Genetically modified species in research: Opportunities and challenges for the histology core laboratory.

Translational research using animal models has traditionally involved genetically modified rodents; however there is increasing use of other novel genetically engineered species. As histology laboratories interface with researchers studying these novel species there will be many situations in which protocols will need to be adapted to the species, model and research goals. This paper gives examples of protocol adaptations to meet research needs and addresses common considerations that should be addressed for all research tissues submitted to the histotechnology laboratory.

Successful Integration of the Histology Core Laboratory in Translational Research.

In a diagnostic setting, the histology laboratory is a key resource for production of quality tissues so the pathologist can make an appropriate diagnosis. In a research setting, the histology laboratory is a valuable resource in providing an excellent quality product for publications and grants for the investigator. Optimal collaboration with research investigators requires that histotechnologists recognize the diverse challenges and opportunities in research.

Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively.

Tumor necrosis factor-related apoptosis-inducing ligand-mediated activation of mitochondria-associated nuclear factor-kappaB in prostatic carcinoma cell lines.

It has been suggested that some nuclear transcription factors may participate in the regulation of mitochondrial functions through transcriptional control of mitochondrial DNA. Very little is known about the response of transcription factors within mitochondria to the activation of death receptors. Recent publications indicate that nuclear factor-kappaB (NF-kappaB) is localized in mitochondria of mammalian cells.

Redox regulation of the G1 to S phase transition in the mouse embryo fibroblast cell cycle.

The hypothesis that intracellular oxidation/reduction (redox) reactions regulate the G(0)-G(1) to S-phase transition in the mouse embryonic fibroblast cell cycle was investigated. Intracellular redox state was modulated with a thiol-antioxidant, N-acetyl-L-cysteine (NAC), and cell cycle progression was measured using BrdUrd pulse-chase and flow cytometric analysis. Treatment with NAC for 12 h resulted in an approximately 6-fold increase in intracellular low-molecular-weight thiols and a decrease in the MFI of an oxidation-sensitive probe, dihydrofluorescein diacetate, indicating a shift in the intracellular redox state toward a more reducing environment.