			Home About us Contact

Vivo Tumor Growth (vivo + tumor_growth)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Imaging the effects of castration on bone turnover and hormone-independent prostate cancer colonization of bone

THE PROSTATE, Issue 15 2008
N.A. Cross
Abstract INTRODUCTION Tumor populations may selectively colonize bone that is being actively remodeled. In prostate cancer patients, androgen deprivation directly inhibits tumor growth initially, whilst induced bone loss may facilitate tumor colonization of bone by androgen-insensitive cells. We have tested this hypothesis using a xenograft model of early growth of prostate cancer in bone. METHODS PC3 cells transfected with Green fluorescent protein (GFP) were injected into castrated and non-castrated athymic mice via intrabial and intracardiac routes. In vivo tumor growth was monitored daily and animals sacrificed 6,9 days following initial GFP-based detection of tumors. Tumor bearing and contra-lateral non-tumor bearing tibias were analyzed extensively by micro-CT and histology/immunohistochemistry for the presence of tumor cells and the effects of tumor and/or castration on bone cells and bone structure evaluated. RESULTS GFP-positive tumors in bone were visible from 12 days post-injection following intratibial injection, allowing tumors <1 mm diameter to be monitored in live animals. Castration did not affect tumor frequency, tumor volume, or time to initial appearance of tumors injected via intratibial or intracardiac routes. Castration decreased trabecular bone volume in all mice. Significant tumor-induced suppression of numbers of osteoblasts, coupled with increased numbers of activated osteoclasts, was evident in both intact animals and castrated animals. CONCLUSIONS In vivo GFP imaging allows the detection of early tumor growth at intra-osseous sites. Castration induces bone loss, but PC3-GFP cells are also capable of inducing bone remodeling in intact animals at early time points, independently of pre-existing castration-induced alterations to bone. Prostate 68: 1707,1714, 2008. © 2008 Wiley-Liss, Inc. [source]

Design and Synthesis of a Focused Library of Novel Aryl- and Heteroaryl-Ketopiperazides

ARCHIV DER PHARMAZIE, Issue 12 2004
Matthias Gerlach
Abstract 1-Phenyl-4-piperazinyl-carbonyl-substituted nitrogen-containing heterocycles were discovered at Zentaris as a new class of potent, synthetic, small molecule tubulin inhibitors with strong antiproliferative activity. The lead structure of this class, D-24203, proved to be a potent inhibitor of in vivo tumor growth in different xenograft models including mammary and renal cancers. As part of our efforts in the lead optimization process to expand structural diversity as well as to optimize bioavailability parameters such as solubility and metabolic stability for these compounds, we produced and evaluated a focused library containing 320 compounds. Five new heterocyclic compound classes with comparable activity properties in the cytotoxicity and tubulin polymerization assay could be identi fied. In silico calculated bioavailability parameters for selected library members provides new compound classes with improved solubility properties. Library design, development of adequate solution phase methodology, and synthesis will be presented, as well as results of lead optimization. [source]

Parameter Estimation in a Gompertzian Stochastic Model for Tumor Growth

BIOMETRICS, Issue 4 2000
L. Ferrante
Summary. The problem of estimating parameters in the drift coefficient when a diffusion process is observed continuously requires some specific assumptions. In this paper, we consider a stochastic version of the Gompertzian model that describes in vivo tumor growth and its sensitivity to treatment with antiangiogenic drugs. An explicit likelihood function is obtained, and we discuss some properties of the maximum likelihood estimator for the intrinsic growth rate of the stochastic Gompertzian model. Furthermore, we show some simulation results on the behavior of the corresponding discrete estimator. Finally, an application is given to illustrate the estimate of the model parameters using real data. [source]

Down regulation of BRCA2 causes radio-sensitization of human tumor cells in vitro and in vivo

CANCER SCIENCE, Issue 4 2008
Dong Yu
In order to study the role of BRCA2 protein in homologous recombination repair and radio-sensitization, we utilized RNA interference strategy in vitro and in vivo with human tumor cells. HeLa cells transfected with small-interfering BRCA2 NA (BRCA2 siRNA) (Qiagen) as well as negative-control siRNA for 48 h were irradiated, and several critical end points were examined. The radiation cell survival level was significantly reduced in HeLa cells with BRCA2 siRNA when compared with mock- or negative-control siRNA transfected cells. DNA double strand break repair as measured by constant field gel-electrophoresis showed a clear inhibition in cells with BRCA2 siRNA, while little inhibition was observed in cells with negative control siRNA. Our immuno-staining experiments revealed a significant delay in Rad51 foci formation in cells with BRCA2 siRNA when compared with the control populations. However, none of the non-homologous end joining proteins nor the phosphorylation of DNA-dependent protein kinase catalytic subunit was affected in cells transfected with BRCA2 siRNA. In addition, the combined treatment with radiation and BRCA2 siRNA in xenograft model with HeLa cells showed an efficient inhibition of in vivo tumor growth. Our results demonstrate down-regulation of BRCA2 leads to radio-sensitization mainly through the inhibition of homologous recombination repair type double-strand break repair; a possibility of using BRCA2 siRNA as an effective radiosensitizer in tumor radiotherapy may arise. (Cancer Sci 2008; 99: 810,815) [source]