BACKGROUND Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity. METHODS Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (...

Kinesin motor proteins comprise an ATPase superfamily that works hand in hand with microtubules in every eukaryote. The mitotic kinesins, by virtue of their potential therapeutic role in cancerous cells, have been a major focus of research for the past 28 years since the discovery of the canonical Kinesin-1 heavy chain. Perhaps the simplest player in mitotic spindle assembly, Kinesin-5 (also kn...

The integration of novel agents (for example, proteasome inhibitors, IMiDS) into frontline therapy for multiple myeloma (MM) has significantly improved response rates and increased progression-free survival. Nevertheless, most patients with MM relapse often with resistant disease. Several clinical trials assessing the current role of high-dose chemotherapy (HDT) with autologous stem cell transp...

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper architecture is established by set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 are essential for this process, genetic or chemical inhibition their activity leads the emergence monopolar spindles cell death. However, these deficiencies can be rescued simultaneou...

UNLABELLED Evaluation of patient's response to chemotherapeutic drugs is often difficult and time consuming. Skin punch biopsies are easily accessible material that can be used for the evaluation of surrogate biomarkers of a patient's response to a drug. In this study, we hypothesized that assessment of phosphorylated histone H3 in human skin punch biopsies could be used as a pharmacodynamics b...

T umors are characterized by excessive proliferation and, therefore, chemotherapeutics that target proteins involved in tumor cell division can be effective anticancer agents. However, as many of these proteins are involved in core mechanisms in dividing and nondividing cells, these therapeutic agents do not selectively kill tumor cells and their efficacy is limited by general toxicity. As new ...

We have developed a new model system for studying spindle elongation in vitro using the pennate, marine diatom Cylindrotheca fusiformis. C. fusiformis can be grown in bulk to high densities while in log phase growth and synchronized by a simple light/dark regime. Isolated spindles can be attained in quantities sufficient for biochemical analysis and spindle tubulin is approximately 5% of the to...

AIM Profiling the efficacy and pharmacodynamic activity of the kinesin spindle protein (KSP) inhibitor ARRY-520 will aid the identification of responsive tumor types and pharmacodynamic profiles that correlate with activity. MATERIALS AND METHODS In vivo activity was evaluated in a diverse panel of 16 different tumor xenograft models. Pharmacodynamic activity was evaluated in selected models....

Eg5/KSP is the kinesin-related motor protein that generates the major plus-end directed force for mitotic spindle assembly and dynamics. Recent work using a dimeric form of Eg5 has found it to be a processive motor; however, its mechanochemical cycle is different from that of conventional Kinesin-1. Dimeric Eg5 appears to undergo a conformational change shortly after collision with the microtub...