Synthesis and Cytotoxicity of Novel 3-Amino-4-indolylmaleimide Derivatives

Sheng-Yin Zhao,Yan-Wu Yang,Hai-Quan Zhang,Yun Yue,Mei Fan 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4

In an attempt to develop potent and selective antitumor agents, a series of novel 3-amino-4-indolylmaleimides were designed and synthesized. The reaction showed high regioselectivity. The structure of compound 7a was determined by an X-ray single crystal diffraction method. The cytotoxicities of the title compounds were evaluated against HeLa, SMMC 7721 and HL 60 cancer cell lines by a standard MTT assay in vitro. The pharmacological results showed that some of the title compounds displayed moderate or high cytotoxic activity against the tested cell lines. Compound 7d was the most promising compound against the tested cancer cell lines. Structure-activity relationships are discussed based on the experimental data obtained. A hydroxyethylamino group at the 3-position in the side chain of indolylmaleimide is associated with an increase in cytotoxicity.

CHMP1A suppresses the growth of renal cell carcinoma cells via regulation of the PI3K/mTOR/p53 signaling pathway

Wu Youping,Wu Yueguo,Xu Cong,Sun Wei,You Zhenqiang,Wang Yin,Zhang Sheng 한국유전학회 2022 Genes & Genomics Vol.44 No.7

Background: CHMP1A, a member of the ESCRT-III complex family, has been indicated as a brand-new inhibitor gene of tumors. Our previous research has revealed that CHMP1A plays a vital role in the development and progression of renal cell carcinoma (RCC). Objective: To investigate the potential target pathway of the regulation of the tumor cell growth by CHMP1A. Methods: The effect of CHMP1A on mTOR pathway was elucidated by western blotting. The effect of CHMP1A on the expression of p53 was evaluated, and A498 cell growth was assessed by colony formation and MTT assays. The expression of p53 was knocked down by shRNA-p53, and the effect of CHMP1A on mTOR after knockdown of p53 was evaluated. The effect of CHMP1A on apoptosis and its relationship with MDM2 pathway were detected by western blotting and FCM. Finally, the relationship between the regulation of p53 by CHMP1A and the PI3K/mTOR pathway was detected. Results: This study showed that the mTOR pathway was suppressed significantly in CHMP1A-overexpressing A498 and 786-0 cells; moreover, the enhanced expression of p53 and the reduced proliferation were shown in CHMP1A-overexpressing A498 cells. Furthermore, CHMP1A was able to regulate the PI3K/PTEN/mTOR and MDM2/p53 pathways in order to suppress RCC. In addition, CHMP1A regulated Bax and Bcl-2 via MDM2/p53 to induce the apoptosis of tumor cells and upregulated the expression of p53 via the PI3K/mTOR pathway. Conclusions: The results convey that CHMP1A-related suppression of RCC is closely related to the PI3K/mTOR/p53 pathway.

Effects of Ginsenosides Rg1 on Osteoblasts Cultured with Ti Particles

( Yu Lin ),( Yin Sheng Wu ),( Jia Cheng He ),( Yun Mei Huang ),( Yan Ping Lin ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.1

The aim of this study was to explore the role and effect of ginsenosides Rg1 on osteoblasts cultured with Ti particles. Osteoblasts from neonatal rats were cultured with particles and different doses of Rg1, the main active ingredient in ginsenosides Rg1. We found that the COX-2, PGE2, TNF-α, IL-1, and IL -6 concentrations in the medium of cells cultured with Ti particles significantly increased as compared with that of the control cells (p<0.05 or p<0.01). In addition, cells cultured with Ti particles alone exhibited the highest concentrations of these molecules. The PGE2, TNF-α, IL-1, and IL-6 levels in the medium of cells cultured with Rg1 were in between those of the control cells and the cells cultured with Ti particles alone. The IL-1ra level in the group cultured with Ti and medium-dose Rg1 was the highest followed by the cells cultured with Ti and high-dose Rg1 and those cultured with Ti and low-dose Rg1 (p<0.05). In conclusion, ginsenosides can reduce the levels of inflammatory cytokines produced by osteoblasts on induction with Ti particles and can prevent prosthesis loosening.

Physical properties and chemical composition of the cores in the California molecular cloud

Zhang, Guo-Yin,Xu, Jin-Long,Vasyunin, A. I.,Semenov, D. A.,Wang, Jun-Jie,Dib, Sami,Liu, Tie,Liu, Sheng-Yuan,Zhang, Chuan-Peng,Liu, Xiao-Lan,Wang, Ke,Li, Di,Wu, Zhong-Zu,Yuan, Jing-Hua,Li, Da-Lei,Gao, Springer-Verlag 2018 Astronomy and astrophysics Vol.620 No.-

<P><I>Aims.</I> We aim to reveal the physical properties and chemical composition of the cores in the California molecular cloud (CMC), so as to better understand the initial conditions of star formation.</P><P><I>Methods.</I> We made a high-resolution column density map (18.2′′) with <I>Herschel</I> data, and extracted a complete sample of the cores in the CMC with the fellwalker algorithm. We performed new single-pointing observations of molecular lines near 90 GHz with the IRAM 30m telescope along the main filament of the CMC. In addition, we also performed a numerical modeling of chemical evolution for the cores under the physical conditions.</P><P><I>Results.</I> We extracted 300 cores, of which 33 are protostellar and 267 are starless cores. About 51% (137 of 267) of the starless cores are prestellar cores. Three cores have the potential to evolve into high-mass stars. The prestellar core mass function (CMF) can be well fit by a log-normal form. The high-mass end of the prestellar CMF shows a power-law form with an index <I>α</I> = −0.9 ± 0.1 that is shallower than that of the Galactic field stellar mass function. Combining the mass transformation efficiency (<I>ε</I>) from the prestellar core to the star of 15 ± 1% and the core formation efficiency (CFE) of 5.5%, we suggest an overall star formation efficiency of about 1% in the CMC. In the single-pointing observations with the IRAM 30m telescope, we find that 6 cores show blue-skewed profile, while 4 cores show red-skewed profile. [HCO<SUP>+</SUP>]/[HNC] and [HCO<SUP>+</SUP>]/[N2H<SUP>+</SUP>] in protostellar cores are higher than those in prestellar cores; this can be used as chemical clocks. The best-fit chemical age of the cores with line observations is ~5 × 10<SUP>4</SUP> yr.</P>

Impact Deformation Behavior of Duplex and Superaustenitic Stainless Steels Welds by Split Hopkinson Pressure Bar

Shing-Hoa Wang,Chih-Sheng Huang,Woei-Shyan Lee,Tao-Hsing Chen,Chia-Chang Wu,Hung-Yin Tsai,Charles Lien 대한금속·재료학회 2009 METALS AND MATERIALS International Vol.15 No.6

A considerable volume of γ phase increases in the fusion zone (weld metal) for two duplex stainless steels after a high-strain-rate impact. The strain-induced γ phase formation in the fusion zone results in local hardness variation depending on the strain rate. The α phase content in the fusion zone decreases as the impact strain rate increases for SAF 2205 DSS and SAF 2507 DSS. The results of the two-phase content measured by Ferritoscope correspond to that assessed by image analyses. In contrast, superaustenite stainless steel is unaffected by such an impact owing to its fully stable austenization. Impacted welds at a high strain rate of 5 × 10 3 s−1 reveal feather-like surface creases along the solidified curved columnar grain boundaries. The apparent surface creases are formed due to the presence of diffuse Lüders bands, which are caused by heavy plastic deformation in coarse-grain materials. A considerable volume of γ phase increases in the fusion zone (weld metal) for two duplex stainless steels after a high-strain-rate impact. The strain-induced γ phase formation in the fusion zone results in local hardness variation depending on the strain rate. The α phase content in the fusion zone decreases as the impact strain rate increases for SAF 2205 DSS and SAF 2507 DSS. The results of the two-phase content measured by Ferritoscope correspond to that assessed by image analyses. In contrast, superaustenite stainless steel is unaffected by such an impact owing to its fully stable austenization. Impacted welds at a high strain rate of 5 × 10 3 s−1 reveal feather-like surface creases along the solidified curved columnar grain boundaries. The apparent surface creases are formed due to the presence of diffuse Lüders bands, which are caused by heavy plastic deformation in coarse-grain materials.

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study

Ting-Yan Shi,Sheng Yin,Jianqing Zhu,Ping Zhang,Jihong Liu,Libing Xiang,Yaping Zhu,Sufang Wu,Xiaojun Chen,Xipeng Wang,Yin-Cheng Teng,Tao Zhu,Aijun Yu,Yingli Zhang,Yanling Feng,He Huang,Wei Bao,Yanli Li 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods: SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. Trial Registration: ClinicalTrials.gov Identifier: NCT03983226

Surgical Outcomes and Predictive Factors in Patients With Detrusor Underactivity Undergoing Bladder Outlet Obstruction Surgery

Ming-Syun Chuang,Yin-Chien Ou,Yu-Sheng Cheng,Kuan-Yu Wu,Chang-Te Wang,Yuan-Chi Huang,Yao-Lin Kao 대한배뇨장애요실금학회 2024 International Neurourology Journal Vol.28 No.1

Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes.Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery.Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor.Conclusions: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention. Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. Conclusions: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Treatment Efficacy and Prognostic Factors for Huge HCC Based on Barcelona Clinic Liver Cancer Staging

Zhang, Zhi-Ming,Zhang, Yu-Mei,Gao, Sheng,Yuan, Wei-Ping,Zhao, Yin-Nong,Xiang, Bang-De,Wu, Fei-Xiang,Wu, Guo-Bin,Liu, Jian-Yong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Objective: To explore the most appropriate treatment for patients with hepatocellular cancer (HCC) >10 cm by using the Barcelona Clinic Liver Cancer (BCLC) classification. Materials and Methods: A total of 124 HCC patients undergoing surgery were selected. Disease-free survival (DFS), overall survival (OS) and prognostic factors were respectively assessed. Results: This study showed that the cumulative 1-, 3-, 5-year survival rates were 79.7%, 59.8% and 41.6% in BCLC-A patients, 76.2%, 9.5% and 0% in BCLC-B patients and 44.9%, 0% and 0% in BCLC-C patients, respectively. The 1-, 3-, 5-year DFS rates were 49%, 24.5% and 9.1% in BCLC-A patients, 7.5%, 0% and 0% in BCLC-B patients, respectively. No BCLC-C patients survived 1 year after surgery. Multivariate analysis indicated that hepatitis B surface antigen (HBsAg), vascular invasion, intra-hepatic metastasis, curative resection, tumor rupture and pathologic differentiation were independent prognostic factors. Conclusions: Surgery is effective and safe for patients with HCC >10 cm with sufficient hepatic reserve.

Magnetoresistance Effect in Co<SUB>x</SUB>(Alq₃)<SUB>1-x</SUB> Granular Films

Gang Ni,Qi Shu,Xiaomeng Zhao,Junqi Wu,Peng Sheng,Jianfang Yin,Bin Ma,Wei Huang,Youwei Du 한국자기학회 2007 한국자기학회 학술연구발표회 논문개요집 Vol.- No.-

Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study

Duo Huang,Emmanuel Wong,Ming-Liang Zuo,Pak-Hei Chan,Wen-Sheng Yue,Hou-Xiang Hu,Ling Chen,Li-Xue Yin,Xin-Wu Cui,Ming-Xiang Wu,Xi Su,Chung-Wah Siu,Jo-Jo Hai 대한혈액학회 2019 Blood Research Vol.54 No.3

BackgroundPrevious Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum peri-od in the Chinese population. We investigated the risk of venous thromboembolism in a “real-world” cohort of pregnant Chinese women with no prior history of venous thromboembolism.MethodsIn this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed.ResultsThe mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29‒36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pul-monary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester.ConclusionChinese women had a substantially lower risk of venous thromboembolism during preg-nancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early preg-nancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.