Single-cell tumors

By now, we have put together a lot of the cancer story. We know that cancer is a disease originating in a single cell that has overcome the normal limits to its growth and proliferation and that mutations in proto-oncogenes and/or tumor suppressor genes are required for this to happen. Beyond that, we know that multiple such mutations are usually required. 

Although tumors begin as clones of single cells, subsequent mutations generally result in tumors that are genetically heterogeneous, one of the problems for tumor therapy. 

The extracellular matrix of mammalian tissue is composed of a complex mix of constitutive proteins. This matrix must be broken down to recover single cells effectively for culture and/or staining (1). Tissue dissociation and its affiliated problems were described and defined over 80 yr ago by Rous and Jones (2). More recent reviews (3,4) have revealed newer methods for creating single-cell suspensions. Numerous procedures exist for dissociating solid tumors. They are usually multistep procedures involving one or a combination of mechanical, enzymatic, or chemical manipulations. Ideally, the dissociation protocol is individualized for the tissue of interest and evaluated relative to both optimal and representative cell yield. 

Premenopausal use There is no indication for premenopausal use of raloxifene. Hepatic function impairment Raloxifene was studied, as a single dose, in Child-Pugh class A patients with cirrhosis and serum total bilirubin ranging from 0.6 to 2 mg/dL. Plasma raloxifene concentrations were approximately 2.5 times higher than in controls and correlated with total bilirubin concentrations. Safety and efficacy have not been evaluated further in patients with severe hepatic insufficiency. Carcinogenesis In long term carcinogenicity studies in animals there was an increased incidence of ovarian tumors, testicular interstitial cell tumors, and prostatic adenocarcinomas. 

Of the mass spectrometric techniques, SIMS has become a useful tool for the imaging of single cells.174 Human liver tumor cells poisoned with Cd, Cu, Cr, Hg and Zn were analyzed using imaging ToF-SIMS (ION-TOF) to visualize the metal distributions on a single cell basis. Among the five metal ions investigated, only Cr and Cu showed a preferential diffusion into the cell after... 

Figure 9.46 ToF-SIMS images of Na, and of an poisoned single liver tumor cell - HepG2 cell. In the upper row are images of the HepG2 cell immersed in 2 4 solution in the lower ones the cells are in CuS04 solution - both solutions having a concentration of 15 p,M. (F. D. Mai, B. /. Chen, L C. Wu, F. Y. Li and W. K. Chen, Appl. Surf. Sci., 252, 6809 (2006). Reproduced by permission of...

A double immunohistochemical method has been used for determining the expression patterns of ER, PR, and EGF receptors in breast biopsies (Van Agthoven et al., 1994). It was demonstrated that ER/PR and EGF receptors in breast tumor cells were inversely related at the single cell level. However, the expression of these three receptors in individual normal luminal cells was not mutually exclusive. 

The assessment of the number of experimental metastases, typically pulmonary metastases, following i.v. injection of a single cell suspension of tumor cells or collagenase-digested primary tumor provides the most common outcomes. Multiple strategies may be used for this enumeration including... 

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