Cancer cells (Cold Spring Harbor, N.Y. : 1989)最新文献

Our laboratory has developed nuclear magnetic resonance (NMR) techniques for detecting cancer. Using water-suppressed proton (H-1) NMR spectroscopy, we observed that the linewidths of the resonances of methyl and methylene moieties in lipoprotein lipids were consistently narrower in plasma samples from cancer patients than in those from controls. These findings have been corroborated by a number of independent laboratories, but other investigators have been unable to reproduce our results. One reason for the variability of results obtained with H-1 NMR may be that hypertriglyceridemia also induces linewidth narrowing of lipoprotein lipid methyl and methylene resonances, and can cause false positive results. We show that this ambiguity can be circumvented by using a second test based on the carbon-13 (C-13) NMR spectrum of plasma. Here we postulate that the cancer-associated changes seen in H-1 and C-13 NMR spectra are caused by peroxidation of lipoprotein lipids, an effect that may be induced by tumor necrosis factor-alpha released during malignancy.

Linking an antitumor cell antibody with an antilymphocyte antibody produces a bifunctional antibody that can redirect T lymphocytes to lyse tumor cells. Bifunctional antibodies that bypass the normal specificity of the T cell antigen receptor can, theoretically, retarget all of a cancer patient's cytotoxic T lymphocytes to kill tumor cells. Studies have demonstrated that bifunctional antibodies redirect effector cells to lyse human tumor cells in vitro and neutralize human tumor xenografts in animal models. Several different effector cell populations have been studied and many different human tumors have been targeted for lysis. Current research goals include the improvement of methods for the preparation of antibody reagents and the enhancement of cellular trafficking to tumors.

Hemopoietic growth factors regulate blood cell production by interacting with specific receptors on hemopoietic progenitor cells. These factors are regarded conventionally as soluble molecules that are freely available to their target cells. There is growing evidence, however, that several of the factors can also exist as biologically active membrane- or matrix-bound entities. Conversely, the receptors for several of the factors, conventionally regarded as membrane-bound molecules, have been shown to exist as soluble entities that retain ligand binding activity. In principle, such soluble receptors could regulate the accessibility of the growth factors to target cells by performing carrier and/or blocking functions. Consideration of these new types of interactions should help us to understand the ways in which target cell responses to multifunctional growth factors can be controlled in vivo.

The nuclear matrix of eukaryotic cells comprises a dynamic framework on which DNA is organized into discrete functional units of replication and transcription. There is growing evidence that matrix-associated DNA and proteins are direct targets of a wide range of clinically active anticancer agents. DNA associated with matrix-bound replication and transcription sites has a relatively open conformation and is preferentially damaged by ionizing radiation and certain alkylating agents. Fludarabine phosphate, a purine antimetabolite, inhibits DNA replication by blocking the synthesis of matrix-associated primer RNA and RNA-primed Okazaki fragments. VM-26 and m-AMSA appear to interact specifically with nuclear matrix topoisomerase II, and one mechanism of cellular resistance to these agents is associated with depletion of the matrix enzyme. Studies of the interactions of anticancer agents with targets in the nuclear matrix should provide further insight into the mechanisms by which these agents exert their therapeutic effects.