Publications by authors named "Ting-Chang Chang"

160 Publications

Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 18;262:13-20. Epub 2021 Apr 18.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, Taoyuan, Taiwan. Electronic address:

Objective: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer.

Study Design: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles.

Results: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively.

Conclusion: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout.
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http://dx.doi.org/10.1016/j.ejogrb.2021.04.017DOI Listing
April 2021

Microencapsulated rhEGF to facilitate epithelial healing and prevent scar formation of cesarean wound: A randomized controlled trial.

Taiwan J Obstet Gynecol 2021 May;60(3):468-473

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Keelung, Taiwan; Chang Gung University College of Medicine, Tao-Yuan, Taiwan; Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital(Linkou), Tao-Yuan, Taiwan. Electronic address:

Objective: Cesarean section (CS) is a major surgical intervention that affects women at childbearing age. Scarring from CS potentially causes discomfort and psychological distress. Emerging evidence indicates that epidermal growth factor (EGF) plays crucial roles in wound healing with the potential of minimizing scar formation. This study aims to investigate the effect of microencapsulated recombinant human EGF (Me-EGF) in scar prevention. Silicone gel was incorporated as part of the routine scar treatment.

Materials And Methods: Healthy women scheduled for cesarean delivery were enrolled and randomized to three groups: (1) no scar treatment, (2) silicone gel only, or (3) silicone gel plus Me-EGF. Vancouver Scar Scale (VSS: vascularity, pigmentation, elasticity, and height) was used for scar assessment at the 6th month and 9th month after CS.

Results: A total of 60 women were enrolled, but one patient withdrew due to noncompliance with the follow-up visit requirement. Me-EGF-containing treatment group consistently scored the lowest on every parameter in the VSS scale, followed by silicone gel group, and the group with no scar treatment. Kruskal-Wallis tests indicated significant differences (p < 0.05) between Me-EGF-containing treatment group and the other two groups in vascularity, pigmentation, elasticity, and the VSS total score, at either 6th month, 9th month, or both time points. The only parameter not showing any significant between-group difference was scar height, but the pattern still remained the same, in which Me-EGF group scored better in both month 6 and 9.

Conclusion: Surgical incisions in lower abdomen posed challenge in scar management. Our findings suggest that Me-EGF is a potential therapeutic option for better wound healing and scar prevention.
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http://dx.doi.org/10.1016/j.tjog.2021.03.014DOI Listing
May 2021

Genetic alterations and their therapeutic implications in epithelial ovarian cancer.

BMC Cancer 2021 May 4;21(1):499. Epub 2021 May 4.

ACT Genomics, Co. Ltd., 3F., No.345, Xinhu 2nd Rd., Neihu Dist, Taipei City, 114, Taiwan.

Background: Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients.

Methods: We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.

Results: Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.

Conclusions: Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.
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http://dx.doi.org/10.1186/s12885-021-08233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097933PMC
May 2021

DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan.

Gynecol Oncol 2021 May 20;161(2):429-435. Epub 2021 Mar 20.

Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, and Chang Gung University Medical College, Taoyuan City, Taiwan. Electronic address:

Objective: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women.

Methods: Three triage tools-cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1-were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear.

Results: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1 and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30-64 years. PAX1 had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1-positive women than in PAX1-negative women.

Conclusions: PAX1 has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1 assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.
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http://dx.doi.org/10.1016/j.ygyno.2021.02.011DOI Listing
May 2021

Incorporating patient centered benefits as endpoints in randomized trials of maintenance therapies in advanced ovarian cancer: A position paper from the GCIG symptom benefit committee.

Gynecol Oncol 2021 May 19;161(2):502-507. Epub 2021 Feb 19.

ANZGOG - The Prince of Wales Clinical School UNSW and Department of Medical Oncology, Prince of Wales Hospital, Randwick, New South Wales, Australia.

Background: Quality of life and patient reported outcome measures (PROMs) are important secondary endpoints and incorporated in most contemporary clinical trials. There have been deficiencies in their assessment and reporting in ovarian cancer clinical trials, particularly in trials of maintenance treatment where they are of particular importance. The Gynecologic Cancer InterGroup (GCIG) symptom benefit committee (SBC) recently convened a brainstorming meeting with representation from all collaborative groups to address questions of how to best incorporate PROMs into trials of maintenance therapies to support the primary endpoint which is usually progression free survival (PFS). These recommendations should harmonize the collection, analysis and reporting of PROM's across future GCIG trials.

Methods: Through literature review, trials analysis and input from international experts, the SBC identified four relevant topics to address with respect to promoting the role of PROMs to support the PFS endpoint in clinical trials of maintenance treatment for OC.

Results: The GCIG SBC unanimously accepted the importance of integrating PROM's in future maintenance trials and developed four guiding principles to be considered early in trial design. These include 1) adherence to SPIRIT-PRO guidelines, 2) harmonization of selection, collection and reporting of PROM's; 3) combining Health Related Quality of Life (HRQL) measures with clinical endpoints and 4) common approaches to dealing with incomplete HRQL data.

Conclusions: Close attention to incorporating HRQL and PROM's is critical to interpret the results of ovarian cancer clinical trials of maintenance therapies. There should be a consistent approach to assessing and reporting patient centered benefits across all GCIG trials to enable cross trial comparisons which can be used to inform practice.
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http://dx.doi.org/10.1016/j.ygyno.2021.02.018DOI Listing
May 2021

TLR4/IL-6/IRF1 signaling regulates androgen receptor expression: A potential therapeutic target to overcome taxol resistance in ovarian cancer.

Biochem Pharmacol 2021 Apr 6;186:114456. Epub 2021 Feb 6.

Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC; Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC; Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan, ROC. Electronic address:

Ovarian cancer is poorly treatable due, at least in part, to induced drug resistance to taxol- and cisplatin-based chemotherapy. Recent studies showed that ectopic overexpression of toll-like receptor 4 (TLR4) in ovarian cancer cells leads to upregulation of the androgen receptor (AR) and transactivation of taxol resistance genes, thereby causing chemoresistance. In the present study, we examined the signaling pathways involving TLR4 and interleukin 6 (IL-6) that enhance AR expression. Based on transcriptomic analysis, we show that IL-6 functions as a hub gene among the upregulated genes in taxol-treated TLR4-overexpressing ovarian cancer cells. Both the TLR4 activator taxol and IL-6 can induce AKT phosphorylation, whereas TLR4 knockdown or inhibition of the IL-6 signal transducer GP130 abrogates AKT activation. Furthermore, expression of AR and IL-6 is downregulated in TLR4-knockdown, taxol-resistant cells. In addition, TLR4 knockdown inhibits GP130 and IL-6 receptor alpha (IL6Rα) activities, indicating that TLR4 plays a critical role in IL-6 signaling. On the other hand, nuclear translocation of AR is induced by IL-6 treatment, whereas knockdown of endogenous IL-6 reduces AR and TLR4 expression in taxol-resistant ovarian cancer cells. These results indicate that TLR4 and IL-6 play a crucial role in AR gene regulation and function. We also identify interferon regulatory factor 1 (IRF1) as a downstream target of IL-6 signaling and as a regulator of AR expression. Moreover, analysis of clinical samples indicates that high IL-6 expression correlates with poor progression-free survival in ovarian cancer patients treated with taxol. Overall, our findings indicate that the TLR4/IL-6/IRF1 signaling axis represents a potential therapeutic target to overcome AR-based taxol resistance in ovarian cancer.
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http://dx.doi.org/10.1016/j.bcp.2021.114456DOI Listing
April 2021

Point-of-care semen analysis of patients with infertility via smartphone and colorimetric paper-based diagnostic device.

Bioeng Transl Med 2021 Jan 18;6(1):e10176. Epub 2020 Aug 18.

Institute of Biomedical Engineering National Tsing Hua University Hsinchu Taiwan.

Male infertility affects millions of males worldwide and is rising in prevalence due to social and environmental conditions. However, men often feel too embarrassed to receive a semen analysis in the hospital due to social stigmas. To overcome this problem, we developed a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test strip to distinguish semen samples with low total motile sperm concentration from those with normal motile sperm concentration. This is a point-of-care colorimetric semen analytical method with a one-step, inexpensive, equipment-free evaluation process, and adequate accuracy validated in a 42-sample clinical trial. In this study, results were evaluated visually and with a smartphone application. Using visual observation methods, the area under the curve (AUC) was 0.71 (95% of confidence interval = 0.55-0.86; = 0.021), sensitivity was 41%, specificity was 95%, positive predictive value was 90%, negative predictive value (NPV) was 59.4%, and accuracy was 67%. Using a smartphone recording and analytical system, AUC was 0.766 (95% of confidence interval = 0.612-0.92; = 0.003), sensitivity was 96%, specificity was 65%, PPV was 75%, NPV was 92.9%, and accuracy was 80.9%. This work demonstrated a screening tool that could elevate semen analysis to the level of routine healthcare and provide for private, in-home self-assessment.
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http://dx.doi.org/10.1002/btm2.10176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823130PMC
January 2021

Exposure to endocrine disruptor alkylphenols and the occurrence of endometrial cancer.

Environ Pollut 2020 Dec 27;267:115475. Epub 2020 Aug 27.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Institute of Environmental Medicine, College of Public Health, China Medical University and Hospital, Taichung, Taiwan; Department of Public Health, National Defense Medical Center, Taipei, Taiwan; Department of Safety, Health, and Environmental Engineering, National United University, Miaoli, Taiwan. Electronic address:

Exposure to environmental chemicals with oestrogenic effects has been associated with the development of endometrial cancer (EMCa). EMCa has become the most commonly diagnosed cancer of the female genital tract. To further understand the potential association between exposure to environmental endocrine disruptors and the occurrence of EMCa, we performed a case-control study between 2011 and 2014. We aimed to detect and compare concentrations of a known hormone disruptor, alkylphenol, between women diagnosed with either EMCa or uterine leiomyoma, and those who did not have either of these. Subjects were women diagnosed with either EMCa or uterine leiomyoma (LM) and healthy controls. A structured questionnaire was administered to collect information on lifestyle and health status. Gas chromatography/mass spectrometry was used to measure urinary NP and OP concentrations in participants. Multiple regression analysis was used to examine the association between exposure and outcomes. Overall, 397 women were recruited, including 49 with EMCa, 247 with LM, and 101 controls. Among them, 73.6% showed detectable levels of NP and 61.0% showed detectable levels of OP. The EMCa group had a significantly higher NP concentration than the control group. Higher OP concentrations were also found in participants with EMCa than those with LM and controls. In addition, women in the upper tertile of the NP group had a significantly increased risk of EMCa occurrence (odds ratio [95% confidence interval] = 4.47 [1.69-11.84] for EMCa vs. control). The same was found in the group of women with more than the median level of OP (odds ratio [95% confidence interval] = 4.32 [2.01-9.30] for EMCa vs. LM). Stratification of pre- and post-menopausal groups resulted in a similar association. The results show that NP/OP exposure is associated with EMCa. Further investigations and exposure minimisation are suggested.
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http://dx.doi.org/10.1016/j.envpol.2020.115475DOI Listing
December 2020

Stabilizing resistive random access memory by constructing an oxygen reservoir with analyzed state distribution.

Nanoscale 2020 Dec;12(46):23532-23536

Department of Physics, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.

In this paper, the instability mechanism of resistive random access memory (RRAM) was investigated, and a technique was developed to stabilize the distribution of high resistance states (HRS) and better concentrate the set voltage. Due to the accumulation of oxygen, an interface-type switching characteristic was observed on the I-V curves beneath the filament-type switching behavior. In this work, the interface-type switching characteristic is used to fit the natural distribution of HRS as an analysis of the instability mechanism. According to the results, the HRS distribution is attributed to the accumulation of excess oxygen ions left from the lower oxygen content and oxygen vacancy recombination during the reset process. The proposed solution with simple plasma treatment, can create an excess oxygen reservoir by changing the surface topography of the electrode to store the surplus oxygen ions from the reset process, eliminating the oxygen accumulation effect and further improving the device stability.
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http://dx.doi.org/10.1039/d0nr04225kDOI Listing
December 2020

Enhancing LiAlO synaptic performance by reducing the Schottky barrier height for deep neural network applications.

Nanoscale 2020 Nov;12(45):22970-22977

Wuhan National Laboratory for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, China.

Although good performance has been reported in shallow neural networks, the application of memristor synapses towards realistic deep neural networks has met more stringent requirements on the synapse properties, particularly the high precision and linearity of the synaptic analog weight tuning. In this study, a LiAlOX memristor synapse was fabricated and optimized to address these demands. By delicately tuning the initial conductance states, 120-level continuously adjustable conductance states were obtained and the nonlinearity factor was substantially reduced from 8.96 to 0.83. The significant enhancements were attributed to the reduced Schottky barrier height (SBH) between the filament tip and the electrode, which was estimated from the measured I-V curves. Furthermore, a deep neural network for realistic action recognition task was constructed, and the recognition accuracy was found to be increased from 15.1% to 91.4% on the Weizmann video dataset by adopting the above-described device optimization method.
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http://dx.doi.org/10.1039/d0nr04782aDOI Listing
November 2020

Adaptive Synaptic Memory via Lithium Ion Modulation in RRAM Devices.

Small 2020 10 29;16(42):e2003964. Epub 2020 Sep 29.

Department of Electronics Engineering and Institute of Electronics, National Chiao Tung University, No.1001 University Road, Hsinchu, 30010, Taiwan.

Biologically plausible computing systems require fine-grain tuning of analog synaptic characteristics. In this study, lithium-doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state-dependent decay to be reliably achieved. As a result, this device offers multi-bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short-term memory and long-term memory are emulated across dynamical timescales. Spike-timing-dependent plasticity and paired-pulse facilitation are also demonstrated. These mechanisms are capable of self-pruning to generate efficient neural networks. Time-dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human's higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.
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http://dx.doi.org/10.1002/smll.202003964DOI Listing
October 2020

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Int J Cancer 2021 Feb 1;148(3):665-672. Epub 2020 Sep 1.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, Taoyuan, Taiwan.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.
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http://dx.doi.org/10.1002/ijc.33251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754315PMC
February 2021

Meridian study on the response current affected by electrical pulse and acupuncture.

Nanoscale Res Lett 2020 Jul 10;15(1):146. Epub 2020 Jul 10.

Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, 70 Lienhai Rd, Kaohsiung, 80424, Taiwan.

Acupuncture and its meridians are important components of traditional Chinese medicine, and numerous opinions have been previously expressed regarding these meridians. This study aims to explore the phenomenon of meridians from the perspective of electronic physics by studying these meridians for the response current affected by electrical pulse and acupuncture. In this study, acupuncture which applies an electrical pulse was used to research the physical properties of the meridians. Different kinds of pulses were applied to the human body to realize abnormal electrical signals. Comparing these electrical measurement results with the isothermal transient ionic current (ITIC) theory, we found that the transmission of meridian messages may be related to ion conduction. The movement of ions induced by acupuncture and electrical stimulation can lead to drift and diffusion currents through the meridians. The ionic conduction of meridian hypothesis is proved in that the substances delivered by meridians are in fact ions.
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http://dx.doi.org/10.1186/s11671-020-03373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352033PMC
July 2020

Comprehensive genomic profiling reveals ubiquitous KRAS mutations and frequent PIK3CA mutations in ovarian seromucinous borderline tumor.

Mod Pathol 2020 12 2;33(12):2534-2543. Epub 2020 Jul 2.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan.

The molecular underpinnings of seromucinous borderline tumor (SMBT) - an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinoma - remain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.
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http://dx.doi.org/10.1038/s41379-020-0611-3DOI Listing
December 2020

Role of the TLR4-androgen receptor axis and genistein in taxol-resistant ovarian cancer cells.

Biochem Pharmacol 2020 07 9;177:113965. Epub 2020 Apr 9.

Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan, Republic of China. Electronic address:

Toll-like receptor 4 (TLR4) is often overexpressed in taxol-resistant cancer cells. Here we used whole-genome transcriptomic analysis to identify 787 upregulated genes in SKOV3 ovarian carcinoma cells that ectopically express TLR4. Using chromatin immunoprecipitation enrichment analysis, we observed that 27.8% of the TLR4-upregulated genes identified were androgen receptor (AR)-regulated genes. Accordingly, AR expression was induced in taxol-resistant SKOV3 cells overexpressing TLR4, whereas depletion of TLR4 by shRNA repressed AR expression. Activation of AR by androgens or silencing of AR using shRNA also regulated expression of AR-related genes. We found that expression of DCDC2, ANKRD18B, ALDH1A1, c14orf105, ITGBL1 and NEB was overexpressed in taxol-resistant cells, suggesting the involvement of these AR-related genes in taxol resistance. Pathway enrichment analysis confirmed that the expression of several upregulated genes enriched in steroid biosynthesis pathways was inducible by androgens, supporting the results of previous studies. We also observed that genistein inhibits AR activation, leading to suppression of AR-driven genes and reduced taxol resistance in ovarian cancer cells. Overall, we identified six TLR4- and AR-regulated genes involved in taxol resistance. Our results reveal that the TLR4/AR axis plays a critical role in taxol resistance and that genistein is a candidate compound to limit chemoresistance and improve cancer treatment in ovarian cancer.
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http://dx.doi.org/10.1016/j.bcp.2020.113965DOI Listing
July 2020

Dose-dense chemotherapy with weekly paclitaxel and 3-weekly carboplatin for recurrent ovarian cancer.

Taiwan J Obstet Gynecol 2020 Jan;59(1):21-27

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taiwan; Chang Gung University, College of Medicine, Taiwan. Electronic address:

Objective: To analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review.

Materials And Methods: Patients accepted weekly paclitaxel 80 mg/m on day 1, 8, 15 and carboplatin on day1 at area under curve (AUC) 6 every 21 days were reviewed for the response rate, progression-free survival, overall survival, and toxicity during January 2012 to April 2016 in Chang Gung Memorial Hospital at Linkou, Taiwan.

Results: Sixteen patients with recurrent ovarian cancer, including 1 platinum-resistant, 7 partially platinum-sensitive, and 8 platinum-sensitive, accepted a median of 6 cycles of chemotherapy (range 3-10). The overall response rate (ORR) and complete response (CR) rate were 93.8%, and 62.5%, respectively. The median PFS of all patients were 10.9 months (range 4.3-40.5). The median time to response (TTR) was 29.0 days (range 19.6-38.4). The median disease-free survival (DFS) after CR was 5.6 months (range 1.2-34.2). Grade 3 at least toxicity included anemia (6.3%), neutropenia (50%), and thrombocytopenia (18.8%). Twenty-nine articles on phase I, II, III, or retrospective studies of dose-dense chemotherapy with weekly paclitaxel were reviewed.

Conclusion: This is the first report using Japanese Gynecologic Oncology Group 3016 protocol, weekly paclitaxel and 3-weely carboplatin, on recurrent ovarian cancer. The current study showed high ORR and CR with tolerable toxicities. Our study suggested dose-dense chemotherapy with paclitaxel, especially combining carboplatin created high efficacy probably by anti-angiogenesis. However, consolidation or maintenance therapy is needed to prolong DFS.
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http://dx.doi.org/10.1016/j.tjog.2019.10.003DOI Listing
January 2020

mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling.

J Gynecol Oncol 2020 May 25;31(3):e24. Epub 2019 Oct 25.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center and Chang Gung University, College of Medicine, Taoyuan, Taiwan.

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by mutation analysis in hospital-based cases.

Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify mutations and large genomic rearrangements, respectively. When mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members.

Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in and 2 in ). All mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were mutation carriers. All of them had family members with -associated malignancies.

Conclusions: Our results provide pilot evidence that mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.
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http://dx.doi.org/10.3802/jgo.2020.31.e24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189074PMC
May 2020

Seeing pressure in color based on integration of highly sensitive pressure sensor and emission tunable light emitting diode.

Opt Express 2019 Nov;27(24):35448-35467

We demonstrate a highly sensitive, low-cost, environmental-friendly pressure sensor derived from a wool-based pressure sensor with wide pressure sensing range using wool bricks embedded with a Ag nano-wires. The easy fabrication and light weight allow portable and wearable device applications. Wth the integration of a light-emitting diode possessing multi-wavelength emission, we illustrate a hybrid multi-functional LED-integrated pressure sensor that is able to convert different applied pressures to light emission with different wavelengths. Due to the high sensitivity of the pressure sensor, the demonstration of acoustic signal detection has also been presented using sound of a metronome and a speaker playing a song. This multi-functional pressure sensor can be implemented to technologies such as smart lighting, health care, visible light communication (VLC), and other internet of things (IoT) applications.
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http://dx.doi.org/10.1364/OE.27.035448DOI Listing
November 2019

Reducing Interface Traps with High Density Hydrogen Treatment to Increase Passivated Emitter Rear Contact Cell Efficiency.

Nanoscale Res Lett 2019 Dec 12;14(1):375. Epub 2019 Dec 12.

Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan.

In this work, a high-density hydrogen (HDH) treatment is proposed to reduce interface traps and enhance the efficiency of the passivated emitter rear contact (PERC) device. The hydrogen gas is compressed at pressure (~ 70 atm) and relatively low temperature (~ 200 °C) to reduce interface traps without changing any other part of the device's original fabrication process. Fourier-transform infrared spectroscopy (FTIR) confirmed the enhancement of Si-H bonding and secondary-ion mass spectrometry (SIMS) confirmed the SiN/Si interface traps after the HDH treatment. In addition, electrical measurements of conductance-voltage are measured and extracted to verify the interface trap density (Dit). Moreover, short circuit current density (Jsc), series resistance (Rs), and fill factor (F.F.) are analyzed with a simulated light source of 1 kW M global AM1.5 spectrum to confirm the increase in cell efficiency. External quantum efficiency (EQE) is also measured to confirm the enhancement in conversion efficiency between different wavelengths. Finally, a model is proposed to explain the experimental result before and after the treatment.
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http://dx.doi.org/10.1186/s11671-019-3216-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908542PMC
December 2019

Management and clinical outcomes of patients with recurrent/progressive ovarian clear cell carcinoma.

J Formos Med Assoc 2020 Apr 6;119(4):793-804. Epub 2019 Dec 6.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients.

Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS).

Results: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS.

Conclusion: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.
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http://dx.doi.org/10.1016/j.jfma.2019.11.018DOI Listing
April 2020

Metabolomic biomarkers in cervicovaginal fluid for detecting endometrial cancer through nuclear magnetic resonance spectroscopy.

Metabolomics 2019 10 29;15(11):146. Epub 2019 Oct 29.

Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, 5 Fuhsing St., Guishan, Taoyuan, 33305, Taiwan.

Introduction: Endometrial cancer (EC) is one of the most common gynecologic neoplasms in developed countries but lacks screening biomarkers.

Objectives: We aim to identify and validate metabolomic biomarkers in cervicovaginal fluid (CVF) for detecting EC through nuclear magnetic resonance (NMR) spectroscopy.

Methods: We screened 100 women with suspicion of EC and benign gynecological conditions, and randomized them into the training and independent testing datasets using a 5:1 study design. CVF samples were analyzed using a 600-MHz NMR spectrometer equipped with a cryoprobe. Four machine learning algorithms-support vector machine (SVM), partial least squares discriminant analysis (PLS-DA), random forest (RF), and logistic regression (LR), were applied to develop the model for identifying metabolomic biomarkers in cervicovaginal fluid for EC detection.

Results: A total of 54 women were eligible for the final analysis, with 21 EC and 33 non-EC. From 29 identified metabolites in cervicovaginal fluid samples, the top-ranking metabolites chosen through SVM, RF and PLS-DA which existed in independent metabolic pathways, i.e. phosphocholine, malate, and asparagine, were selected to build the prediction model. The SVM, PLS-DA, RF, and LR methods all yielded area under the curve values between 0.88 and 0.92 in the training dataset. In the testing dataset, the SVM and RF methods yielded the highest accuracy of 0.78 and the specificity of 0.75 and 0.80, respectively.

Conclusion: Phosphocholine, asparagine, and malate from cervicovaginal fluid, which were identified and independently validated through models built using machine learning algorithms, are promising metabolomic biomarkers for the detection of EC using NMR spectroscopy.
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http://dx.doi.org/10.1007/s11306-019-1609-zDOI Listing
October 2019

Investigation of the Capacitance-Voltage Electrical Characteristics of Thin-Film Transistors Caused by Hydrogen Diffusion under Negative Bias Stress in a Moist Environment.

ACS Appl Mater Interfaces 2019 Oct 15;11(43):40196-40203. Epub 2019 Oct 15.

Department of Electronics Engineering , National Chiao Tung University , Hsinchu 300 , Taiwan , R. O. C.

In this study, the impact of moisture on the electrical characteristics of an amorphous In-Ga-Zn-O thin-film transistor (a-IGZO TFT) was investigated. In commercial applications of such TFTs, high stability and quality performance in humid environments are essential. During TFT operation under ambient moisture, the electrolysis of water molecules occurs via the tip electric field effect. Hydrogen diffuses from the etch-stop layer or back-channel into the main channel under a negative electric field. The hydrogen atoms act as shallow donors (which causes the carrier concentration in the channel to rise), causing the threshold voltage (V) to shift in the negative direction. Hydrogen diffusion from the overlap of the source/drain and gate electrodes to the channel center caused by the tip electric field induces a significant barrier lowering and V shifts in a short-channel device. However, under negative bias stress (NBS) in ambient moisture, the negative V shift is more obvious in short- than in long-channel devices, indicating suppressed hydrogen diffusion in long-channel devices. This is attributed to the electrolysis of water by the tip electric field at the source, drain, and gate electrodes, which causes hydrogen to diffuse to the center of the channel. Here, a novel physical model of the capacitance-voltage (-) electrical property changes under ambient moisture is proposed, based on the early appearance of abnormalities in the - measurements. The electrolysis of water caused by the tip electric field and electrical abnormalities caused by hydrogen diffusion into the a-IGZO active layer are explained by this model. A secondary-ion mass spectrometry analysis shows that hydrogen content in the channel generally increases under NBS in ambient moisture. The degradation behavior due to moisture in a-IGZO is clarified. Thus, inhibiting the tip electric field may benefit future flexible-display and gas-sensing applications.
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http://dx.doi.org/10.1021/acsami.9b11637DOI Listing
October 2019

Utility of diffusion-weighted and contrast-enhanced magnetic resonance imaging in diagnosing and differentiating between high- and low-grade uterine endometrial stromal sarcoma.

Cancer Imaging 2019 Sep 12;19(1):63. Epub 2019 Sep 12.

Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, 5 Fuhsing St., Guishan, Taoyuan, Taiwan, 33382.

Background: Endometrial stromal sarcoma (ESS) is a rare uterine malignancy that features different prognoses for its high- and low-grade subtypes. We investigated the diagnostic accuracy of magnetic resonance (MR) imaging in diagnosing and differentiating between high- and low-grade ESS.

Methods: We retrospectively reviewed the preoperative pelvic MR images of consecutive patients who received histologically confirmed diagnoses of high-grade ESS (n = 11) and low-grade ESS (n = 9) and T2-hyperintense leiomyoma (n = 16). Two radiologists independently evaluated imaging features in T1-, T2-, and diffusion-weighted and contrast-enhanced MR images. Statistical analysis included Mann-Whitney tests and Fisher's exact test, with sensitivity, specificity and diagnostic accuracy of imaging features.

Results: High-grade ESS was associated with significantly more extensive necrosis and hemorrhage and distinct feather-like enhancement compared with low-grade ESS (P < .05 for all). The feather-like enhancement pattern yielded a diagnostic accuracy of 95%, sensitivity of 91%, and specificity of 100% in differentiating high-grade from low-grade ESS. This imaging characteristic was significantly superior to the necrosis (80%, P = .033) or hemorrhage (75%, P = .007). Both high- and low-grade ESS demonstrated T2 hypointense bands, marginal nodules, intratumoral nodules, and worm-like intra-myometrial nodules, and their tumor apparent diffusion coefficient (ADC) values were significantly lower than those of T2-hyperintense leiomyomas (P < .001).

Conclusions: Diffusion-weighted MR imaging is useful in diagnosing ESS against T2-hyperintense leiomyomas, and contrast enhancement aids in further differentiating between high- and low-grade ESS.
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http://dx.doi.org/10.1186/s40644-019-0247-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739916PMC
September 2019

An electro-photo-sensitive synaptic transistor for edge neuromorphic visual systems.

Nanoscale 2019 Oct;11(38):17590-17599

Wuhan National Laboratory for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, China.

The practical application of optoelectronic artificial synapses in neuromorphic visual systems is still hindered by their limited functionality, reliability and the challenge of mass production. Here, an electro-photo-sensitive synapse based on a highly reliable amorphous InGaZnO thin-film transistor is demonstrated. Not only does the synapse respond to electrical voltage spikes due to charge trapping/detrapping, but also the weight is modified directly by persistent photocurrent effects under UV-light stimulation. Representative forms of synaptic plasticity, including inhibitory and excitatory postsynaptic currents, frequency-dependent characteristics, short-term to long-term plasticity transitions, and summation effects, are successfully demonstrated. In particular, optoelectronic synergetic modulation leads to reconfigurable excitatory and inhibitory synaptic behaviors, which provides a promising way to achieve the homeostatic regulation of synaptic weights. Moreover, the analogue channel conductance with 100 states is used as the weight update rule to perform MNIST handwritten digit recognition, using system-level LeNet-5 convolutional neural network simulations. The network shows a high recognition accuracy of 95.99% and good tolerance to noisy input patterns. This study highlights the commercial potential of mature optoelectronic InGaZnO transistor technology in edge neuromorphic systems.
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http://dx.doi.org/10.1039/c9nr04195hDOI Listing
October 2019

Effectiveness and appropriateness in the application of office hysteroscopy.

J Formos Med Assoc 2019 Nov 2;118(11):1480-1487. Epub 2019 Jan 2.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital (Linkou), Tao-Yuan, Taiwan; Chang Gung University College of Medicine, Tao-Yuan, Taiwan.

With the advances in miniature instruments, office hysteroscopy on conscious patients has been the standard to explore the intrauterine pathology, with the ability to perform some minor procedures concomitantly. Patients usually appreciate the efficient "see and treat" procedures with such minimal discomfort that exempt from the inconvenience of going into the operating room and the need for anesthesia. However, controversies exist in the appropriateness of its application in some clinical situations. Concerns include (1) the criteria for hysteroscopy applied in the vast number of patients suffering from abnormal uterine bleeding or subfertility, and (2) the frequency for repeated hysteroscopy on some kinds of patients, such as those of endometrial cancer with fertility-sparing treatment for monitoring the disease, or those of severe intrauterine adhesion who need adhesiolysis for subsequent conception, in whom the appropriate protocol of repeatedly applying hysteroscopy lacks consensus. This article reviews the literature to find the best available evidence on the effectiveness of office hysteroscopy in comparison with other clinical diagnostic tools, as well as the current opinions on such controversies in its application.
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http://dx.doi.org/10.1016/j.jfma.2018.12.012DOI Listing
November 2019

Androgen receptor transcriptional activity and chromatin modifications on the ABCB1/MDR gene are critical for taxol resistance in ovarian cancer cells.

J Cell Physiol 2019 06 14;234(6):8760-8775. Epub 2018 Oct 14.

Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan.

We report here that the androgen receptor (AR) and ABCB1 are upregulated in a model of acquired taxol resistance (txr) in ovarian carcinoma cells. AR silencing sensitizes txr cells to taxol threefold, whereas ectopic AR expression in AR-null HEK293 cells induces resistance to taxol by 1.7-fold. AR activation using the agonist dihydrotestosterone (DHT) or sublethal taxol treatment upregulates ABCB1 expression in both txr cells and AR-expressing HEK293 cells. In contrast, AR inactivation using the antagonist bicalutamide downregulates ABCB1 expression and enhances cytotoxicity to taxol. A functional ABCB1 promoter containing five predicted androgen-response elements (AREs) is cloned. Deletion assays reveal a taxol-responsive promoter segment which harbors ARE4. Notably, DHT- or taxol-activated AR potentiates binding of the AR to ARE4 as revealed by the chromatin immunoprecipitation. On the other hand, txr cells display an increase in chromatin remodeling. AR/H3K9ac and AR/H3K14ac complexes bind specifically to ARE4 in response to taxol. Furthermore, acetyltransferase protein levels (p300 and GCN5) are upregulated in txr cells. Silencing of p300 or GCN5 reduces chromatin modification and enhances cytotoxicity in both parental and txr SKOV3 cells. While the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (AKT) pathway is significantly activated by taxol, taxol-induced ABCB1 expression, histone posttranslational modifications, and p300 binding to ARE4 are suppressed following inhibition of the PI3K/AKT cellular pathway. These results demonstrate that the AKT/p300/AR axis can be activated to target ABCB1 gene expression in response to taxol, thus revealing a new treatment target to counter taxol resistance.
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http://dx.doi.org/10.1002/jcp.27535DOI Listing
June 2019

Outcomes for Cervical Cancer Patients Treated With Radiation in High-Volume and Low-Volume Hospitals.

Int J Radiat Oncol Biol Phys 2018 09 24;102(1):184-193. Epub 2018 May 24.

Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan; Institute for Radiological Research, Chang Gung Memorial Hospital/Chang Gung University, Taiwan. Electronic address:

Purpose: To investigate the effects of different hospital patient loads on the standard of care and treatment outcomes of patients with cervical cancer treated primarily with radiation therapy and to identify factors that may contribute to survival differences among hospitals.

Methods And Materials: We used the Taiwan Cancer Registry database to extract data on a total of 2582 International Federation of Gynecology and Obstetrics stage IB to IVA patients with uterine cervical cancer diagnosed from 2007 to 2013 who underwent primarily curative radiation therapy (with or without chemotherapy). We explored associations among hospital patient loads, clinical parameters, the type of care given, and survival.

Results: Patients who received treatment at hospitals with small and medium patient loads (≤5 cases annually) were older and had more advanced-stage disease than other patients. Positive associations were evident between the use of chemotherapy and brachytherapy and hospital patient load. Patients treated at hospitals with large patient loads (>5 cases annually) experienced better overall survival than those treated at hospitals with small or medium patient loads (P < .001). Stepwise addition of variables to multivariable analyses indicated that greater use of chemotherapy and brachytherapy were major contributors to the better survival of patients treated at hospitals with large patient loads. However, larger hospital patient load per se (>5 vs ≤5 cases annually) was also independently prognostic for better survival of patients with bulky tumors or advanced-stage disease.

Conclusions: We found that the inferior survival rate of patients with cervical cancer treated at hospitals with smaller patient loads was attributable not only to a lower standard of care in such hospitals but also to the smaller patient load. Our findings indicate how treatment should be improved in hospitals with small and medium patient loads.
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http://dx.doi.org/10.1016/j.ijrobp.2018.05.038DOI Listing
September 2018

Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer.

Br J Cancer 2018 08 3;119(5):530-537. Epub 2018 Aug 3.

Department of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 05080, Korea.

Background: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer.

Methods: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS).

Results: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs.

Conclusions: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.
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http://dx.doi.org/10.1038/s41416-018-0206-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162273PMC
August 2018

Presurgical Identification of Uterine Smooth Muscle Malignancies through the Characteristic FDG Uptake Pattern on PET Scans.

Contrast Media Mol Imaging 2018 19;2018:7890241. Epub 2018 Jun 19.

Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.

The unidentified presence of uterine smooth muscle malignancies poses a tremendous risk in women planning surgery for presumed benign leiomyomas. We sought to investigate whether preoperative FDG PET may be useful to identify leiomyosarcomas (LMS) and smooth muscle tumors of uncertain malignant potential (STUMP). . We investigated patients with rapidly growing uterine masses which were suspected of being malignant on ultrasound or MRI. Among the 21 patients who underwent FDG PET, we identified 7 LMS, 1 STUMP, and 13 leiomyomas. PET-derived parameters and FDG uptake patterns were analyzed retrospectively. . The SUV values of LMS/STUMP (range: 3.7-11.8) were significantly higher than those observed in leiomyomas (range: 2.0-9.4; =0.003) despite a significant overlap. The metabolic tumor/necrosis ratio was significantly higher in LMS/STUMP than in leiomyomas ( < 0.001), with no significant intergroup overlaps. All LMS/STUMP revealed a characteristic pattern of FDG uptake, identifying a specific "hollow ball" sign (corresponding to areas of coagulative tumor necrosis). In contrast, this sign was invariably absent in patients with leiomyomas. . The characteristic FDG uptake pattern instead of SUV on PET images allows identifying LMS/STUMP in patients with rapidly growing uterine masses, avoiding the deleterious consequences of regular surgery for presumed benign leiomyomas.
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http://dx.doi.org/10.1155/2018/7890241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029472PMC
July 2019

Risk of pleural empyema in patients with schizophrenia: a nationwide propensity-matched cohort study in Taiwan.

BMJ Open 2018 07 6;8(7):e021187. Epub 2018 Jul 6.

Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.

Objective: Thoracic infection and pneumonia are prevalent in patients with schizophrenia; however, it is unclear whether patients with schizophrenia are at an increased risk of developing pleural empyema.

Design: A retrospective cohort study with propensity-matched cohorts with and without schizophrenia.

Setting: Using the National Health Insurance Research Database of Taiwan.

Participants: We identified 55 888 patients with schizophrenia newly diagnosed in 2000-2011 and same number of individuals without schizophrenia as the comparison cohort, frequency matched by propensity scores estimated using age, sex, occupation, income, urbanisation, year of diagnosis and comorbidities.

Primary Outcome Measures: We assessed incident pleural empyema by the end of 2011 and used the Cox proportional hazards model to calculate the schizophrenia cohort to comparison cohort HR of pleural empyema.

Results: The overall incidence of pleural empyema was 2.44-fold greater in the schizophrenia cohort than in the comparison cohort (4.39vs1.80 per 10 000 person-years), with an adjusted HR of 2.87(95% CI 2.14 to 3.84). Stratified analyses by age, sex, occupation, income, urbanisation and comorbidity revealed significant hazards for pleural empyema associated with schizophrenia in all subgroups.

Conclusions: Patients with schizophrenia are at an increased risk of developing pleural empyema and require greater attention and appropriate support.
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http://dx.doi.org/10.1136/bmjopen-2017-021187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042618PMC
July 2018