Tumor cells separation

A major advantage of DNA as a carrier is that no chemical synthesis or manipulations are needed to obtain DNA-drug complex. The efficacy of the DNA-drug complex depends on stability in the bloodstream, endocytic behavior of normal and tumor cells, presence of extra-cellular deoxyribonuclease activity in the tumor tissues, and capillary barriers that separate normal and tumor cells from the bloodstream. 

A cyclic nucleotide, 2, 3 -bis(2-chloroethyl)aminophosphoryl-3 -amino-3 -deoxyadenosine (139) showing antitumor activity, was prepared in 40% yield starting from 3 -amino-3 -deoxyadenosine 133 by its phosphorylation with N,N-bis-(2-chloroethyl) amidophosphoryl dichloride 138. Both P-diastcrcomers separated by column chromatography exhibit activity against KB tumor cell cultures (Scheme 40) [71]. 

In another detailed study,62 the target tumor cells for the DC treatment were mouse mastocytoma P815. The current was passed in a three compartment cell in which the cathode compartment (CC) was separated from the anode compartment (AC) by the insertion of an intermediary chamber (IC) which had neither the anode nor the cathode the three compartments were connected in series via filter-paper bridges (Figure 9). Each of the three compartments contained 2 ml of cell suspension and 2 mA current was passed through platinum electrodes inserted in the AC and CC chambers (Figure 9). The salient results of this study are as follows ... 

Another variation to conjugate antibodies is to use bispecific antibodies. These are produced using chemical means and recombinant techniques to fuse separate hybridomas into a hybrid hybridoma (Fig. 4.6). Bispecific antibodies use one arm of the Fv to target the antigen or tumor cell and the other arm carries the effector molecule of toxins, radioisotopes, or other drugs. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Rous, Peyton (1911) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. Journal of Experimental Medicine. 13,397-411. Varmus, H. and Weinburg R. A. (1993) Genes and the Biology of Cancer. 

Also consistent with LCM uptake being an active (endo-cytic) process is the separate finding, in an in vitro kinetic study with both C6 and 9L tumor cells, that both dinitrophenol and sodium azide (i.e., energy blockers) inhibit LCM uptake in both tumor cell lines. Addition of glucose to the medium as an alternate source of energy restored the LCM uptake, indicating an energy-dependent uptake (ref. 534). 

Partridge, M., Phillips, E., Francis, R., and Li, S. (1999) Immuno-magnetic separation for enrichment and sensitive detection of disseminated tumor cells in patients with head and neck SCC. J. Pathol. 189, 368-377. 

A key clinical classification of breast cancer tumors is estrogen receptor (ER) expression. The more ERs are present on tumor cells, the more likely an anti-estrogen therapy such as tamoxifen can be successfully applied. Classification of each tumor is important, as only about 60%) of breast cancers are ER-positive. Initial studies set out to demonstrate that breast cancers with distinct pathological features could be separated by microarrays. Several groups demonstrated that supervised data analysis could be used to distinguish ER-positive from ER-negative tumors (74—76). 

Radiotherapeutics attack cancer by causing radiation damage to DNA in cells. The requirements differ from those for drug delivery because the radiotherapeutic can act at a distance and does not have to separate from the delivery particle. Radiotherapeutics can be selected to provide action over a range of distances, from tens of nanometers to hundreds of microns. Three radiotherapy modalities can be identified. Brachytherapy, most often used with beta-emitters, uses tightly enclosed radioactive material that is brought in close proximity to the tumor. A second modality is intravenous injection so that the radiopharmaceutical binds to the outside of the tumor cells or is taken up by the cell and irradiates from within. The third approach uses a carrier loaded with the radiotherapeutic that is transported to the vicinity of the target cells, and then released. 

Examples of the use of analytical-scale column systems for the small-scale (i.e., 1 fig to 1 mg) preparative separation of peptides include the extraordinarily potent opoid peptide, dynorphin (I4S) insulin A-, B-, and C-chain peptides (24, 72) j8-chain peptides of the pituitary glycoprotein hormones (8) endorphins (28,60, 126, 137), adrenocorticotropic peptides in plasma, pituitary, and other endocrine glands or secreted from tumor cells iVt vitro (84, I2S, 127, 138, 142. I Si) hypothalamic releasing factors... 

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