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排序方式: 共有638条查询结果,搜索用时 11 毫秒
1.
Eugen Musch Mouhamad Malek Jasna Peter-Katalinic Heinz Egge Hermann Rink Bernd Lathan Eberhard Riedel 《Cancer chemotherapy and pharmacology》1992,29(4):297-304
Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen 相似文献
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The reaction of the potassium salt of acrylic acid with the potassium salt of a dicarboxylic acid and 1,4-dibromobutane was applied to the synthesis of three series of acrylate-terminated copolyesters: poly(tetramethylene maleate-co-tetramethylene phthalate) (BMPA), poly(tetramethylene fumarate-co-tetramethylenephthalate) (BFPA) and poly(tetramethylene phthalate-co-tetramethylene succinate) (BPSA). The monofunctional monomer, the potassium salt of acrylic acid, was used for the introduction of double bonds at the end of the chains and for the regulation of the molecular weight of the polyesters. The telechelic copolyesters were characterized by 1H and 13C NMR spectroscopy, in almost all cases providing an acrylate functionality of two. 相似文献
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Jasna E. Deluce Luisa Cardenas Aly-Khan Lalani Saman Maleki Vareki Ricardo Fernandes 《Current oncology (Toronto, Ont.)》2022,29(7):5054
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy. 相似文献
5.
Barbara Fumić Jasna Jablan Dominik Cinčić Marijana Zovko Končić 《Journal of microencapsulation》2018,35(1):1-12
This work aimed to investigate the potential effect of cyclodextrin encapsulation on intrinsic ability of daidzein (DAD) and genistein (GEN) to inhibit the glycosaminoglycan (GAG) synthesis in fibroblasts originating from patients with mucopolysaccharidosis (MPS), type II and III. DAD or GEN encapsulation with either 2-hydroxypropyl-β-cyclodextrin or sulphobuthylether-β-cyclodextrin were achieved by neat grinding and were characterised by thermal analysis, X-ray powder diffraction, scanning electron microscopy and solubility testing which confirmed the complexes formation with increased solubility with respect to starting compounds. Both isoflavones, as well as their co-ground cyclodextrin complexes reduced GAG levels in the fibroblasts of MPS II and MPS III patients from 54.8–77.5%, in a dose dependent manner, without any significant cytotoxic effect. Cyclodextrin encapsulation did not change the intrinsically high effect of both DAD and GEN on the GAG level reduction in the treated cells, thus could be considered as a part of combination therapies of MPS. 相似文献
6.
I Bohacek P Cordeau M Lalancette Hébert D Gorup YC Weng S Gajovic J Kriz 《Journal of neuroinflammation》2012,9(1):191
ABSTRACT: BACKGROUND: : Using live imaging approach we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll like Receptor 2 (TLR2) biophotonic signals. However, the role of TLR2 (and potentially other TLRs), beyond the acute innate immune response and an early neuroprotection against ischemic injury is not well understood. METHOD: S: The TLR2 -/- mice were subjected to transient middle cerebral artery occlusion (MCAO) followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. RESULTS: : Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2 -/- mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24-72hrs) were smaller in TLR2 -/- mice, the observed alterations in innate immune response were more pronounces at later time-points (at day 7) after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared to WT mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/antiapoptotic factor IGF-1, expressed by microglia in the areas in- and around ischemic lesion. CONCLUSION: Altogether our results clearly suggest that optimal and timely microglial activation/innate immune response is needed to limit neuronal damage after stroke. 相似文献
7.
Nicolas Biais Dustin L. Higashi Jasna Bruji? Magdalene So Michael P. Sheetz 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(25):11358-11363
Through evolution, nature has produced exquisite nanometric structures, with features unrealized in the most advanced man-made devices. Type IV pili (Tfp) represent such a structure: 6-nm-wide retractable filamentous appendages found in many bacteria, including human pathogens. Whereas the structure of Neisseria gonorrhoeae Tfp has been defined by conventional structural techniques, it remains difficult to explain the wide spectrum of functions associated with Tfp. Here we uncover a previously undescribed force-induced quaternary structure of the N. gonorrhoeae Tfp. By using a combination of optical and magnetic tweezers, atomic force microscopy, and molecular combing to apply forces on purified Tfp, we demonstrate that Tfp subjected to approximately 100 pN of force will transition into a new conformation. The new structure is roughly 3 times longer and 40% narrower than the original structure. Upon release of the force, the Tfp fiber regains its original form, indicating a reversible transition. Equally important, we show that the force-induced conformation exposes hidden epitopes previously buried in the Tfp fiber. We postulate that this transition provides a means for N. gonorrhoeae to maintain attachment to its host while withstanding intermittent forces encountered in the environment. Our findings demonstrate the need to reassess our understanding of Tfp dynamics and functions. They could also explain the structural diversity of other helical polymers while presenting a unique mechanism for polymer elongation and exemplifying the extreme structural plasticity of biological polymers. 相似文献
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Tom Platteau Katrien Fransen Ludwig Apers Chris Kenyon Laura Albers Tine Vermoesen Jasna Loos Eric Florence 《Journal of medical Internet research》2015,17(9)