US-Led Economic Sanctions Strangle Iran’s Drug Supply.

US-led economic sanctions strangle Iran’s drug supply.

Filed under: Drug and Alcohol Rehabilitation

Lancet. 2013 Jan 26; 381(9863): 279
Mohammadi D

HubMed – drug


WNT5A-NFAT Signaling Mediates Resistance to Apoptosis in Pancreatic Cancer.

Filed under: Drug and Alcohol Rehabilitation

Neoplasia. 2013 Jan; 15(1): 11-22
Griesmann H, Ripka S, Pralle M, Ellenrieder V, Baumgart S, Buchholz M, Pilarsky C, Aust D, Gress TM, Michl P

WNT5A belongs to the Wnt family of secreted signaling molecules. Using transcriptional profiling, we previously identified WNT5A as target of the antiapoptotic transcription factor CUX1 and demonstrated high expression levels in pancreatic cancer. However, the impact of WNT5A on drug resistance and the signaling pathways employed by WNT5A remain to be elucidated.This project aims to decipher the impact of WNT5A on resistance to apoptosis and the signaling pathways employed by WNT5A in pancreatic cancer.The impact of WNT5A and its downstream effectors on tumor growth and drug resistance was studied in vitro and in xenograft models in vivo. Tissue microarrays of pancreatic cancer specimens were employed for immunohistochemical studies.Knockdown of WNT5A results in a significant increase in drug-induced apoptosis. In contrast, overexpression of WNT5A or addition of recombinant WNT5A mediates resistance to apoptosis in vitro. In our attempt to identify downstream effectors of WNT5A, we identified the transcription factor nuclear factor of activated T cells c2 (NFATc2) as transcriptional target of WNT5A signaling. NFATc2 confers a strong antiapoptotic phenotype mediating at least in part the effects of WNT5A on drug resistance and tumor cell survival. In vivo, WNT5A expression leads to resistance to gemcitabine-induced apoptosis in a xenograft model, which is paralleled by up-regulation of NFATc2. Both WNT5A and NFATc2 proteins are highly expressed in human pancreatic cancer tissues and their expression levels correlated significantly.We identified the WNT5A-NFATc2 axis as important mediator of drug resistance in pancreatic cancer.
HubMed – drug


CPT-11 Chemotherapy Rescued A Patient with Atypical Sclerosing Epithelioid Fibrosarcoma from Emergent Condition.

Filed under: Drug and Alcohol Rehabilitation

Chin J Cancer Res. 2012 Sep; 24(3): 253-6
Pan CH, Han XQ, Li JS

Sclerosing epithelioid fibrosarcoma (SEF) is a rare and poorly defined variant of fibrosarcoma, but generally insensitive to chemotherapy and progresses with poor prognosis. We report the marvelous effect of irinotecan hydrochloride (CPT-11) chemotherapy in rescuing a patient with atypical SEF from emergent condition, who underwent recurrences after several treatment methods. Small dose of CPT-11 was administered to the patient, with which, the size of superficial mass (cervical lymph node) gradually decreased observed by the naked eyes in 5 days. X-ray and CT image proved a marked reduction in the size of the tumor. CPT-11 is valuable for the treatment of this aggressive sarcoma. In condition of emergency caused by sarcoma oppression, administering a tolerable small dose of topoisomerase I-inhibiting drug could be a beneficial choice.
HubMed – drug


Short hairpin RNA-mediated MDR1 gene silencing increases apoptosis of human ovarian cancer cell line A2780/Taxol.

Filed under: Drug and Alcohol Rehabilitation

Chin J Cancer Res. 2012 Jun; 24(2): 138-42
Xu H, Hong FZ, Li S, Zhang P, Zhu L

Recurrent ovarian cancer is often resistant to drugs such as paclitaxel. Short hairpin RNA (shRNA) targeting MDR1, a gene involved in the process of drug resistance, may be a promising strategy to overcome drug resistance.Construction and identification of eukaryotic expression plasmid of shRNA targeting on MDR1 gene. The plasmid was transiently transfected into human ovarian cancer cell line A2780/Taxol. Apoptosis was determined by flow cytometry using annexin V-FITC/PI double labeling. Expression of MDR1 mRNA was detected by quantitative polymerase chain reaction (qPCR) and P-glycoprotein expression was detected using Western blot.The IC50 of paclitaxel in MDR1shRNA-transfected group was significantly reduced (1.986±0.153) ?mol/ml as compared with that in negative control (5.246±0.107) ?mol/ml and empty vector-transfected group (5.212±0.075) ?mol/ml (P<0.05). The percent of the relative reverse sensitivity to paclitaxel on A2780/Taxol cells was 67.1%, and the apoptotic rate was significantly increased [(6.977±0.333)%] compared with control [(1.637±0.111)%] and empty vector-transfected group [(1.663±0.114)%] (P<0.05). Expressions of MDR1 mRNA and P-glycoprotein were significantly reduced compared with control (P<0.05).The present study demonstrated that the eukaryotic expression plasmid of shRNA targeting on MDR1 inhibited the expression of MDR1 effectively, thus enhance the sensitivity of A2780/Taxol cells to paclitaxel. HubMed – drug


Glycogen Synthase Kinase 3? Inhibitor (2’Z,3’E)-6-Bromo-indirubin- 3′-Oxime Enhances Drug Resistance to 5-Fluorouracil Chemotherapy in Colon Cancer Cells.

Filed under: Drug and Alcohol Rehabilitation

Chin J Cancer Res. 2012 Jun; 24(2): 116-23
Liu KP, Luo F, Xie SM, Tang LJ, Chen MX, Wu XF, Zhong XY, Zhao T

To explore the effects and mechanism of glycogen synthase kinase 3? (GSK-3?) inhibitor (2’Z,3’E)-6-bromo-indirubin-3′-oxime (BIO) on drug resistance in colon cancer cells.The colon cancer SW480 and SW620 cells were treated with BIO, 5-fluorouracil (5-FU) and BIO/5-FU, separately. Cell cycle distribution, apoptosis level and efflux ability of rhodamine 123 (Rh123) were detected by flow cytometry. The protein expressions of P-glycoprotein (P-gp), multidrug resistance protein 2 (MRP2), thymidylate synthase (TS), ?-catenin, E2F-1 and Bcl-2 were detected by Western blot. ?-catenin and P-gp were stained with double immunofluorescence and observed under a confocal microscope.BIO up-regulated ?-catenin, P-gp, MRP2 and TS, enhanced the efflux ability of Rh123, decreased Bcl-2 protein and gave the opposite effect to E2F-1 protein in SW480 and SW620 cells. Furthermore, BIO significantly inhibited cell apoptosis, increased S and G(2)/M phase cells, and reduced the cell apoptosis induced by 5-FU in SW480 cells, whereas the effects were slight or not obvious in SW620 cells.GSK-3? was involved in drug resistance regulation, and activation of ?-catenin and inhibition of E2F-1 may be the most responsible for the enhancement of 5-FU chemotherapy resistance induced by GSK-3? inhibitor BIO in colon cancer.
HubMed – drug


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