Search results for "Spheroid"
showing 10 items of 133 documents
Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells
2020
A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 μM, and 0.29–12.2 μM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), elici…
Microelectrode Measurements of Oxygen Tension Distributions in Multicellular Spheroids Cultured in Spinner Flasks
1984
Since multicellular spheroids were introduced into cancer research by Sutherland et al. (1970, 1971), they have been widely used for studying the susceptibility of cancer cells to various treatment modalities. Many of these investigations provided evidence for a major role of oxygen in controlling the metabolic and cell cycle state of the tumor cells, thus modifying the responsiveness of the cells to therapy. Several investigators have measured O2 tension (PO2) distributions in spheroids with O2-sensitive microelectrodes (Carlsson et al. 1979; Kaufman et al. 1981; Mueller-Klieser and Sutherland 1982a, b, 1983; Mueller-Klieser et al. 1983). The measurements produced PO2 values that varied co…
Electronic-structure-induced deformations of liquid metal clusters
1995
Ab initio molecular dynamics is used to study deformations of sodium clusters at temperatures $500\cdots 1100$ K. Open-shell Na$_{14}$ cluster has two shape isomers, prolate and oblate, in the liquid state. The deformation is stabilized by opening a gap at the Fermi level. The closed-shell Na$_8$ remains magic also at the liquid state.
3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study
2021
Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with…
Colon Cancer Stem Cells Dictate Tumor Growth and Resist Cell Death by Production of Interleukin-4
2007
A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, trea…
Lack of the Cell-Cycle Inhibitor p27Kip1 Results in Selective Increase of Transit-Amplifying Cells for Adult Neurogenesis
2002
The subventricular zone (SVZ) is the largest germinal layer in the adult mammalian brain and comprises stem cells, transit-amplifying progenitors, and committed neuroblasts. Although the SVZ contains the highest concentration of dividing cells in the adult brain, the intracellular mechanisms controlling their proliferation have not been elucidated. We show here that loss of the cyclin-dependent kinase inhibitor p27Kip1 has very specific effects on a population of CNS progenitors responsible for adult neurogenesis. Using bromodeoxyuridine and [3H]thymidine incorporation to label cells in S phase and cell-specific markers and electron microscopy to identify distinct cell types, we compared th…
Bizarre alterations of the morphology of pineal synaptic bodies under constant light and an evaluation of suitable 3D-reconstruction software
2004
Three dimensional (3D) reconstruction and modelling software was evaluated to find a procedure suitable for visualization of small subcellular structures in transmission electron microscope images. The method applied in this study demonstrates bizarre alterations of the structure of synaptic bodies (SBs) in pinealocytes of the guinea-pig pineal gland caused by constant illumination. It can, in general, be used for any 3D reconstruction from serial sections. Pineal glands of five guinea-pigs (two kept under a LD cycle of 12:12 h; three kept in constant light, for 4 months) were investigated. SBs consist of an electron-dense centre with attached vesicles. Under normal lighting conditions most…
A Model‐Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs
2021
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid. The simulated drug-induced response in bile acid concentrations was then scaled with the applied drug doses to calculate the cholestatic potential for each compound. A ranking of the cholest…
Subventricular zone localized irradiation affects the generation of proliferating neural precursor cells and the migration of neuroblasts
2012
Radiation therapy is a part of the standard treatment for brain tumor patients, often resulting in irreversible neuropsychological deficits. These deficits may be due to permanent damage to the neural stem cell (NSC) niche, damage to local neural progenitors, or neurotoxicity. Using a computed tomography-guided localized radiation technique, we studied the effects of radiation on NSC proliferation and neuroblast migration in the mouse brain. Localized irradiation of the subventricular zone (SVZ) eliminated the proliferating neural precursor cells and migrating neuroblasts. After irradiation, type B cells in the SVZ lacked the ability to generate migrating neuroblasts. Neuroblasts from the u…
Radiobiological characterization of human tumor cell multilayers after conventional and particle irradiation.
2006
The goal of this study was to establish planar multilayers from human tumor cells (WiDr and SiHa) as a model for irradiation of solid tumors. In addition to using conventional X rays (250 kV) as a reference standard, multilayers were tested for their suitability in cell survival studies with heavy-ion irradiation ((12)C(6+)) in the plateau and the extended Bragg peak with a scanned ion beam. Multilayers of both cell lines showed decreased survival compared to the corresponding monolayers after both X and heavy-ion irradiation. This multicellular sensitization effect is in contrast to the multicellular resistance or contact effect commonly described in the literature. Flow cytometry measurem…