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921.
922.
Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies 总被引:4,自引:0,他引:4
Hau P Jachimczak P Schlingensiepen R Schulmeyer F Jauch T Steinbrecher A Brawanski A Proescholdt M Schlaier J Buchroithner J Pichler J Wurm G Mehdorn M Strege R Schuierer G Villarrubia V Fellner F Jansen O Straube T Nohria V Goldbrunner M Kunst M Schmaus S Stauder G Bogdahn U Schlingensiepen KH 《Oligonucleotides》2007,17(2):201-212
Transforming growth factor-beta2 (TGF-beta2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-beta2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitro experiments have been performed to prove specificity and efficacy of the TGF-beta2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase I/II-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-beta2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-beta-2-overexpressing tumors. 相似文献
923.
Dong A Xu X Edwards AM;Midwest Center for Structural Genomics;Structural Genomics Consortium Chang C Chruszcz M Cuff M Cymborowski M Di Leo R Egorova O Evdokimova E Filippova E Gu J Guthrie J Ignatchenko A Joachimiak A Klostermann N Kim Y Korniyenko Y Minor W Que Q Savchenko A Skarina T Tan K Yakunin A Yee A Yim V Zhang R Zheng H Akutsu M Arrowsmith C Avvakumov GV Bochkarev A Dahlgren LG Dhe-Paganon S Dimov S Dombrovski L Finerty P Flodin S Flores A Gräslund S Hammerström M Herman MD Hong BS 《Nature methods》2007,4(12):1019-1021
We tested the general applicability of in situ proteolysis to form protein crystals suitable for structure determination by adding a protease (chymotrypsin or trypsin) digestion step to crystallization trials of 55 bacterial and 14 human proteins that had proven recalcitrant to our best efforts at crystallization or structure determination. This is a work in progress; so far we determined structures of 9 bacterial proteins and the human aminoimidazole ribonucleotide synthetase (AIRS) domain. 相似文献
924.
925.
Bettendorff L Wirtzfeld B Makarchikov AF Mazzucchelli G Frédérich M Gigliobianco T Gangolf M De Pauw E Angenot L Wins P 《Nature chemical biology》2007,3(4):211-212
Several important cofactors are adenine nucleotides with a vitamin as the catalytic moiety. Here, we report the discovery of the first adenine nucleotide containing vitamin B1: adenosine thiamine triphosphate (AThTP, 1), or thiaminylated ATP. We discovered AThTP in Escherichia coli and found that it accumulates specifically in response to carbon starvation, thereby acting as a signal rather than a cofactor. We detected smaller amounts in yeast and in plant and animal tissues. 相似文献
926.
Akunevich Anastasia Aleksandrovna Khrustalev Vladislav Victorovich Khrustaleva Tatyana Aleksandrovna Poboinev Victor Vitoldovich Shalygo Nikolai Vladimirovich Stojarov Aleksander Nicolaevich Arutyunyan Alexander Migranovich Kordyukova Larisa Valentinovna Sapon Yehor Gennadyevich 《The protein journal》2022,41(2):245-259
The Protein Journal - An interplay between monomeric and dimeric forms of human epidermal growth factor (EGF) affecting its interaction with EGF receptor (EGFR) is poorly understood. While EGF... 相似文献
927.
928.
Aquatic Ecology - The invasive crayfish Faxonius immunis is regarded as a threat to amphibians and macroinvertebrates in the Upper Rhine Valley, Germany, eradicating macrophytes and establishing... 相似文献
929.
930.
Ryan Greenway Rachel McNemee Alexander Okamoto Martin Plath Lenin Arias‐Rodriguez Michael Tobler 《Evolution; international journal of organic evolution》2019,73(6):1200-1212
Divergence of genital traits among lineages has the potential to serve as a reproductive isolating barrier when copulation, insemination, and fertilization are inhibited by incompatibilities between female and male genitalia. Despite widespread evidence for genital trait diversity among closely related lineages and coevolution of female and male genitalia within lineages, few studies have investigated genital evolution during the early stages of speciation. We quantified genital variation in replicated population pairs of Poecilia mexicana with ongoing ecological speciation between sulfidic (H2S containing) and nearby nonsulfidic habitats. These analyses revealed rapid and correlated divergence of female and male genitalia across evolutionarily independent population pairs exposed to divergent selection regimes. Both sexes exhibited convergent evolution of genital traits among populations inhabiting similar habitat types. Our results demonstrate that genital evolution can occur during the early stages of speciation‐with‐gene‐flow, potentially as a result of variation in the intensity of sexual conflict among populations. Our results suggest genitalia may contribute to early stages of divergence and challenge the generality of previously suggested mechanisms of genital evolution in poeciliids. 相似文献