Almost all known conventional cytotoxic anticancer drugs are less effective in killing tumor cells grown as multicellular spheroids than in killing tumor cells grown as monolayer cell cultures. This "multicellular resistance" reflects the relative intrinsic drug-resistant phenotype of most solid tumors growing in vivo and is due to factors such as limited drug penetration or reduced fractions o...

Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefor...

Magnetic resonance imaging has been used to follow noninvasively tumor neovascularization and tumor growth in a model system of multicellular C6 rat glioma spheroids implanted s.c. in nude mice. By position ing a single spheroid approximately 1 cm from the site of incision both the vascularization of the tumor and the wound healing processes were spa tially separated and could be simultaneously...

Several years ago, we detected the formation of multicellular spheroids in experiments with human thyroid cancer cells cultured on the Random Positioning Machine (RPM), a ground-based model to simulate microgravity by continuously changing the orientation of samples. Since then, we have studied cellular mechanisms triggering the cells to leave a monolayer and aggregate to spheroids. Our work fo...

BACKGROUND The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. METHODS A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulati...

Although electroporation is gaining increased attention as a technology to enhance clinical chemotherapy and gene therapy of tissues, direct measurements of electroporation-mediated transport in multicellular environments are lacking. In this study, we used multicellular tumor spheroids of DU145 prostate cancer cells as a model tissue to measure the levels and distribution of molecular uptake i...

Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low att...

We present a flexible and highly reproducible method using three-dimensional (3D) multicellular tumor spheroids to quantify chemotherapeutic and nanoparticle penetration properties in vitro. We generated HeLa cell-derived spheroids using the liquid overlay method. To properly characterize HeLa spheroids, scanning electron microscopy, transmission electron microscopy, and multiphoton microscopy ...

This report discusses the cross-section shapes and growth curves created by different proliferation algorithms in an in silico model of in vitro multicellular tumor spheroid growth (MTS). The in vitro MTS system is a model of in vivo tumor growth. The in silico model described herein represents aspects of MTS growth, including its layered structure and growth patterns. An exploration of four al...

Purpose:Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor–stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1–dependent resistanc...