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1.
Prim Care Diabetes ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423826

RESUMO

Increasing prevalence of type 2 DM (T2DM) and diabetic kidney disease (DKD) has posed a great impact in Taiwan. However, guidelines focusing on multidisciplinary patient care and patient education remain scarce. By literature review and expert discussion, we propose a consensus on care and education for patients with DKD, including general principles, specifics for different stages of chronic kidney disease (CKD), and special populations. (i.e. young ages, patients with atherosclerotic cardiovascular disease or heart failure, patients after acute kidney injury, and kidney transplant recipients). Generally, we suggest performing multidisciplinary patient care and education in alignment with the government-led Diabetes Shared Care Network to improve the patients' outcomes for all patients with DKD. Also, close monitoring of renal function with early intervention, control of comorbidities in early stages of CKD, and nutrition adjustment in advanced CKD should be emphasized.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36981909

RESUMO

INTRODUCTION: This study looked into the effectiveness of a 6 month health coaching intervention in smoking cessation and smoking reduction for patients with type 2 diabetes. METHODS: The study was carried out via a two-armed, double-blind, randomized-controlled trial with 68 participants at a medical center in Taiwan. The intervention group received health coaching for 6 months, while the control group only received usual smoking cessation services; some patients in both groups participated in a pharmacotherapy plan. The health coaching intervention is a patient-centered approach to disease management which focuses on changing their actual behaviors. By targeting on achieving effective adult learning cycles, health coaching aims to help patients to establish new behavior patterns and habits. RESULTS: In this study, the intervention group had significantly more participants who reduced their level of cigarette smoking by at least 50% than the control group (p = 0.030). Moreover, patients participating in the pharmacotherapy plan in the coaching intervention group had a significant effect on smoking cessation (p = 0.011), but it was insignificant in the control group. CONCLUSIONS: Health coaching can be an effective approach to assisting patients with type 2 diabetes participating in a pharmacotherapy plan to reduce smoking and may help those who participate in pharmacotherapy plan to quit smoking more effectively. Further studies with higher-quality evidence on the effectiveness of health coaching in smoking cessation and the use of oral smoking cessation drugs in patients with type 2 diabetes are needed.


Assuntos
Diabetes Mellitus Tipo 2 , Tutoria , Abandono do Hábito de Fumar , Redução do Consumo de Tabaco , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego
3.
Artigo em Inglês | MEDLINE | ID: mdl-36497755

RESUMO

INTRODUCTION: along with the rapidly aging population in many countries around the world, the global prevalence of diabetes and suffering from diabetes-related depression have risen in middle-aged and elderly adults. However, given that psychological stress is deeply influenced by culture, gender inequality in these statistics is often exhibited and increases with age. The aim of this study was to explore the gender difference in diabetes distress among middle-aged and elderly diabetic patients. METHODS: 395 participants from four hospitals were recruited for a cross-sectional survey. The Taiwan Diabetes Distress Scale (TDDS) was used to measure diabetes distress. Linear regression was conducted to assess the gender difference in different types of diabetes distress. RESULTS: there was significant gender difference in each diabetes distress domain. In particular, men who had received diabetes education in the past six months seemed to be more concerned about diabetes complications and felt pressured to communicate with doctors. In addition, women seemed to be more affected by diabetes distress because of their marital status, especially for married women. CONCLUSIONS: diabetes distress seems to have significant gender differences; however, more longitudinal research is needed on the causal relationship between gender and diabetes distress.


Assuntos
Diabetes Mellitus , Estresse Psicológico , Pessoa de Meia-Idade , Adulto , Idoso , Masculino , Humanos , Feminino , Estudos Transversais , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Ansiedade , Diabetes Mellitus/epidemiologia , Comunicação
4.
Front Public Health ; 10: 838661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372236

RESUMO

Introduction: The aim of this study was to develop and validate a new diabetes distress scale suitable for Chinese and Taiwanese culture. Methods: This study collected the current diabetes distress measurement tools, re-organized current definitions about the domains of diabetes distress, and then developed a new tool. Three hundred and ninety-five participants from four hospitals in northern Taiwan were recruited by cluster randomized sampling for validity test. Results: We found the new diabetes distress scale had appropriate reliability and validity, including an acceptable model fit for the 12-item scale. Conclusions: This new diabetes distress scale might be more directly related to emotional distress issues blood glucose control, improve the clinical conspicuity of diabetes distress, and even benefit the overall care of diabetic patients in Taiwan. Further studies about the validity and reliability of this new tool in a nationwide setting are needed.


Assuntos
Diabetes Mellitus , Competência Cultural , Humanos , Angústia Psicológica , Psicometria , Reprodutibilidade dos Testes , Taiwan
5.
FEBS Open Bio ; 12(5): 993-1005, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35313079

RESUMO

Squamous and anaplastic thyroid cancers are the most aggressive and life-threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is < 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti-cancer therapies to suppress VEGF/VEGFR-mediated cancer development in patients with clinical advanced thyroid cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Glândula Tireoide , Linhagem Celular , Humanos , Sunitinibe , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
6.
Sci Total Environ ; 806(Pt 3): 151261, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715222

RESUMO

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92-2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24-0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates. This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern.


Assuntos
Ácidos Ftálicos , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Exposição Materna/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Gravidez , Inquéritos e Questionários , Taiwan/epidemiologia
7.
Nutrients ; 13(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34836135

RESUMO

BACKGROUND: The study aimed to look into the effectiveness of a 6-month health coaching intervention for HbA1c and healthy diet in the treatment of patients with type 2 diabetes. METHODS: The study was carried out via a two-armed, randomized controlled trial that included 114 diabetic patients at a medical center in Taiwan. During the 6-month period, the intervention group had health coaching and usual care for 6 months, and the control group had usual care only. The outcome variables were HbA1c level and healthy diet for follow-up measurement in the third and sixth month. RESULTS: The study discovered a significant decrease in HbA1c and health diet improvement after the 6-month health coaching. Patients in the intervention group decreased their daily intake of whole grains, fruits, meats and protein, and fats and oils while increasing their vegetables intake. CONCLUSIONS: Health coaching may be conducive to the blood sugar control and healthy diet of patients with type 2 diabetes. Further study on health coaching with higher-quality evidence is needed.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Controle Glicêmico/métodos , Estilo de Vida Saudável/fisiologia , Tutoria/métodos , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas/análise , Controle Glicêmico/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan , Resultado do Tratamento
8.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638520

RESUMO

Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage's integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.


Assuntos
Lesões do Ligamento Cruzado Anterior/patologia , Ligamento Cruzado Anterior/patologia , Colecalciferol/sangue , Metaloproteinase 3 da Matriz/sangue , Osteoartrite/diagnóstico , Adiponectina/sangue , Animais , Ligamento Cruzado Anterior/cirurgia , Biomarcadores/sangue , Cartilagem Articular/patologia , Colágeno Tipo II/sangue , Modelos Animais de Doenças , Leptina/sangue , Meniscectomia , Meniscos Tibiais/cirurgia , Osteoartrite/sangue , Osteoartrite/patologia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Wistar , Tíbia/patologia
9.
Front Public Health ; 9: 580032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055704

RESUMO

Introduction: The aim of this study was to explore the impact of diabetes self-management and HbA1c affected by the COVID-19 pandemic and the epidemic prevention work. Methods: This quasi-experimental study collected a pooled data from a randomized-control study between February and May 2020 in which 114 participants who presented type 2 diabetes were recruited. The intervention group had health coaching and usual care, whereas the control had usual care only. The main outcome variables of this observation study were the change of HbA1c, physical activity, and eating out behavior within this time interval. Results: We found that the eating out behavior of both groups had decreased, and if a health coach helped the patients set physical activity goals in the two groups, the physical activity behavior will not be impacted due to the pandemic. Conclusions: While every country is focusing on COVID-19 pandemic prevention, especially when strict home quarantine measures and social distancing are adopted, reminding and assisting chronic patients to maintain good self-management behavior may lessen the social and medical system burdens caused by the deterioration of chronic conditions due to the excessive risk prevention behavior and the epidemic prevention work. Trial Registration: www.isrctn.com, identifier number: ISRCTN14167790, date: 12 July, 2019.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Tutoria , Diabetes Mellitus Tipo 2/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
10.
Biomol Ther (Seoul) ; 29(5): 551-561, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34031270

RESUMO

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.

11.
PeerJ ; 8: e9998, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240585

RESUMO

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

12.
Oncol Lett ; 19(4): 3021-3026, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218859

RESUMO

Thyroid cancer is the most commonly diagnosed endocrine cancer. Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer and has a poor prognosis. Loss of p53 function has been reported to lead to poorly differentiated thyroid tumors; therefore, mutant p53 protein can be considered a crucial therapeutic target in patients with ATC. Sorafenib, a multi-kinase inhibitor, has been approved for the treatment of metastatic and differentiated thyroid cancer. Combined targeted therapy, including sorafenib, may be clinically significant for patients with ATC harboring p53 mutations. In the present study, CP-31398, a p53-restoring agent, was used to improve the therapeutic efficacy of sorafenib in SW579 cells, an ATC cell line harboring p53 mutations. The molecular function of CP-31398 was evaluated using western blot analysis and a luciferase reporter assay. The decreased viability of SW579 cells, following CP-31398 treatment, was augmented by sorafenib, and CP-31398 enhanced the antimitogenic effect of sorafenib; thus, sorafenib and CP-31398 synergistically inhibited the growth of SW579 cells. These results indicate a potential clinical application of CP-31398 for patients with ATC harboring p53 abnormalities, since these individuals generally respond poorly to sorafenib alone.

13.
Front Public Health ; 7: 314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737593

RESUMO

Introduction: The aim of this study was to explore the effectiveness in HbA1c lowering and self-efficacy of diabetes self-management of a 6 months coaching intervention. Methods: This paper was a two-armed coaching intervention study in which 116 participants who presented type 2 diabetes were recruited at a medical center. The intervention group had health coaching and usual care for 6 months, whereas the control had usual care only. The main outcome variables were HbA1c level and self-efficacy of diabetes self-management, in followed-up measure at 3 and 6 months. Results: We found that an approximate 0.68% (CI = 0.40 to 0.96) reduction in HbA1c was achieved after a 6-month health coaching. Both physical activity and self-efficacy of diabetes self-management were shown to benefit by health coaching. Conclusions: Health coaching might be an effective strategy to enhance self-management for diabetes patients in Taiwan where "Diabetes Shared Care Network" had been implemented for over 20 years. Consider limitations of this study, more studies with designs that yield higher quality evidence for the role of health coaching in diabetic patients are needed. Clinical Trial Registration: www.isrctn.com (ID number: ISRCTN52454940, date: 10 May, 2018, retrospectively registered).

14.
Int J Mol Sci ; 20(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669676

RESUMO

Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.


Assuntos
Apoptose/genética , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Acetilação , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Edição de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo
15.
Dis Markers ; 2018: 3835783, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849821

RESUMO

Anaplastic carcinoma of the thyroid (ATC), also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P = 0.017 in CCLE and P = 0.001 in TCGA). Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.


Assuntos
Sistemas CRISPR-Cas , Receptores ErbB/genética , Edição de Genes/métodos , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Afatinib , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia
16.
Int J Mol Sci ; 19(2)2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29393914

RESUMO

Breast cancer is the most common malignancy in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER (estrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor 2) expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether histone deacetylation inhibitor (HDACi) could be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enriched breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence-based live cell non-invasive apoptosis detection sensor (NIADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also contribute a synergic anti-cancer effect with co-treatment of chemotherapeutic agent such as doxorubicin on TNBC cells (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in the clinic.


Assuntos
Antineoplásicos/farmacologia , Bioensaio , Regulação Neoplásica da Expressão Gênica , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Sulfonamidas/farmacologia , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Citometria de Fluxo , Histona Desacetilases/metabolismo , Humanos , Glândulas Mamárias Humanas/efeitos dos fármacos , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Panobinostat , Receptor ErbB-2/deficiência , Receptor ErbB-2/genética , Receptores de Estrogênio/deficiência , Receptores de Estrogênio/genética , Receptores de Progesterona/deficiência , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
17.
Sci Total Environ ; 618: 635-644, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29055577

RESUMO

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQDEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (ß=-0.63 (-1.20 to -0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised.


Assuntos
Exposição Dietética , Dietilexilftalato/análise , Contaminação de Alimentos , Ácidos Ftálicos/urina , Adulto , Feminino , Humanos , Gravidez , Taiwan
18.
Front Cell Neurosci ; 11: 336, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163048

RESUMO

Triple-negative breast cancer (TNBC) subtype is associated with poor prognosis and a high risk of recurrence-related death in women. Despite the aggressiveness of TNBCs, targeted TNBC therapy is not yet available in the clinic. To overcome this challenge, we generated highly metastatic TNBC cells (LM) derived from metastasized lung cells via a serial spontaneous pulmonary metastasis animal model to identify targetable molecules for attenuating the progression of TNBC metastasis. Gene analysis of primary tumor (P), first-round (1LM) and second-round (2LM) metastasized lung cells revealed that mesenchymal-related genes were significantly expressed in LM cells, especially in 2LM cells. Interestingly, α9-nAChR gene expression was also dramatically induced in LM cells, confirming our previous finding that α9-nAChR plays important roles in receptor-mediated carcinogenic signals in human breast cancer development. Using α9-nAChR as a biomarker, we transfected 2LM cells with CRISPR/Cas9 lentivirus targeting the α9-nAChR genomic region (2LM-α9-nAChR-null), showing that mesenchymal markers and the migration and invasion abilities of 2LM cells were significantly attenuated in 2LM-α9-nAChR-null cells both in vitro and in vivo. In addition, the high efficiency of editing the α9-nAChR gene using a CRISPR/Cas9 lentivirus was demonstrated by gene sequencing, genomic indel frequency and protein expression analyses. Collectively, these results confirmed those of our previous study that advanced-stage breast tumors are associated with substantially higher levels of α9-nAChR gene expression, indicating that α9-nAChR expression is essential for mediating TNBC metastasis during cancer development and may potentially act as a biomarker for targeted therapy in clinical investigations.

19.
Clin Nucl Med ; 42(11): 857-859, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28902735

RESUMO

A positive captopril renography indicates that patient's hypertension is renin dependent, most commonly caused by renal artery stenosis. The authors reported a case of positive captopril renography; however, CT demonstrated that renal arteries were intact, but there was a huge chromophobe renal cell carcinoma. Renin-dependent hypertension was relieved soon after nephrectomy. It is an uncommon cause of positive captopril renography.


Assuntos
Captopril , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Renografia por Radioisótopo , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Hipertensão Renal/complicações , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Nefrectomia , Nefrite/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Sensibilidade e Especificidade
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