Tumor heterogeneity

PET and PET/CT therefore enable to assess regional tumor hypoxia and associated tumor heterogeneity. Less spatial heterogeneity in hypoxia might represent a more localized process. The former is more likely to be accessible by a... 

Microarrays for Cancer Research Historical Perspectives Tumor Heterogeneity Stem Cell Theory of Cancer Profiling Small Samples with Microarrays Amplification... 

Tumor heterogeneity refers to the existence of distinct subpopulations of tumor cells with specific characteristics within a single neoplasm. Breast cancer is a classic example of a heterogeneous disease. First, the term breast cancer does not itself refer to a single disease. Breast cancers include many different diseases including (but not limited to) adenomas, papillomas, invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS) (6). 

The reproducibility of PCNA immunostaining analysis can be improved by computer-assisted image analysis (Sallinen et al, 1994). This approach also improves the reproducibility of quantitation among observers. The effect of tumor heterogeneity is minimized through this protocol because large tissue areas can be analyzed. Moreover, compared with visual assessment, computer-assisted analysis is faster. However, even in the computerized... 

Note that immunohistochemical reactions do not always yield homogeneous results but are subject to variations from slide to slide and from case to case. Because tumors are heterogeneous, caution is warranted in assuming that a particular section of the tumor is representative of the whole tumor (see page 14 for discussion on tumor heterogeneity). 

Controls should be placed on each TMA block, for quality control and to address tumor heterogeneity. Three types of control tissues may be used ... 

Dracopoli, N. C., Houghton, A. N. and Old, L. J. (1985). Loss of polymorphic restriction fragments in malignant melanoma implications for tumor heterogeneity. Proc. Natl. Acad. Sci. USA 82, 1470-1474. 

Greller, L. D., Tobin, R L. and Poste, G. (1996). Tumor heterogeneity and progression Conceptual foundations for modeling. Invasion Metastasis 16, 177-208. 

Hart, I, R. and Fidler, I. J. (1981). The implications of tumor heterogeneity for studies on the biology and therapy of cancer metastasis. Biochim. Biophys. Acta 651, 37-50. 

Dexter, D. and Leith, J. (1986) Tumor heterogeneity and drug resistance. J. Clin. Oncol. 4, 244-257. 

Fidler, 1. J. (1978). Tumor heterogeneity and die biology of cancer invasion and metastasis. Cancer Res 38(9), 2651-2660. 

Shipitsin, M., Campbell, L. L., Argani, P., et al. (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11, 259-273. 

One of the most common explanations for unresponsiveness of apparently estrogen receptor positive tumors to hormonal therapy is tumor heterogeneity. We found that 38% of the results change when comparing the estrogen receptor proteins from the primary tissue with those from the metastatic tissue. Although there are extrinsic factors, as already mentioned, there could be intrinsic factors that alter the receptor measurement. These findings underscore the need to conduct biopsies and assay readily accessible recurrences rather than to rely on the results of prior specimens. Variation of results also occurred with metastatic tissue from some patients, obtained usually after a period of 19 months (R4). 

Under certain conditions, the Gompertzian tumor model provides an accurate barometer for tumor growth in vivo. However, deviations occur over time due to selection and expansion sub-clones that are chemo-resistant. Skipper s Cell Kill Hypothesis is based on the notion that chemotherapy will lead first-order cell kill kinetics. Therefore, each administration of chemotherapy will produce tiie same fraction of tumor cell death. In theory, it is believed that a log-cell drop of 9 to 11 orders of magnitude is required for tumor eradication. Clinically this scenario is complicated by the chemosen-sitivity of normal tissue and tumor, pharmacokinetic hetereogeneity of patients, and tumor heterogeneity. 

Cimino, J., Calligaris, D., Far, J., Debois, D., Blacher, S., Sounni, N.E., Noel, A. and De Pauw, E. (2013) Towards Upidomics of low-abundant species for exploring tumor heterogeneity guided by high-resolution mass spectrometry imaging. Int. J. Mol. Sci. 14, 24560-24580. 

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