Association Between Thyroid Disorders and Colorectal Cancer Risk in Adult Patients in Taiwan

IMPORTANCE Thyroid hormones have been shown to affect several important pathways in cancer development, including colorectal cancer (CRC). Clinical studies examining the association between thyroid disorders and colorectal cancer have conflicting results and have predominantly involved white populations. OBJECTIVE To determine if a diagnosis of hyperthyroidism or hypothyroidism is associated with the risk of developing colorectal cancer in an East Asian population. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based case-control study was conducted from April 27, 2018, to November 8, 2018, using the Taiwanese National Health Insurance Research Database. Participants were adults (n = 139 426) either with a new diagnosis (between 2008 and 2013) of primary colorectal cancer without a history of cancer, or without cancer. Cases and controls were matched 11 by age, sex, and index date. Diagnosis of hyperthyroidism or hypothyroidism prior to the diagnosis of colorectal cancer (or the same index date in controls) was then determined. MAIN OUTCOMES AND MEASURES Risk differences in developing colorectal cancer among patients with a medical history of hyperthyroidism or hypothyroidism. RESULTS A total of 139 426 patients were included in the study, and 69 713 individuals made up each case and control group, which were both predominantly male (39 872 [57.2%]). The mean (SD) age for those with CRC was 65.8 (13.7) years and for those without CRC was 66.0 (13.6) years. Both hyperthyroidism (adjusted odds ratio [aOR], 0.77; 95% CI, 0.69-0.86; P < .001) and hypothyroidism (aOR, 0.78; 95% CI, 0.65-0.94; P = .008) were associated with a decreased risk of being diagnosed with colorectal cancer. An inverse association of rectal cancer was found among patients aged 50 years or older with a history of hypothyroidism despite treatment (aOR, 0.54; 95% CI, 0.39-0.74; P < .001). A history of hyperthyroidism in all age groups was associated with a lower risk of colon cancer (aOR, 0.74; 95% CI, 0.64-0.85; P < .001), with a stronger association seen among those younger than 50 years (aOR, 0.55; 95% CI, 0.36-0.85; P = .007). CONCLUSIONS AND RELEVANCE In this study, hypothyroidism appeared to be associated with a lower risk of rectal cancer, whereas hyperthyroidism appeared to be associated with a lower risk of colon cancer. Because of this, biochemical in vivo research and epidemiologic studies appear to be needed to further clarify the nature of these associations.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system

Predicting the Severity and Prognosis of Trismus after Intensity-Modulated Radiation Therapy for Oral Cancer Patients by Magnetic Resonance Imaging

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal–Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

<p>Abstract</p> <p>Background</p> <p>In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.</p> <p>Methods</p> <p>Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.</p> <p>Results</p> <p>Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (<it>p </it>< 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.</p> <p>Conclusions</p> <p>HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.</p

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival

Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide

<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide (As₂O₃) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells <it>in vitro</it>. Here, we investigated the effect of the natural alkaloid berberine on As₂O₃-mediated inhibition of cancer cell migration using rat and human glioma cell lines.</p> <p>Methods</p> <p>The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As₂O₃or berberine, and after co-treatment with As₂O₃and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As₂O₃and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As₂O₃and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA.</p> <p>Results</p> <p>The cell viability studies demonstrated that berberine enhances As₂O₃-mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As₂O₃. The latter effect was even more pronounced in the presence of 10 μM berberine. The As₂O₃-mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As₂O₃and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also significantly reduced.</p> <p>Conclusion</p> <p>Upon co-treatment of glioma cells with As₂O₃and berberine, cancer cell metastasis can be significantly inhibited, most likely by blocking the PKC-mediated signaling pathway involved in cancer cell migration. This study is potentially interesting for the development of novel chemotherapeutic approaches in the treatment of malignant gliomas and cancer development in general.</p

Perivascular adipose tissue and adipocyte-derived exosomal miRNAs maintain vascular homeostasis

Perivascular adipose tissue (PVAT), a fat layer that provides structural support to the blood vessels, is a cushion protecting the vessel wall from neighbouring tissues during contraction and relaxation. PVAT actively regulates vascular tone by secreting vasoactive (vasodilatory and vasoconstrictive) factors (e.g., adipokines, batokines, and lipokines) or microRNA (miRNA)-containing exosomes to reduce the hyperreactivity induced by obesity. Of particular interest are adipocyte-derived exosomal miRNAs, which act as crucial regulators, counteracting the detrimental effects of obesity on cardiovascular well-being. These exosomes serve as potent messengers, facilitating the transport of miRNAs and other bioactive molecules involved in intercellular communication. Undoubtedly, the unique function of exosomal miRNAs promotes vascular homeostasis by fine-tuning endothelial function, vascular remodelling, and inflammatory environment, thereby preventing cardiovascular disease. The collective findings comprehensively explain their protective functions by exploring the intricate mechanisms through which PVAT and adipocyte-derived exosomal miRNAs collaboratively orchestrate vascular health. Taken together, this review strategically focuses on PVAT, exosomes, and adipocyte-derived miRNAs, offering valuable insights that can potentially inform the development of targeted interventions for cardiovascular diseases