMGB1-mediated Smad2 and ERK1/2 phosphorylation as well as α-SMA up-regulation in HSC-T6 cells. Furthermore, anti-RAGE treatment significantly ameliorated CCl4-induced liver fibrosis. In conclusion, the nuclear HMGB1 peptides released from parenchymal hepatocytes during liver injuries may directly activate HSCs through stimulating HSC proliferation and transformation, eventually leading to the fibrotic changes of livers. Blockade of HMGB1/RAGE signaling cascade may constitute a therapeutic strategy for treatment of liver fibrosis

Effects of virtual reality training on decreasing the rates of needlestick or sharp injury in new-coming medical and nursing interns in Taiwan

Purpose Senior nursing and medical interns’ lack of familiarity and confidence with respect to practicing universal precaution for the prevention of occupational needlestick or sharp injuries may harm themselves. Trainees’ self-reported needlestick or sharp injury rate was known to be especially high during the first 2 months of internship in Taiwan. This prospective cohort study aimed to assess the effect of newly developed virtual reality (VR) game, which uses Gagne’s learning model to improve universal precaution for needlestick or sharp injury prevention and decrease the rates of needle stick or sharp injuries in new-coming medical and nursing interns in Taiwan. Methods From 2017 to 2019, the VR system was developed and applied in training of 59 new-coming nursing and 50 medical interns. Occupational needlestick or sharp injury prevention was sought to be achieved through a game of right and wrong choices for safe or unsafe universal precaution behaviors. Results In comparison with medical interns, a higher proportion of nursing interns had past experiences of deep occupational needlestick or sharp injury. Before VR training, the familiarity and confidence for needlestick or sharp injury prevention were higher among nursing interns than medical interns. Trainees with past experiences of deep needlestick or sharp injury exhibited better performance on the accuracy rate and time needed to complete 20 decisions than those without past experiences in VR practice. All trainees showed an improved performance after VR training. A high proportion of trainees reported that the VR-based training significantly decreased their anxiety about needlestick or sharp injury prevention. Conclusion This self-developed VR game system using Gagne’s flow improved universal precaution for needlestick or sharp injury prevention and reduced the needlestick or sharp injury rates in the first 2 months of nursing and medical internship

Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells

HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaPE and ARCaPM cells in an EMT model. Cocultured ARCaPE or ARCaPM cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaPE exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaPE cells compared to ARCaPM cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaPE- and ARCaPM-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation

Analysis of Mechanisms Associated with Loss of Infectivity of Clonal Populations of Borrelia burgdorferi B31MI

Numerous studies have provided suggestive evidence that the loss of plasmids correlates with the loss of infectivity of the Lyme disease spirochetes. In this study we have further investigated this correlation. Clonal populations were obtained from the skin of a mouse infected for 3 months with a clonal population of Borrelia burgdorferi B31MI. The complete plasmid compositions of these populations were determined using a combination of PCR and Southern hybridization. The infectivities of clones differing in plasmid composition were tested using the C3H-HeJ murine model for Lyme disease. While several clones were found to be noninfectious, a correlation between the loss of a specific plasmid and loss of infectivity in the clones analyzed in this report was not observed. While it is clear from recent studies that the loss of some specific plasmids results in attenuated virulence, this study demonstrates that additional mechanisms also contribute to the loss of infectivity