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排序方式: 共有391条查询结果,搜索用时 15 毫秒
191.
目的 探讨小剂量HA(LD-HA)方案及标准方案序贯诱导法治疗高危急性非淋巴细胞白血病(ANLL)的疗效.方法 对50例不适合常规诱导的高危ANLL患者(LD-HA组)进行了序贯诱导.第1个周期诱导方案为LD-HA,首次诱导仍未缓解者,更换为标准方案(DA或HA)诱导.选择同期以DA或HA方案诱导治疗的23例ANLL患者(DA/HA组)作为对照,最多诱导2个周期.结果 LD-HA组患者完全缓解率为80.0%(40/50),诱导过程死亡2例;中位无瘤生存时间为19.6个月,中位生存时间为12.2个月;1、3、5年生存率分别为57.0%、24.1%、18.8%.DA/HA组共17例完全缓解,缓解率为73.9%;中位无瘤生存时间为19.8个月,中位生存时间为12.1个月;1、3、5年生存率分别为56.58%、27.1%、27.1%,两组相比,1、3、5年生存率差异无统计学意义(x2值分别为0.009、0.237、1.807,P值均>0.05).结论 以LD-HA及标准方案序贯诱导高危ANLL患者,可获得较高的完全缓解率及长期生存率. 相似文献
192.
Elena A. Filippova Marina V. Fridman Alexey M. Burdennyy Vitaly I. Loginov Irina V. Pronina Svetlana S. Lukina Alexey A. Dmitriev Eleonora A. Braga 《International journal of molecular sciences》2021,22(13)
Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., E2F1, EZH2, and YAP), DNA (e.g., the insulin receptor promoter), and various microRNAs (miRNAs). In breast cancer, GAS5 binds with miR-21, miR-222, miR-221-3p, miR-196a-5p, and miR-378a-5p that indicates the presence of several elements for miRNA binding (MREs) in GAS5. Mediated by the listed miRNAs, GAS5 is involved in the upregulation of a number of mRNAs of suppressor proteins such as PTEN, PDCD4, DKK2, FOXO1, and SUFU. Furthermore, the aberrant promoter methylation is involved in the regulation of GAS5 gene expression in triple-negative breast cancer and some other carcinomas. GAS5 can stimulate apoptosis in breast cancer via diverse pathways, including cell death receptors and mitochondrial signaling pathways. GAS5 is also a key player in the regulation of some crucial signal pathways in breast cancer, such as PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB signaling. Through epigenetic and other mechanisms, GAS5 can increase sensitivity to multiple drugs and improve prognosis. GAS5 is thus a promising target in the treatment of breast cancer patients. 相似文献
193.
Berger O Kaniti A van Ba CT Vial H Ward SA Biagini GA Bray PG O'Neill PM 《ChemMedChem》2011,6(11):2094-2108
Four different series of triazole diamidines have been prepared by the Pinner method from the corresponding triazole dinitriles. Copper‐catalyzed “click chemistry” was used for the synthesis of 1,4‐ and 4,5‐substituted triazoles, aryl magnesium acetylide reagents for the 1,5‐substituted triazoles, with a thermal dipolar addition reaction employed for the 2,4‐substituted triazoles. In vitro antimalarial activity against two different PfCRT‐modified parasite lines (Science 2002 , 298, 210–213) of Plasmodium falciparum and inhibition of hemozoin formation were determined for each compound. Several diamidines with potent nanomolar antimalarial activities were identified, and selected molecules were resynthesized as their diamidoxime triazole prodrugs. One of these prodrugs, OB216, proved to be highly potent in vivo with an ED50 value of 5 mg kg?1 (po) and an observed 100 % cure rate (CD100) of just 10 mg kg?1 by oral (po) administration in mice infected with P. vinckei. 相似文献
194.
195.
Doreen Kunze Kati Erdmann Michael Froehner Manfred P. Wirth Susanne Fuessel 《International journal of molecular sciences》2013,14(6):12297-12312
The overexpression of antiapoptotic genes, such as Bcl-xL and survivin, contributes to the increased survival of tumor cells and to the development of treatment resistances. In the bladder cancer cell lines EJ28 and J82, the siRNA-mediated knockdown of survivin reduces cell proliferation and the inhibition of Bcl-xL sensitizes these cells towards subsequent chemotherapy with mitomycin C and cisplatin. Therefore, the aim of this study was to analyze if the simultaneous knockdown of Bcl-xL and survivin might represent a more powerful treatment option for bladder cancer than the single inhibition of one of these target genes. At 96 h after transfection, reduction in cell viability was stronger after simultaneous inhibition of Bcl-xL and survivin (decrease of 40%–48%) in comparison to the single target treatments (decrease of 29% at best). Furthermore, simultaneous knockdown of Bcl-xL and survivin considerably increased the efficacy of subsequent chemotherapy. For example, cellular viability of EJ28 cells decreased to 6% in consequence of Bcl-xL and survivin inhibition plus cisplatin treatment whereas single target siRNA plus chemotherapy treatments mediated reductions down to 15%–36% only. In conclusion, the combination of simultaneous siRNA-mediated knockdown of antiapoptotic Bcl-xL and survivin—a multitarget molecular-based therapy—and conventional chemotherapy shows great potential for improving bladder cancer treatment. 相似文献
196.
Patricia Urbán Joan Estelrich Alberto Adeva Alfred Cortés Xavier Fernàndez-Busquets 《Nanoscale research letters》2011,6(1):620
Paul Ehrlich''s dream of a ''magic bullet'' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusively to the selected targets. In a previous work, we engineered an immunoliposomal nanovector for the targeted delivery of its contents exclusively to Plasmodium falciparum-infected red blood cells [pRBCs]. In preliminary assays, the antimalarial drug chloroquine showed improved efficacy when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal antibody BM1234. Because difficulties in determining the exact concentration of the drug due to its low amounts prevented an accurate estimation of the nanovector performance, here, we have developed an HPLC-based method for the precise determination of the concentrations in the liposomal preparations of chloroquine and of a second antimalarial drug, fosmidomycin. The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs. The targeting antibody used binds preferentially to pRBCs containing late maturation stages of the parasite. In accordance with this observation, the best performing immunoliposomes are those added to Plasmodium cultures having a larger number of late form-containing pRBCs. An average of five antibody molecules per liposome significantly improves in cell cultures the performance of immunoliposomes over non-functionalized liposomes as drug delivery vessels. Increasing the number of antibodies on the liposome surface correspondingly increases performance, with a reduction of 50% parasitemia achieved with immunoliposomes encapsulating 4 nM chloroquine and bearing an estimated 250 BM1234 units. The nanovector prototype described here can be a valuable platform amenable to modification and improvement with the objective of designing a nanostructure adequate to enter the preclinical pipeline as a new antimalarial therapy. 相似文献
197.
Shreyas P. Vaidya Dr. Malay Patra 《Chembiochem : a European journal of chemical biology》2021,22(21):2998-3000
Chemotherapy is the primary treatment modality employed in the clinic for the treatment of cancer. Despite proven clinical success, adverse side effects are one of the drawbacks of this approach. The prodrug strategy has emerged as an alternative approach with the aim of alleviating these drawbacks. Prodrug activation is typically achieved by either endogenous or exogenous triggers. Exogenous triggers like light are appealing as they are independent of inherent patient and/or cancer-type variations. However, tissue penetration depth remains the Achilles’ heel of this approach. In this context, usage of X-rays as the external trigger with infinite tissue penetration depth opens up exciting prospects in prodrug activation strategies. 相似文献
198.
Bakhshali Massoumi Mojtaba Abbasian Rana Jahanban‐Esfahlan Sanaz Motamedi Hadi Samadian Aram Rezaei Hossein Derakhshankhah Amir Farnudiyan‐Habibi Mehdi Jaymand 《Polymer International》2020,69(5):519-527
Novel pH‐responsive PEGylated hollow nanocapsules (HNCaps) were fabricated through a combination of distillation–precipitation copolymerization and surface thiol–ene ‘click’ grafting reaction. For this purpose, SiO2 nanoparticles were synthesized using the Stöber approach, and then modified using 3‐(trimethoxysilyl)propyl methacrylate (MPS). Afterward, a mixture of triethyleneglycol dimethacrylate (as crosslinker), acrylic acid (AA; as pH‐responsive monomer) and MPS‐modified SiO2 nanoparticles (as sacrificial template) was copolymerized using the distillation–precipitation approach to afford SiO2@PAA core–shell nanoparticles. The SiO2 core was etched from SiO2@PAA using HF solution, and the obtained PAA HNCaps were grafted with a thiol‐end‐capped poly(ethylene glycol) (PEG) through a thiol–ene ‘click’ reaction to produce PAA‐g‐PEG HNCaps. The fabricated HNCaps were loaded with doxorubicin hydrochloride (DOX) as a model anticancer drug, and their drug loading and encapsulation efficiencies as well as pH‐dependent drug release behavior were investigated. The anticancer activity of the drug‐loaded HNCaps was extensively evaluated using MTT assay against human breast cancer cells (MCF7). The cytotoxicity assay results as well as superior physicochemical and biological features of the fabricated HNCaps mean that the developed DOX‐loaded HNCaps have excellent potential for cancer chemotherapy. © 2020 Society of Chemical Industry 相似文献
199.
Tianqun Lang Yiran Liu Zhong Zheng Wei Ran Yihui Zhai Qi Yin Pengcheng Zhang Yaping Li 《Advanced materials (Deerfield Beach, Fla.)》2019,31(5)
Metastatic breast cancer may be resistant to chemo‐immunotherapy due to the existence of cancer stem cells (CSC). Also, the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing the therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti‐CSC agent thioridazine (THZ), and the PD‐1/PD‐L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual‐sensitive nanoparticle with a micelle–liposome double‐layer structure. The particle size shrinks when the nanoparticle transfers from circulation to tumor tissues, favoring both pharmacokinetics and cellular uptake, meanwhile achieving sequential drug release where needed. This nano device, named PM@THL, increases the intratumoral drug concentrations in mice and exhibits significant anticancer efficacy, with tumor inhibiting rate of 93.45% and lung metastasis suppression rate of 97.64%. It also reduces the proportion of CSC and enhances the T cells infiltration in tumor tissues, and thus prolongs the survival of mice. The cocktail therapy based on the spatio‐temporally controlled nano device will be a promising strategy for treating breast cancer. 相似文献
200.
Katsunori Matsushita Takumi Okuda Dr. Shohei Mori Dr. Masamitsu Konno Dr. Hidetoshi Eguchi Dr. Ayumu Asai Dr. Jun Koseki Dr. Yoshifumi Iwagami Dr. Daisaku Yamada Dr. Hirofumi Akita Dr. Tadafumi Asaoka Dr. Takehiro Noda Dr. Koichi Kawamoto Dr. Kunihito Gotoh Dr. Shogo Kobayashi Dr. Yuuya Kasahara Dr. Kunihiko Morihiro Prof. Dr. Taroh Satoh Prof. Dr. Yuichiro Doki Prof. Dr. Masaki Mori Prof. Dr. Hideshi Ishii Prof. Dr. Satoshi Obika 《ChemMedChem》2019,14(15):1384-1391
The main concern in the use of anticancer chemotherapeutic drugs is host toxicity. Patients need to interrupt or change chemotherapy due to adverse effects. In this study, we aimed to decrease adverse events with gemcitabine (GEM) in the treatment of pancreatic ductal adenocarcinoma and focused on the difference of hydrogen peroxide levels in normal versus cancer cells. We designed and synthesized a novel boronate-ester-caged prodrug that is activated by the high H2O2 concentrations found in cancer cells to release GEM. An H2O2-activatable GEM (A-GEM) has higher selectivity for H2O2 over other reactive oxygen species (ROS) and cytotoxic effects corresponding to the H2O2 concentration in vitro. A xenograft model of immunodeficient mice indicated that the effect of A-GEM was not inferior to that of GEM when administered in vivo. In particular, myelosuppression was significantly decreased following A-GEM treatment compared with that following GEM treatment. 相似文献