The deensity of clonogenic cless in human solid tumors

Abstract

Considering that tumors are maintained by clonogenic cells, and that the primary target in the therapy of cancer is the clonogenic cell, the density of clonogens in a tumor could become an important parameter in quantitating the response to therapy. Indirect methods for determining the density of clonogenic cells in human tumors based on the response of tumors to radiation suggest there are circa 1 X 10(5) clonogens per gram with a large range. Direct methods, based on the measurement of cloning efficiency of enzymatically disaggregated biopsies of human tumors in soft agar, suggest a clonogen density of approximately 1,500 clonogens per gram. As this value is inconsistent with the prior data, we chose to determine the density of clonogenic cells in human tumors by assaying the enzyme digest of biopsies of human tumors for clonogenic cells using an enriched monolayer clonogenic assay. We determined the average clonogen density to be 1.12 x 10(5) clonogens per gram with a large range. The agreement with the indirect method suggests that the enriched monolayer clonogenic assay supports the proliferation of the cell population responsible for maintaining the tumor.

A Caenorhabditis elegans tissue model of radiation-induced reproductive cell death

“…Although radiation has been in practice for over a century, the precise mechanism by which radiation induces injury and death to normal and tumor tissues remains largely unknown. It is believed that tissue multipotential precursor cells (referred to as ''clonogens'') are the critical and determinant targets of radiation (1,2). Clonogens are loosely defined as cells within a tissue or tumor with the capacity to produce a family of descendants and are often referred to as clonogenic ''stem'' cells (3,4), without evidence that these are true stem cells capable of producing identical daughter progeny.…”

Radiobiological Modelling in Radiation Oncology

“…with a best estimate of 10 5 (Baker and Sanger 1991). Using the target volume along with a value of 10 7 cm −3 for clonogen density uniformly distributed is a flawed approach and leads to an inflated estimate of the total initial clonogen number which in turn leads to an inflated estimate of radiosenstivity.…”

Local tumor control probability to evaluate an applicator‐guided volumetric‐modulated arc therapy solution as alternative of 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecological cancer

“…1(a)). Our hypothesis was that p decreased exponentially in the microscopic extension region with a very wide and clinically likely range of values, from ${10}^4\text{cells}/{\text{cm}}^3$ to ${10}^7\text{cells}/{\text{cm}}^3$, ( 19 ) to simulate different values of subclinical clonogens in the microscopic extension region and a residual of clonogens in the tumor bed, respectively. Likewise, various decay coefficients (${\mathrm{normalr}}_0=1\hspace{0.17em}\text{mm}$, 0.62 mm, 0.31 mm, and ∞) were adopted to simulate different shapes of density reduction along the distance from the surface of the vaginal applicator.…”