Weekly topotecan chemotherapy in the treatment of recurrent ovarian cancer patients

( Wan Yi Huang ),( Wen Fang Cheng ),( Chang Yao Hsieh ),( Chi An Chen ) 대한산부인과학회 2007 대한산부인과학회 학술대회 Vol.93 No.-

Public Service Motivation and Perception of Self-efficacy: An Empirical Study in Taiwan

( Irving Yi Feng Huang ),( Wan Ling Huang ) 한국행정학회 2011 한국행정학회 학술발표논문집 Vol.2011 No.-

The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

Enhancement of Immunotherapeutic Effects of HPV16E7 on Cervical Cancer by Fusion with CTLA4 Extracellular Region

Yi Zheng,Yijuan Zhang,Yuandong Ma,Jun Wan,Chaofan Shi,Laiqiang Huang 한국미생물학회 2008 The journal of microbiology Vol.46 No.6

Cervical cancer is caused by infection by high-risk human papillomavirus (HPV), especially HPV16. Limitations in current treatments of cervical cancers call for the development of new and improved immunotherapies. This study aims at investigating the efficacy of a novel vaccine consisting of modified HPV 16E7 fused with human cytotoxic T-lymphocyte antigen 4 (CTLA4). The regions in HPV16 E7 gene associated with its transformation and CTL-enhanced response were modified; the resultant HPV16mE7 was fused with extracellular region of CTLA4 to generate HPVm16E7-eCTLA4 fusion protein. Binding of this fusion protein to B7 molecules expressed on antigen presenting-cells (APCs) was demonstrated. C57BL/6 (H-2b) mice immunized with low dose of the fusion protein (10 μg) produced higher titer antibody and stronger specific CTL response, and expressed higher levels of IFN-γ and IL-12, compared with those immunized with HPVm16E7 only or admixture of HPVm16E7 and CTLA4, or PBS; and were protected from lethal dose tumor challenge. Tumor growth was retarded and survival prolonged in mouse models with the fusion protein treatment. Our results demonstrate that fusion of HPV16 E7 with eCTLA4 targeting APCs resulted in enhanced immunity, and that this fusion protein may be useful for improving the efficacy of immunotherapeutic treatments of cervical cancer and other HPV16 infection-associated tumors.

Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

Zhang, Yi,Wang, Peng,Zhou, Xing-Chun,Bao, Guo-Qiang,Lyu, Zhuo-Ming,Liu, Xiao-Nan,Wan, Shao-Gui,He, Xian-Li,Huang, Qi-Chao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Background: Hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-$1{\alpha}$ has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. Materials and Methods: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. Results: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. Conclusions: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.

Development of a Serum-Free Culture Method for Endothelial Cells of the Stria Vascularis and Their Pro-inflammatory Secretome Changes Induced by Oxidative Stress

Ying Yi,Shu-Bin Fang,Guan-Xia Xiong,Xian-Ren Wang,Hui-Ting Chen,Wan-Yi Huang,Li-Xuan Feng 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.1

Objectives. Reactive oxygen species in the stria vascularis (SV) of the cochlea may be involved in the pathogenesis of sen-sorineural hearing loss. However, the effects of oxidative stress on SV endothelial cells (SV-ECs) remain largely un-known, and no feasible in vitro cell culture model exists for the functional study of SV-ECs. Methods. We isolated primary SV-ECs from the SV of neonatal mice. The apoptosis-reducing effects of fibronectin in SV-ECs cultured with serum-free medium were determined using β-galactosidase staining and flow cytometry. SV-ECsincubated in serum-free medium were treated with various H2O2 concentrations to evaluate the effects of H2O2 ontheir viability. The secretome of SV-ECs treated with or without H2O2 (100 μM or 500 μM) was analyzed using high-resolution mass spectrometry. The function of the SV-EC secretome was evaluated by a macrophage assay. Results. We successfully isolated and characterized the SV-ECs. Treatment with H2O2 at concentrations up to 500 μM for2 hours and further incubation with serum-free medium in plates precoated with fibronectin showed no significanteffect on apoptosis. Compared to the control SV-ECs, the amount of differential proteins in the secretome of SV-ECsstimulated with 500 μM H2O2 was much higher than in those treated with 100 μM H2O2. Kyoto Encyclopedia ofGenes and Genomes and Gene Ontology analyses suggested that the proteins differentially expressed in SV-ECstreated with 500 μM H2O2 were involved in the regulation of multiple signaling pathways and cellular processes. Thesecretome of H2O2-stimulated SV-ECs exhibited significant pro-inflammatory effects on macrophages. Conclusion. We successfully established an in vitro serum-free culture method, identified the differential proteins releasedby oxidative stress-induced ECs and their functions, and revealed the pro-inflammatory effects of the secretome ofH2O2-stimulated SV-ECs. Therefore, SV-ECs might elicit immunoregulatory effects on bystander cells in the microen-vironment of oxidative stress-induced cochlea, especially cochlear macrophages.

Examining the effect of spatial distribution of disintegrant particles on tablet disintegratability

Zheng Audrey Yi,Huang Wei Wei,Poon Li Ying Jolene,Wong Eunice Siying,Heng Paul Wan Sia,Chan Lai Wah 한국약제학회 2024 Journal of Pharmaceutical Investigation Vol.54 No.2

Purpose Superdisintegrants are typically used at low concentrations in tablets. As a result, the spatial distribution of disintegrant particles within the tablet may be inhomogeneous, resulting in varied disintegration times. This study aimed to investigate the effect of disintegrant spatial distribution on tablet disintegratability. Methods Tablets with various degrees of disintegrant spatial distribution were engineered using a novel experimental design. The effects of relative spatial distribution of disintegrant particles on tablet tensile strength, liquid penetration rate and disintegration time were investigated. Results It was observed that increased clustering of disintegrant particles generally promoted faster tablet disintegration due to more localized swelling and strain recovery of sodium starch glycolate and crospovidone, respectively. However, for tablets with insoluble fillers and sodium starch glycolate, a high degree of disintegrant clustering prolonged disintegration due to the formation of gel plugs which impeded liquid penetration into the tablet and caused the tablet to break up into floccules instead. Tablets made with insoluble fillers were also found to be more sensitive to changes in disintegrant spatial distribution compared to those containing soluble fillers. Conclusion Overall, the effects of disintegrant spatial distribution were dependent on the type of disintegrant and filler used.

Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract

Xiu-Feng Huang,Lue Xiang,Wan Cheng,Fei-Fei Cheng,Kai-Wen He,Bo-Wen Zhang,Si-Si Zheng,Ru-Yi Han,Yi-Han Zheng,Xiao-Tao Xu,Huan-Yun Yu,Wenjuan Zhuang,Yuk Fai Leung,Zi-Bing Jin 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p. R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholinooligonucleotide- induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.

Adaptive OFDMA with Partial CSI for Downlink Underwater Acoustic Communications

Yuzhi Zhang,Yi Huang,Lei Wan,Shengli Zhou,Xiaohong Shen,Haiyan Wang 한국통신학회 2016 Journal of communications and networks Vol.18 No.3

Multiuser communication has been an important researcharea of underwater acoustic communications and networking. This paper studies the use of adaptive orthogonal frequencydivisionmultiple access (OFDMA) in a downlink scenario, wherea central node sends data to multiple distributed nodes simultaneously. In practical implementations, the instantaneous channelstate information (CSI) cannot be perfectly known by the centralnode in time-varying underwater acoustic (UWA) channels, due tothe long propagation delays resulting from the low sound speed. In this paper, we explore the CSI feedback for resource allocation. An adaptive power-bit loading algorithm is presented, which assignssubcarriers to different users and allocates power and bits toeach subcarrier, aiming to minimize the bit error rate (BER) underpower and throughput constraints. Simulation results show considerableperformance gains due to adaptive subcarrier allocationand further improvement through power and bit loading, as comparedto the non-adaptive interleave subcarrier allocation scheme. In a lake experiment, channel feedback reduction is implementedthrough subcarrier clustering and uniform quantization. Althoughthe performance gains are not as large as expected, experiment resultsconfirm that adaptive subcarrier allocation schemes based ondelayed channel feedback or long term statistics outperform theinterleave subcarrier allocation scheme.

Prognostic Values of Various Clinical Factors and Genetic Subtypes for Diffuse Large B-cell lymphoma Patients: A Retrospective Analysis of 227 Cases

Zhou, De,Xie, Wan-Zhuo,Hu, Ke-Yue,Huang, Wei-Jia,Wei, Guo-Qing,He, Jing-Song,Shi, Ji-Min,Luo, Yi,Li, Li,Zhu, Jing-Jing,Zhang, Jie,Lin, Mao-Fang,Ye, Xiu-Jin,Cai, Zhen,Huang, He Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-cell lymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectively reviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), ${\beta}2$-microglobulin (${\beta}2$-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predicting the prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-cell-like (GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOP management, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%, P=0.288). Conclusion: Elevated LDH and ${\beta}2$-M levels, positive B symptoms, Ann Arbor stage III/IV, and primary nodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have a better prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment with the addition of rituximab can improve the prognosis of patients with DLBCL.