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Lai, Whalen, and Chan Hok-lam. "Liu Po-wen yu No-chan Ch'eng [Liu Po-wen and the No-chan City: A Legend of the Building of Peking]." Asian Folklore Studies 56, no. 1 (1997): 178. http://dx.doi.org/10.2307/1178800.
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Rošker, Jana S. "Chan ali zen?" Ars & Humanitas 16, no. 2 (December 29, 2022): 91–109. http://dx.doi.org/10.4312/ars.16.2.91-109.
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Šola budistične meditacije, ki predstavlja transformacijo Bodhidharmovih naukov in ki je tipična za teorije in prakse vzhodnoazijskega budizma, je na Zahodu znana pod pojapončenim imenom zen. Le malo ljudi se zaveda dejstva, da gre pri tej šoli za specifično vrsto kitajskega budizma, ki se izvorno imenuje chan 禅. Ker pa se ta pismenka v japonščini izgovarja kot zen, se je japonski prevod imena te šole udomačil v Evropi 19. stoletja, ko je v procesu kolonializacije in modernizacije Vzhodne Azije Japonska predstavljala most med Evropo in vzhodnoazijsko regijo. Medtem ko se je ta meditacijska šola na Kitajskem osnovala in razvijala od 6. stoletja dalje, segajo korenine pojapončenega chana, ki se je na Japonskem razvil pod imenom zen, šele v 12. stoletje, ko ga je po svojem obisku Kitajske na Japonskem predstavil in razširil budistični menih Myōan Eisai. Pričujoči članek namerava zapolniti to vrzel v evropskem poznavanju vzhodnoazijskega budizma in popraviti napačne predstave o izvoru in naravi omenjene budistične šole. V ta namen na kratko predstavi zgodovino kitajskega budizma chan ter razloži njegov nastanek in razvoj, ki je osnovan na sintezi budizma, daoizma in izvornega konfucijanstva.
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Harris, Amanda, Suzanne Belton, Lesley Barclay, and Jenny Fenwick. "Midwives in China: ‘jie sheng po’ to ‘zhu chan shi’." Midwifery 25, no. 2 (April 2009): 203–12. http://dx.doi.org/10.1016/j.midw.2007.01.015.
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Pach, Janina. "Znaczenie małych i średnich przedsiębiorstw w Polsce po 2000 r." Przedsiębiorczość - Edukacja 4 (January 1, 2008): 92–109. http://dx.doi.org/10.24917/20833296.4.8.
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Small and middle enterprises (SME) are the basic part of the economy in European Unionincluding Poland. Typical feature of them are: high level of flexibility in adaptation to the chan-ges in business environment, strong motivation of entrepreneurs because of the relation betweenprofitability of an enterprise and income of its owner, high efficiency of prospering of SME thatcorresponds to the big financial discipline that dominates in SME sector and low absorptionof capital in the production areas.All these characteristics cause SME sector plays very important role in increasing GrossDomestic Product and added value as well as in increasing the employment. In 2004 the numberof active enterprises of this sector in Poland was estimated to over 1 690 000 which was the99,8% of all enterprises in this country. The number of employees in Polish SME sector in 2005was about 8234,1 that was over 71% of total number of employees working in all the enterprises.Moreover, in 2005 the SME sector generated 47,7% of gross domestic product and 54,2% of ad-ded value. It should be emphasized that importance of micro, middle and small enterprises wasdifferent in particular sectors of economy like: industrial processing, trade, constructions, ho-tels and restaurants, transport etc.Unfortunately, some problems occurred in development of SME sector, for example: thedecreasing number of active enterprises in total number of registered enterprises, low innovativeness of Polish middle and small enterprises, short time of life, high rate of employment in thegrey zone. It shows the importance of supporting this sector by national or local governmentunder the auspices of EU which formulated the rules of common politics for SME sector. You canfind these regulations in common European SME Policy and European Competition Policy. It isnecessary to remove all barriers to the SME sector progress by reducing off-pay costs, decre-asing taxes, limiting number of concessions and certificates of approval.
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Shen, Chien-Lung, Tzu-Hao Huang, Po-Chun Hsu, Ya-Chi Ko, Fen-Ling Chen, Wei-Chun Wang, Tsair Kao, and Chia-Tai Chan. "Correction to: Respiratory Rate Estimation by Using ECG, Impedance, and Motion Sensing in Smart Clothing." Journal of Medical and Biological Engineering 40, no. 5 (July 23, 2018): 1. http://dx.doi.org/10.1007/s40846-018-0440-8.
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The article “Respiratory Rate Estimation by Using ECG, Impedance, and Motion Sensing in Smart Clothing”, written by Chien-Lung Shen, Tzu-Hao Huang, Po-Chun Hsu, Ya-Chi Ko, Fen-Ling Chen, Wei-Chun Wang, Tsair Kao, Chia-Tai Chan was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 1 July 2017 without open access. After publication in volume [37], issue [6], page [826–842] the authors decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Brzostek, Piotr. "Odpowiedzialność karna za przestępne współdziałanie w prawie angielskim po wyroku R v. Jogee; Ruddock v. The Queen." Studia Iuridica 76 (January 17, 2019): 98–121. http://dx.doi.org/10.5604/01.3001.0012.8612.
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The combined decisions of the UK Supreme Court and Judicial Committee of the Privy Council in R v. Jogee; Ruddock v. The Queen caused upheaval in the English law on criminal complicity. The Supreme Court/Privy Council decided that the law on criminal complicity „took a wrong turn” 33 years ago in the Privy Council ruling in Chan Wing-Siu which concerned a controversial doctrine of parasitic joint enterprise liability. According to the said doctrine, if A and B set out to commit a crime X (e.g. robbery) and B foresees that A might commit crime Y (e.g. murder) in the course of committing crime X, B will be liable for crime Y, even if he does not intend that crime Y be committed. The mere fact of foresight on B’s part is enough for him to be criminally liable. Decision in Jogee; Ruddock is of seminal importance as it overturned the doctrine of parasitic joint enterprise liability. It is doubtful, however, to what extent the Supreme Court has resolved the problems that have bedeviled this area of law. This article presents in outline the English law on criminal complicity and attempts to assess the changes that were introduced in Jogee; Ruddock. A number of issues still call for further refinement and resolution. It appears, however, that the emphasis the Supreme Court put on intention as a required standard of fault, draws, at least superficially, the continental (Polish and German) and English criminal law closer together in terms of mens rea requirements for secondary liability.
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Wong, Chi Hin, Ut Kei Lou, Frederic Khe-Cheong Fung, Joanna H. M. Tong, Ka-Fai To, Stephen Lam Chan, and Yangchao Chen. "Abstract PO-006: CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein." Cancer Research 81, no. 22_Supplement (November 15, 2021): PO—006—PO—006. http://dx.doi.org/10.1158/1538-7445.panca21-po-006.
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Abstract Background & Aims: Circular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC). Methods: CircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1. Results: circRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC. Conclusion: The upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT. Citation Format: Chi Hin Wong, Ut Kei Lou, Frederic Khe-Cheong Fung, Joanna H. M. Tong, Ka-Fai To, Stephen Lam Chan, Yangchao Chen. CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-006.
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Zhu, Hengyan, Liuyang Cai, Zigui Chen, and Jason Y. K. Chan. "Abstract PO-100: Fusobacterium nucleatum promotes epithelial-mesenchymal transition (EMT) of oral squamous cell carcinoma (OSCC) via INHBA-dependent SMAD/Laminin332/PI3K/AKT pathway." Clinical Cancer Research 29, no. 18_Supplement (September 15, 2023): PO—100—PO—100. http://dx.doi.org/10.1158/1557-3265.aacrahns23-po-100.
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Abstract Introduction The enrichment of Fusobacterium nucleatum has been reported in both oral rinses and lesion samples from oral squamous cell carcinoma (OSCC) patients based on several case-control sequencing analyses, but studies on the potential role of F. nucleatum in OSCC tumorigenesis are still limited. In this study, we sought to elucidate the relationship between F. nucleatum and host transcriptome dysregulation in potentially carcinogenic pathways. Method The association between microbiota dysbiosis and host gene transcriptome was profiled by bacterial 16S rRNA V3-V4 amplicon sequencing and host gene long non-coding RNA sequencing (lncRNA-seq) for tumor and adjacent normal (AN) tissues from OSCC patients. Cell migration and invasion assays were performed using the in vitro bacteria-cell co-culture model. EMT-related molecular mechanisms induced by F. nucleatum were further validated by IncRNA-seq, real-time PCR, and western blot for bacteria-infected cells, respectively, at the genetic and proteomic levels. Result Significant enrichment of Fusobacterium was observed in OSCC tumor samples when compared to the paired AN samples. Correlation analysis between mucosal oral bacteria and host transcriptome in the OSCC tumor microenvironment elucidated the positive relationship between Fusobacterium and EMT pathways including significantly upregulated genes INHBA, SNAI2, and LAMC2. Using in-vitro cell models, we further observed that F. nucleatum significantly promoted cell migration and invasion, and significantly dysregulated the expression of several EMT factors including the increased inducer inhibin beta A (INHBA), core regulators SNAI1 (snai1) and SLUG (snai2), effectors vimentin (VIM) and N-cadherin (CDH2), and decreased E-cadherin (CDH1). Following the INHBA/SMAD pathway induced by F. nucleatum infection, the expression of an essential extracellular matrix glycoprotein, Laminin 332, was dramatically enhanced, which may trigger the phosphorylation of phosphatidylinositol 3-kinase and AKT kinase in the downstream PI3K/AKT pathway for the promoted cell migration and invasion ability. Conclusion Our study confirms the enrichment of Fusobacterium in the OSCC tumor microenvironment and reveals that F. nucleatum infection induces the INHBA/SAMD pathway and subsequently increases Laminin 332 expression, which may further promote the phosphorylation of PI3K/AKT and enhance OSCC migration and invasion. Citation Format: Hengyan Zhu, Liuyang Cai, Zigui Chen, Jason Y. K. Chan. Fusobacterium nucleatum promotes epithelial-mesenchymal transition (EMT) of oral squamous cell carcinoma (OSCC) via INHBA-dependent SMAD/Laminin332/PI3K/AKT pathway [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-100.
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Chan, Anthony T. C., Victor Ho Fun Lee, Ruey-Long Hong, Myung-Ju Ahn, Wan Qin Chong, Anna Spreafico, Sung-Bae Kim, et al. "Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122." Clinical Cancer Research 29, no. 18_Supplement (September 15, 2023): PO—008—PO—008. http://dx.doi.org/10.1158/1557-3265.aacrahns23-po-008.
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Abstract Introduction: Plasma Epstein-Barr virus (EBV) DNA has been shown to be a sensitive and specific biomarker for prognosis, surveillance of recurrence, and treatment response of nasopharyngeal cancer (NPC). The phase 3 KEYNOTE-122 trial (NCT02611960) was conducted to evaluate pembrolizumab (pembro) vs standard of care (SOC) chemotherapy (chemo) in patients with platinum-pretreated recurrent/metastatic (R/M) NPC. This exploratory analysis was designed to evaluate association between plasma EBV DNA load and clinical response in patients treated with pembro or SOC in KEYNOTE-122. Materials and Methods: Patients who received ≥1 prior platinum-based chemo with histologically confirmed EBV-positive R/M NPC measurable per RECIST v1.1 and an ECOG PS ≤1, were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for ≤35 cycles or investigator’s choice of SOC chemo (capecitabine, gemcitabine, or docetaxel). Association between baseline plasma EBV DNA load, as measured using a high-sensitivity qPCR assay, and clinical outcomes (ORR, PFS, OS) was evaluated within each treatment arm. Significance of continuous EBV DNA load was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included association between clinical outcomes and plasma EBV DNA load fold change from baseline at cycle 2, day 1 (C2D1), after baseline adjustment, and descriptive comparison between baseline plasma EBV DNA load and tumor volume in predicting clinical outcomes. Clinical data cutoff: November 30, 2020. Results: 215/228 (94.3%) treated patients had evaluable plasma EBV DNA load data at baseline (pembro, 111; SOC, 104). Baseline plasma EBV DNA load (as a continuous variable) was significantly associated with PFS and OS for pembro and SOC (both P < 0.005) but not ORR (P = 0.105, pembro; 0.473, SOC). Association between plasma EBV DNA load fold change from baseline at C2D1 and ORR, PFS, or OS was P ≤ 0.005 for both pembro and SOC. Baseline plasma EBV DNA load was numerically more predictive of OS and PFS than tumor volume for both pembro (C index [95% CI]: EBV DNA [OS: 0.71, 0.64-0.77; PFS: 0.67, 0.60-0.74] vs tumor volume [OS: 0.47, 0.41-0.54; PFS: 0.42, 0.35-0.49]) and SOC (EBV DNA [OS: 0.67, 0.60-0.73; PFS: 0.64, 0.56-0.71] vs tumor volume [OS: 0.58, 0.51-0.65; PFS: 0.54, 0.46-0.62]). Conclusions: In this post hoc exploratory analysis of KEYNOTE-122, higher baseline plasma EBV DNA load was negatively associated with PFS and OS in patients with NPC treated with pembro or SOC. Independent of baseline association, a larger decrease in plasma EBV DNA load at C2D1 relative to baseline was associated with improved clinical outcomes to both treatments. EBV DNA was more predictive of clinical outcomes than tumor volume. While definitive conclusions are limited, these findings provide additional support for plasma EBV DNA as a prognostic biomarker for NPC, which could guide treatment decisions. Citation Format: Anthony T. C. Chan, Victor Ho Fun Lee, Ruey-Long Hong, Myung-Ju Ahn, Wan Qin Chong, Anna Spreafico, Sung-Bae Kim, Gwo Fuang Ho, Priscilla B. Caguioa, Nuttapong Ngamphaiboon, Ramona F. Swaby, Bo Wei, Andrea Webber, John Kang, Burak Gumuscu, Jianda Yuan, Lillian Siu. Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-008.
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Rickards, Guy. "Music by women composers." Tempo 59, no. 234 (September 21, 2005): 66–72. http://dx.doi.org/10.1017/s0040298205300325.
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HOWELL: Violin Sonata in F minor; Rosalind for violin & piano; Piano Sonata in E minor; Humoresque for piano; 5 Studies for piano. Lorraine McAslan (vln), Sophia Rahman (pno). Dutton Epoch CDLX 7144.BACEWICZ: Violin Sonatas Nos. 4–5; Oberek No. 1; Sonata No. 2 for violin solo; Partita; Capriccio; Polish Capriccio. Joanna Kurkowicz (v;n), Gloria Chien (pno). Chandos CHAN 10250.MARIC: Byzantine Concerto1; Cantata: Threshold of Dream2,3,6; Ostinato Super Thema Octoïcha4–6; Cantata: Song of Space7. 1Olga Jovanovic (pno), Belgrade PO c. Oskar Danon, 2Dragoslava Nikolic (sop, alto), 3Jovan Milicevic (narr), 4Ljubica Maric (pno), 5Josip Pikelj (hp), 6Radio-TV Belgrade CO c. Oskar Danon, 7Radio-TV Belgrade Mixed Choir & SO c. Mladen Jagušt. Chandos Historical 10267H.MUSGRAVE: For the Time Being: Advent1; Black Tambourine2–3; John Cook; On the Underground Sets1–3. 1Michael York (narr), 2Walter Hirse (pno), 3Richard Fitz, Rex Benincasa (perc),New York Virtuoso Singers c. Harold Rosenbaum. Bridge 9161.KUI DONG: Earth, Water, Wood, Metal, Fire1; Pangu's Song2; Blue Melody3; Crossing (electronic/computer tape music); Three Voices4. 1Sarah Cahill (pno), 2Tod Brody (fl), Daniel Kennedy (perc), 3San Francisco Contemporary Music Players c. Olly Wilson, 4Hong Wang (Chinese fiddle), Ann Yao (Chinese zither), Chen Tao (bamboo fl). New World 80620-2.FIRSOVA: The Mandelstam Cantatas: Forest Walks, op. 36; Earthly Life, op. 31; Before the Thunderstorm, op. 70. Ekaterina Kichigina (sop), Studio for New Music Moscow c. Igor Dronov. Megadisc MDC 7816.KATS-CHERNIN: Ragtime & Blues. Sarah Nicholls (pno). Nicola Sweeney (vln). Signum SIGCD058.CHAMBERS: A Mass for Mass Trombones. Thomas Hutchinson (trb), Ensemble of 76 trombones c. David Gilbert. Centaur CRC 2263.
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Hsu, Po-Yen, Yu-Ming Chuang, Shu-Hui LIN, Yu-Ting Lee, Yin-Chen Chen, Enders K. W. Ng, Kun-Tu YEH, Alfred S. L. Cheng, and Michael W. Y. Chan. "Abstract 6428: Targeting SMARCAL1 as a therapeutic strategy to enhance cGAS/STING signaling in gastric cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6428. http://dx.doi.org/10.1158/1538-7445.am2023-6428.
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Abstract Gastric cancer is one of the leading causes of cancer death in Eastern Asia. Although immunotherapy, such as immune checkpoint blockade, is an emerging therapeutic strategy against gastric cancer, only a fraction of cancer patients show a therapeutic response. Therefore, developing a novel therapeutic strategy to turn a “cold” tumor into a “hot” tumor is considered a crucial issue in cancer treatment. By methylomic analysis, we found that SMARCAL1 is one of the STAT3 targets which might be regulated by STAT3-mediated promoter methylation. Moreover, an inverse correlation between SMARCAL1 promoter methylation and expression was observed in the TCGA online database and in our cell lines experiment. Bisulfite pyrosequencing also showed a significant hypomethylation of SMARCAL1 compared to gastritis and adjacent normal in our in-house cohort (gastritis n=15; IM n=13; cancer n=58). More importantly, SMARCAL1 knockdown showed increased sensitivity of gastric cancer cell lines to DNA-damaging agents and increase the expression of cGAS and its downstream target, IFNB1. Therefore, in this study, we propose SMARCAL1 as a therapeutic target for improving the efficiency of immunotherapy by enhancing the cGAS/STING signaling pathway. Citation Format: Po-Yen Hsu, Yu-Ming Chuang, Shu-Hui LIN, Yu-Ting Lee, Yin-Chen Chen, Enders K.W. Ng, Kun-Tu YEH, Alfred S.L. Cheng, Michael W.Y. Chan. Targeting SMARCAL1 as a therapeutic strategy to enhance cGAS/STING signaling in gastric cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6428.
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Chan, Cerise Yuen Ki, Po Yee Wong, Helen Do Gai Xue, Chi Ching Goh, Jacinth Wing Sum Cheu, Aki Pui Wah Tse, Misty Shuo Zhang, and Carmen Chak Lui Wong. "Abstract 511: Cell cycle inhibitors exhibit anti-tumor immunomodulatory roles through the HIF-1-DDX41 cytosolic DNA sensing pathway in HCC." Cancer Research 84, no. 6_Supplement (March 22, 2024): 511. http://dx.doi.org/10.1158/1538-7445.am2024-511.
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Abstract Cell cycle inhibitors have a long history as anti-cancer therapeutics in clinical applications. Uncontrolled and infinite cell cycles are hallmarks of cancer, which enable them to proliferate rapidly and survive. To target these key features of cancer cells, cell cycle inhibitors are used to arrest their active cell cycle and induce cell death. In this study, beyond the known primary effect on cell cycle control, we identified that an expected and a secondary effect in immune modulation by the cell cycle inhibitors. Anti-mitotic agents including Paclitaxel (microtubule stabilizer), Palbociclib (CDK4/6 inhibitor) and AZD1152 and GSK1070916 (Aurora Kinase B inhibitors) can also eliminate cancer cells via an alternative mechanism - the activation of STING signaling. Our results demonstrated that these anti-mitotic agents caused DNA damage and cytosolic DNA accumulation. The cytosolic DNA was captured by a cytosolic DNA sensor DDX41,which triggered STING-TBK1-IRF3/7 pathway to upregulate secretion of pro-inflammatory senescence-associated secretory phenotype (SASP) factors in cancer cells. In addition, we revealed that transcription of DDX41 was mediated by the transcription factor known ashypoxia-inducible factor (HIF). In HCC, hypoxia induced DDX41 expression through HIF-1,thus hypoxic HCC cells were more prone to STING activation and SASP production under mitotic stress induced by cell cycle inhibitors. In the tumor microenvironment, the SASP enhanced infiltration of immune cells into the tumor core to eliminate cancer cells. We also observed the additive effects of cell cycles inhibitors (Paclitaxel, Palbociclib, and AZD1152)with anti-PD-1 mAb to arrest growth of HCC in mouse models. In summary, this study exhibited the novel immune-mediated aspect of cell cycle inhibitors in suppressing tumor growth. Our data suggested the potential combination regimen of cell cycle inhibitors and currently available immunotherapy with promising result. Citation Format: Cerise Yuen Ki Chan, Po Yee Wong, Helen Do Gai Xue, Chi Ching Goh, Jacinth Wing Sum Cheu, Aki Pui Wah Tse, Misty Shuo Zhang, Carmen Chak Lui Wong. Cell cycle inhibitors exhibit anti-tumor immunomodulatory roles through the HIF-1-DDX41 cytosolic DNA sensing pathway in HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 511.
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Wu, Cheng-Heng, Te-Wei Tseng, Chen-Yang Huang, Ping-Hsun Ou, Yi-Chen Lin, Pin-Jung Chen, Po-Ting Lin, et al. "Abstract 1520: A novel cluster of cytolytic alpha/beta TCR+CD4−CD8−T cells originating from CD8+T cells with potent innate-like T cell killing ability: implicating adoptive T cell transfer therapy for hepatocellular carcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1520. http://dx.doi.org/10.1158/1538-7445.am2024-1520.
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Abstract Tumor immunotherapies represent promising strategies for treating various cancers, including hepatocellular carcinoma. In this context, immune cells, including the adoptive T cell transfer treatment, become the focus of interests. Notably, alpha/beta TCR+CD4−CD8−T (DNT) cells is a subgroup of T cells that is ignored for a long time but was re-focused recently. These DNT cells are a group of cells with opposite functions in different condition, including pro-inflammatory or suppressive functions and possibly originated from over-stimulation of peripheral CD4+T cells/CD8+T cells or a special group of T cells formed in thymus. In our research results, we have found these DNT cells increased in murine hepatoma model, especially in the tumor microenvironment. In addition, these DNT cells from tumor microenvironment of murine hepatoma possessed potent tumor-killing ability. Furthermore, we analyzed the transcriptome profile of T cells in tumor microenvironment by single cell RNAseq approach (CITE-seq). We found DNT cells could be categorized into two main clusters, one is cytolytic DNT cells, resemble the potent CD8+T cells, and another is the CD4+T cell-like DNT cells. These cytolytic DNT cells are not exhausted but with high expression of cytolytic molecule and low hypoxia-inducible factor-1alpha (HIF-1a) expression. By trajectory analysis, cytolytic DNT cells come from the conventional CD8+T cells but following a unique developmental pathway that is different from the exhausted CD8+T cells. Interesting, these cytolytic DNT cells also expressed high level of Fcer1g molecule, a marker of innate CD8+T cells. In addition, these DNT cells could be generated and expanded in-vitro by IL-15 without TCR activation. In conclusion, we identified a cluster of cytolytic DNT cells, originated from CD8+T cells, exhibits innate T cells behavior and potent killing ability. In addition, these cytolytic DNT cells could be generated and expanded in-vitro for the adoptive T cell transfer treatment of hepatoma. Citation Format: Cheng-Heng Wu, Te-Wei Tseng, Chen-Yang Huang, Ping-Hsun Ou, Yi-Chen Lin, Pin-Jung Chen, Po-Ting Lin, Chan-Keng Yang, Wei Teng, Tsung-Han Wu, Yung-Chang Lin, Chun-Yen Lin. A novel cluster of cytolytic alpha/beta TCR+CD4−CD8−T cells originating from CD8+T cells with potent innate-like T cell killing ability: implicating adoptive T cell transfer therapy for hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1520.
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Lin, Po-Ting, Wei-Ting Ku, Tsung-Han Wu, Cheng-Heng Wu, Chan-Keng Yang, Wei Teng, Yung-Chang Lin, and Chun-Yen Lin. "Abstract 2695: A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2695. http://dx.doi.org/10.1158/1538-7445.am2024-2695.
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Abstract The primary hurdle in improving outcomes for hepatocellular carcinoma (HCC) patients after curative treatment is the high early recurrence rate. The existing literature indicates the presence of type 2 macrophages (M2), renowned for their immunosuppressive capabilities, has been implicated in creating a microenvironment conducive to tumor growth and recurrence. However, the intricate interplay involving M2 macrophages and the recurrence of HCC is underexplored. Therefore, we conducted an analysis involving HCC patients who underwent hepatectomy at our hospital between 2013 and 2017. We collected samples from both the tumor and non-tumor regions and subjected them to bulk RNA sequencing for comprehensive molecular profiling. The proportion of immune cells was calculated by CIBERSORTx.In our study, we enrolled fifty patients, with sixty percent presenting with cirrhosis and seventy-three percent having viral hepatitis. Twenty-three patients experienced tumor recurrence, with a median time to recurrence of 12.6 months. First, we found no correlation between five TIMR subtypes defined by TIMELASER (Xue R, Nature, 2022) and recurrence. However, as for the proportions of immune cell, a significantly lower NK/Treg ratio (p= 0.0163) and high within the resected tumor section in recurrent group was found. On the other hand, the ratio of M2 macrophages to total macrophages (M2/M) was significantly higher within the non-tumor region in patients experiencing tumor recurrence after hepatectomy (p=0.0357). Furthermore, the expression of the ACGT2 gene in non-tumor part, which strongly correlates with Treg function, was significantly higher (p=0.0056) in recurrent group. In addition, the innate T cells score was increased in non-tumor pat in recurrent group but with borderline significance (p=0.0628). However, in multivariable analysis, only a higher M2/M ratio within the non-tumor region (HR 3.756, p=0.0072) were identified as independent risk factors for tumor recurrence. We also found that patients with a higher M2/M ratio had a lower percentage of cirrhotic patients (p=0.0049) and less association with TIME-IA (immune activation) subtype of HCC by TIMELASER classification (p=0.0030). In conclusion, a higher M2/M ratio within the non-tumor region predict the tumor recurrence in patients with hepatocellular carcinoma. Citation Format: Po-Ting Lin, Wei-Ting Ku, Tsung-Han Wu, Cheng-Heng Wu, Chan-Keng Yang, Wei Teng, Yung-Chang Lin, Chun-Yen Lin. A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2695.
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Lee, Seung Joon, Won Suk Lee, Eun-Jin Go, Hannah Yang, Hong Ro Kim, Bong-Seog Kim, Chan Kim, and Hong Jae Chon. "Abstract 1800: An oral triple inhibitor of PI3Kδ/γ and DNA-PK elicits anticancer immunity and potentiates therapeutic efficacy of immune checkpoint blockade." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1800. http://dx.doi.org/10.1158/1538-7445.am2023-1800.
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Abstract Background: PI3Kδ and PI3Kγ are mainly expressed in leukocytes, indicating that they are involved in immune modulation of the tumor microenvironment (TME). Additionally, DNA-dependent protein kinase (DNA-PK) plays a pivotal role as a mediator in repairing DNA damage in cancer cells. Here, we developed a triple inhibitor of PI3Kδ/γ and DNA-PK, BR101801, to promote antitumor immune responses and thereby enhance therapeutic efficacy of the PD-1 immune checkpoint inhibitor. Methods: CT26 and MC38 colon tumor-bearing immunocompetent mice were treated with BR101801 (50 mg/kg, PO) daily and/or anti-PD-1 (8 mg/kg, IP) twice a week. The tumors were comprehensively analyzed using flow cytometry, multiplex tissue imaging, and NanoString profiling methods. Results: Oral administration of BR101801 suppressed tumor growth without significant toxicities. The optimal schedule for BR101801 was determined by activation of T cell immunity in the TME. BR101801 monotherapy significantly increased CD8+ cytotoxic T cells and decreased CD4+CD25+Foxp3+ regulatory T cells, while no changes were observed in tumor-associated macrophages. Moreover, BR101801 increased AH-1+ tumor-specific CD8+ T cells within BR101801-treated CT26 tumors. BR101801 induced extensive immune remodeling of the TME by altering immune-related genes. Notably, gene signatures related to DNA damage and inflammatory responses were more enriched in BR101801-treated tumors. Furthermore, the combination immunotherapy of BR101801 and anti-PD-1 antibody strongly suppressed tumor growth and improved antitumor immunity within the TME, leading to complete tumor regression. Conclusion: Our study demonstrates that BR101801, an oral triple inhibitor of PI3Kδ/γ and DNA-PK, effectively elicited anticancer immune responses within the TME and potently inhibited tumor progression in combination with immune checkpoint blockade. Citation Format: Seung Joon Lee, Won Suk Lee, Eun-Jin Go, Hannah Yang, Hong Ro Kim, Bong-Seog Kim, Chan Kim, Hong Jae Chon. An oral triple inhibitor of PI3Kδ/γ and DNA-PK elicits anticancer immunity and potentiates therapeutic efficacy of immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1800.
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Leung, Carmen Oi Ning, Shilpa Gurung, Katherine Po Sin Chung, Sze Man Chan, and Terence Kin Wah Lee. "Abstract 574: Adipocyte-derived FABP4 promotes non-alcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma by driving ITGB1-mediated β-catenin activation." Cancer Research 84, no. 6_Supplement (March 22, 2024): 574. http://dx.doi.org/10.1158/1538-7445.am2024-574.
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Abstract Nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed countries. However, the mechanisms contributing to its formation remain largely unknown. Given the role of cancer stem cells (CSCs) in tumor initiation and therapeutic resistance, we hypothesize that adipocytes, one of the key cellular factors within the tumor microenvironment of NAFLD-induced HCC, may play a critical role in HCC development and drug resistance by regulating liver CSCs. Using a co-culture system in which differentiated adipocytes were grown with HCC cells, we found that adipocytes enhanced the self-renewal ability of HCC cells through indirect paracrine secretion. HCC cells pre-incubated with conditioned medium from adipocytes showed enhanced liver CSC properties including self-renewal, tumorgenicity, invasiveness and chemo-resistance to doxorubicin and sorafenib. Secretome profiles showed that FABP4 was preferentially secreted by adipocytes and its level was further augmented when co-cultured with HCC cells. Concurrently, recombinant FABP4 enhanced CSC properties of HCC cells. Drastic delay in the onset of tumor development in FABP4−/- mice upon DEN-injected and high fat diet-induced mouse models of NAFLD-HCC. Mass spectrometry analysis revealed ITGB1 as a direct binding partner of FABP4 for the first time. This data, together with the observation of significant downregulation of the Wnt/β-catenin pathway in tumors of FABP4−/− mice, revealed the role of adipocyte-derived FABP4 promotes liver CSC function by activating the PI3K/Akt/β-catenin signaling pathway via ITGB1. Overexpression of ITGB1 led to poorer survival of HCC patients with NAFLD as a risk factor. The development of a monoclonal neutralizing antibody against FABP4 successfully blocked FABP4-driven CSC functions, implicating the targetability of FABP4 for the treatment of NAFLD-induced HCC. Citation Format: Carmen Oi Ning Leung, Shilpa Gurung, Katherine Po Sin Chung, Sze Man Chan, Terence Kin Wah Lee. Adipocyte-derived FABP4 promotes non-alcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma by driving ITGB1-mediated β-catenin activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 574.
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Lo, Jae Ho, Shivani Soni, Goar Smbatyan, Lesly Torres-Gonzalez, Pooja Mittal, Yan Yang, Francesca Battaglin, et al. "Abstract 7221: A compound targeting the circadian clock protein CRY2 enhances therapeutic efficacy of bevacizumab in a colorectal cancer (CRC) xenograft model." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7221. http://dx.doi.org/10.1158/1538-7445.am2024-7221.
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Abstract Anti VEGF A antibody Bevacizumab combined with standard chemotherapy has improved outcomes for CRC patients. However, a subset of CRC patients acquires resistance to anti-VEGF treatment and underlying mechanism is poorly understood. Our recent study reported that circadian clock transcription factor BMAL1 drives transcription of VEGFA conferring resistance to bevacizumab treatment. Our rational is to stabilize negative regulator of circadian clock CRY protein to inhibit BMAL1 activity in a negative feedback loop. In this study, we evaluated whether CRY stabilizers SHP656 and SHP1705 in combination with bevacizumab can synergistically enhance anti-tumor effect in CRC mouse models. Methods: In vitro tube formation assay was performed with HUVECs cells to investigate the effect of CRY stabilizer on tube formation. For in vivo experiments, 106 HCT116 human CRC cells were injected subcutaneously into the right flank of 8-week-old nude mice. Mice (5mice/group) were randomized into: A. vehicle (2% carboxymethylcellulose PO 5 days/week; control IgG IP, 2 days/week); B. bevacizumab (5mg/kg IP, twice/week); C. 10mg/kg SHP656; D. 30mg/kg SHP656; E. 30mg/kg SHP1705; F. 10mg/kg SHP656 + bevacizumab; G. 30mg/kg SHP656 + bevacizumab; G. 30mg/kg SHP1705 + bevacizumab. SHP 656 & 1705 was given PO; 5days/week. Tumor volume was measured three times a week. The survival curve was plotted using Kaplan and Meier method and assessed for statistical significance with log-rank test. Results: The in vitro tube formation assay showed significant inhibition of tube formation in HUVEC cells treated with SHP1705 plus bevacizumab compared to treated with bevacizumab alone. In in vivo study, the tumors treated with 30mg/kg SHP1705 + bevacizumab significantly suppressed tumor growth compared to bevacizumab monotherapy (one way-ANOVA, P <0.05). 30mg/kg SHP1705 + bevacizumab significantly improved survival of the mice (Log-rank test, P <0.05). No significant survival benefit was observed with bevacizumab alone. 3/5 mice treated with SHP1705 + bevacizumab showed decreased tumor volume and achieved complete regression for more than 4 months without additional treatment. In combination with bevacizumab, higher dose of SHP656 (30mg/kg) delayed tumor growth and extended survival compared with bevacizumab monotherapy (though did not reach statistical significance) whereas the lower dose of 10mg/kg did not show anti-tumor effect, demonstrating a dose dependent response. Conclusion: Our study shows that CRY stabilizers in combination with bevacizumab significantly enhances anti-tumor efficacy in CRC mouse models. Although mechanism of action of SHP compounds on angiogenesis pathway still needs further investigation, these findings may support development of novel treatment strategies modulating circadian clock to overcome bevacizumab resistance in CRC patients. Citation Format: Jae Ho Lo, Shivani Soni, Goar Smbatyan, Lesly Torres-Gonzalez, Pooja Mittal, Yan Yang, Francesca Battaglin, Priscilla Chan, Yuanzhong Pan, Sandra Algaze, Priya Jayachandran, Karam Ashouri, Alexandra Wong, Wu Zhang, Joshua Millstein, Indrakant K. Singh, Evanthia T. Roussos Torres, Shannon M. Mumenthaler, Steve A. Kay, Heinz-Josef Lenz. A compound targeting the circadian clock protein CRY2 enhances therapeutic efficacy of bevacizumab in a colorectal cancer (CRC) xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7221.
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이민수. "Chang Po-Go Leadership and His Entrepreneurship." Review of Business History 26, no. 1 (March 2011): 59–91. http://dx.doi.org/10.22629/kabh.2011.26.1.002.
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Ear, Po Hien, Min Hu, Jonathan S. Shilyansky, Naomi H. Fei, Sam Coleman, Rebecca Hoyd, Caroline E. Wheeler, et al. "Abstract 7615: Epithelial-mesenchymal-transition gene signature changes and poor oncological outcome in Candida-positive pancreatic ductal adenocarcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7615. http://dx.doi.org/10.1158/1538-7445.am2024-7615.
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Abstract Candida are commonly found in bile collected during surgery in pancreatic ductal adenocarcinoma (PDAC) patients. However, their significance in tumor biology and oncological outcome is unclear. PDAC patients receiving neoadjuvant therapy and pancreatectomy with intraoperative bile fungal culture were identified (N=40) in a prospective single-institution cohort. Tumor regression scores (TRS) were abstracted from pathology reports and correlated with bile fungal cultures. Bulk tumor RNASeq data were obtained from the Oncology Research Information Exchange Network (ORIEN). Tumor microbiome data of non-metastatic PDAC patients with upfront surgery were extracted using the {exotic} tool (Hoyd et al. Cancer Res. Commun., 2023). Gene expression profiles were compared between Candida+ and Candida- tumors, defined by a cutoff microbial count of 0. Overall survival (OS) of resected PDAC patients with Candida+ and Candida- tumors was compared using Kaplan Meier survival analysis. From the single-institution PDAC cohort, Candida+ bile was associated with poor pathological response to neoadjuvant therapy (Table 1). Using the ORIEN cohort, Candida were detected in 67% (106/158) of the PDAC tumors. Patients with Candida+ tumors had worse OS (median 28 vs. 56 months, Log-Rank p<0.008). Gene Set Enrichment Analysis (GSEA) using Hallmark gene sets showed an enrichment of epithelial-mesenchymal-transition (EMT) gene set and a reduction of metabolic and DNA repair gene sets in Candida+ tumors. GSEA for Immune signature and Tumor Immune Microenvironment Deconvolution (TIMEx) cell types showed an enrichment of Stromal-Fibroblast and EMT signature in Candida+ tumors. Further investigations are underway to determine the causal and metabolic relationship between Candida and this tumor microenvironment with EMT and stromal fibroblasts which is a well-known contributor to poor chemotherapy response and oncological outcome of PDAC. Table 1: Pathological Response to Neoadjuvant Therapy for PDAC Bile Culture TRS0/1 TRS2 TRS3 Candida - 5 (25%) 15 (75%) 0 (0%) Candida + 1 (5%) 11 (55%) 8 (40%) TRS: Tumor Regression Score (TRS0: complete response; TRS1: near-complete response; TRS2: partial response; TRS3: no response). Chi-Square Test, P=0.0035. Citation Format: Po Hien Ear, Min Hu, Jonathan S. Shilyansky, Naomi H. Fei, Sam Coleman, Rebecca Hoyd, Caroline E. Wheeler, Kelsey L. Steckly, Michelle L. Churchman, Nicholas Denko, Rebecca D. Dodd, Sheetal Hardikar, Ning Jin, Qin Ma, Martin D. McCarter, Abdul Rafeh Naqash, Afaf E. Osman, Gregory Riedlinger, Lary A. Robinson, Bryan P. Schneider, Eric A. Singer, Ahmad A. Tarhini, Gabriel Tinoco, Cornelia M. Ulrich, Yousef Zakharia, Daniel Spakowicz, Aik Choon Tan, Carlos H. Chan. Epithelial-mesenchymal-transition gene signature changes and poor oncological outcome in Candida-positive pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7615.
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Hurvitz, Sara, Sherene Loi, Joyce O'Shaughnessy, Alicia Okines, Sara Tolaney, Joo Hyuk Sohn, Cristina Saura, et al. "Abstract GS01-10: HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): GS01–10—GS01–10. http://dx.doi.org/10.1158/1538-7445.sabcs23-gs01-10.
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Abstract Background Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor approved in combination with trastuzumab and capecitabine for previously treated HER2+ locally advanced or metastatic breast cancer (LA/MBC). Trastuzumab emtansine (T-DM1) is a HER2-directed antibody-drug conjugate approved to treat HER2+ LA/MBC previously treated with trastuzumab and a taxane. This is the first report of HER2CLIMB-02 (NCT03975647), a randomized, double-blind, placebo-controlled phase 3 study assessing the efficacy and safety of tucatinib combined with T-DM1 in patients with previously treated HER2+ LA/MBC. Methods Eligible patients had HER2+ LA/MBC previously treated with trastuzumab and a taxane in any setting with ECOG performance status ≤1 and adequate hepatic, renal, hematologic, and cardiac function. Patients with previously treated stable, progressing, or untreated brain metastases (BMs) not requiring immediate local therapy were also eligible. Patients were randomly assigned 1:1 to receive 21-day cycles of either tucatinib (300 mg orally twice a day [PO BID]) or placebo (PO BID), combined with T-DM1 (3.6 mg/kg intravenously every 3 weeks). The primary endpoint was progression-free survival (PFS) by investigator assessment per RECIST v1.1. Alpha-controlled secondary endpoints included overall survival (OS) and objective response rate (ORR) per RECIST v1.1 for the overall population, and PFS and OS for the subset of patients with BMs at baseline. Safety was analyzed as a secondary endpoint. Results From October 8, 2019, to June 16, 2022, 463 patients were randomly assigned, comprising 228 to the tucatinib arm (tucatinib + T-DM1) and 235 to the control arm (placebo + T-DM1). The median duration of follow-up (OS) was 24.4 months for the overall population. Patient demographics and baseline characteristics were balanced between the 2 arms. Almost half (44.1%) of the overall population had either active or stable BMs at baseline. As of the data cutoff (June 29, 2023), the study met its primary endpoint with a statistically significant improvement in PFS in the tucatinib arm vs control arm. The risk of progression or death decreased by 24.1% in the tucatinib arm (hazard ratio [HR]=0.759 [95% CI, 0.607-0.950]; P=0.0163). Median PFS was 9.5 months (95% CI, 7.4-10.9) vs 7.4 months (95% CI, 5.6-8.1) for the tucatinib and control arms, respectively. HRs for PFS across all prespecified subgroups were consistent with the HR of the overall population, including patients with BMs at baseline (HR=0.639 [95% CI, 0.459-0.891]). The interim OS results were immature with 134 of 253 total required events (53%) and did not meet the prespecified crossing boundary. The confirmed ORR was numerically higher in the tucatinib arm (42.0%) vs the control arm (36.1%). The most common treatment-emergent adverse events (TEAEs) included nausea (65.4% vs 49.4% for tucatinib and control arms, respectively), diarrhea (56.7% vs 26.6%), and fatigue (48.9% vs 37.3%). The most common grade ≥3 TEAEs in the tucatinib arm were alanine and aspartate aminotransferase elevations, each reported in 38 patients (16.5%) in the tucatinib arm and 6 patients (2.6%) in the control arm. TEAEs associated with any treatment discontinuation occurred in 51 patients (22.1%) in the tucatinib arm and 27 (11.6%) in the control arm. TEAEs leading to deaths occurred in 3 patients (1.3%) in the tucatinib arm and 2 patients (0.9%) in the control arm. Conclusion HER2CLIMB-02 demonstrated that the addition of tucatinib to T-DM1 significantly improved median PFS in patients with previously treated HER2+ LA/MBC, including those with BMs. Although discontinuations due to TEAEs were more common in the tucatinib arm, no new safety signals emerged for the combination therapy. Citation Format: Sara Hurvitz, Sherene Loi, Joyce O'Shaughnessy, Alicia Okines, Sara Tolaney, Joo Hyuk Sohn, Cristina Saura, Xiaofu Zhu, David Cameron, Thomas Bachelot, Erika Hamilton, Giuseppe Curigliano, Antonio Wolff, Nadia Harbeck, Norikazu Masuda, Linda Vahdat, Khalil Zaman, Frances Valdes-Albini, Margaret Block, Timothy Pluard, Tira Tan, Chelsea Gawryletz, Arlene Chan, Philippe Bedard, Rinat Yerushalmi, Binghe Xu, Konstantinos Tryfonidis, Michael Schmitt, Joan Xie, Virginia Borges. HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-10.
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STINGA, Viorela Georgiana, and Ana Cornelia OLTEANU. "The Process of Choosing Transport Modes in a Logistic Chain." Postmodern Openings 10, no. 4 (December 19, 2019): 209–18. http://dx.doi.org/10.18662/po/104.
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Shohani, S., and A. Kardan. "Shape coexistence in even–even Po isotopic chain." International Journal of Modern Physics E 28, no. 10 (October 2019): 1950086. http://dx.doi.org/10.1142/s0218301319500861.
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The Po isotopes show the presence of coexisting structures having different deformations with increasing neutron number within the macroscopic–microscopic Nilsson–Strutinsky formalism. The model is based on the Lublin Strasbourg Drop (LSD) method for the macroscopic energy calculation. We study the shape evolution in a long chain of polonium isotopes, [Formula: see text]Po.
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Chang, Hannah, Isabela Anawate, Alyssa Low, Shao-Po Huang, Julia Maues, Christine Hodgdon, and Isaac Chan. "Abstract PO4-14-10: Circulating Tumor DNA as a Biomarker for ADCs in Metastatic Breast Cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO4–14–10—PO4–14–10. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-14-10.
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Abstract Background: Breast cancer is a complex disease characterized by heterogeneity, and the analysis of circulating tumor DNA (ctDNA) holds promise for capturing this heterogeneity. Recently, ctDNA testing has been employed in clinical practice to guide targeted therapies for metastatic breast cancer, particularly in cases of hormone receptor-positive disease with mutations in PIK3CA and ESR1. This approach becomes necessary when traditional tumor biopsies are inadequate for next-generation sequencing (NGS) testing or fail to capture the full extent of the cancer's heterogeneity. Moreover, the utilization of antibody-drug conjugates (ADC) in addressing tumor heterogeneity continues to expand. However, there has been no biomarker, outside of HER2 protein expression, to predict ADC response. In this project, we test the hypothesis that ctDNA can be utilized as a biomarker to predict response to novel therapies such as ADCs. Methods: We analyzed a subset of patients from the Dallas Metastatic Breast Cancer Study comprised of patients with metastatic breast cancer (n= 109) who underwent ctDNA testing using the Tempus xF liquid biopsy ctDNA sequencing panel. This panel detects 105-genes that are known oncogenic drivers and resistance mutations. The data was collected from a single academic medical center between the initial year of ctDNA collection in 2019 and 2023. Results: Among these patients, 85 (77.9%) had hormone receptor-positive disease, 13 (11.9%) had triple-negative breast cancer, and 11 (10.0%) had HER2-positive disease (including 3 (2.75%) patients with triple-positive disease). Only 22 of these patients had tissue biopsies that underwent NGS testing. Analysis of all patients revealed that the most common gene alteration was PIK3CA, which was identified in 70 patients. Specifically, the most frequently observed alteration was PIK3CA p.545K, found in 25 patients. Table 1 further details the frequency of each gene in this subset of patients. Among the patients, 34 out of 109 (31%) received an ADC, while only 8 out of 109 (7%) received immunotherapy. Patients with CDKN2A achieved the longest progression-free survival (PFS) on an ADC, with a median PFS of 7 months, whereas patients carrying mutations in TP53, PIK3R1, PIK3CA, PTEN, NF1, BRAF, RHOA, FGFR4, KRAS, TERT, GATA3, HNF1A, FB1, STOP had median PFSs of 2 months or less. Table 2 provides additional information on the response of patients with specific mutations to ADCs. Notably, only one patient received sequential ctDNA testing, and in that case, there was a gain of TP53 p.N239S following sacituzumab govitecan administration compared to the baseline ctDNA test, followed by a gain of PIK3CA p.P449_L455del after trastuzumab deruxtecan administration. Conclusions: As we observe changes in subtypes following treatment progression, researchers are actively seeking biomarkers to better characterize real-time changes in tumor biology that can predict response and resistance to treatments. Further studies are needed to identify additional genes present in ctDNA that can provide mechanistic insights into why certain patients respond favorably to ADCs while others do not. We are currently enrolling patients for a prospective study that aims to assess baseline ctDNA levels and monitor changes in variant allele frequency following treatment with ADCs and immunotherapy. Table 2 Median PFS on ADC by Gene Citation Format: Hannah Chang, Isabela Anawate, Alyssa Low, Shao-Po Huang, Julia Maues, Christine Hodgdon, Isaac Chan. Circulating Tumor DNA as a Biomarker for ADCs in Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-14-10.
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Ahmed, Minhaz, Lubna Alam, Che Mohamed, Mazlin Mokhtar, and Goh Ta. "Health Risk of Polonium 210 Ingestion via Drinking Water: An Experience of Malaysia." International Journal of Environmental Research and Public Health 15, no. 10 (September 20, 2018): 2056. http://dx.doi.org/10.3390/ijerph15102056.
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The presence of toxic polonium-210 (Po-210) in the environment is due to the decay of primordial uranium-238. Meanwhile, several studies have reported elevated Po-210 radioactivity in the rivers around the world due to both natural and anthropogenic factors. However, the primary source of Po-210 in Langat River, Malaysia might be the natural weathering of granite rock along with mining, agriculture and industrial activities. Hence, this is the first study to determine the Po-210 activity in the drinking water supply chain in the Langat River Basin to simultaneously predict the human health risks of Po-210 ingestion. Therefore, water samples were collected in 2015–2016 from the four stages of the water supply chain to analyze by Alpha Spectrometry. Determined Po-210 activity, along with the influence of environmental parameters such as time-series rainfall, flood incidents and water flow data (2005–2015), was well within the maximum limit for drinking water quality standard proposed by the Ministry of Health Malaysia and World Health Organization. Moreover, the annual effective dose of Po-210 ingestion via drinking water supply chain indicates an acceptable carcinogenic risk for the populations in the Langat Basin at 95% confidence level; however, the estimated annual effective dose at the basin is higher than in many countries. Although several studies assume the carcinogenic risk of Po-210 ingestion to humans for a long time even at low activity, however, there is no significant causal study which links Po-210 ingestion via drinking water and cancer risk of the human. Since the conventional coagulation method is unable to remove Po-210 entirely from the treated water, introducing a two-layer water filtration system at the basin can be useful to achieve SDG target 6.1 of achieving safe drinking water supplies well before 2030, which might also be significant for other countries.
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Gelle, Zsóka. "Tibeti források sNgags ‘chang Shākya bZang po életéről." Keréknyomok, no. 15 (2023): 80–97. http://dx.doi.org/10.56213/kerekny.15.2023.04.
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SNgags ‘chang Shākya bZang po volt az a rnying ma pa iskolához tartozó, 15–16. században élt kincsmester (gter ston), aki felfedezte a Bya rung kha shor sztúpa legendájáról szóló kincsszöveget, és Tibetből a Kathmandu-völgybe utazott, hogy a szövegben foglalt próféciát a Bódhnáth-i sztúpa feltárásával és helyreállításával megvalósítsa. Ő nyitotta meg Jolmó elrejtett földjét (sbas yul), és először emelt buddhista templomot azon a vidéken, melyet ma Helambuként ismerünk (Nepál). Ő lett posztumusz az első Yol mo ba Chen po, az első lámája annak a hagyományvonalnak, melynek köszönhetően az Északi Kincs hagyomány (byang gter) tanításai széles körben elterjedtek a Himalája vidékén a 16–18. század között.1 Jelen tanulmány célja az, hogy öt tibeti szöveg fordítása és további források vizsgálata nyomán részletes képet adjon e fontos, ám kevéssé ismert mester életéről és tevékenységéről, és szembenézzen a szövegek természetéből adódó szövegkritikai problémákkal.
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Johnson, B. D., L. E. Wilson, W. Z. Zhan, J. F. Watchko, M. J. Daood, and G. C. Sieck. "Contractile properties of the developing diaphragm correlate with myosin heavy chain phenotype." Journal of Applied Physiology 77, no. 1 (July 1, 1994): 481–87. http://dx.doi.org/10.1152/jappl.1994.77.1.481.
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The objective of this study was to determine the relationship between developmental transitions in myosin heavy chain (MHC) composition and changes in maximum unloaded shortening velocity (Vo) and maximum specific force (Po) of the rat diaphragm muscle. The diaphragm was excised at postnatal days 0, 3, 7, 14, 21, and 28 and in adults. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry. In muscle fiber bundles, Vo was determined at 15 degrees C by use of the “slack” test. Isometric Po was determined at 15 and 26 degrees C. Simple and stepwise regressions were used to evaluate the correlations between Vo, Po, and MHC phenotype transitions and the various developmental ages. The progressive increases in Vo and Po with age were found to be inversely correlated to MHC-neonatal isoform expression (r2 = -0.84 and -0.63, respectively) and positively correlated to MHC-2X (r2 = 0.78 and 0.57) and MHC-2B (r2 = 0.51 and 0.40) isoform expression (P < 0.001). Changes in MHC-neonatal isoform expression contributed to most of the developmental variance in Vo and Po, with changes in MHC-2X and MHC-2B expression also contributing significant increments to total variance. The postnatal increase in Vo most likely relates to differences in the actomyosin adenosinetriphosphatase activity between neonatal and adult fast MHC phenotypes. The increase in Po may reflect inherent differences in myofibrillar density, cross-bridge cycling kinetics, and/or the force produced per cross bridge among fibers composed of the different MHC isoforms.
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Suwannakham, Parichart, and Kritsana Sagarik. "Dynamics of structural diffusion in phosphoric acid hydrogen-bond clusters." RSC Advances 7, no. 35 (2017): 21492–506. http://dx.doi.org/10.1039/c7ra01829k.
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For protonated H3PO4 clusters, the Eigen–Zundel–Eigen mechanism is enhanced by fluctuations in the H-bond chain length and local-dielectric environment, and can proceed without the reorientation of H3PO4 molecules as in the case of neat liquid H3PO4.
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Piotrowska, Zofia, Mehlika Hazar-Rethinam, Coleen Rizzo, Brandon Nadres, Emily E. Van Seventer, Heather A. Shahzade, Inga T. Lennes, et al. "Heterogeneity and Coexistence of T790M and T790 Wild-Type Resistant Subclones Drive Mixed Response to Third-Generation Epidermal Growth Factor Receptor Inhibitors in Lung Cancer." JCO Precision Oncology, no. 2 (November 2018): 1–15. http://dx.doi.org/10.1200/po.17.00263.
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Purpose Third-generation epidermal growth factor receptor (EGFR) inhibitors like nazartinib are active against EGFR mutation–positive lung cancers with T790M-mediated acquired resistance to initial anti-EGFR treatment, but some patients have mixed responses. Methods Multiple serial tumor and liquid biopsies were obtained from two patients before, during, and after treatment with nazartinib. Next-generation sequencing and droplet digital polymerase chain reaction were performed to assess heterogeneity and clonal dynamics. Results We observed the simultaneous emergence of T790M-dependent and -independent clones in both patients. Serial plasma droplet digital polymerase chain reaction illustrated shifts in relative clonal abundance in response to various systemic therapies, confirming a molecular basis for the clinical mixed radiographic responses observed. Conclusion Heterogeneous responses to treatment targeting a solitary resistance mechanism can be explained by coexistent tumor subclones harboring distinct genetic signatures. Serial liquid biopsies offer an opportunity to monitor clonal dynamics and the emergence of resistance and may represent a useful tool to guide therapeutic strategies.
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Hong, David S., Yasutoshi Kuboki, Rona Yaeger, John H. Strickler, Toshiki Masuishi, Corey Langer, Ardaman Shergill, et al. "Abstract 2308: Biomarkers of acquired resistance to sotorasib (soto) plus panitumumab (pani) in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC)." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2308. http://dx.doi.org/10.1158/1538-7445.am2023-2308.
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Abstract Introduction: New RTK alterations emerge at progression when patients (pts) with KRAS G12C-mutated mCRC are treated with soto monotherapy, suggesting addition of an EGFR inhibitor may help counter soto resistance and inhibit further tumor growth. Soto plus pani has shown a 3-fold higher objective response rate than monotherapy but may give rise to new patterns of resistance. We report emerging mutations after treatment with the doublet in the dose exploration/expansion cohorts of CodeBreaK 101 Subprotocol H. Methods: We evaluated pts who had KRAS G12C-mutated mCRC, were KRASG12C inhibitor-naïve, and had paired plasma samples at baseline and progression after treatment with soto (960 mg PO daily) plus pani (6 mg/kg IV Q2W). Samples were analyzed using the 74-gene Guardant 360® ctDNA test. Acquired genomic alterations were defined as absent at baseline and present at progression. We also studied the association between acquired mutations and time to progression (TTP). Results: Of 21 pts with paired plasma samples, 17 (81%) had ≥1 acquired genomic alteration. RTK alterations and secondary (2°) RAS alterations were most common; each occurred in 57% of pts (Table). KRAS amplification was the most common single alteration (43%). Of the 74 acquired alterations observed, 23 (32%) were potentially actionable per OncoKB™, including BRAF V600E, METex14, and ERBB2 S310F. EGFR alterations and RAS single nucleotide variants (SNVs) were not seen in pts with TTP <3 months. Discussion: A higher rate of acquired 2° RAS and RTK mutations at progression was observed after treatment with the doublet compared to prior analysis of soto monotherapy. Many detected EGFR mutations and RAS SNVs are functionally oncogenic and not seen in pts with early progression, suggesting clonal evolution mediating 2° resistance. Our results reinforce the dependence of continued tumor growth on RAS and EGFR signaling in mCRC and may suggest the need for triplet therapy. Table. Acquired genomic alterations observed ALTERATION PATIENTS, n (%) RTK alteration 12 (57) EGFR 7 (33) EGFR amplification 3 (14) EGFR G465R 1 (5) EGFR G465D 1 (5) EGFR G465E 1 (5) EGFR S464L 1 (5) EGFR L704V 1 (5) EGFR G87R 1 (5) 2° RAS genomic alterations 12 (57) KRAS amplification 9 (43) KRAS Q61H 1 (5) NRAS Q61R 1 (5) NRAS Q61L 1 (5) NRAS Q61H 1 (5) NRAS Q61K 1 (5) NRAS G60E 1 (5) Citation Format: David S. Hong, Yasutoshi Kuboki, Rona Yaeger, John H. Strickler, Toshiki Masuishi, Corey Langer, Ardaman Shergill, Edward Kim, Antreas Hindoyan, Qui Tran, Lata Mukundan, Emily Chan, Abraham Anderson, Marwan G. Fakih. Biomarkers of acquired resistance to sotorasib (soto) plus panitumumab (pani) in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2308.
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Tran, Catherine G., Luis C. Borbon, Dane H. Tow, Jonathan Shilyansky, Guiying Li, James Egan, Scott K. Sherman, et al. "Abstract 3578: A systematic NEN spheroid drug screen reveals a novel drug resistance mechanism in small bowel NETs." Cancer Research 84, no. 6_Supplement (March 22, 2024): 3578. http://dx.doi.org/10.1158/1538-7445.am2024-3578.
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Abstract Neuroendocrine neoplasms (NENs) are rare cancers that arise from neuroendocrine cells. NENs are classified as well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Small bowel NETs (SBNETs) and pancreatic NETs (PNETs) are generally slow growing but they commonly metastasize to the liver and can become aggressive cancers. NECs are rapidly growing, and patients have poor prognosis. Little is known about the drug sensitivity profile of SBNETs, PNETs and NECs due to a paucity of cellular and animal models of these malignancies. We have successfully cultured NEN cells from clinical samples as patient-derived spheroids (PDS) and showed that they express appropriate tumor markers. We systematically screened 20 NEN (12 SBNET, 5 PNET, and 3 NEC) spheroid cultures against a library of 175 compounds (147 FDA-approved anti-cancer drugs, 8 lab selected compounds, and 20 structurally diverse molecules) and compared their drug sensitivity profiles to identify the most effective drug classes and to better understand the biology of each NEN subtype. Top drug hits were validated for their anti-tumor properties in NEN PDS and patient-derived xenograft (PDX) mouse models. Our NEN PDS cultures identified common and unique drug sensitivity profiles for each type of NEN. SBNET spheroids were more resistant to many classes of anti-cancer drugs, which was due to overexpression of cytochrome P450 genes. Consistent with clinical findings, PNET spheroids showed increased sensitivity to tyrosine kinase and mTOR/PI3K inhibitors compared to SBNET & NEC spheroids. NEC spheroids showed the broadest sensitivity to many anti-neoplastic compounds. The top candidate drug identified from our screen was romidepsin, a histone deacetylase inhibitor. Romidepsin displayed anti-tumor properties in vitro and in vivo for all 3 NEN models and was highly synergistic with rapamycin, an mTOR inhibitor similar to the SBNET approved drug everolimus. Excitingly, low-dose romidepsin effectively inhibited tumor growth when combined with low-dose rapamycin in an SBNET PDX mouse model. These NEN PDS drug screens enabled direct drug testing in primary tumor cultures to identify promising drugs that could be used alone or in combination with currently approved-NEN therapies. Histone deacetylase inhibitors, such as romidepsin, may be effective against SBNETs. NEN PDS models also serve as a valuable resource for understanding the unique biology and mechanisms of drug resistance for specific NEN subtypes. Citation Format: Catherine G. Tran, Luis C. Borbon, Dane H. Tow, Jonathan Shilyansky, Guiying Li, James Egan, Scott K. Sherman, Ellen Abusada, Jing Tang, Ramaswamy govindan, Ryan C. Fields, Terry A. Braun, Carlos HF Chan, Chandrikha Chandrasekharan, Douglas Spitz, Dawn E. Quelle, Andrew M. Bellizzi, James R. Howe, Po Hien Ear. A systematic NEN spheroid drug screen reveals a novel drug resistance mechanism in small bowel NETs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3578.
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Shilyansky, Jonathan, Casandro J. Chan, Kristen L. Coleman, Mariah Leidinger, Sharathkumar Bhagavathi, Anjali Sharathkumar, and Po Hien Ear. "Abstract 146: Development of a novel pediatric patient-derived xenograft model with THPO and NDUFB3 mutations." Cancer Research 84, no. 6_Supplement (March 22, 2024): 146. http://dx.doi.org/10.1158/1538-7445.am2024-146.
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Abstract Familial myeloproliferative neoplasms (MPN) of childhood are extremely rare and have propensity towards malignant transformation such as leukemia and lymphoma. Due to the rarity of these cases, few cellular and mouse models are available for understanding the tumor biology. Therefore, the molecular mechanisms of malignant transformation remain poorly understood limiting the therapeutic progress to treat these conditions. Here, we report the development of a novel pediatric patient-derived xenograft (PDX) mouse model harboring mutations in the THPO and mitochondrial subunit NDUFB3 genes and characterization of their functions. THPO is a regulator of hematopoiesis and induces trilineage hematopoiesis through HSPC proliferation while NDUFB3 is a subunit of the mitochondrial complex 1. We isolated malignant cells from an enlarged spleen sample and blood sample from a pediatric patient with TPO mediated MPN and established a PDX model (PDX-2333) that recapitulates the patient’s disease. Short tandem repeat analyses confirmed an exact match between the PDX-2333 tumors and patient samples. Exome and Sanger sequencing analyses were performed to identify mutations. Immunohistochemistry staining was used for tumor characterization. Wildtype (WT) and mutant forms of NDUFB3 genes were cloned into expression plasmids with a puromycin selection marker and stably transfected in HEK-293 cells. Stable clones of HEK-293 overexpressing WT and NDUFB3 mutants were tested for growth and sensitivity to anti-cancer therapies. We established a novel PDX model of lymphomagenesis harboring unique mutations in THPO and NDUFB3 genes. The THPO (c.-52C>T) mutation in upstream open reading frame causes loss of inhibition of THPO mRNA expression. The NDUFB3 (c.23 A>G) mutation results in a change of amino acid from glutamine 8 (E8) to glycine 8 (G8) (Ndufb3_E8) and is highly conserved in many vertebrate species. HEK-293 cell lines stably overexpressing WT or NDUFB3 mutants were tested for growth and their sensitivity to ruxolitinib, a Jak2 inhibitor and doxorubicin, an FDA-approved treatment for leukemia and lymphoma. Our data showed that cells overexpressing Ndufb3_E8 have increased proliferation and are highly resistant to ruxolitinib and doxorubicin in comparison to the WT NDUFB3. Developing a novel pediatric PDX model and exome sequencing allow us to identify novel genes involved in malignant transformation leading to lymphoma development. Our data demonstrated that mutations in the THPO (c.-52C>T) and NDUFB3 (c.23 A>G) genes play a key role in the pathogenesis of a lymphoma and in regulating drug sensitivity. Citation Format: Jonathan Shilyansky, Casandro J. Chan, Kristen L. Coleman, Mariah Leidinger, Sharathkumar Bhagavathi, Anjali Sharathkumar, Po Hien Ear. Development of a novel pediatric patient-derived xenograft model with THPO and NDUFB3 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 146.
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Mehmood, Andleeb, Xiaowei Xu, Xiaohui Kang, and Yi Luo. "Origin of different chain-end microstructures in ethylene/vinyl halide copolymerization catalysed by phosphine–sulfonate palladium complexes." New Journal of Chemistry 44, no. 39 (2020): 16941–47. http://dx.doi.org/10.1039/d0nj03350b.
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Ethylene and vinyl halide (VX, X = F or Cl) copolymerization mechanism in the presence of catalysts A ((POOMe,OMe)PdMe, POOMe,OMe = {2(2-MeOC6H4)(2-SO3-5-MeC6H3)P}) and A′ ((POBp,OMe)PdMe, POBp,OMe = {(2-MeOC6H4)(2-{2,6-(MeO)2C6H3}C6H4)(2-SO3-5-MeC6H3)P}) has been comparatively studied via density functional theory (DFT) calculations.
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Shin, Byung Chul, Hyun Lee Kim, and Jong Hoon Chung. "Light chain deposition disease in kidney transplantation: a case report." Korean Journal of Transplantation 35, no. 1 (October 7, 2021): S69. http://dx.doi.org/10.4285/atw2021.po-1154.
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Chang, Hannah, Pallavi Dev, Luise Froessl, Shao-Po Huang, Christine Hodgdon, Julia Maues, and Isaac Chan. "Abstract PO5-06-13: Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO5–06–13—PO5–06–13. http://dx.doi.org/10.1158/1538-7445.sabcs23-po5-06-13.
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Abstract Background: Metastatic triple negative breast cancer (TNBC) is a diverse disease with the propensity to spread to visceral organs and the central nervous system (CNS). While systemic chemotherapy is commonly used, there is a growing utilization of immune checkpoint inhibitors (ICI) and antibody drug conjugates (ADC). However, few studies have examined the impact of specific therapies on individual metastatic sites, limiting clinical guidance for solitary metastases. Objective: This study aimed to evaluate the efficacy of various systemic therapies in TNBC patients with lung, liver, and CNS metastases. Methods: We analyzed data from the Dallas Metastatic Breast Cancer Study, a retrospective cohort study that includes all patients with metastatic breast cancer treated at a single academic medical center and identified 52 TNBC patients with visceral and CNS metastases diagnosed between 2009 and 2021. We correlated the site of metastasis with and treatment response, which was assessed based on imaging findings using RECIST 1.1 criteria. Results and Discussion: The median age at diagnosis of visceral metastatic disease was 52 years. Of the patients, 60% presented with de novo metastatic disease, while 40% experienced disease recurrence. The most prevalent metastatic sites were the lung (n=28), CNS (n=28), and liver (n=9). Among patients with detectable circulating tumor DNA, the most prevalent gene mutations in lung metastases were TP53 (36%), PTEN (13%), and PIK3R1 (10%). In liver metastases, TP53 (53%) and BRCA1 (15%) mutations were the most frequently observed. Similarly, in CNS metastases, TP53 (40%) and BRCA1 (13%) mutations were again most frequently detected. The notable frequency of TP53 mutations indicates the necessity for further investigations to explore potential differences in treatment approaches for patients with these mutations. The median overall survival (OS) was 14.43 months ±15.53, with the longest survival observed in patients with lung metastases (15 months), followed by liver metastases (6 months) and CNS metastases (5 months). Patients with involvement of a single visceral or CNS site had a mean OS of 15.80±18.19 months, whereas those with two sites of involvement had a mean OS of 13.08±10.18 months. Patients with metastases in all three sites had a mean OS of 8.33±8.50 months. Treatment modalities varied among patients. For liver metastases, chemotherapy (n=6), ICI (n=2), ADC (n=1), radiation therapy (n=2), and surgery (n=1) were administered. Lung metastases were treated with chemotherapy (n=26), ICI (n=4), ADC (n=5), radiation therapy (n=4), and surgery (n=1). CNS metastases were managed with chemotherapy (n=14), ICI (n=2), ADC (n=1), radiation therapy (n=21), and surgery (n=4). Systemic therapy for liver metastases resulted in stable disease (75%) and progressive disease (25%). In lung metastases, it led to stable disease (56%), partial response (23%), complete response (13%), and progressive disease (8%). CNS metastases treated with systemic therapy demonstrated stable disease (86%) and progressive disease (14%). The most commonly used systemic therapy was paclitaxel. Immunotherapy achieved a partial response (60%), stable disease (20%), and progressive disease (20%) in metastatic lesions. Treatment with ADCs resulted in stable disease (43%), partial response (29%), and progressive disease (29%). Compared to lung metastases, liver and CNS metastases exhibited lower response rates and overall survival. CNS metastases were less likely to receive systemic therapies, indicating a need for improvement. These findings highlight the importance of personalized treatment strategies tailored to individual metastatic sites in TNBC. Citation Format: Hannah Chang, Pallavi Dev, Luise Froessl, Shao-Po Huang, Christine Hodgdon, Julia Maues, Isaac Chan. Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-13.
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Chen, Xiao-Hui, Run-Ze Guo, Ya-Xi Huang, Yuanming Pan, and Jin-Xiao Mi. "Crystal structure and magnetic properties of the magnetically isolated zigzag chain in KGaCu(PO4)2." Dalton Transactions 50, no. 22 (2021): 7835–42. http://dx.doi.org/10.1039/d1dt00819f.
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Williams, P. Mickey, Thomas Forbes, Steven P. Lund, Kenneth D. Cole, Hua-Jun He, Chris Karlovich, Cloud P. Paweletz, et al. "Validation of ctDNA Quality Control Materials Through a Precompetitive Collaboration of the Foundation for the National Institutes of Health." JCO Precision Oncology, no. 5 (May 2021): 910–20. http://dx.doi.org/10.1200/po.20.00528.
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PURPOSE We report the results from a Foundation for the National Institutes of Health Biomarkers Consortium project to address the absence of well-validated quality control materials (QCMs) for circulating tumor DNA (ctDNA) testing. This absence is considered a cause of variance and inconsistencies in translating ctDNA results into clinical actions. METHODS In this phase I study, QCMs with 14 clinically relevant mutations representing single nucleotide variants, insertions or deletions (indels), translocations, and copy number variants were sourced from three commercial manufacturers with variant allele frequencies (VAFs) of 5%, 2.5%, 1%, 0.1%, and 0%. Four laboratories tested samples in quadruplicate using two allele-specific droplet digital polymerase chain reaction and three (amplicon and hybrid capture) next-generation sequencing (NGS) panels. RESULTS The two droplet digital polymerase chain reaction assays reported VAF values very close to the manufacturers’ claimed concentrations for all QCMs. NGS assays reported most single nucleotide variants and indels, but not translocations, close to the expected VAF values. Notably, two NGS assays reported lower VAF than expected for all translocations in all QCM mixtures, possibly related to technical challenges detecting these variants. The ability to call ERBB2 copy number amplifications varied across assays. All three QCMs provided valuable insight into assay precision. Each assay across all variant types demonstrated dropouts at 0.1%, suggesting that the QCM can serve for testing of an assay’s limit of detection with confidence claims for specific variants. CONCLUSION These results support the utility of the QCM in testing ctDNA assay analytical performance. However, unique designs and manufacturing methods for the QCM, and variations in a laboratory’s testing configuration, may require testing of multiple QCMs to find the best reagents for accurate result interpretation.
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van Wezel, Esther M., Lieke M. J. van Zogchel, Jalenka van Wijk, Ilse Timmerman, Ngoc-Kim Vo, Lily Zappeij-Kannegieter, Boris deCarolis, et al. "Mesenchymal Neuroblastoma Cells Are Undetected by Current mRNA Marker Panels: The Development of a Specific Neuroblastoma Mesenchymal Minimal Residual Disease Panel." JCO Precision Oncology, no. 3 (December 2019): 1–11. http://dx.doi.org/10.1200/po.18.00413.
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PURPOSE Patients with neuroblastoma in molecular remission remain at considerable risk for disease recurrence. Studies have found that neuroblastoma tissue contains adrenergic (ADRN) and mesenchymal (MES) cells; the latter express low levels of commonly used markers for minimal residual disease (MRD). We identified MES-specific MRD markers and studied the dynamics of these markers during treatment. PATIENTS AND METHODS Microarray data were used to identify genes differentially expressed between ADRN and MES cell lines. Candidate genes were then studied using real-time quantitative polymerase chain reaction in cell lines and control bone marrow and peripheral blood samples. After selecting a panel of markers, serial bone marrow, peripheral blood, and peripheral blood stem cell samples were obtained from patients with high-risk neuroblastoma and tested for marker expression; survival analyses were also performed. RESULTS PRRX1, POSTN, and FMO3 mRNAs were used as a panel for specifically detecting MES mRNA in patient samples. MES mRNA was detected only rarely in peripheral blood; moreover, the presence of MES mRNA in peripheral blood stem cell samples was associated with low event-free survival and overall survival. Of note, during treatment, serial bone marrow samples obtained from 29 patients revealed a difference in dynamics between MES mRNA markers and ADRN mRNA markers. Furthermore, MES mRNA was detected in a higher percentage of patients with recurrent disease than in those who remained disease free (53% v 32%, respectively; P = .03). CONCLUSION We propose that the markers POSTN and PRRX1, in combination with FMO3, be used for real-time quantitative polymerase chain reaction–based detection of MES neuroblastoma mRNA in patient samples because these markers have a unique pattern during treatment and are more prevalent in patients with poor outcome. Together with existing markers of MRD, these new markers should be investigated further in large prospective studies.
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Kiss, Konrád, and Zoltán Horváth. "THE APPROACH OF PRODUCERS ORGANISATIONS TO THEIR SMALLEST MEMBERS – AN EVIDENCE FROM HUNGARIAN FRUIT AND VEGETABLE SECTOR." Annals of the Polish Association of Agricultural and Agribusiness Economists XX, no. 4 (August 23, 2018): 73–77. http://dx.doi.org/10.5604/01.3001.0012.2947.
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In today’s food-retail industry, it is very hard for small-sized agricultural producers to become suppliers of large chain stores, as these require products in large volumes and with consistent quality. Participating in producer organisations (PO-s) and selling collectively is an alternate solution for them. Producer organisations receive support from the EU. On the other hand, very small producers are even unable to successfully join PO-s. The present Hungarian case-study examines the attitudes of PO-s to the membership of small producers. We were looking for the answer that how it is worth for small-sized producers to sell through PO-s. Without the organisations, mostly the conventional sales channels (i.e. markets, small shops) or short supply chains remain for them as sale opportunities. According to the most general and comprehensive opinion of our survey, rather the reliability and keeping of the rules are important for the PO-s, and not the plant size. Specific costs of PO-s are higher in the case of small producers, but discrimination was fundamentally atypical.
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Qiao, Min, Jingzhi Wu, Nanxiao Gao, Guangcheng Shan, Fei Shen, Jian Chen, and Bosong Zhu. "Preparation and Properties of Different Polyether-Type Defoamers for Concrete." Materials 15, no. 21 (October 25, 2022): 7492. http://dx.doi.org/10.3390/ma15217492.
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In this study, a series of polyether-type defoamers for concrete which consist of the same alkyl chain (hydrophobic part) but different polyether chains (hydrophilic part) was prepared, and the structure–property relationship of the defoamers was investigated for the first time. Using oleyl alcohol (OA) as the starting agent (alkyl chain), the polyether defoamers with different polyether chains were prepared by changing the amount and sequence of ethylene oxide (EO) and propylene oxide (PO) units. The properties of different defoamers were tested in aqueous solutions, and fresh and hardened mortars; the structure–property relationship of the defoamers was thus studied. The results indicated that the defoaming capacity of the polyether defoamers decreased with an increased EO amount, and the defoamers linked with both EO and PO units (PO before EO) had a stronger defoaming capacity than those linked with EO only. This study is beneficial for the development and applications of novel synthetic polyether-type defoamers for concrete.
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Cardoso, L., M. L. Del Valle, L. Gómez, S. Pena, Á. Sanz, M. I. Garavís, M. Herrera, et al. "PO-1180 Incidental vs elective irradiation of internal mammary chain." Radiotherapy and Oncology 170 (May 2022): S1000—S1001. http://dx.doi.org/10.1016/s0167-8140(22)03144-9.
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Kozubek, A. "Determination of octanol/water partition coefficients for long-chain homologs of orcinol from cereal grains." Acta Biochimica Polonica 42, no. 2 (June 30, 1995): 247–51. http://dx.doi.org/10.18388/abp.1995_4617.
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Polycratic reversed-phase high-performance liquid chromatography (RPHPLC) was used for estimation of the octanol/water partition coefficient for three highly hydrophobic long chain orcinol homologs. The homologs studied (C 15:0, C 17:0 and C 19:0) showed high preference for hydrophobic phase as evidenced by their high octanol/water partition coefficient (log Po/w) values of 7.02-7.74; 8.71-9.47 and 10.49-11.32 for the 95% prediction interval, respectively. Experimentally estimated values were compared with log P values calculated with the use of several fragmental systems. The experimental values of log Po/w are in best agreement to those calculated with the use of the Klopman system (Klopman, G., Namboodiri, K. & Schochet, M., 1985, J. Comput. Chem. 6, 28-38). The lack of appropriate standard compounds with known log Po/w in the range over 6 markedly affected the accuracy of experimental determinations.
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Puchalska, Ewa. "Selection for resistance to acequinocyl in Amblyseius andersoni(Chant) (Anactinotrichida: Phytoseiidae)." Annals of Warsaw University of Life Sciences - SGGW - Horticulture and Landscape Architecture, no. 41 (December 2, 2020): 17–27. http://dx.doi.org/10.22630/ahla.2020.41.2.
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Większośćpestycydów stosowanych w zwalczaniu szkod-ników w sadach jest szkodliwa dla pożytecznych stawonogów. Wyselekcjonowanie drapieżców i parazytoidów odpornych na chemiczne środki ochrony roślin mogłoby przyczynić się do ich lepszego wykorzystania w uprawach, w których stosowanie pestycydów jest konieczne. Celem niniejszej pracy była selekcja linii drapieżnego roztocza Amblyseius andersoni odpornej na ace-kwinocyl – akarycyd należący do grupy inhibi-torów transportu elektronów w kompleksie III mitochondrialnego łańcucha oddechowego. Jako dawkę selekcyjną zastosowano stężenie pesty-cydu powodujące śmiertelność 55–65% zapłod-nionych samic drapieżcy. U wyselekcjonowanej laboratoryjnie linii odnotowano dziewięciokrotny wzrost oporności na acekwinocyl po dwóch cy-klach selekcyjnych i ponad 30-krotny wzrost po czterech cyklach. Wyselekcjonowana populacja A. andersoni rozwinęła również umiarkowanąoporność krzyżową na fenpiroksymat.
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Abkowicz, Anna. "Babie lato w Taszkencie." Awazymyz. Pismo historyczno-społeczno-kulturalne Karaimów 25, no. 4 (45) (December 30, 2014): 14–15. http://dx.doi.org/10.33229/az.728.
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Lutz, Gordon J., Shashank R. Sirsi, Sarah A. Shapard-Palmer, Shannon N. Bremner, and Richard L. Lieber. "Influence of myosin isoforms on contractile properties of intact muscle fibers from Rana pipiens." American Journal of Physiology-Cell Physiology 282, no. 4 (April 1, 2002): C835—C844. http://dx.doi.org/10.1152/ajpcell.00482.2001.
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The myosin heavy chain (MHC) and myosin light chain (MLC) isoforms in skeletal muscle of Rana pipiens have been well characterized. We measured the force-velocity (F- V) properties of single intact fast-twitch fibers from R. pipiens that contained MHC types 1 or 2 (MHC1 or MHC2) or coexpressed MHC1 and MHC2 isoforms. Velocities were measured between two surface markers that spanned most of the fiber length. MHC and MLC isoform content was quantified after mechanics analysis by SDS-PAGE. Maximal shortening velocity ( V max) and velocity at half-maximal tension ( V P 50) increased with percentage of MHC1 (%MHC1). Maximal specific tension (Po/CSA, where Po is isometric tension and CSA is fiber cross-sectional area) and maximal mechanical power ( W max) also increased with %MHC1. MHC concentration was not significantly correlated with %MHC1, indicating that the influence of %MHC1 on Po/CSA and W max was due to intrinsic differences between MHC isoforms and not to concentration. The MLC3-to-MLC1 ratio was not significantly correlated with V max, V P 50, Po/CSA, or W max. These data demonstrate the powerful relationship between MHC isoforms and F- V properties of the two most common R. pipiensfiber types.
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Vandenboom, R., J. Xeni, N. M. Bestic, and M. E. Houston. "Increased force development rates of fatigued mouse skeletal muscle are graded to myosin light chain phosphate content." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 272, no. 6 (June 1, 1997): R1980—R1984. http://dx.doi.org/10.1152/ajpregu.1997.272.6.r1980.
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Phosphorylation of myosin regulatory light chain (R-LC) increases the Ca2+ sensitivity of cross-bridge transitions, which determine rate of force development in skinned skeletal muscle fibers. The purpose of this study was to determine whether phosphorylation of R-LC is the molecular basis for the increased force development rates (+dF/dtmax) observed in fatigued mouse extensor digitorum longus muscle (EDL) (stimulated in vitro at 25 degrees C). Parameters of twitch and tetanic force were obtained after the application of different-frequency conditioning stimuli (CS), which were used to vary R-LC phosphorylation and reduce peak tetanic force (Po). Without CS, R-LC phosphorylation (in moles phosphate per mole R-LC) was not elevated above rest (0.11 +/- 0.02 vs. 0.13 +/- 0.02, respectively), and no aspect of the twitch (Pt) Po was altered. Stimulating muscles at 2.5-20 Hz increased R-LC phosphorylation in a frequency-dependent manner, from 0.23 +/- 0.04 to 0.82 +/- 0.03, respectively. Moreover, stimulation at 2.5-20 Hz potentiated Pt (range: 4 +/- 2-28 +/- 2%), increased the +dF/dtmax of potentiated twitches (range: 5 +/- 1-28 +/- 2%), and reduced Po (range: 6 +/- 1-21 +/- 1%). Higher-frequency stimulation (40 or 100 Hz) did not phosphorylate R-LC or potentiate Pt or twitch +dF/dtmax further. Stimulation at 40 and 100 Hz did, however, have different effects on Po compared with 20-Hz data (Po reduced 27 +/- 2 and 11 +/- 2%, respectively). The increased +dF/dtmax of potentiated twitches observed after different CS procedures were graded to R-LC phosphorylation (r = 0.97, P < 0.001). It is concluded that phosphorylation of R-LC increases extent of twitch force development in mouse EDL muscle fatigued by CS.
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Sieck, Gary C., and Wen-Zhi Zhan. "Denervation alters myosin heavy chain expression and contractility of developing rat diaphragm muscle." Journal of Applied Physiology 89, no. 3 (September 1, 2000): 1106–13. http://dx.doi.org/10.1152/jappl.2000.89.3.1106.
Full textAbstract:
We hypothesized that unilateral denervation (DNV) of the rat diaphragm muscle (Diam) in neonates at postnatal day 7 (D-7) alters normal transitions of myosin heavy chain (MHC) isoform expression and thereby affects postnatal changes in maximum specific force (Po) and maximum unloaded shortening velocity ( V o). The relative expression of different MHC isoforms was analyzed electrophoretically. With DNV at D-7, expression of MHCneo in the Diam persisted, and emergence of MHC2X and MHC2B was delayed. By D-21 and D-28, relative expression of MHC2A and MHC2Bwas reduced in DNV compared with control (CTL) animals. Expression of MHCneo also reappeared in adult Diam by 2–3 wk after DNV, and relative expression of MHC2B was reduced. At each age, Po was reduced and V o was slowed by DNV, compared with CTL. In CTL Diam, postnatal changes in Po and V o were associated with an increase in fast MHC isoform expression. In DNV Diam, no such association existed. We conclude that, in the Diam, DNV induces alterations in both MHC isoform expression and contractile properties, which are not necessarily causally linked.
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Huang, Qincheng, Xiaodan Wang, Jiadai Liu, Han Wang, Yixin Miao, Cong Zhang, Meiling Zhang, Chuanjie Qin, Jianguang Qin, and Liqiao Chen. "Effect of Vitamin A Supplementation on Growth Performance, Lipid Deposition, Antioxidant Ability, and Immunity in Juvenile Chinese Mitten Crab Eriocheir sinensis Fed Diet with Fish Oil Totally Replaced by Palm Oil." Aquaculture Nutrition 2022 (May 14, 2022): 1–19. http://dx.doi.org/10.1155/2022/3746245.
Full textAbstract:
This research evaluated the protective effect of vitamin A (VA) on the adverse effect of fish oil (FO) substitution with palm oil (PO) in an economical crab Eriocheir sinensis. Three diets of FO, PO, and PO + 8000 IU / kg VA as the main lipid sources were fed to crabs, respectively, for 8 weeks. Compared to crabs fed FO diet, crabs fed PO diet showed reduced hemolymph VA concentration, feed utilization efficiency, and growth performance. Besides, crabs fed PO diet showed elevated lipid content in hepatopancreas and body and triglyceride content in hepatopancreas, leading to decreased antioxidant enzyme and immune parameters activities from biochemical analysis, enzymatic determination, and quantitative polymerase chain reaction. In contrast, compared to crabs fed PO only, VA supplementation in PO improved the growth performance and utilization of fatty acids and reduced lipid deposition in the hepatopancreas. In addition, VA supplementation suppressed gene expression related to triglyceride synthesis (dgat1) and positively affected gene expression related to lipid catabolism (cpt1a, cpt1b, cpt2, and caat). Furthermore, VA supplementation upregulated antioxidant genes (CuZnSOD and CAT) through downregulating gene expression of upstream regulator Keap1. Furthermore, VA supplementation upregulated immune genes (Lzm and proPO) expression and reduced proinflammatory genes (LITAF, ADAM17, and IL-16) expression related to Toll2/MyD88/Relish signaling pathway. This study shows the necessity of VA addition in the feed with FO totally replaced by PO because it can relieve PO’s adverse effects and improve the growth of crabs.
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Abdullahi, N., N. B. Umar, A. U. Tsoho, A. Sani, Z. M. Yazeed, M. A. Tsangaya, Y. A. Yahaya, et al. "NIGERIAN PALM OIL: QUALITY DISPARITY, CONTAMINATION AND PROCESSING WASTES HANDLING." FUDMA JOURNAL OF SCIENCES 7, no. 1 (February 28, 2023): 126–35. http://dx.doi.org/10.33003/fjs-2023-0701-1263.
Full textAbstract:
The review article intended to provide an overview of quality variation and various contaminants in locally processed palm oil (PO). The paper also deliberates on the pros and cons of wastes generated during PO processing. There is a serious concern about the quality and safety of crude PO in Nigeria resulting from poor quality raw materials, inadequate processing know-how, inappropriate packaging and storage facilities, poor handling and transportation system and more importantly adulteration by producers and marketers. Wide disparities in the chemical and physical composition were reported in the literature. This may result from the variations in the chemical composition of the palm fruit, environmental factors, variation in processing operations which is determined by the location and abuse during handling and transportation. Microbial contamination is the foremost safety challenge in Nigerian crude PO processing. Higher microbial counts and the presence of toxic microorganisms including aflatoxins-producing fungi were reported by many researchers. Oil palm production in contaminated soil account for PO heavy metals contamination, though, heavy metals contamination below permissible limits was reported in most cases. Wastes generated from PO processing can be detrimental to the environment. Alternately, various benefits can be derived from the proper handling and utilisation of PO processing wastes. Palm oil mill effluent (POME) is a good substrate for the production of organic manure, biomolecules and amendment of oil-contaminated soil. Recommendations on how to tackle various challenges along the PO supply chain were presented at the end of the paper.
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Widrick, Jeffrey J., Julian E. Stelzer, Todd C. Shoepe, and Dena P. Garner. "Functional properties of human muscle fibers after short-term resistance exercise training." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 2 (August 1, 2002): R408—R416. http://dx.doi.org/10.1152/ajpregu.00120.2002.
Full textAbstract:
The aim of this study was to assess the relationships between human muscle fiber hypertrophy, protein isoform content, and maximal Ca2+-activated contractile function following a short-term period of resistance exercise training. Six male subjects (age 27 ± 2 yr) participated in a 12-wk progressive resistance exercise training program that increased voluntary lower limb extension strength by >60%. Single chemically skinned fibers were prepared from pre- and posttraining vastus lateralis muscle biopsies. Training increased the cross-sectional area (CSA) and peak Ca2+-activated force (Po) of fibers containing type I, IIa, or IIa/IIx myosin heavy chain by 30–40% without affecting fiber-specific force (Po/CSA) or unloaded shortening velocity (Vo). Absolute fiber peak power rose as a result of the increase in Po, whereas power normalized to fiber volume was unchanged. At the level of the cross bridge, the effects of short-term resistance training were quantitative (fiber hypertrophy and proportional increases in fiber Po and absolute power) rather than qualitative (no change in Po/CSA, Vo, or power/fiber volume).
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Jeon, Jong Yeob, Seong Chan Eo, Jobi Kodiyan Varghese, and Bun Yeoul Lee. "Copolymerization and terpolymerization of carbon dioxide/propylene oxide/phthalic anhydride using a (salen)Co(III) complex tethering four quaternary ammonium salts." Beilstein Journal of Organic Chemistry 10 (August 5, 2014): 1787–95. http://dx.doi.org/10.3762/bjoc.10.187.
Full textAbstract:
The (salen)Co(III) complex 1 tethering four quaternary ammonium salts, which is a highly active catalyst in CO2/epoxide copolymerizations, shows high activity for propylene oxide/phthalic anhydride (PO/PA) copolymerizations and PO/CO2/PA terpolymerizations. In the PO/PA copolymerizations, full conversion of PA was achieved within 5 h, and strictly alternating copolymers of poly(1,2-propylene phthalate)s were afforded without any formation of ether linkages. In the PO/CO2/PA terpolymerizations, full conversion of PA was also achieved within 4 h. The resulting polymers were gradient poly(1,2-propylene carbonate-co-phthalate)s because of the drift in the PA concentration during the terpolymerization. Both polymerizations showed immortal polymerization character; therefore, the molecular weights were determined by the activity (g/mol-1) and the number of chain-growing sites per 1 [anions in 1 (5) + water (present as impurity) + ethanol (deliberately fed)], and the molecular weight distributions were narrow (M w/M n, 1.05–1.5). Because of the extremely high activity of 1, high-molecular-weight polymers were generated (M n up to 170,000 and 350,000 for the PO/PA copolymerization and PO/CO2/PA terpolymerization, respectively). The terpolymers bearing a substantial number of PA units (f PA, 0.23) showed a higher glass-transition temperature (48 °C) than the CO2/PO alternating copolymer (40 °C).