BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2018
·
IF 1.492
Ao Man,Xiao Xu,Ao Yazhou
In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 1
·e14434
·
IF 3.2
Liyang Liu,Wusong Xue
Heaps of studies have verified the effects of thalidomide (THA) on colorectal cancer (CRC). Howbeit, the corresponding mechanism awaits illustration, which is the foothold of this study. Following the treatment of 0, 1.94, 7.75, or 19.36 μM THA, CRC cell viability, apoptosis, migration, and invasion were evaluated by methyl tetrazolium, flow cytometry, wound-healing, and transwell assays. Homeobox B7 (HOXB7) expression in CRC was analyzed and detected by bioinformatics analysis, quantitative real-time PCR or western blot. After the corresponding transfection or treatment with inhibitor of catenin-responsive transcription-3 (iCRT-3), abovementioned CRC cell biological behaviors as well as expression levels of HOXB7 and β-catenin were evaluated. 7.75 and 19.36 μM THA dwindled CRC cell viability, migration, and invasion, and facilitated apoptosis. HOXB7 upregulation was detected in CRC cells, which promoted the viability, migration, invasion, and β-catenin expression, and weakened the apoptosis of CRC cells. Also, HOXB7 upregulation counteracted the effects of THA on CRC cells. iCRT-3 restrained β-catenin expression, viability, migration, and invasion, whereas promoting the apoptosis of CRC cells. In addition, iCRT-3 antagonized the effects of overexpressed HOXB7 on CRC cells. THA inhibits the migration and invasion of CRC cells, which is achieved by suppressing HOXB7-mediated activation of Wnt/β-catenin signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Xuanrong Sun,Yubei Gong,Ting Xie,Zixi Fu,Dongze Lu,Bin Wei,Yue Cai,Wenlong Yao,Jie Shen
Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy. To optimize the synergistic treatment of CPT-11 and THA, co-loaded liposomes are constructed using cholesterol, lecithin, and 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG) as the “immune and gut microbiota regulator.” The co-loaded liposomes, which possess good stability, are prepared by the solvent injection method. After the treatment with the co-loaded liposomes, tumor growth in CRC-bearing mice is significantly inhibited. In particular, the co-loaded liposomes demonstrate favorable diarrhea-relieving effects through the modulation of inflammatory cytokines and gut microbiota. These findings suggest that the co-loaded liposomes have great potential as a combined drug-delivery platform for CRC therapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2014
·Vol. 11
·期 3
·2341-2347
·
IF 1.484
Xin‑Yu Wu,Rui‑Tai Fan,Xin‑Hui Yan,Jing Cui,Jun‑Ling Xu,Hao Gu,Yong‑Ju Gao
Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X‑box binding protein 1 splice process, glucose‑regulated protein 78 kD and ER degradation‑enhancing α‑mannosidase‑like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co‑γ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation‑induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.
研究领域:
肿瘤学
·
辐射生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Jia Liu,Liu-Huan Yi,Yi-Xuan He,Wen-Jie Chen,Yan-Fang Wang,Liu-Pan Yang,Li-Li Wang
Thalidomide ( THD ) is a pharmacological agent characterized by notable immunomodulatory and anti-angiogenic activities. However, due to its severe teratogenicity and toxicity, regular monitoring of blood concentrations in patients is essential for preventing and controlling adverse reactions, as well as for tailoring individualized dosing regimens. Herein, by utilizing the indicator displacement assay (IDA) approach, a supramolecular sensor for highly sensitive and selective detection of THD was successfully developed based on an amide hybridtube ( HT ) and phenoxazine dyes. Attributed to the high affinity and selective binding of HT for THD in water (up to 2.49 × 10 6 M −1 ), the sensor exhibited excellent detection performance in both phosphate buffer and serum matrices, with linear ranges of 0.15–5.8 μM and detection limits of 0.017 μM and 0.059 μM, respectively. What's more, the method successfully achieved accurate detection of THD in pharmaceutical formulations and clinical serum samples, demonstrating its high sensitivity and remarkable anti-interference capability. To our knowledge, this is the first “turn-on” fluorescent probe capable of effectively quantifying THD in complex matrices. This breakthrough is poised to offer critical technical support for both research and clinical applications
研究领域:
分析化学
·
生物化学
·
药学
·
超分子化学
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Zhengjie Meng,Bowen Fu,Zheng Yang,Yuhua Xu,Haixiao Huang,Yunhao Bai,Xue Fang,Shuilin Shen,Jing Yang,Jiahui Yong,Xinyue Tao,Chenyu Ma,Wenjun Miao,Hao Ren,Yonglu Wang,Hao Xu,Xueming Li
High levels of proinflammatory cytokines, macrophage polarization status and immune-mediated angiogenesis play pivotal roles in the pathogenesis of inflammatory bowel disease (IBD). Thalidomide, an anti-inflammatory, immunomodulatory and antiangiogenic agent, is used off-label for treatment of IBD. The therapeutic potential of thalidomide is limited by its poor solubility and side effects associated with its systemic exposure. To address these issues and promote its therapeutic effects on IBD, thalidomide nanocrystals (Thali NCs) were prepared and coated with polydopamine (PDA), a potential macrophage polarization modulator, to form PDA coated Thali NCs ( [email protected] ). [email protected] possessed a high drug loading and displayed average particle size of 764.7 ± 50.30 nm. It showed a better anti-colitis effect than bare thalidomide nanocrystals at the same dose of thalidomide. Synergistic effects of polydopamine on anti-inflammatory and anti-angiogenic activities of thalidomide were observed. Furthermore, PDA coating could direct polarization of macrophages towards M2 phenotype, which boosted therapeutic effects of [email protected] on IBD. Upon repeated dosing of [email protected] for one week, symptoms of IBD in mice were significantly relieved, and histomorphology of the colitis colons were normalized. Key proinflammatory cytokine levels in the inflamed intestines were significantly decreased. Toxicity study also revealed that [email protected] is a safe formulation.
研究领域:
药理学
·
免疫学
·
纳米技术
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 40
·期 1
·e71387
·
IF 4.2
Jingya Zhu,Xinyue Yu,Chaojuan Wen,Youao Zhang,Xielan Kuang,Nan Sun,Shiyu Tang,Bing Xiao,Sainan Xiao,Xun Wang,Kaili Wu,Qingjiong Zhang,Huangxuan Shen
Thalidomide, a glutamate derivative with teratogenicity, possesses anti-inflammatory, immunomodulatory, and anti-angiogenic properties that enable its use in treating refractory diseases unresponsive to conventional therapies. Dry age-related macular degeneration (AMD), characterized by retinal pigment epithelium (RPE) degeneration and lacking effective therapies, represents a significant unmet medical need. Our findings demonstrated that thalidomide significantly restores mitochondrial function, alleviates G2/M phase cell cycle arrest, and suppresses sustained endoplasmic reticulum (ER) stress in oxidatively injured RPE cells. Mechanistically, these effects are coordinated through E2F2 activation, which subsequently regulates FBXO5 expression. Moreover, thalidomide was able to ameliorate oxidative stress-induced retinal structural disorders and RPE degeneration, and improve visual function in mice. In summary, this study elucidates that thalidomide synergistically regulates cell cycle progression and endoplasmic reticulum homeostasis through the E2F2-FBXO5 signaling pathway, providing a new drug candidate and therapeutic target for the prevention and treatment of dry AMD. Graphical Schematic diagram of the cytoprotective mechanism of thalidomide in RPE cells. Thalidomide activates the transcription factor E2F2, which upregulates FBXO5 expression. This E2F2-FBXO5 pathway coordinately alleviates G2/M phase cell cycle arrest, restores mitochondrial function, and suppresses endoplasmic reticulum stress, thereby protecting RPE cells from oxidative damage.
研究领域:
眼科学
·
分子生物学
·
细胞生物学
·
药理学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）