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155 result(s) for "CHIANG, CHIH-HUNG"
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Imlunestrant with or without Abemaciclib in Advanced Breast Cancer
The selective estrogen-receptor degrader imlunestrant plus abemaciclib led to a median progression-free survival of 9.4 months among patients with ER-positive, HER2-negative breast cancer (vs. 5.5 months with imlunestrant alone).
Significant Association of Matrix Metalloproteinase-9 Polymorphisms With Triple Negative Breast Cancer Risk
Background/Aim: Matrix metalloproteinase-9 (MMP-9) has been associated with the development and progression of breast cancer (BCa). However, the relationship between MMP-9 genetic variants and BCa susceptibility remains contentious and inconclusive. This study aimed to evaluate the association of MMP-9 rs3918242 promoter polymorphisms with BCa, with a particular focus on the risk of triple-negative breast cancer (TNBC).Materials and Methods: A case-control study was conducted involving 1,232 BCa patients and 1,232 healthy controls. The MMP-9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Results: The genotype distribution of MMP-9 rs3918242 among the control group adhered to Hardy-Weinberg equilibrium (p=0.3265). No statistically significant differences were observed in the genotype frequencies between BCa cases and controls (p for trend=0.2555). Although the homozygous variant genotype (TT) showed a potential risk-increasing effect, this was not statistically significant [odds ratio (OR)=1.43, 95% confidence interval (CI)=0.88-2.36, p=0.1869]. Similarly, allele frequency analysis indicated no significant association between the variant T allele and overall BCa risk (OR=1.13, 95%CI=0.97-1.33, p=0.1265). Additionally, no interaction was detected between MMP-9 rs3918242 genotypes and the age of BCa onset (both p>0.05). Notably, the TT genotype of MMP-9 rs3918242 was significantly associated with an increased risk of TNBC (OR=2.49, 95%CI=1.32-4.72, p=0.0072).Conclusion: The MMP-9 rs3918242 TT genotype may serve as a potential predictive biomarker for TNBC in the Taiwanese population.
The clinical outcome of postoperative radiotherapy using hybrid planning technique in left breast cancer after breast‐conserving surgery
Background The purpose of this study is to observe the preliminary clinical outcome and acute toxicity of hybrid intensity modulated radiotherapy and volumetric modulated arc therapy planning technique with simultaneous integrated boost (SIB). Methods From November 2015 to December 2018, 149 female patients with left‐side breast cancer who underwent adjuvant radiotherapy with hybrid IMRT and VMAT planning technique with SIB were reviewed retrospectively. The primary endpoint was acute toxicities and the secondary endpoints were local recurrence‐free survival (LRFS), distant metastasis‐freesurvival (DMFS), disease‐free survival (DFS), and overall survival (OS). Results The median age was 52 years old and median follow‐up was 43.4 months. Eighty‐six percent of patients had acute grade 0 to grade1 dermatitis and 14% had grade 2 dermatitis. No acute radiation pneumonitis, esophagitis, or cardiovascular events were recorded during follow‐up. The 3‐year LRFS, DMFS, DFS, and OS rates were 95.1%, 95.1%, 90.3%, and 97.9%, respectively. The subgroup analysis revealed that patients with lymphovascular invasion had more local recurrence rate and worse DFS rate. Patients with advanced N stage had the trend of worse DMFS. Conclusion In conclusion, the hybrid IMRT and VMAT technique is feasible, safe and has less acute radiation related toxicities in SIB postoperative radiotherapy for left‐sided breast cancer. This study was to observe the preliminary clinical outcome and acute toxicity of hybrid intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) planning technique with simultaneous integrated boost (SIB). The result showed the hybrid technique was feasible, safe and had less acute radiation related toxicities in SIB postoperative radiotherapy for left‐sided breast cancer.
Polygenic risk score-based prediction of breast cancer risk in Taiwanese women with dense breast using a retrospective cohort study
Mammographic screening has contributed to a significant reduction in breast cancer mortality. Several studies have highlighted the correlation between breast density, as detected through mammography, and a higher likelihood of developing breast cancer. A polygenic risk score (PRS) is a numerical score that is calculated based on an individual's genetic information. This study aims to explore the potential roles of PRS as candidate markers for breast cancer development and investigate the genetic profiles associated with clinical characteristics in Asian females with dense breasts. This is a retrospective cohort study integrated breast cancer screening, population genotyping, and cancer registry database. The PRSs of the study cohort were estimated using genotyping data of 77 single nucleotide polymorphisms based on the PGS000001 Catalog. A subgroup analysis was conducted for females without breast symptoms. Breast cancer patients constituted a higher proportion of individuals in PRS Q4 (37.8% vs. 24.8% in controls). Among dense breast patients with no symptoms, the high PRS group (Q4) consistently showed a significantly elevated breast cancer risk compared to the low PRS group (Q1–Q3) in both univariate (OR = 2.25, 95% CI 1.43–3.50, P  < 0.001) and multivariate analyses (OR: 2.23; 95% CI 1.41–3.48, P  < 0.001). The study was extended to predict breast cancer risk using common low-penetrance risk variants in a PRS model, which could be integrated into personalized screening strategies for Taiwanese females with dense breasts without prominent symptoms.
Demoralization and Its Association with Quality of Life, Sleep Quality, Spiritual Interests, and Suicide Risk in Breast Cancer Inpatients: A Cross-Sectional Study
With decreasing mortality, the quality of life, spiritual needs, and mental health of breast cancer patients have become increasingly important. Demoralization is a poor prognostic factor for cancer patients. The extent of demoralization in breast cancer patients and its association with these factors remains unclear. This cross-sectional study was conducted at a Taiwanese medical center. We enrolled 121 participants (34 with high demoralization and 87 with low demoralization, as per the Mandarin Version of Demoralization Scale). High demoralization was associated with reduced quality of life, sleep quality, and spiritual interests. Multivariate analyses revealed that the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ≥ 62.5 (OR = 0.21, p = 0.002) and Spiritual Interests Related to Illness Tool Chinese Version ≥ 3.66 (OR = 0.11, p < 0.001) were associated with low demoralization. Demoralized patients with depression had a poorer quality of life and sleep quality. Although not statistically significant, depressed and demoralized participants were at a higher risk of suicide. Cancer patients with both depression and demoralization had the worst prognosis. Breast cancer patients exhibited demoralization when they had unmet bio-psycho-social-spiritual needs. An early assessment of demoralization may improve holistic healthcare for breast cancer patients.
Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial)
Background Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS. Methods/design This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene ( BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial. Discussion This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT. Trial registration ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.
Effect of Tungsten Doping on the Properties of Titanium Dioxide Dye-Sensitized Solar Cells
Tungsten-doped TiO2 thin films were prepared by sol–gel method on fluorine-doped tin oxide-coated substrates as working electrodes of dye-sensitized solar cells. The influences of different W doping (0, 2, 4, 6, and 8 at%) on the microstructure, optical, and photovoltaic properties of the W-TiO2 thin-film DSSCs were studied by the measurement of X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET) analysis, and electrochemical impedance spectroscopy (EIS). An optimal DSSCs performance was observed with a 6 at% W-doped TiO2 thin film, resulting in a Voc of 0.68 V, a Jsc of 20.2 mA/cm2, an FF of 68.6%, and an efficiency (η) of 9.42%. The efficiency of DSSCs with 6 at% W-doped TiO2 photoanode improved by 75%. This is because the 6 at% W-doped TiO2 thin film increases the specific surface area and electron transfer rate.
Mechanistic insights of lenvatinib: enhancing cisplatin sensitivity, inducing apoptosis, and suppressing metastasis in bladder cancer cells through EGFR/ERK/P38/NF-κB signaling inactivation
Background The persistent activation of the epidermal growth factor receptor (EGFR) leads to the activation of downstream oncogenic kinases and transcription factors, resulting in tumor progression and an increased resistance to cisplatin in bladder cancer (BC) cells. Lenvatinib, an oral multikinase inhibitor, has the potential to offer therapeutic benefits as an adjuvant treatment for BC patients. The investigation into its application in bladder cancer treatment is a valuable endeavor. The primary goal of this study is to confirm the effectiveness and mechanism of lenvatinib in inhibiting the progression of BC and enhancing the anticancer efficacy of cisplatin. Materials Three BC cell lines, namely, TSGH-8301, T24, and MB49, along with an MB49-bearing animal model, were utilized in this study. Results In vitro experiments utilizing MTT assays demonstrated that lenvatinib sensitized BC cells to cisplatin, exhibiting a synergistic effect. Flow cytometry indicated apoptotic events and signaling, presenting that lenvatinib effectively induced apoptosis and triggered extrinsic/intrinsic apoptotic pathways. In vivo studies using a mouse model of BC confirmed the antitumor efficacy of lenvatinib, demonstrating significant tumor growth suppression without inducing toxicity in normal tissues. Western blotting analysis and immunohistochemistry stain revealed EGF-phosphorylated EGFR and EGFR-mediated ERK/P38/NF-κB signaling were suppressed by treatment with lenvatinib. In addition, lenvatinib also suppressed anti-apoptotic (MCL1, c-FLIP, and XIAP) and metastasis-related factors (Twist, Snail-1, ZEB-1, ZEB-2, and MMP9) and promoted epithelial markers (E-cadherin) while reducing mesenchymal markers (N-cadherin). Conclusion In conclusion, the induction of apoptosis and the inhibition of EGFR/ERK/P38/NF-κB signaling are correlated with lenvatinib’s ability to hinder tumor progression and enhance the cytotoxic effects of cisplatin in bladder cancer. These findings underscore the potential of lenvatinib as a therapeutic option for bladder cancer, either as a standalone treatment or in combination with cisplatin.
Utilizing polygenic risk score for breast cancer risk prediction in a Taiwanese population
Breast cancer has been the most frequently diagnosed cancer among women in Taiwan since 2003. While genetic variants play a significant role in the elevated risk of breast cancer, their implications have been less explored within Asian populations. Variant-based polygenic risk scores (PRS) have emerged as valuable tools for assessing the likelihood of developing breast cancer. In light of this, we attempted to establish a predictive breast cancer PRS tailored specifically for the Taiwanese population. The cohort analyzed in this study comprised 28,443 control subjects and 1501 breast cancer cases. These individuals were sourced from the Taiwan Precision Medicine Initiative (TPMI) array and the breast cancer registry lists at Taichung Veterans General Hospital (TCVGH). Utilizing the breast cancer-associated Polygenic Score (PGS) Catalog, we employed logistic regression to identify the most effective PRS for predicting breast cancer risk. Subsequently, we subjected the cohort of 1501 breast cancer patients to further analysis to investigate potential heterogeneity in breast cancer risk. The Polygenic Score ID PGS000508 demonstrated a significant association with breast cancer risk in Taiwanese women with a 1.498-fold increase in cancer risk(OR = 1.498, 95 % CI(1.431–1.567, p=5.38×10^-68). Individuals in the highest quartile exhibited a substantially elevated risk compared to those in the lowest quartile, with an odds ratio (OR) of 3.11 (95 % CI: 2.70–3.59; p=1.15×10^-55). In a cohort of 1501 breast cancer cases stratified by PRS distribution, women in the highest quartile were diagnosed at a significantly younger age (p=0.003) compared to those in the lowest quartile. However, no significant differences were observed between PRS quartiles in relation to clinical stage (p=0.274), pathological stage (p=0.647), or tumor subtype distribution (p=0.244). In our study, we pinpointed PGS000508 as a significant predictive factor for breast cancer risk in Taiwanese women. Furthermore, we found that a higher PGS000508 score was associated with younger age at the time of first diagnosis among the breast cancer cases examined. •Breast cancer has maintained its position as the most common cancer diagnosis among Taiwanese women since 2003, highlighting a significant public health concern in the region.•While genetic factors are known to substantially influence breast cancer risk, research on these genetic variants and their impacts has been predominantly focused on non-Asian populations, creating a notable gap in our understanding of their effects in Asian communities.•Our research identified PGS000508 as a crucial polygenic risk score (PRS) that effectively predicts breast cancer risk specifically in Taiwanese women, with our findings revealing that higher PGS000508 scores correlate significantly with earlier age of breast cancer onset among affected individuals.