Prostate cancer marker panel with single cell sensitivity in urine.

Background: Over one million men undergo prostate biopsies annually in the United States, a majority of whom due to elevated serum PSA. More than half of the biopsies turn out to be negative for prostate cancer (CaP). The limitations of both the PSA test and the biopsy procedure have led to the development for more precise CaP detection assays in urine (e.

A bioenergetic profile of non-transformed fibroblasts uncovers a link between death-resistance and enhanced spare respiratory capacity.

Apoptosis-resistance and metabolic imbalances are prominent features of cancer cells. We have recently reported on populations of human fibroblasts that exhibit resistance to mitochondrial-mediated apoptosis, acquired as a result of a single genotoxic exposure. The objective of the present study was to investigate the intrinsic bioenergetic profile of the death-resistant cells, as compared to the clonogenic control cells.

Acquisition of mitochondrial dysregulation and resistance to mitochondrial-mediated apoptosis after genotoxic insult in normal human fibroblasts: a possible model for early stage carcinogenesis.

Acquisition of death-resistance is critical in the evolution of neoplasia. Our aim was to model the early stages of carcinogenesis by examining intracellular alterations in cells that have acquired apoptosis-resistance after exposure to a complex genotoxin. We previously generated sub-populations of BJ-hTERT human diploid fibroblasts, which have acquired death-resistance following exposure to hexavalent chromium [Cr(VI)], a broad-spectrum genotoxicant.

Chromium genotoxicity: A double-edged sword.

Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through non-specific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III).

Polo-like kinase 1 enhances survival and mutagenesis after genotoxic stress in normal cells through cell cycle checkpoint bypass.

Polo-like kinase 1 (Plk1) is a key regulator of mitosis. Aberrant Plk1 activity is found in tumors, but little is known regarding its role in the DNA damage response of normal cells and its potential contribution to the early stages of carcinogenesis. Inappropriate survival signaling after DNA damage may facilitate clonal expansion of genetically compromised cells, and it is known that protein tyrosine phosphatase (PTP) inhibitors activate key survival pathways.