Cyclophosphamide "metronomic" chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer

BACKGROUND: Evaluation of the clinical efficacy and tolerance of metronomic chemotherapy as salvage therapy in a young patient with advanced, platinum resistant, ovarian carcinoma and bad performance status. CASE PRESENTATION: We tried palliative chemotherapy with daily low dose oral cyclophosphamide with a patient suffering from stage IIIC ovarian cancer that responded to daily cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and carboplatin as first line and progression after second line with topotecan. The progression-free survival time on daily low dose oral cyclophosphamide treatment was 65 months without side effects. She was well during the chemotherapy and lived a normal working and social life. CONCLUSION: We think that use of low dose of oral CTX should be investigated further as a strategy against tumour progression after standard chemotherapy in patients who are platinum resistant with poor performance status

Three-dimensional simulations of electron cyclotron heating

Many heating problems in tokamaks are inherently three dimensional, involving the velocity coordinates parallel and perpendicular to the ambient magnetic field and the plasma radial coordinate. We will describe a new three-dimensional, Fokker-Planck/rf quasilinear code. This code is based upon a two-dimensional in velocity space Fokker-Planck code which solves for the distribution evaluated at the outer equatorial plane (theta = 0) of each flux surface in a radial mesh

Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis

SummaryHerein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible “metastatic conditioning” in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments

Advances in the simulation of toroidal gyro Landau fluid model turbulence

The gyro-Landau fluid (GLF) model equations for toroidal geometry have been recently applied to the study ion temperature gradient (ITG) mode turbulence using the 3D nonlinear ballooning mode representation (BMR). The present paper extends this work by treating some unresolved issues conceming ITG turbulence with adiabatic electrons. Although eddies are highly elongated in the radial direction long time radial correlation lengths are short and comparable to poloidal lengths. Although transport at vanishing shear is not particularly large, transport at reverse global shear, is significantly less. Electrostatic transport at moderate shear is not much effected by inclusion of local shear and average favorable curvature. Transport is suppressed when critical E{times}B rotational shear is comparable to the maximum linear growth rate with only a weak dependence on magnetic shear. Self consistent turbulent transport of toroidal momentum can result in a transport bifurcation at suffciently large r/(Rq). However the main thrust of the new formulation in the paper deals with advances in the development of finite beta GLF models with trapped electron and BMR numerical methods for treating the fast parallel field motion of the untrapped electrons

Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib

Metronomic chemotherapy refers to the administration of chemotherapy at low, nontoxic doses on a frequent schedule with no prolonged breaks. The aim of the study is to rationally develop a CPT-11 metronomic regimen in preclinical settings of colon cancer. In vitro cell proliferation, apoptosis and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on endothelial (HUVEC, HMVEC-d) and colorectal cancer (HT-29, SW620) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11. HT-29 human colorectal cancer xenograft model was used, and tumour growth, microvessel density and VEGF/TSP-1 quantification was performed in tumours. In vitro and in vivo combination studies with the tyrosine inhibitor semaxinib were also performed. SN-38 preferentially inhibited endothelial cell proliferation alone and interacted synergistically with semaxinib; it induced apoptosis and increased the expression and secretion of TSP-1. Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues. In vitro results show the antiangiogenic properties of low-concentration SN-38, suggesting a key role of TSP-1 in this effect. In vivo, the CPT-11 metronomic schedule is effective against tumour and microvessel growth without toxic effect on mice