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At least 811 records · Page 45Linked to original sources
PubMed1988

Cytotoxic drug penetration studies in multicellular tumour spheroids.

1. The three-dimensional structure of human lung tumour spheroids conferred a degree of resistance to the anthracyclines adriamycin, 4'-deoxydoxorubicin, daunomycin and daunomycin-low density lipoprotein complex in comparison with cells grown as a monolayer, as assessed by delayed growth and clonogenic cell survival. 2. 4'-Deoxydoxorubicin induced a longer growth delay and greater clonogenic cell kill than adriamycin in spheroids, although it was no more cytotoxic in monolayer. 3. Fluorescent microscopy demonstrated that the more lipophilic analogues partitioned into the spheroid more rapidly and to a greater degree than adriamycin. 4. The spheroid model demonstrated that penetration is an important aspect of resistance to anthracycline drugs, and this approach may represent a better in vitro system for testing lipophilic analogues of cytotoxic drugs.

Antibiotics, Antineoplastic↗
PubMed1988

Regulation of the brain angiotensin system: a thesis of multicellular involvement.

Many potential sites of regulation may be envisioned for the brain angiotensin system. However, new findings indicate that regulatory mechanisms may be more complex and detailed then previously recognized. These results, summarized below, include the recent findings of probable glial involvement in the brain angiotensin system, the potential for neuronal-glial interaction and the role of peptidases in either the activation of the relevant angiotensin peptide or in the termination of action of angiotensin II. A hypothesis is presented which proposes that a subpopulation of glia function to convert angiotensin II to angiotensin III so as to facilitate the rapid inactivation of the octapeptide. This could be a mechanism both for terminating action of the peptide at a neuronal receptor as well as for shielding receptors from exogenous angiotensins. Glia may also scavenge angiotensinogen from extracellular fluids, thereby limiting the lifetime of the prohormone. Thus, cross-talk between glia and neurons is proposed as one element of regulation of the brain angiotensin system.

Angiotensin II↗
PubMed1999

Apoptosis induction of human lung cancer cell line in multicellular heterospheroids with humanized antiganglioside GM2 monoclonal antibody.

The chimeric antiganglioside GM2 monoclonal antibody (MAb) KM966, which showed high effector functions such as complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), potently suppressed growth and metastases of GM2-positive human cancer cells inoculated into mice. To further improve the therapeutic efficacy of the anti-GM2 MAb in humans, we constructed a humanized anti-GM2 MAb, KM8969. The humanized KM8969 was more efficient in supporting ADCC against GM2-positive human cancer cell lines than the chimeric KM966, whereas complement-dependent cytotoxicity was slightly reduced in the humanized KM8969. In addition, the humanized KM8969 was shown to exert potent ADCC mediated by both lymphocytes and monocytes. To investigate the effect of the humanized KM8969 on the biological function of GM2 in the condition physiologically mimicking formation and growth of cancer masses, the heterospheroids composed of normal human dermal fibroblasts and GM2-positive human lung cancer cells were developed. Interestingly, the humanized KM8969 gave rise to growth inhibition of heterospheroids without dependence of the effector functions. Morphological and immunocytochemical analysis suggested that the inhibitory effect was due to the apoptosis of GM2-positive cancer cells in the heterospheroids. The result indicates that GM2 captured by the antibody on the cell surface loses its physiological function that plays a critical role in maintaining the three-dimensional growth of cancer cells in contact with its own cells or other type of cells in a microenvironment. The humanized KM8969, which can destroy the cancer cells via blocking functional GM2 on the cell surface as well as the effector functions, would have extraordinary potential in human cancer therapy.

Animals↗
PubMedDate not supplied

The plant plan: multicellular life in the other Kingdom.

One must conclude, then, that plants and animals may have evolved in quite different fashions. There is no doubt that they have independently evolved development, and this is demonstrated by the nonhomology of genes serving identical developmental functions in prepattern formation. There is nonetheless also no doubt that plants and animals have evolved from a common eukaryotic ancestor, as indicated by the clear homology of the genes that control the chromatin level of gene regulation. There is also little doubt that some developmentally important genes of plants, such as the ethylene and red light receptors, have derived from an event of horizontal evolutionary transfer specific to plants. And it is at least possible to think that the variation on which Darwinian evolution acts in plants results in part from phenomena that are not seen in animals, namely, the controlled appearance and Mendelian inheritance of epigenetically silenced genes. Genomic and genetic analyses of plants thus reveal a type of organism with familiar features, but profound differences from the more-studied animals. Only by further study of plants and of animals can we fully understand the differences between plants and animals, and consequently distinguish between those features of developmental pattern formation and cellular signaling that are necessary aspects of complex organisms, and those that are accidents of evolutionary history.

Animals↗
PubMedDate not supplied

Microencapsulated multicellular spheroid of rat hepatocytes transplanted intraperitoneally after 90% hepatectomy.

BACKGROUND/AIMS: The aim of this preliminary study was to investigate the metabolic activity of hepatocyte spheroids encapsulated with agarosehydrogel in vitro and the effect of encapsulated hepatocyte spheroids transplanted intraperitoneally on survival in the 90% hepatectomized rats for preparing future xeno-hepatocyte spheroids transplantation. METHODOLOGY: Hepatocytes were prepared by Seglen's method and cultured with epidermal growth factor. Hepatocytes formed spheroids 4 days after inoculation. Hepatocyte spheroids were encapsulated into 5% concentration agarose-hydrogel microbeads before being transplanted into the peritoneum of the rats. RESULTS: Hepatocyte spherois showed better metabolic activity compared to isolated hepatocytes. Hepatocyte spheroids function cultured in vitro were not deteriorated by encapsulation with agarose-hydrogel. Survival rates of 90% hepatectomized rats were improved by the intraperitoneal transplantation of encapsulated hepatocyte spheroids. CONCLUSIONS: Rat hepatocyte spheroids encapsulated with agarose-hydrogel and transplanted intraperitoneally were considered as effective for the improvement of survival rates in acute liver failure produced by 90% hepatectomy.

Animals↗
PubMedDate not supplied

Induction of apoptosis or necrosis by ionizing radiation is dose-dependent in MG-63 osteosarcoma multicellular spheroids.

This study investigates cell growth and death (apoptosis and necrosis) in actively proliferating MG-63 osteosarcoma spheroids in response to two doses of ionizing radiation (5 and 30 Gy). Cell growth was examined by growth curves and by cell cycle analyses utilizing flow cytometry. Death was examined in both disaggregated and whole spheroids by the chromatin dye Hoechst and by Western blot analysis of the bcl-2 family of proteins known to be involved in the apoptotic process. The results indicate that after exposure to 5 Gy MG-63 spheroids die by apoptosis, while after exposure to 30 Gy they die by necrosis. The analysis of the bcl-2 family of proteins demonstrates that bcl-2, bax and bcl-XL are involved in triggering apoptosis in spheroids exposed to 5 Gy. The possibility of studying the mechanisms responsible for radiation-induced cell death in three-dimensional spheroids (which represent much more closely in vivo tumors) is extremely important if the foundations for more selective and controllable clinical radiotherapeutic protocols are to be laid.

Apoptosis↗