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Background: Papillary thyroid carcinoma occasionally presents with concomitant hyperparathyroidism; however, the clinical significance has not been well established. This study aimed to evaluate the long-term cancer prognosis following a multimodality therapy. Methods: We conducted a case-control study using prospectively maintained data from a medical center thyroid cancer database between 1980 and 2013. The study cohort comprised patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patients with papillary thyroid carcinoma only were matched using the propensity score method. Therapeutic outcomes, including the non-remission rate of papillary thyroid carcinoma and patient mortality, were compared. Results: We identified 27 study participants from 2537 patients with papillary thyroid carcinoma, with 10 patients having primary hyperparathyroidism and 17 having renal hyperparathyroidism. Eighty-five percent of the cohort was found to have tumor–node–metastasis stage I disease. During a mean follow-up of 7.7 years, we identified 3 disease non-remission and 4 mortality events. The non-remission risk did not increase (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.43–6.40; p = 0.47); however, the overall mortality risk significantly increased (HR, 4.43; 95% CI, 1.11–17.75; p = 0.04). All mortality events were not thyroid cancer related, including two identified cardiovascular diseases. Conclusions: Patients with papillary thyroid carcinoma who present with concomitant hyperparathyroidism are usually diagnosed at an early cancer stage with compatible therapeutic outcomes. However, hyperparathyroidism-related comorbidity may decrease long-term survival. Keywords: Papillary thyroid carcinoma, Hyperparathyroidism, Therapeutic outcomes

Background/Purpose: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). Results: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β = −4.720, p = 0.046 and β = −5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β = −5.839, p = 0.034 and β = −7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β = −26.632, p = 0.013; β = −28.353, p = 0.024; β = −25.648, p = 0.026; and β = −34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. Conclusion: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions. Keywords: Taiwan acromegaly registry, Quality of life, Clinical parameters

Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC.

Objective The aim of this study was to evaluate outcomes of the recurrent and non-recurrent groups including disease-specific mortality of patients with well-differentiated thyroid carcinoma after multimodality treatment. In addition, prognostic factors for disease-specific mortality were analyzed. Summary of Background Data Among 2,844, there were 166 patients with recurrent disease. Recurrent disease was defined as the presence of papillary or follicular thyroid cancer 6 months after the initial thyroidectomy, including locoregional or distant metastasis, diagnosed using diagnostic or therapeutic 131I scans or other imaging techniques. Methods The study was a retrospective analysis of prospectively collected data for a long-term follow-up result of well-differentiated thyroid carcinoma patients. Results The mean age of 166 patients was 45.8 ± 1.2 years, 116 (69.9%) were women, 111 (66.9%) had locoregional neck recurrence, and 55 (33.1%) had metastatic recurrence in distant organs. We found that when recurrences were observed, more than half were detected within the first 5 years following the initial therapy. The longest period of time before relapse was 29.8 years. After a mean follow-up period of 12.7 ± 0.5 years, 37 (22.3%) patients experienced disease-specific mortality. Multivariable analysis revealed that older age, male sex, and development of a second primary malignancy were associated with disease-specific mortality. Higher post-operative levels of thyroglobulin predicted a shorter time to relapse. Conclusions These data indicate that among the recurrent cases over 50% of recurrent well-differentiated thyroid carcinomas were diagnosed within 5 years after initial thyroidectomy. Additionally, more than 20% of the patients died of thyroid cancer.

Background: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. Methods: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. Result: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. Conclusions: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p

Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer.Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses.The EpCAMCEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.

Chia-Lin Li,1,2 Fiona F Stanaway,3 Jen-Der Lin,2 Hsing-Yi Chang4 1Department of Health Care Management, College of Management, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Tao-Yuan 333, Taiwan; 3Sydney School of Public Health, University of Sydney, Sydney 2006, NSW, Australia; 4Division of Preventive Medicine and Health Service Research, Institute of Population Health Sciences, National Health Research Institutes, Maoli 350, Taiwan Purpose: The aims of this study were to investigate the prevalence of frailty and its relationship with health care use among community-dwelling older adults with diabetes.Methods: We analyzed data from a nationally representative sample of people aged 65 years and above (n=3,203) participating in the 2013 National Health Interview Survey in Taiwan. Atotal of 719 participants had a history of self-reported physician-diagnosed diabetes. The presence of frailty was determined based on the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) scale proposed by the International Association of Nutrition and Aging. FRAIL scores range from 0 to 5 and are categorized as frail (3–5), pre-frail (1–2), and robust (0). Participants were asked whether they had been hospitalized or had visited an emergency department in the past year.Results: Among community-dwelling older adults with diabetes, 9.4% of participants were frail and 35.3 % were pre-frail. After adjustment for other factors, being frail was significantly associated with hospitalization during the past year (OR =5.31, 95% CI =1.87–15.10), whereas being pre-frail was not associated with hospitalization. Both being pre-frail and frail were significantly associated with emergency department visits during the past year (OR =2.64, 95% CI =1.35–5.17 and OR =4.05, 95% CI =1.31–12.49, respectively) after adjustment for other factors.Conclusion: Our results highlight the high prevalence of frailty in community-dwelling older adults with diabetes. Furthermore, being frail is associated with a greater burden of hospitalizations and emergency department visits. Keywords: diabetes mellitus, elderly, frailty, health care use, Taiwan&nbsp

Objective Radioactive iodine (131I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of 131I (>600 mCi) for the treatment of well-differentiated thyroid cancer. Patients and methods In this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016. Results For our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received 131I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075). Conclusion 131I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated 131I doses were administered.

Altered cyclin-dependent kinase activity is observed in many human malignancies. Cyclin-dependent kinases that promote cell cycle progression may be promising targets in the treatment of cancer. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for medullary thyroid cancer were investigated in the present study. Roniciclib inhibited medullary thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib induced caspase-3 activity and contributed to apoptosis. Cell cycle progression was arrested in the G2 phase. In vivo, roniciclib treatment retarded the growth of tumors of medullary thyroid cancer xenografts. In addition, roniciclib in combination with sorafenib was more effective than either single treatment in a xenograft model. No morbidity was observed in animals treated with single roniciclib therapy and combination treatment of roniciclib and sorafenib. These data provide a rationale for clinical assessment of using roniciclib in the treatment of patients with medullary thyroid cancer.

Background Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg. Methods A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM+-CECs and TSHR+-CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n = 7) and remission group (n = 18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM+-CECs and TSHR+-CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity + specificity − 1). Results The median numbers of EpCAM+-CECs (72.5 vs. 10.75) and TSHR+-CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM+-CECs (0.937) and TSHR+-CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM+-CECs and TSHR+-CECs were set at 48 cells/ml and 10 cells/ml, respectively and showed a sensitivity (EpCAM+-CECs: 85.7%; TSHR+-CECs: 85.7%) and a specificity (EpCAM+-CECs: 100%; TSHR+-CECs: 77.8%) in predicting the recurrence. Conclusions Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg.

// Chia-Chun Wu 1, * , Jen-Der Lin 4, * , Jeng-Ting Chen 7 , Chih-Min Chang 1 , Hsiao-Fen Weng 4 , Chuen Hsueh 5 , Hui-Ping Chien 5 and Jau-Song Yu 1, 2, 3, 6 1 Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan 2 Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan 3 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 5 Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 6 Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 7 Department of Surgery, Department of Medical Research and Development Linkou Branch, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan * These authors contributed equally to this work Correspondence to: Jau-Song Yu, email: yusong@mail.cgu.edu.tw Keywords: papillary thyroid carcinoma; fine needle aspiration cystic fluid; proteome profiles; secretome; biomarker Received: April 20, 2017 Accepted: November 15, 2017 Published: January 04, 2018 ABSTRACT Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively. Comparative analysis revealed that 191 proteins were detected in the PTC but not the benign cystic fluid samples, and thus may represent potential PTC biomarkers. Among these proteins, 101 were detected in the PTC cell line secretomes, and seven of them (NPC2, CTSC, AGRN, GPNMB, DPP4, ERAP2, and SH3BGRL3) were reported in public PTC transcriptome datasets as having 4681 elevated mRNA expression in PTC. Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies from near 100 pairs of PTC tissue and their adjacent non-tumor counterparts further showed that AGRN ( n = 98), CTSC ( n = 99), ERAP2 ( n = 98) and GPNMB ( n = 100) were significantly ( p < 0.05) overexpressed in PTC and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis of PTC patients. Collectively, our results indicate that an integrated analysis of FNA cystic fluid proteome, cancer cell secretome and tissue transcriptome datasets represents a useful strategy for efficiently discovering novel PTC biomarker candidates.

The efficacy of thyroxine suppressive therapy in reducing nodular growth and its effect to bone mineral density (BMD) in postmenopausal women is still debated. This study aimed to evaluate the therapeutic effect of thyroxine and its influence on BMD. Postmenopausal women with nodular or multinodular goiter during 2013-2015 at Chang Gung Memorial Hospital were enrolled and retrospectively traced back to the first date of visit or treatment. Ninety-four eligible patients were enrolled, of whom 45 were thyroxine-treated (LT-4 group) and 49 were treatment-naïve (control group). Data, including volume of nodules, were analyzed retrospectively. BMD was measured in each LT-4 group patient since the year of enrollment. Nodular volumes were reduced in both LT-4 (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, p = 0.033) and control group (3.48 ± 4.36 to 3.09 ± 2.88 mL, p = 0.239) at initial 2-year follow-up. Nodular volume in LT-4 group increased insignificantly (from 4.89 ± 4.46 to 4.91 ± 5.40 mL, p = 0.711) at the end of 7-year follow-up. The best cut-off predictive nodular volume that may have responded to thyroxine is 2.6 mL (AUC, 0.740; sensitivity, 0.750; specificity, 0.733) during first 2 year. Lumbar spine, total hip and femoral neck BMD were not significantly changed during 2 year's thyroxine suppression therapy. In conclusion, thyroxine suppressive therapy in postmenopausal women had significant reduction in nodule volume at initial 2 years of treatment, especially in volume larger than 2.6 mL. Prolonged thyroxine treatment did not benefit nodular size reduction and may affect BMD minimally in postmenopausal women.

Background Surgical management of Graves' disease (GD) is changing from subtotal to total thyroidectomy because the latter eliminates the risk of recurrence. However, to preserve thyroid function in a euthyroid state, subtotal thyroidectomy is still performed for GD in non-Western countries. Therefore, we designed a study to investigate the long-term outcomes in GD patients after subtotal thyroidectomy and the correlation between remnant weight and postoperative thyroid function. Materials and methods This was a retrospective cohort observation study. Between January 2005 and December 2011, 415 consecutive GD patients treated by subtotal thyroidectomy were enrolled. All data were collected from 385 patients who underwent bilateral subtotal thyroidectomy and 57 patients who underwent the Hartley-Dunhill operation. The median postoperative follow-up time was 72 months (range 12-144 months). Results The mean weight of the preserved thyroid remnant was 5.1 g. Persistent or recurrent hyperthyroidism was observed in 119 (28.7%) patients. The median time of recurrence was 36 months (range 12-120 months). Hypothyroidism developed in over 50% of patients. A euthyroid state was achieved in only 19.3% of patients, and the rate did not increase significantly as remnant weight increased. Based on a Cox regression analysis, the remnant weight is an independent risk factor for persistent or recurrent hyperthyroidism (hazard ratio: 1.323, 95% confidence interval: 1.198-1.461, P Conclusions Subtotal thyroidectomy with the intent to maintain a euthyroid state is not an optimal surgical strategy for the definitive treatment of GD because the persistence or recurrence rate is high and the euthyroid rate is lower than expected.

// Shu-Fu Lin 1 , Jen-Der Lin 1 , Chuen Hsueh 2 , Ting-Chao Chou 3, 4 and Richard J. Wong 5 1 Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 2 Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 3 Laboratory of Preclinical Pharmacology Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Current address: PD Science, Inc., Paramus, NJ, USA 5 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Shu-Fu Lin, email: mmg@cgmh.org.tw Keywords: roniciclib, cyclin-dependent kinase, anaplastic thyroid cancer Received: March 02, 2017 Accepted: May 23, 2017 Published: July 08, 2017 ABSTRACT Many human cancers have altered cyclin-dependent kinase activity. Inhibition of cyclin-dependent kinases may arrest cell cycle progression and represents an important strategy in the treatment of malignancies. We evaluated the therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor, as a treatment for anaplastic thyroid cancer. Roniciclib inhibited anaplastic thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in G2/M phase. In vivo , the growth of anaplastic thyroid cancer xenograft tumors was retarded by roniciclib treatment without evidence of toxicity. These data provide a rationale for further clinical evaluation using roniciclib in the treatment of patients with anaplastic thyroid cancer.

Objectives It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. Methods The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. Results The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I–III) had a median US risk score of 6 (range, 0–11), which was higher than that of nodules with high categorization (IV–VI; median, 3; range, 0–11). Conclusions The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

Aims The aims of the present study were to investigate the co-occurrence of depressive symptoms and cognitive impairment in community dwelling older adults with diabetes and its relationship with specific diabetes self-care behaviors. Methods We analyzed data from two national samples of older adults (65 years or older) with self-reported physician-diagnosed diabetes (N = 1034), who participated in the 2005 or 2009 National Health Interview Survey in Taiwan. The Mini-Mental State Examination was used to assess cognitive function. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms. The study assessed self-care behaviors including medication adherence, exercise, healthy diet, and self-monitoring of blood glucose. Results In this study, 8.8% of participants with diabetes had both depressive symptoms and cognitive impairment. After adjusting for other factors, participants with both cognitive impairment and depressive symptoms were less likely to exercise (Prevalence Ratios (PR) = 0.66; 95% Confidence Intervals (CI) = [0.47–0.91]; P-value = 0.011), and have a healthy diet (PR = 0.82; 95%CI = [0.70–0.96]; P-value = 0.012). Conclusions Our results illustrate the high prevalence of combined depressive symptoms and cognitive impairment and that this combination is associated with worse self-care behaviors in older adults with diabetes. These findings highlight the difficulty that some older adults with diabetes may have in maintaining self-care behaviors in the presence of depressed mood and cognitive impairment, particularly in the areas of diet and exercise. The results emphasize the importance of providing more support for these aspects of self-care to such older adults.

// Shu-Fu Lin 1 , Jen-Der Lin 1 , Chuen Hsueh 2 , Ting-Chao Chou 3, 7 , Chun-Nan Yeh 4 , Ming-Huang Chen 5 and Richard J. Wong 6 1 Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 2 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3 Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 4 Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan 5 Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 6 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 7 Current address: PD Science, Inc., Paramus, NJ, USA Correspondence to: Shu-Fu Lin, email: mmg@cgmh.org.tw Keywords: HSP90 inhibitor, ganetespib, thyroid cancer Received: October 29, 2016 Accepted: March 30, 2017 Published: April 18, 2017 ABSTRACT Heat shock protein 90 is a molecular chaperon that maintains the correct folding and function of multiple client proteins. The inhibition of heat shock protein 90, which leads to the simultaneous degradation of multiple proteins involved in oncogenic signaling pathways, has revealed an innovative strategy to treat a variety of cancer types. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90 inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferation in a dose-dependent manner in eight cell lines originating from four major histologic types of thyroid cancer (papillary, follicular, anaplastic and medullary). Ganetespib decreased cyclin-dependent kinase 1 and arrested cell cycle progression in G2/M phase. The expression of proteins involved in RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways was also inhibited. The RET level was decreased in a medullary thyroid cancer cell line. Ganetespib increased Bim expression, activated caspase-3 and induced apoptosis. In vivo , ganetespib retarded the tumor growth of anaplastic and medullary thyroid cancer xenografts with acceptable safety profiles. These findings indicate that ganetespib has potential in the treatment of patients with thyroid cancer.