Publications by authors named "Hsin Hung"

5 Publications

  • Page 1 of 1

The effects of phthalate ester exposure on human health: A review.

Sci Total Environ 2021 Sep 28;786:147371. Epub 2021 Apr 28.

Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Research Center of Environmental Trace Toxic Substances, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Electronic address:

Phthalate esters (PAEs) are one of the most widely used plasticizers in polymer products and humans are increasingly exposed to them. The constant exposure to PAEs-contained products has raised some concerns against human health. Thus, the impacts of PAEs and their metabolites on human health require a comprehensive study for a better understanding of the associated risks. Here, we attempt to review eight main health effects of PAE exposure according to the most up-to-date studies. We found that epidemiological studies demonstrated a consistent association between PAE exposure (especially DEHP and its metabolites) and a decrease in sperm quality in males and symptom development of ADHD in children. Overall, we found insufficient evidence and lack of consistency of the association between PAE exposure and cardiovascular diseases (hypertension, atherosclerosis, and CHD), thyroid diseases, respiratory diseases, diabetes, obesity, kidney diseases, intelligence performance in children, and other reproductive system-related diseases (anogenital distance, girl precocious puberty, and endometriosis). Future studies (longitudinal and follow-up investigations) need to thoroughly perform in large-scale populations to yield more consistent and powerful results and increase the precision of the association as well as enhance the overall understanding of potential human health risks of PAEs in long-term exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147371DOI Listing
September 2021

Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer.

Mol Cancer Ther 2018 10 11;17(10):2238-2247. Epub 2018 Jul 11.

Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan.

Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker; however, ctDNA as a marker for mCRC patients is not well established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next-generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage ( = 0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of <80% (HR, 0.22; = 0.015). The objective response rate among patients with a ctDNA decrease of >80% was better than those with a ctDNA decrease <80% (OR, 0.026; = 0.007). In conclusion, this study demonstrates that monitoring of genetic ctDNA variants can serve as a valuable biomarker for therapeutic efficacy in mCRC patients, and that using a moderate-sized 12-gene NGS panel may be suitable for such clinical monitoring. .
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http://dx.doi.org/10.1158/1535-7163.MCT-17-1306DOI Listing
October 2018

Recognizing spatial and temporal clustering patterns of dengue outbreaks in Taiwan.

BMC Infect Dis 2018 06 4;18(1):256. Epub 2018 Jun 4.

Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 1 University Road Tainan, 701, Tainan, Taiwan.

Background: Dengue fever is the most common arboviral infection in humans, with viral transmissions occurring in more than 100 countries in tropical regions. A global strategy for dengue prevention and control was established more than 10 years ago. However, the factors that drive the transmission of the dengue virus and subsequent viral infection continue unabated. The largest dengue outbreaks in Taiwan since World War II occurred in two recent successive years: 2014 and 2015.

Methods: We performed a systematic analysis to detect and recognize spatial and temporal clustering patterns of dengue incidence in geographical areas of Taiwan, using the map-based pattern recognition procedure and scan test. Our aim was to recognize geographical heterogeneity patterns of varying dengue incidence intensity and detect hierarchical incidence intensity clusters.

Results: Using the map-based pattern recognition procedure, we identified and delineated two separate hierarchical dengue incidence intensity clusters that comprise multiple mutually adjacent geographical units with high dengue incidence rates. We also found that that dengue incidence tends to peak simultaneously and homogeneously among the neighboring geographic units with high rates in the same cluster.

Conclusion: Beyond significance testing, this study is particularly desired by and useful for health authorities who require optimal characteristics of disease incidence patterns on maps and over time. Among the integrated components for effective prevention and control of dengue and dengue hemorrhagic fever are active surveillance and community-based integrated mosquito control, for which this study provides valuable inferences. Effective dengue prevention and control programs in Taiwan are critical, and have the added benefit of controlling the potential emergence of Zika.
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http://dx.doi.org/10.1186/s12879-018-3159-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987425PMC
June 2018

Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.

Int J Mol Med 2018 Jul 30;42(1):182-192. Epub 2018 Mar 30.

Neurophysiology Laboratory, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan, R.O.C.

Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKR‑like endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.
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http://dx.doi.org/10.3892/ijmm.2018.3607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979830PMC
July 2018

Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients.

Oncotarget 2016 Apr;7(16):22257-70

Division of Hematology-Oncology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan.

Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients.
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http://dx.doi.org/10.18632/oncotarget.8076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008360PMC
April 2016