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1.
Chun A. Changou Her-Shyong Shiah Li-Tzong Chen Servina Liu Frank Luh Shwu-Huey Liu Yung-Chi Cheng Yun Yen 《The oncologist》2021,26(3):e367-e373
Lessons Learned
- A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
- This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.
2.
Ta-Kun Chen Chung-Chieh Chang Hsian-Hong Chang Ai-Hua Fang Chih-Han Wang Wei-Hsiang Chao Chuan-Ming Tseng Yung-Chi Lee Yu-Ruei Wu Min-Hsueh Wen Hsin-Yu Tang Fu-Rong Chen Ming-Jye Wang Maw-Kuen Wu Dirk Van Dyck 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(1):63-68
Several superconducting transition temperatures in the range of 30–46 K were reported in the recently discovered intercalated FeSe system (A1-xFe2-ySe2, A = K, Rb, Cs, Tl). Although the superconducting phases were not yet conclusively decided, more than one magnetic phase with particular orders of iron vacancy and/or potassium vacancy were identified, and some were argued to be the parent phase. Here we show the discovery of the presence and ordering of iron vacancy in nonintercalated FeSe (PbO-type tetragonal β-Fe1-xSe). Three types of iron-vacancy order were found through analytical electron microscopy, and one was identified to be nonsuperconducting and magnetic at low temperature. This discovery suggests that the rich-phases found in A1-xFe2-ySe2 are not exclusive in Fe-Se and related superconductors. In addition, the magnetic β-Fe1-xSe phases with particular iron-vacancy orders are more likely to be the parent phase of the FeSe superconducting system instead of the previously assigned β-Fe1+δTe.The iron pnictide superconductors have opened the door to a new way to obtain superconductivity at very high temperatures. β-Fe1+δSe is remarkable among those superconductors in that it contains the essential electronic and structural constituents required for superconductivity without the conceptual complexity seen in other systems (1). Previous studies showed that the superconducting property of β-Fe1+δSe made under high-temperature thermodynamic conditions is very sensitive to stoichiometry (1, 2). In the Fe-Se binary phase diagram (2–4), the PbO-type tetragonal structure (the β phase) only stabilized at the Fe-rich side (δ = 0.01–0.04), whereas bulk superconductivity was observed in samples with δ close to 0.01 (5). McQueen et al. showed no superconductivity for samples with δ = 0.03 (5). On the other hand, the fact that only one superconducting phase has been reported in FeSe, unlike the other Fe-As–based superconductors that exhibit clear doping dependence of superconductivity and the absence of superconductivity in FeTe, led to the suggestion that FeTe is the nonsuperconducting parent compound of FeSe (6). Thus, the phase diagram derived from this picture shows very different features compared with other Fe-As–based superconductors (6, 7). In this work, we use low-temperature synthesis methods to prepare β-Fe1-xSe for a wide range of compositions, which allows for the determination for the composition-dependent electronic behavior for this important superconducting system.The recent discovered alkali/alkaline-intercalated iron selenide (A1-xFe2-ySe2) superconductors with rich superconducting phases, where A = K, Rb, Cs, Tl, attracted great attention not only due to its high superconducting transition temperature (Tc, up to 46 K) (8), but also because of their dissimilar characteristics compared with other iron-based superconductors, especially its seemingly intrinsic multiphase nature and the presence of iron vacancies and orders in the nonsuperconducting regime (9–13). The most frequently observed Fe-vacancy order in A1-xFe2-ySe2 is the × × 1 superstructure, which yields a phase of A0.8Fe1.6Se2 (or A2Fe4Se5). Scanning tunneling microscopy (STM) (11, 14, 15) and transport studies (12, 13, 16, 17) showed that A2Fe4Se5 is an antiferromagnetic (AFM) insulator. Neutron scattering measurements (9) revealed a blocked checkerboard AFM with magnetic moments along the c axis for A2Fe4Se5, ordered at a temperature as high as >500 K, with an unexpected large ordered magnetic moment of ∼3.3 μB/Fe at 10 K. Experiments have further shown that the type of vacancy and magnetic orders is highly sensitive to the stoichiometry (x and y) of A1-xFe2-ySe2. Reports have shown the existence of other Fe-vacancy order with the forms × × 1 (10), × 2 × 1 (13, 18), and × × 1 (19). However, the magnetic properties such as the type and transition temperature of the magnetic order are far less studied compared with that of the K2Fe4Se5 phase. In addition, there were also results showing in K1-xFe2-ySe2 samples with a typical Tc = 31 K and additional superconducting phase with Tc = 44 K (20), whereas no clear identification of the new phases was available.The complexity of phases and phase separation during crystal preparation in A1-xFe2-ySe2 make it difficult to conclusively verify the phase-property relationship, even for the superconducting phases. β-Fe1+δSe, on the other hand, has the simplest structure among all iron-based superconductor families. Several surprising results related to the Fe-Se system appeared in the literature during the last few years, including the enhancement of Tc to about 40 K under high pressure (21–23) and the intriguing extremely high Tc (with a superconducting energy gap of ∼20 meV) in molecular beam epitaxy (MBE)-grown single-layer FeSe (24–26). We also demonstrated the presence of a superconducting-like feature with Tc close to 40 K in samples of nano-dimensional form (27). Therefore, it is quite natural to ask whether the presence of the complex phases observed in A1-xFe2-ySe2 compounds and Fe-vacancy order exist in samples without alkaline metals. Here we present the first discovery of iron vacancies and three types of vacancy orders in tetragonal β-Fe1-xSe, characterized by analytical transmission electron microscopy (TEM). Our observations imply that an unprecedented phase diagram should be considered in the Fe-Se superconductors. 相似文献
3.
Tzu-Fang Wang Someswara Rao Kosuru Shu-Chun Yu Yung-Chi Chang Hsin-Yu Lai Yu-Lun Chang Kuo-Hui Wu Shangwu Ding Hsuan-Ying Chen 《RSC advances》2020,10(67):40690
Using TiOiPr4 with a pyrazole ligand for one-pot LA polymerization improved catalytic activity compared with using TiOiPr4 only. At 60 °C, TiOiPr4 with furPz exhibited a higher catalytic activity (approximately 3-fold) than TiOiPr4. At room temperature, TiOiPr4 with BuPz exhibited a higher catalytic activity (approximately 17-fold) than TiOiPr4. High molecular mass PLA (MnGPC = 51 100, and Đ = 1.10) could be produced by using TiOiPr4 with furPz in melt polymerization ([TiOiPr4] : [furPz] = 1000 : 1 : 1 at 100 °C, 240 min). The crystal structure of MePz2Ti2OiPr7 revealed the cooperative activation between two Ti atoms during LA polymerization.Using TiOiPr4 with a pyrazole ligand for one-pot LA polymerization improved catalytic activity compared with using TiOiPr4 only. 相似文献
4.
Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates 总被引:5,自引:0,他引:5
Pyrimidine nucleoside monophosphate kinase [UMP/CMP kinase (UMP/CMPK);EC 2.7.4.14] plays a crucial role in the formation of UDP, CDP, and dCDP, which are required for cellular nucleic acid synthesis. Several cytidine and deoxycytidine analogues are important anticancer and antiviral drugs. These drugs require stepwise phosphorylation to their triphosphate forms to exert their therapeutic effects. The role of UMP/CMPK for the phosphorylation of nucleoside analogues has been indicated. Thus, we cloned the human UMP/CMPK gene, expressed it in Escherichia coli, and purified it to homogeneity. Its kinetic properties were determined. UMP and CMP proved to be far better substrates than dCMP. UMP/CMPK used all of the nucleoside triphosphates as phosphate donors, with ATP and dATP being the best donors and CTP being the poorest. Furthermore, UMP/CMPK was able to phosphorylate all of the deoxycytidine analogue monophosphates that we tested. The relative efficiency was as follows: arabinofuranosyl-CMP > dCMP > beta-L-2',3'-dideoxy-3'-thia-CMP > Gemcitabine monophosphate > beta-D-2',3'-dideoxy-CMP; beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluoro-CMP; beta-L-2',3'-dideoxy-5-fluoro-3'-thia-CMP > beta-L-2',3'-dideoxy-CMP > beta-L-dioxolane-CMP. By comparing the relative V(max)/K(m) values of D- and L-form dideoxy-CMP, we showed that this kinase lacked stereoselectivity. Reducing agents, such as DTT, 2-mercaptoethanol, and thioredoxin, were able to activate this enzyme, suggesting that its activity may be regulated by redox potential in vivo. UMP/CMPK localized predominantly to the cytoplasm. In addition, 196-amino acid UMP/CMPK was the actual form of UMP/CMPK, rather than the 228-amino acid form as suggested before. 相似文献
5.
Yan Z Kern ER Gullen E Cheng YC Drach JC Zemlicka J 《Journal of medicinal chemistry》2005,48(1):91-99
Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC(50) 0.25-1.1 microM). The Z-pronucleotides 7a and 7b had EC(50) 3.6-25.2 and 3-18.4 microM, respectively. The EC(50) of cyclic phosphate 10a was 6.0-20 microM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC(50) 2.3-3.4 microM against EBV/H-1, but 7b was cytotoxic (CC(50) 3.8 microM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC(50) 0.96 microM), but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC(50) 6.3 and 7.3 microM, respectively, and hepatitis B virus (HBV, EC(50) 4.1 microM). Cyclic phosphate 10a was the most effective analogue against HBV (EC(50) 0.8 microM). 相似文献
6.
Chang YC Hsu TL Lin HH Chio CC Chiu AW Chen NJ Lin CH Hsieh SL 《Journal of leukocyte biology》2004,75(3):486-494
Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily and is readily detected in certain cancer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell responses to a T helper cell type 2 phenotype. In this study, we further asked its ability to modulate CD14+ monocyte differentiation into macrophages induced by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able to modulate the expression of several macrophage markers, including CD14, CD16, CD64, and human leukocyte antigen-DR. In contrast, the expression of CD11c, CD36, CD68, and CD206 (mannose receptor) was not affected in the in vitro culture system. Moreover, phagocytic activity toward immune complexes and apoptotic bodies as well as the production of free radicals and proinflammatory cytokines in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte-derived macrophages. This suggests that DcR3.Fc might have potent, suppressive effects to down-regulate the host-immune system. 相似文献
7.
Chen X Kern ER Drach JC Gullen E Cheng YC Zemlicka J 《Journal of medicinal chemistry》2003,46(8):1531-1537
A series of 13 new (S,Z)-2-aminopurine methylenecyclopropane analogues was synthesized, and their antiviral activity was investigated. The nucleophilic displacement of chlorine of 2-amino-6-chloropurine derivative 5 with allyl-, propargyl-, cyclopropylmethyl-, isopropyl-, benzyl-, cyclohexyl-, and 2-hydroxyethylamine gave N(6)-alkyl compounds 2a, 2b, 2c, 2d, 2e,2f, and 2g. A similar reaction of 5 with allyl, cyclopropylmethyl, propyl, or pentyl alcohol catalyzed by K(2)CO(3) afforded O(6)-alkyl analogues 3a, 3c, 3h and 3i. Propane- and pentanethiol furnished S(6)-alkyl compounds 4h and 4i. The N(6)-alkyl derivatives 2a, 2b, O(6) analogues 3a, 3c, 3h, 3i, and S(6) compounds 4h, 4i which were highly effective in all CMV assays and exhibited the lowest cytotoxicity in proliferating HFF cells appear to be good candidates for in vivo assays. Activity of new analogues against HSV-1 or HSV-2 was restricted to BSC-1 and Vero cultures. Compounds 2c, 2b, 3a and 3h were effective against EBV in one of two assays (Daudi or H-1). Analogues 3a and 4i were the most active anti-VZV agents whereas compounds 3h, 3i, and 4h inhibited the replication of HBV in a micromolar concentration range. 相似文献
8.
Antiviral Action and Cellular Toxicity of Four Thymidine Analogues: 5-Ethyl-, 5-Vinyl-, 5-Propyl-, and 5-Allyl-2′-Deoxyuridine 下载免费PDF全文
Yung-Chi Cheng Barbara A. Domin Ram A. Sharma Miroslav Bobek 《Antimicrobial agents and chemotherapy》1976,10(1):119-122
5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2'-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK(-) cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK(-) mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK(-) cells at a concentration of 25 muM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK(-) cells at a concentration of 1 muM. 相似文献
9.
10.
Kummar S Copur MS Rose M Wadler S Stephenson J O'Rourke M Brenckman W Tilton R Liu SH Jiang Z Su T Cheng YC Chu E 《Clinical colorectal cancer》2011,10(2):85-96
PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38. 相似文献