Tumor tissues heterogeneity

Tumor Tissues Heterogeneity A Basis for Multi-targeted Drug Development... 

Biodistribution studies significant tumor uptake over 12 hours. Heterogeneous distributicm within tumor tissue, related to alkaline phosphatase positive areas. Therapy with 0.125-20 /iCi. Survival ( ) dose (D) relationship of a Langmuir-t3rpe saturation equation +... 

Figure 20.3 Heterogeneous distribution of liposomes in tumor tissues. Human colon adenocarcinoma cells (LS174T) were transplanted in dorsal skinfold chambers in severe combined immunodeficient mice. Fifteen to 32 days post tumor cell transplantation, fluorescently labeled liposomes were injected intravenously. The photos were taken at two days post injections. Liposomes accumulated only in perivascular regions in solid tumors. The arrows indicate liposomes internalized by cells. Iiar=100um. Reproduced with permission (Yuan etal., 1994).

Heterogeneous distribution of liposomes in tumor tissues. Human colon adenocarcinoma 405... 

One of the limitations of the TMA is that the tissues in the tumor cores have been processed at different types and often with different protocols. This will lead to optimal staining of some tumors but also sub-optimal staining (over or under-staining) of quite a few tumor cores. However, the large number of cases included in the TMA can to some extent compensate for the tissue heterogeneity. 

Since tumor tissue is the primary manifestation of cancer, it contains the most immediate information and is the preferred material to investigate molecular targets. Experimental approaches will benefit from the enhanced protein concentration compared to body fluids. However, one major drawback of analyzing tumor biopsies is their limited availability and their heterogenicity which often requires microdissection. Alternatively, body fluids are the preferred clinical sources because they are most readily available in a noninvasive and continuous manner. 

The technique is reproducible, more sensitive than methods such as alkaline elution, requires fewer cells and has the important advantage that analysis can be made at the single cell level. It is therefore possible to determine heterogeneity of ISC formation and its repair in a cell population. The method is applicable to studies with cultured cell lines, human lymphocytes and solid tumor tissue. Correlations can therefore be made between both the level of ISCs and the efficiency of their repair with both inherent and acquired resistance to DNA crosslinking agents in vitro and in vivo. 

Primary tumors with heterogeneous cell populations exhibiting different expression intensity of the HER-2 oncoprotein and consequently different scores, must be particularly documented. In such cases, the assessment of metastatic tissue to determine the metastasizing cell population is recommended. This phenomenon is described in about 5% of breast tumors. 

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