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631.
Kun-Chun Chiang Chun-Nan Yeh Jun-Te Hsu Ta-sen Yeh Yi-yin Jan Chun-Te Wu Huang-Yang Chen Shyh-Chuan Jwo Masashi Takano Atsushi Kittaka Horng-Heng Juang Tai C. Chen 《Cell cycle (Georgetown, Tex.)》2013,12(8):1316-1325
Pancreatic cancer is a lethal disease with no known effective chemotherapy and radiotherapy, and most patients are diagnosed in the late stage, making them unsuitable for surgery. Therefore, new therapeutic strategies are urgently needed. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is known to possess antitumor actions in many cancer cells in vitro and in vivo models. However, its clinical use is hampered by hypercalcemia. In this study, we investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We demonstrate that MART-10 is at least 100-fold more potent than 1α,25(OH)2D3 in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner, accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21 and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4 and 5, leading to a greater increase in the fraction of cells in G0/G1 phase. No induction of apoptosis and no effect on Cdc25 phosphatases A and C were observed in the presence of either MART-10 or 1α,25(OH)2D3. In a xenograft mouse model, treatment with 0.3 µg/kg body weight of MART-10 twice/week for 3 weeks caused a greater suppression of BxPC-3 tumor growth than the same dose of 1α,25(OH)2D3 without inducing hypercalcemia and weight loss. In conclusion, MART-10 is a promising agent against pancreatic cancer growth. Further clinical trial is warranted. 相似文献
632.
Bishoy El-Aarag Alshaimaa Attia Magdy Zahran Ali Younes Ehab Tousson 《Saudi Journal of Biological Sciences》2021,28(11):6384-6395
The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms. 相似文献
633.
Markus Weber Kambiz Taraz Herbert Budzikiewicz Valérie Geoffroy Jean-Marie Meyer 《Biometals》2000,13(4):301-309
From Pseudomonas sp. CFML 96.188 a pyoverdine was isolated and its primary structure was elucidated by spectroscopic methods and degradation reactions. This strain is of interest as it accepts the structurally different pyoverdines from several other Pseudomonas strains. They all have in common as a specific structural feature a C-terminal cyclic substructure, the importance of which for the recognition of a pyoverdine at the cell surface of a given strain will be discussed. 相似文献
634.
E Lam 《FEBS letters》1984,172(2):255-260
The reconstituted system containing Photosystem I, plastocyanin and the cytochrome b6-f complex is used to study the effects of various quinone analogues on the redox behavior of cytochrome b6. The effects of DBMIB, DNP-INT and HQNO are compared in an attempt to discern the modes of action of these quinone analogues. Both DBMIB and DNP-INT are potent inhibitors of the plastocyanin reductase activity of the isolated cytochrome complex. However, while DBMIB abolished the oxidant-induced reduction of cytochrome b6, DNP-INT only inhibited about 25% of the net reduction. On the other hand, HQNO does not show any significant inhibition of plastocyanin reductase activity of the isolated cytochrome complex at concentrations up to 20 microM. An enhancement of the net amount of cytochrome b6 reduced is observed in the presence of HQNO. Both DNP-INT and HQNO inhibited the dark oxidation rate of cytochrome b6. The possible identity of the oxidant for cytochrome b6 is discussed. Plastoquinone is concluded to be the most likely candidate. DNP-INT is concluded to have at least two sites of inhibition in the cytochrome complex. The implications of these findings on quinone functions in the cytochrome b6-f complex are discussed. 相似文献
635.
Siderophore activity of chemically synthesized dihydroxybenzoyl derivatives of spermidines and cystamide 总被引:1,自引:1,他引:0
Chemically synthesized dihydroxybenzoyl derivatives of spermidine and cystamide containing two-, three- and four-bidentates with the hydroxyl groups in 2,3 or 3,4 position were examined in cross-feeding tests using Gram-negative siderophore indicator strains carrying different iron-related markers, and two Mycobacterium spp. The catecholates were unable to feed tonB mutants of E. coli and S. typhimurium as well as the fepA, fiu, cir mutant of E. coli, pointing to a tonB- and fepA, cir, fiu-dependent transport. Bis(2,3-dihydroxybenzoyl)derivatives promoted Salmonella spp, E. coli, K. pneumoniae and P. aeruginosa strains significantly better than did 3,4-dihydroxybenzoyl derivatives. N-substituted spermidines acted more effectively than non-substituted derivatives. Bis(2,3-dihydroxybenzoyl) cystamide was superior to the other catecholates tested in growth promotion of Gram-negative bacteria. The two four-bidentates and the tri-bidentate reacted to K. pneumoniae in an inhibitory mode. The position of the hydroxyl groups did not significantly influence the growth promotion of M. smegmatis and M. fortiutum in the cases of substituted spermidines and of cystamides. 相似文献
636.
637.
David Samuel Johnston Sukhpal Sanghera Arturo Manjon-Rubio Dennis Chapman 《生物化学与生物物理学报:生物膜》1980,602(1):213-216
Diacetylenic fatty acid monolayers at the air/water interface and multilayers on suitable supports polymerise when exposed to ultraviolet radiation. It has been found that polymerisation still occurs when monolayers are diluted with cholesterol or gramicidin. The rigid, crystalline nature of the films formed makes them useful biomembrane models. Phospholipids made from the fatty acids were less reactive. Multilayers deposited on hydrophobic supports would polymerise but not monolayers on water. 相似文献
638.
639.
Noriyuki Okujo Miki Saito Shigeo Yamamoto Takashi Yoshida Shinichi Miyoshi Sumio Shinoda 《Biometals》1994,7(2):109-116
A new siderophore named vulnibactin has been isolated from low iron cultures of Vibrio vulnificus, a human pathogen. The structure was established as N-[3-(2,3-dihydroxybenzamido)propyl]-1,3-bis[2-(2-hydroxyphenyl)-trans-5-methyl-2-oxazoline-4-carboxamido]propane by a combination of acid hydrolysis, nuclear magnetic resonance spectroscopy and positive fast atom bombardment mass spectrometry. Vulnibactin is characterized as containing one residue of 2,3-dihydroxybenzoic acid as well as two residues of salicylic acid, both of which are involved in the formation of oxazoline rings with l-threonine bound to a norspermidine backbone. In addition, two other compounds with siderophore activity were purified and their structures were also determined. These two compounds provided further support for the structure of vulnibactin. 相似文献
640.
To test the efficacy and clinical safety of a low and high dose of the GnRH antagonist, acyline, on estrous cycle interruption and anovulation in female dogs, 20 proestrous (<3 d) bitches were randomly assigned to one of the following pharmacological protocols (given sc): acyline 110 μg/kg (ACY-L; n = 6); acyline 330 μg/kg (ACY-H; n = 8); or placebo (PLACE, n = 6). The animals were monitored (clinical and vaginal cytology examinations) daily for 60 d. Blood samples for serum progesterone serum concentrations were collected 14 d after treatment to determine if ovulation had occurred. Appearance of side effects and days to the onset of the first spontaneous estrous cycle after treatment were also recorded. In both ACY groups, but not the PLACE group, estrous cycles were interrupted after treatment (P < 0.05). The interval from treatment to estrus interruption in ACY-L and ACY-H groups was 3.0 ± 0.6 and 3.2 ± 0.2 d, respectively (LSM ± SEM; P > 0.05). In the PLACE bitches, physical, behavioral and cytological proestrus slowly progressed to estrus and diestrus. Ovulation was absent in all ACY, but not in PLACE bitches (P < 0.05). None of the females manifested side effects related to the treatments (P > 0.05). Spontaneous return to a normal estrous cycle during the study period occurred in all ACY (ACY-L 19.5 ± 2.7 d vs ACY-H 24.8 ± 2.0 d; P > 0.05), but in none of the PLACE bitches (P < 0.05). In conclusion, acyline efficiently, safely and reversibly interrupted an early phase of the estrous cycle in bitches by preventing ovulation. 相似文献