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Selective Killing (selective + killing)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma

EXPERIMENTAL DERMATOLOGY, Issue 6 2003
Heike Rothfels
Abstract:, Selective killing of tumors can be achieved by targeting the transcription of suicide genes via specific DNA control elements to malignant cells. Three different enhancer-promoter systems were constructed and evaluated for their capability to direct gene expression to melanoma. Two tissue-specific (tyrosinase and MIA) promoters and one weak viral promoter were fused to multiple tandem copies of a melanocyte-specific enhancer element. Reporter gene assays revealed a maximum increase in transcription by combining each promoter with 3,4 copies of the enhancer and demonstrated that all enhancer-promoter combinations exhibited tissue-specific activity. Though this activity was still significantly less than that of the strong but unspecific cytomegalo virus (CMV) promoter. In contrast, when these combinations were employed to drive the expression of two suicide genes, encoding the diphtheria toxin A chain (DT-A) and the prodrug-activating herpes simplex virus thymidine kinase (TK), respectively, only those constructs in which transcription was under the control of tissue-specific promoter elements mediated selective killing of melanoma cells. This killing was in the range of cell death induced by CMV promoter activity. Our data indicate that the enhancer/tyrosinase and enhancer/MIA promoter constructs but not the viral promoter constructs can provide a valuable tool for selective suicide gene expression in melanoma. [source]

Identification and targeting of cancer stem cells

BIOESSAYS, Issue 10 2009
Tobias Schatton
Abstract Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self-renewal and give rise to bulk populations of non-tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker-specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof-of-principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC-targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC. [source]

Implications of a simple mathematical model to cancer cell population dynamics

CELL PROLIFERATION, Issue 1 2006
A. L. Garner
Many potential treatments preferentially interact with cells at certain stages of the cell cycle by either selective killing or halting the cell cycle, such as intense, nanosecond-duration pulsed electric fields (nsPEFs). Simple mathematical models of unfed cancer cell populations at the plateau of their growth characteristics may estimate the long-term consequences of these treatments on proliferating and quiescent cell populations. Applying such a model with no transition from the quiescent to proliferating state shows that it is possible for the proliferating cell population to fall below 1 if the quiescent cell population obtains a sufficient competitive advantage with respect to nutrient consumption and/or survival rate. Introducing small, realistic transition rates did not appreciably alter short-term or long-term population behaviour, indicating that the predicted small cell population behaviour (< 1 cell) is not an artefact of the simpler model. Experimental observations of nsPEF-induced effects on the cell cycle suggest that such a model may serve as a first step in assessing the viability of a given cancer treatment in vitro prior to clinical application. [source]