How the Warburg effect supports aggressiveness and drug resistance of cancer cells?

Cancer cells employ both conventional oxidative metabolism and glycolytic anaerobic metabolism. However, their proliferation is marked by a shift towards increasing glycolytic metabolism even in the presence of O2 (Warburg effect). HIF1, a major hypoxia induced transcription factor, promotes a dissociation between glycolysis and the tricarboxylic acid cycle, a process limiting the efficient production of ATP and citrate which otherwise would arrest glycolysis. The Warburg effect also favors an intracellular alkaline pH which is a driving force in many aspects of cancer cell proliferation (enhancement of glycolysis and cell cycle progression) and of cancer aggressiveness (resistance to various processes including hypoxia, apoptosis, cytotoxic drugs and immune response). This metabolism leads to epigenetic and genetic alterations with the occurrence of multiple new cell phenotypes which enhance cancer cell growth and aggressiveness. In depth understanding of these metabolic changes in cancer cells may lead to the development of novel therapeutic strategies, which when combined with existing cancer treatments, might improve their effectiveness and/or overcome chemoresistance.

Reinvigorating the role of science in democracy.

Private and political interests routinely conspire to sideline and misrepresent science and evidence in the public policy process. The Center for Science and Democracy, a new initiative at the Union of Concerned Scientists, endeavors to change this dynamic to strengthen the role of science in decision making.

Innovative monochromatic x-ray source for high-quality and low-dose medical imaging.

PURPOSE: An estimated 377 million diagnostic and interventional radiological exams are performed annually in the United States and approximately 4 to 5 billion globally. All use x-ray tubes that emit x-rays over a broad energy band, a technology that is more than a century old. Only a small fraction of the radiation is useful for imaging while the remaining fraction either increases the radiation dose received by the patient or degrades the image. Monochromatic x-rays can provide lower dose images in many of these radiological applications while maintaining or improving image quality. We report the development of the first monochromatic x-ray source suitable for low-dose, high-quality imaging in the clinic and demonstrate its first application and performance with mammography phantoms. METHODS: X-ray fluorescence was used to generate monochromatic x-rays with selectable energies from 18 to 60 keV. This patented technology was incorporated into a laboratory prototype of a monochromatic x-ray mammography system. Image quality was evaluated as a function of radiation dose in standard breast phantoms using the signal-to-noise ratio (SNR) measured for high and low contrast masses and microcalcifications. Spatial imaging properties were assessed from these images as well as from modulation transfer function (MTF) analysis. Measurements using an iodine contrast agent were also performed. The results were compared to those obtained using a commercially available, conventional x-ray mammography system. RESULTS: Our prototype system reduced radiation dose by factors of five to ten times for the same SNRs as obtained from the conventional system. This performance was demonstrated in phantoms simulating a wide range of lesion sizes and microcalcifications in a variety of breast thicknesses. The high SNRs for very thick breast phantoms provide evidence that screening with less breast compression is possible while maintaining image quality. Contrast-enhanced digital mammography (CEDM) with monochromatic x-rays was shown to provide a simpler and more effective technique at substantially lower radiation dose. The MTF value at 20% was 9 lp/mm. CONCLUSIONS: The monochromatic x-ray system is more sensitive for imaging a wide range of breast sizes and compositions than conventional broadband mammography. High image quality and lower dose are its hallmarks. It also makes CEDM much more effective than current methods developed for use with conventional broadband mammography systems.