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Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4'-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2'-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed superior effects in inhibiting the proliferation of several cisplatin-resistant human cancer cell lines, including MDA-MB-231 breast cancers, COLO205 colon cancers and SK-OV-3 ovarian cancers. TFBPC bound to DNA and formed DNA crosslinks that resulted in DNA degradation, triggering the cell death program through the PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. Moreover, TFBPC significantly inhibited tumor growth in both animal models which include a cell line-derived xenograft model (CDX) of cisplatin-resistant MDA-MB-231, and a patient-derived xenograft (PDX) model of triple-negative breast cancers (TNBCs). Furthermore, the biopsy specimen from TFBPC-treated xenografts revealed decreased expressions of P53, Ki-67 and PD-L1 coupled with higher expression of cleaved caspase 3, suggesting TFBPC treatment was effective and resulted in good prognostic indications. No significant pathological changes were observed in hematological and biochemistry tests in blood and histological examinations from the specimen of major organs. Therefore, TFBPC is a potential candidate for treatments of patients suffering from TNBCs as well as other cisplatin-resistant cancers. [ABSTRACT FROM AUTHOR]

Background: Shared decision-making (SDM) is significantly associated with promoting the quality of end-of-life (EOL). The attitude of nurses toward the end of life can affect EOL care, but there are few SDM-related clinical learning programs focused on EOL. In this study, therefore, we evaluated the effectiveness of an EOL-simulation education program on attitudes toward SDM among nurses, using an objective structured clinical examination (OSCE). Methods: We used a quasi-experimental study design to evaluate nurses working at a medical center in Taiwan. We recruited 100 nurses and assigned them to an experimental group (n = 50) and a control group (n = 50). The experimental group received the SDM attitude (SDMA) cultivation program, and the control group did not. After the intervention, all participants were examined in an OSCE to assess the efficacy of their learning. A p value of.05 was considered statistically significant. Results: The average score of the experimental group was higher than that of the control group in the dimensions "empathic communication" and "mastery learning", but these differences were not significant. SDMA score is significantly and positively correlated with SDMA global score, standardized patient survey (SPS) score, and SPS global score (r =.92,.56, and.50, respectively; p <.01). Conclusions: Simulations concerning EOL care that incorporate SDM components would be effective for training clinical nurses. This study can serve as a reference for nursing-administration managers who may consider designing SDM-related education programs to improve the quality of clinical nursing care. [ABSTRACT FROM AUTHOR]

The measurement of hypertensive patients' stroke knowledge is an important stroke prevention indicator of health care service quality. The aim of this study was to develop a Chinese version of the Stroke Knowledge Test and examine its psychometric properties, reliability, and validity for hypertensive patients. A sample of 200 hypertensive patients completed the Chinese version of the Stroke Knowledge Test, and 30 of the participants were retested after 2 weeks. The final Chinese version of the Stroke Knowledge Test included 20 items with acceptable content validity (I-CVI = 0.88 ~ 1.00, S-CVI/Ave = 0.97). These items showed satisfactory internal reliability consistency (Kuder Richardson-20 = 0.62) and test–retest reliability was 0.77. The 40% of the difficulty index was in the acceptable range, and 25% was in the difficult range, as well as the 90% items overall values for discrimination were ranged from 0.2 to > 0.4. Known-group validity testing was performed based on the education level, and the result exhibited significant difference (F = 21.21, p < 0.001). The Chinese version of the Stroke Knowledge Test demonstrated acceptable psychometric properties, thus providing a new tool for the future care of hypertensive patients in Taiwan. It also could be as a reference for healthcare providers to educate hypertensive patients on stroke prevention. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 21 tricyclic and tetracyclic sulfamates as STS inhibitors. • Design novel nonsteroidal tetracyclic coumarin skeleton for STS inhibition. • Para substitutions at the phenyl ring of tricyclic analogs gave the best STS inhibition. • 9e and 10c had k inact / K I of 28.6 and 19.1 nM−1min−1 on human STS, respectively. • Cytotoxicity of 9e (IC 50 of 0.65 µM) and 10c (IC 50 of 4.7 µM) on T-47D cells. Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with K I of 0.05 and 0.4 nM, and k inact / K I ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 32 tricyclic sulfamates as STS irreversible inhibitors. • SAR studies revealed that adjacent halogen-bearing phenyl gave the best inhibition. • 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM against STS. • Cellular potency is significant correlated with covalent kinetics (k inact/ K I). Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates , focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM and k inact / K I ratios of 8.8–17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19 m , 19v , and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75–1 cell, which was a hormone-dependent cancer cell line with high STS expression. [ABSTRACT FROM AUTHOR]