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Tsai Yi-Chih,Chen Su-Liang,Peng Shu-Ling,Tsai Ya-Li,Chang Zuong-Ming,Chang Vincent Hung-Shu,Ch’ang Hui-Ju 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC. Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT01666184.
Credibility Judgment Predictors for Child Sexual Abuse Reports in Forensic Psychiatric Evaluations
Ling-Hsiang Wang,Yu-Yung Hung,Philip C,Chow,Che-Sheng Chu,Hsing-Jung Li,Ti Lu,Ching-Hong Tsai 대한신경정신의학회 2019 PSYCHIATRY INVESTIGATION Vol.16 No.2
Objective We intended to analyze the credibility judgment in written forensic psychiatric reports of child sexual abuse registered in Southern Taiwan. Methods Ninety-six cases of child sexual abuse between August 2010 and October 2017 encountered in two hospitals were analyzed. The results in these reports were categorized into credible and non-credible. We identified the factors that distinguished between the two groups in bivariate analyses using chi-square test. A binary logistic regression analysis was performed to determine whether the factors that significantly correlated in the bivariate analyses were independent predictors of credible judgments. Results Among 96 cases, 70 (73%) were judged as credible. Consistent testimonies of children (odds ratio=40.82) and multiple abuse events (odds ratio=6.05) were positive variables independently related to the sexual abuse allegations judged as credible. Conclusion The number of allegations judged as credible in this study was slightly higher than that reported in other studies. Our findings about predictors for credible cases are not in line with those reported previously. Due to the differences in resources of the cases and backgrounds of the evaluators among multiple studies, direct comparisons with previous studies must be treated with caution.
( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
Lin, Wen-Li,Sun, Jia-Ling,Chang, Shu-Chan,Wu, Pei-Hua,Tsai, Tsung-Chih,Huang, Wen-Tsung,Tsao, Chao-Jung Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2
Background: The number of colorectal cancer (CRC) patients in Taiwan has increased in recent years; therefore, the effective dissemination of information related to symptom care has become especially important. Previous studies indicated that the physical and psychological status of cancer patients can be effectively improved by telephone counseling services (TCS). Thus, determining the most effective means of establishing a TCS to support the clinical practice of oncology has become a crucial goal for nursing. The purposes of this study were to analysis the content of the TCS for CRC and explore stratification of the TCS. Materials and Methods: The study design was retrospective. A total of 850 calls were made to CRC patients in the cancer center of Southern Taiwan during the period of January 2007- December 2011. A structure questionnaire was adopted to analysis satisfaction. Results: Responses provided by the TCS included information regarding nutrition, side effects resulting from chemotherapy and pain. Moreover, 28.7% of CRC patients needed advanced treatment. More than 90% satisfaction with all aspects of the calls was found. Conclusions: The TCS coulkd be shown to provide an effective means by which to expand the reach of nursing care to different times, places and patients, allowing for greater cost efficiency and more rapid service.