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4. The impact of frailty on breast cancer outcomes: evidence from analysis of the Nationwide Inpatient Sample, 2005-2018

Author

Tsai, Hsueh-Han, Yu, Jyh-Cherng, Hsu, Huan-Ming, Chu, Chi-Hong, Hong, Zhi-Jie, Feng, An-Chieh, Fu, Chun-Yu, Dai, Ming-Shen, and Liao, Guo-Shiou

Subjects
Original Article
Abstract

The aims of the present study were to examine whether and how frailty impacts the outcomes of breast cancer. Data of women with breast cancer hospitalized during 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS) database. Frailty was identified using a novel algorithm, Hospital Frailty Risk Score (HFRS). Propensity-score (PS) matching was utilized to balance the baseline characteristics between frail and non-frail groups. In-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), and total hospital cost were compared using univariate and multivariable logistic regression analyses. A total of 19,522 patients with metastatic (frailty n = 9,906; no frailty n = 9,716) and 135,200 with non-metastatic breast cancer (frailty n = 30,235; no frailty n = 104,965) were included. After adjustment, frailty was significantly and independently associated with higher risk for in-hospital mortality, unfavorable discharge, prolonged LOS, and greater hospital cost in both metastatic and non-metastatic diseases, in which the impacts of frailty was greater in women with non-metastatic disease. In stratified analysis, frailty had the greatest impact on in-hospital mortality among women had had non-metastatic disease and aged

Published
2022

19. Additional file 2: of Integrated omics-based pathway analyses uncover CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer

Author

Apaya, Maria, Jeng-Yuan Shiau, Guo-Shiou Liao, Yu-Jen Liang, Chia-Wei Chen, Hsin-Chou Yang, Chu, Chi-Hong, Jyh-Cherng Yu, and Lie-Fen Shyur

Abstract

Supporting information for delineation of CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer (Figures S1-S8). (PDF 28634 kb)

Published
2019
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20. Additional file 1: of Integrated omics-based pathway analyses uncover CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer

Author

Apaya, Maria, Jeng-Yuan Shiau, Guo-Shiou Liao, Yu-Jen Liang, Chia-Wei Chen, Hsin-Chou Yang, Chu, Chi-Hong, Jyh-Cherng Yu, and Lie-Fen Shyur

Abstract

Table S1. Publicly available resources utilized to download and process relevant data for multi-omics network and pathway analysis. Table S2. Clinico-pathological characteristics of patient-derived breast tissue specimen included in the study. Table S3. Oxylipin metabolites identified in patient-derived mammary tumor or adjacent normal tissues. Table S4. Discovery and validation cohorts used for multi-omics network and pathway analysis. Table S5. List of pathways upregulated in histologically classified ER−/PR−/HER2+ mammary tumor samples with mRNA expression of CYP2J2 z-score ≥ 2.0. Table S6. List of pathways upregulated in histologically classified ER+/PR+/HER2- and TPBC tumor samples with gene expression of CYP2J2 z-score ≥ 2.0. Table S7. List of pathways upregulated in histologically classified TNBC tumor samples with gene expression of CYP2J2 z-score ≥ 2.0. (DOCX 98 kb)

Published
2019
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21. Protective role of programmed death 1 ligand 1 (PD-L1) in nonobese diabetic mice: the paradox in transgenic models

Author

Wang, Chia-Jen, Chou, Feng-Cheng, Chu, Chi-Hong, Wu, Jen-Chine, Lin, Shih-Hua, Chang, Deh-Ming, and Sytwu, Huey-Kang

Subjects
Ligands (Biochemistry) -- Research -- Usage -- Physiological aspects, Diabetes -- Research -- Physiological aspects, Lymphocytes -- Research -- Physiological aspects -- Usage, Animal models in research -- Usage -- Research -- Physiological aspects, Health, Usage, Physiological aspects, Research
Abstract

OBJECTIVE--Coinhibitory signals mediated via programmed death 1 (PD-1) receptor play a critical role in downregulating immune responses and in maintaining peripheral tolerance. Programmed death 1 ligand 1 (PD-L1), the interacting ligand for PD-1, widely expressed in many cell types, acts as a tissue-specific negative regulator of pathogenic T-cell responses. We investigated the protective potential of PD-L1 on autoimmune diabetes by transgenically overexpressing PD-L1 in pancreatic p-cells in nonobese diabetic (NOD) mice. RESEARCH DESIGN AND METHODS--We established an insulin promoter-driven murine PD-L1 transgenic NOD mouse model to directly evaluate the protective effect of an organ-specific PD-L1 transgene against autoimmune diabetes. Transgene expression, insulitis, and diabetic incidence were characterized in these transgenic NOD mice. Lymphocyte development, Th1 cells, and regulatory T-cells were analyzed in these transgenic mice; and T-cell proliferation, adoptive transfer, and islet transplantation were performed to evaluate the PD-L1 transgene-mediated immuneprotective mechanisms. RESULTS--The severity of insulitis in these transgenic mice is significantly decreased, disease onset is delayed, and the incidence of diabetes is markedly decreased compared with littermate controls. NOD/SCID mice that received lymphocytes from transgenic mice became diabetic at a slower rate than mice receiving control lymphocytes. Moreover, lymphocytes collected from recipients transferred by lymphocytes from transgenic mice revealed less proliferative potential than lymphocytes obtained from control recipients. Transgenic islets transplanted in diabetic recipients survived moderately longer than control islets. CONCLUSIONS--Our results demonstrate the protective potential of transgenic PD-L1 in autoimmune diabetes and illustrate its role in downregulating diabetogenic T-cells in NOD mice. Diabetes 57:1861-1869, 2008, Programmed death 1 (PD-1) is an immunoreceptor of the CD28/CTLA-4 family whose expression is induced in activated T- and B-cells and in macrophages (1,2). PD-1 has two cytoplasmic tyrosine motifs: [...]

Published
2008

23. Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

Author

Tsay Jwu-Guh, Weng Bor-Chun, Chang Yung-Fu, Chen Shu-Wun, Chu Chi-Hong, Chiu Cheng-Hsun, Lin Jui-Ming, Chiou Chien-Shun, Chen Chyi-Liang, Liu Chien-Hsing, and Chu Chishih

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Nontyphoidal Salmonella is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 Salmonellae isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE) and antibiotic resistance profiles of Salmonella enterica serovars Bareilly (S. Bareilly) and Braenderup (S. Braenderup) were compared, and multi-drug resistance (MDR) plasmids were characterized. Results Over 95% of human salmonellosis in Taiwan was caused by five Salmonella serogroups: B, C1, C2-C3, D1, and E1. S. Typhymurium, S. Enteritidis, S. Stanley and S. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 Salmonellae. The prevalence was decreasing for S. Choleraeuis and S. Braenderup, and S. Virchow and increasing for S. Bareilly. S. Braenderup mainly caused gastroenteritis in children; in contrast, S. Bareiley infected children and elderly people. Both serovars differed by XbaI-PFGE patterns. Almost all S. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in S. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, blaTEM, IS26, and a class 1 integron with the genes dfrA12-orfF-aadA2-qacEΔ1-sulI. Type 2 plasmids belonged to incompatibility group IncI, contained tnpA-blaCMY-2-blc-sugE genetic structures and lacked both IS26 and class 1 integrons. Although type 2 plasmids showed higher conjugation capability, type 1 plasmids were the predominant plasmid. Conclusions Serogroups B, C1, C2-C3, D1, and E1 of Salmonella caused over 95% of human salmonellosis. Two prevalent serovars within serogroup C1, S. Bareilly and cluster B of S. Braenderup, were clonal and drug-susceptible. However, cluster A of S. Braenderup was MDR and probably derived from susceptible isolates by acquiring one of two distinct conjugative R plasmids.

Published
2009
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24. Site-directed in vitro immunization leads to a complete human monoclonal IgG4λ that binds specifically to the CDR2 region of CTLA-4 (CD152) without interfering the engagement of natural ligands

Author

Hsu Shu-Ching, Chen Han-Min, Chu Chishih, Chin Li-Te, Weng Bor-Chun, and Chu Chi-Hong

Subjects
Biotechnology, TP248.13-248.65
Abstract

Abstract Background The ability to acquire fully human monoclonal antibodies (mAbs) with pre-defined specificities is critical to the development of molecular tags for the analysis of receptor function in addition to promising immunotherapeutics. Yet most of the arriving affinity maturated and complete human immunoglobulin G (IgG) molecules, which are actually derived from single human B cells, have not widely been used to study the conserved self antigens (Ags) such as CD152 (cytotoxic T lymphocyte antigen-4, CTLA-4) because proper hosts are lacking. Results Here we developed an optimized protocol for site-directed in vitro immunizing peripheral blood mononuclear cells (PBMC) by using a selected epitope of human CD152, an essential receptor involved in down-regulation of T cell activation. The resultant stable trioma cell lines constantly produce anti-CD152 mAb (γ4λhuCD152), which contains variable (V) regions of the heavy chain and the light chain derived from the VH3 and Vλ human germline genes, respectively, and yet displays an unusual IgG4 isotype. Interestingly, γ4λhuCD152 has a basic pI not commonly found in myeloid monoclonal IgG4λs as revealed by the isoelectric focusing (IEF) analysis. Furthermore, γ4λhuCD152 binds specifically, with nanomolar affinity, to an extracellular constituency encompassing the putative second complementarity determining region (CDR2) of CD152, whereby it can react to activated CD3+ cells. Conclusion In a context of specific cell depletion and conditioned medium,in vitro induction of human Abs against a conserved self Ag was successfully acquired and a relatively basic mAb, γ4λhuCD152, with high affinity to CDR2 of CD152 was thus obtained. Application of such a human IgG4λ mAb with designated CDR2 specificity may impact upon and prefer for CD152 labeling both in situ and ex situ, as it does not affect the binding of endogenous B7 ligands and can localize into the confined immunological synapse which may otherwise prevent the access of whole IgG1 molecules.

Published
2007
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25. A Proteomics-Based Translational Approach Reveals an Antifolate Resistance Inherent in Human Plasma Derived from Blood Donation

Author

Chin, Li-Te, Huang, Pei-Ru, Hu, Kuang-Yu, Huang, Nai-Kuei, Chiu, Cheng-Di, Hour, Ai-Ling, Shui, Hao-Ai, Chu, Chi-Hong, and Chen, Han-Min

Abstract

The inhibition of dihydrofolate reductase (DHFR) by antifolates is a common practice both in cell culture and in chemotherapy. Surprisingly, antifolate resistance was also observed in cultured murine myeloma cells (SP2/0) in the presence of human plasma (HP); thus, we used a proteomic approach to identify novel plasma biomarker(s) for this condition. In contrast to the in vitroantifolate response, metabolic enzymes and translation machinery proteins were found to be up-regulated in the presence of HP. The antifolate resistance inherent in HP may be explained by a simultaneous promotion of cell proliferation and the maintenance of DNA integrity. Furthermore, the factor(s) was found to be extrinsic, heat stable and very small in size. Adenine, a supplemented additive in erythrocyte preservation, was subsequently identified as the contributing factor and exogenous addition in cultures reversed the cytotoxicity induced by antifolates. Importantly, adenine-containing blood components, which may provide enhanced survival to otherwise sensitive antifolate-targeted cells, showed a dose-dependent adverse effect in transfusion recipients receiving antifolate (methotrexate) medications. These findings not only highlight a previously unnoticed role of adenine, but also emphasize a novel mechanistic link between transfusion and subsequently reduced survival in patients taking methotrexate.

Published
2024
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26. Management for primary thyroid lymphoma: Experience from a single tertiary care centre in Taiwan

Author

Wu, Si-Yuan, Chu, Chi-Hong, Duh, Quan-Yang, Hsieh, Chung-Bao, Yu, Jyh-Cherng, and Shih, Ming-Lang

Abstract

Diverse treatments are available for different histological types of thyroid lymphoma: concurrent chemoradiotherapy for diffuse large B cell lymphoma (DLBCL) and radiotherapy or thyroidectomy for low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. However, diagnosing lymphomas before operation is difficult, because the diagnostic yield of fine-needle biopsies is limited by the rarity of the disease. Therefore, patients may undergo unnecessary thyroidectomies.

Published
2024
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27. Prognostic role of lymphovascular invasion and lymph node status among breast cancer subtypes

Author

Yu, Jyh-Cherng, primary, Liao, Guo-Shiou, additional, Hsu, Huan-Ming, additional, Chu, Chi-Hong, additional, Hong, Zhi-Jie, additional, Fu, Chun-Yu, additional, Chou, Yu-Ching, additional, Golshan, Mehra, additional, Dai, Ming-Shen, additional, Chen, Teng-Wei, additional, De-Chian, Chan, additional, Tsai, Wan-Chen, additional, Pan, Chao-Wen, additional, Hsu, Kuo-Feng, additional, Kao, En-Nung, additional, Hsu, Yi-Chih, additional, and Chang, Tsun-Hou, additional

Published
2018
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48. Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

Author

Chiou, Chien-Shun, primary, Lin, Jui-Ming, additional, Chiu, Cheng-Hsun, additional, Chu, Chi-Hong, additional, Chen, Shu-Wun, additional, Chang, Yung-Fu, additional, Weng, Bor-Chun, additional, Tsay, Jwu-Guh, additional, Chen, Chyi-Liang, additional, Liu, Chien-Hsing, additional, and Chu, Chishih, additional

Published
2009
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