Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

( 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.

Patients’ Perceptions and Expectations of Family Participation in the Informed Consent Process of Elective Surgery in Taiwan

Mei-Ling Lin,Wai-Ming Kan,Ching-Huey Chen 한국간호과학회 2012 Asian Nursing Research Vol.6 No.2

Purpose: This study investigated patients’ perceptions and expectations of their families’ participation in the informed consent process of elective surgery. Methods: This is a survey study. Anonymous questionnaires that were mailed to potential participants included a demographic data sheet and a scale, measuring patients’ perceptions of themselves and their families’ participation level in the informed consent process. A convenience sample of patients who had undergone surgery and had been discharged within 4 months from a medical center in southern Taiwan (n ¼ 1,737) were recruited. Results: One hundred and forty-five recipients replied, gaining a response rate of 10.0%, and 120 provided complete data. The mean age of the participants was 56.0 years (range 20e85, SD ¼ 14.98), and more than half were female (54.2%). Twenty-one participants (17.5%) perceived having less family participation than their own participation in the surgery informed consent process, and 40% expected more family participation in the process. The mean scores of the self-rated participation level was significantly higher than that of the families (p < .001). Patients' expectations of family participation were significantly higher than their perceptions of family participation (p < .001). Eleven patients (9.2%) reported having more family participation than they expected. Participants received the most information about the disease during the informed consent process and the least information about alternatives to surgery. Age,gender, number of previous surgeries and admissions influenced the study participants' perceived level of participation in the informed consent process. Conclusion: This preliminary study demonstrates that patients’ perceptions and expectations for family participation in the surgical informed consent process vary. Healthcare providers should be aware of patients’ expectation to appropriately invite their family into the informed consent process. Purpose: This study investigated patients’ perceptions and expectations of their families’ participation in the informed consent process of elective surgery. Methods: This is a survey study. Anonymous questionnaires that were mailed to potential participants included a demographic data sheet and a scale, measuring patients’ perceptions of themselves and their families’ participation level in the informed consent process. A convenience sample of patients who had undergone surgery and had been discharged within 4 months from a medical center in southern Taiwan (n ¼ 1,737) were recruited. Results: One hundred and forty-five recipients replied, gaining a response rate of 10.0%, and 120 provided complete data. The mean age of the participants was 56.0 years (range 20e85, SD ¼ 14.98), and more than half were female (54.2%). Twenty-one participants (17.5%) perceived having less family participation than their own participation in the surgery informed consent process, and 40% expected more family participation in the process. The mean scores of the self-rated participation level was significantly higher than that of the families (p < .001). Patients' expectations of family participation were significantly higher than their perceptions of family participation (p < .001). Eleven patients (9.2%) reported having more family participation than they expected. Participants received the most information about the disease during the informed consent process and the least information about alternatives to surgery. Age,gender, number of previous surgeries and admissions influenced the study participants' perceived level of participation in the informed consent process. Conclusion: This preliminary study demonstrates that patients’ perceptions and expectations for family participation in the surgical informed consent process vary. Healthcare providers should be aware of patients’ expectation to appropriately invite their family into the informed consent process.

The Moderated Mediating Effects of Nutrition and Physical Activity Between Fatigue and Quality of Life in Childhood Cancer Survivors

Wu Wei-Wen,Shiu Cheng-Shi,Tang Chia-Chun,Jou Shiann-Tang,Chen Huey-Ling 한국간호과학회 2023 Asian Nursing Research Vol.17 No.1

Purpose: The aim of this study was to investigate the associations between nutrition, physical activity, fatigue, and quality of life (QoL) among childhood cancer survivors. The specific purpose was to examine whether nutrition mediated and physical activity moderated the relationship between fatigue and QoL in this population. Methods: A pooled sample of 120 childhood cancer survivors was recruited at pediatric oncology wards and ambulatory settings between August 2020 and May 2021. We collected data on participants’ demographic characteristics, fatigue, nutritional status, physical activity, and QoL. We then adapted Hayes Process Macro to examine the mediating and moderating effects of nutrition and physical activity on the relationship between fatigue and QoL. Results: In models adjusted for age and sex, (1) the simple mediation analysis identified the mediating effect of nutrition on the relationship between fatigue and QoL; and (2) the mediation and moderation analysis identified that the direct effect of nutrition between fatigue and QoL was significant when adding (a) physical activity and (b) fatigue physical activity. There were significantly decreasing trends in physical activity at 1 standard deviation below the mean and at the mean, but not at 1 standard deviation above the mean. Conclusions: Our findings demonstrate that nutrition mediated and physical activity moderated the relationship between fatigue and QoL. This highlights an opportunity to enhance QoL among childhood cancer survivors through healthy lifestyle interventions. To ensure that future interventions address children's needs and promote the greatest impact, such interventions should include nutrition and physical activity components that involve nurses, pediatric oncology physicians, nutritionists, and physical therapists.