PD173074, a selective FGFR inhibitor, reverses MRP7 (ABCC10)-mediated MDR

Multidrug resistance protein 7 (MRP7, ABCC10) is a recently identified member of the ATP-binding cassette (ABC) transporter family, which adequately confers resistance to a diverse group of antineoplastic agents, including taxanes, vinca alkaloids and nucleoside analogs among others. Clinical studies indicate an increased MRP7 expression in non-small cell lung carcinomas (NSCLC) compared to a normal healthy lung tissue. Recent studies revealed increased paclitaxel sensitivity in the Mrp7(-/-) mouse model compared to their wild-type counterparts. This demonstrates that MRP7 is a key contributor in developing drug resistance. Recently our group reported that PD173074, a specific fibroblast growth factor receptor (FGFR) inhibitor, could significantly reverse P-glycoprotein-mediated MDR. However, whether PD173074 can interact with and inhibit other MRP members is unknown. In the present study, we investigated the ability of PD173074 to reverse MRP7-mediated MDR. We found that PD173074, at non-toxic concentration, could significantly increase the cellular sensitivity to MRP7 substrates. Mechanistic studies indicated that PD173074 (1 μmol/L) significantly increased the intracellular accumulation and in-turn decreased the efflux of paclitaxel by inhibiting the transport activity without altering expression levels of the MRP7 protein, thereby representing a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients.

Comprehensive Review of Asian Cosmetic Upper Eyelid Oculoplastic Surgery: Asian Blepharoplasty and the Like

BACKGROUND: Asian Aesthetic Oculoplastic Surgery is a fast-growing field, both within the United States and abroad. With growing interest, there have also been multiple terminologies used for the same concepts. This has created redundant and confusing language - prone to errors in patient-physician communication. In addition, there has been an upsurge of various techniques or variations to existing techniques that has created unnecessary confusion among plastic surgeons. The objective of this article is to provide organization and simplification to the terminology and to the techniques used in what some broadly refer to as "Asian Blepharoplasty" or perhaps more correctly termed Asian Aesthetic Oculoplastic Surgery. METHODS: Unified terminology, aesthetic goal and detailed operative technique of commonly conducted Asian blepharoplasty were suggested by experienced oculoplastic surgeons. RESULTS: The main procedures of Asian Aesthetic Oculoplastic Surgery including supratarsal crease surgery and medial epicanthoplasty were presented with figure and video in this paper. We also have provided author's preferred selection of the major techniques with evaluation of its advantages and disadvantages. CONCLUSIONS: The most important element in patient satisfaction is clear communication of surgical expectations. Then, proper selection of the most suitable pre-operative design, type of surgery performed, and specific crease configuration based on the individual's anatomic and physiological characteristics can be achieved.

Efficacy and safety of Firebird sirolimus-eluting stent in treatment of complex coronary lesions in Chinese patients: one-year clinical and eight-month angiographic outcomes from the FIREMAN registry / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Off-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.</p><p><b>METHODS</b>The FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.</p><p><b>RESULTS</b>Long lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.</p><p><b>CONCLUSIONS</b>The results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)</p>

Numerical simulations of ice accumulation under ice cover along a river bend

In this paper, the k-epsilon two-equation turbulence model has been used to simulate ice accumulation under ice cover along a river bend. A 2D depth-averaged numerical model has been developed in a nonorthogonal coordinate system with nonstaggered curvilinear grids. In this model, the contravariant velocity has been treated as an independent variable. To avoid the pressure oscillation in the nonstaggered grids, the momentum interpolation has been introduced to interpolate variables at the interface. The discretization equations have been solved by using pressure correction algorithms. An equation has been developed for describing the deformation of ice jam bottom. The thickness distribution of ice accumulation [ice jam] along the bend has been simulated. The developed model has been applied to the experimental studies under different conditions carried out at the Hefei University of Technology. Results indicate that all simulated thickness of ice accumulation agrees reasonably well with the measured thickness of ice accumulation in laboratory

Validation of a multiplex RT-PCR assay for screening significant oncogene fusion transcripts in children with acute lymphoblastic leukaemia

In childhood acute lymphoblastic leukaemia (ALL), cytogenetics play an important role in diagnosis, allocation of treatment and prognosis. Conventional cytogenetic analysis, involving mainly karyotyping in our experience, has not been successful in a large proportion of cases due to inadequate metaphase spreads and poor chromosome morphology. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent fusion transcripts resulting from specific chromosomal translocations, namely, both the CML- and ALLtype BCR-ABL transcripts of t(9;22), E2A-PBX1 transcript of t(1;19), the MLL-AF4 transcript of t(4;11) and TEL-AML1 (also termed ETV6-CBFA2) of the cryptic t(12;21). A multiplex reverse transcription polymerase chain reaction protocol (RT-PCR) was developed and tested out on archival bone marrow samples and leukaemia cell lines. In all samples with a known translocation detected by cytogenetic techniques, the same translocation was identified by the multiplex-PCR assay. Multiplex RT-PCR assay is an effective, sensitive, accurate and cost-effective diagnostic tool which can improve our ability to accurately and rapidly risk-stratify patients with childhood ALL.