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101.
102.
Istvn Kacsir Adrienn Sipos Attila Bnyei Eszter Janka Pter Bugly Lszl Somsk Pter Bai va Bokor 《International journal of molecular sciences》2022,23(2)
Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: (1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; (2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; (3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents. 相似文献
103.
肺黏膜相关淋巴组织型淋巴瘤的免疫组织化学和电镜观察 总被引:1,自引:0,他引:1
探讨肺黏膜相关淋巴组织型淋巴瘤(MALTLoma)的免疫表型和超微结构特点,对3例经开胸肺活检病理诊断的肺MALTLoma进行光镜和透射电镜观察以及免疫组化染色。光镜观察发现,瘤细胞主要由中心细胞样淋巴细胞、小淋巴细胞样瘤细胞组成;3例均有淋巴上皮性损伤和反应性淋巴滤泡以及淋巴滤泡的克隆化。免疫组化显示瘤细胞表达B细胞相关抗原。透射电镜观察发现,在支气管黏膜上皮和肺泡上皮细胞周围以及肺泡腔内有较多的淋巴细胞源性瘤细胞浸润,瘤细胞具有淋巴细胞的超微结构特点。对肺MALToma的超微结构观察为该瘤的研究提供了形态学依据,电镜观察对判断瘤细胞的来源和免疫表型有帮助。 相似文献
104.
Jiewei Wei David Y Chin Dallia Catzel Natasha Pera Stephen M Mahler 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2005,80(7):782-795
Human CD48, a membrane‐bound, glycosylphosphatidylinositol (GPI)‐linked glycoprotein, is a potential tumour target for the treatment of leukaemias and lymphomas. CD48 is expressed on T‐ and B‐cells, however <5% of CD34+ progenitor cells express CD48. A truncated, 45 kDa soluble form of the full length CD48 was expressed in Chinese hamster ovary (CHO) cells, and was shown to consist of a broad range of charge isoforms, with the most abundant isoforms between pI 4.5 and 5.0. The truncated form of CD48 was shown to bind to antibodies raised against native, GPI‐linked CD48 by surface plasmon resonance analysis. A synthetic, human, scFv immunoglobulin gene library was screened against recombinant CD48 by phage display, and an scFv antibody fragment, (designated N2A) was isolated after four rounds of biopanning. N2A was reassembled as a human IgG1 human monoclonal antibody, expressed in CHO cells and the binding of IgG1‐N2A to recombinant CD48 was confirmed by surface plasmon resonance. Flow cytometry studies of IgG1‐N2A binding to Raji cells showed the specificity of N2A for GPI‐linked CD48 was conserved, and presents the potential for IgG1‐N2A as a lead antibody candidate for the treatment of white blood cell malignancies. Copyright © 2005 Society of Chemical Industry 相似文献
105.
目的报告2例外周T细胞淋巴瘤-非特指型(peripheral T lymphocytes unspecified,PTCL-U)患者的临床、实验室指标及诊治和预后,以提高对该类疾病的认识。方法对2例PTCL-U患者的病例资料进行分析,并结合国内外相关文献进行复习。结果 PTCL-U临床特点为发热、淋巴结肿大,易侵犯肝、脾、骨髓、皮肤等结外部位和并发噬血细胞综合征。病情进展快,对化疗不敏感,2例均死亡。结论 PTCL-U恶性程度高,进展快,侵袭性强,预后极差,需提高对该病的识别,以期早期诊断和积极治疗。 相似文献
106.
af Gennäs GB Mologni L Ahmed S Rajaratnam M Marin O Lindholm N Viltadi M Gambacorti-Passerini C Scapozza L Yli-Kauhaluoma J 《ChemMedChem》2011,6(9):1680-1692
In anaplastic large-cell lymphomas, chromosomal translocations involving the kinase domain of anaplastic lymphoma kinase (ALK), generally fused to the 5' part of the nucleophosmin gene, produce highly oncogenic ALK fusion proteins that deregulate cell cycle, apoptosis, and differentiation in these cells. Other fusion oncoproteins involving ALK, such as echinoderm microtubule-associated protein-like 4-ALK, were recently found in patients with non-small-cell lung, breast, and colorectal cancers. Recent research has focused on the development of inhibitors for targeted therapy of these ALK-positive tumors. Because kinase inhibitors that target the inactive conformation are thought to be more specific than ATP-targeted inhibitors, we investigated the possibility of using two known inhibitors, doramapimod and sorafenib, which target inactive kinases, to design new urea derivatives as ALK inhibitors. We generated a homology model of ALK in its inactive conformation complexed with doramapimod or sorafenib in its active site. The results elucidated why doramapimod is a weak inhibitor and why sorafenib does not inhibit ALK. Virtual screening of commercially available compounds using the homology model of ALK yielded candidate inhibitors, which were tested using biochemical assays. Herein we present the design, synthesis, biological activity, and structure-activity relationships of a novel series of urea compounds as potent ALK inhibitors. Some compounds showed inhibition of purified ALK in the high nanomolar range and selective antiproliferative activity on ALK-positive cells. 相似文献
107.
108.
Isaias Hernndez-Verdin Karim Labreche Marion Benazra Karima Mokhtari Khê Hoang-Xuan Agusti Alentorn 《International journal of molecular sciences》2021,22(1)
B-cell non-Hodgkin’s lymphoma (NHL) risk associations had been mainly attributed to family history of the disease, inflammation, and immune components including human leukocyte antigen (HLA) genetic variations. Nevertheless, a broad range of genome-wide association studies (GWAS) have shed light into the identification of several genetic variants presumptively associated with B-cell NHL etiologies, survival or shared genetic risk with other diseases. The present review aims to overview HLA structure and diversity and summarize the evidence of genetic variations, by GWAS, on five NHL subtypes (diffuse large B-cell lymphoma DLBCL, follicular lymphoma FL, chronic lymphocytic leukemia CLL, marginal zone lymphoma MZL, and primary central nervous system lymphoma PCNSL). Evidence indicates that the HLA zygosity status in B-cell NHL might promote immune escape and that genome-wide significance variants can give biological insight but also potential therapeutic markers such as WEE1 in DLBCL. However, additional studies are needed, especially for non-DLBCL, to replicate the associations found to date. 相似文献
109.
110.
Ekaterina Mikhailovna Stasevich Aksinya Nicolaevna Uvarova Matvey Mikhailovich Murashko Elmira Ramilevna Khabusheva Saveliy Andreevich Sheetikov Vladimir Sergeyevich Prassolov Dmitriy Vladimirovich Kuprash Denis Eriksonovich Demin Anton Markovich Schwartz 《International journal of molecular sciences》2022,23(9)