Alix tidmarsh biography of mahatma gandhi
Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer
Abstract
Simple Summary
About one third of all breast cancers are classified as HER2-positive due to high levels of the HER2 cell surface protein. Drugs that target HER2 have been mostly successful, but this type of cancer returns at a high frequency once treatment has been completed. The high levels of HER2 also cause elevated activation of mechanistic target of rapamycin (mTOR) and enhanced glucose metabolism, both of which support cancer growth. Based on this, drugs have been developed to block mTOR and tested in clinical studies alone or in combination with drugs that target HER2. These treatments are successful but have more toxic effects and a higher chance that the cancer will return. Using drugs that mimic glucose deprivation in HER2-positive breast cancer patients has not been tested; however, preclinical studies have shown HER2-positive breast tumors are reduced by combining drugs that mimic glucose deprivation with mTOR inhibitors.
Abstract
Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast
The Practice of Peace
Picturing
The April editorial offered a picture, drawn chiefly from reports by gifted children, of variously-colored light streaming out of humans and other animals. Different visionaries may or may not agree in what they see or what a given color signifies. But they generally report clear, beautiful colors when the person viewed is in a loving or otherwise positive state of mind, whereas gloomy, turbid colors correspond to depressed states, and sharp projectiles to anger. Such reports resemble the conception of ki discussed in the March issue as a powerful stream of energy directed outwards in the martial arts, energy which, in aikido especially, is understood to be either violent and destructive, or peaceful and affirmative.
While it is unwise to dismiss these ideas out of hand, and worthwhile to pursue them further, one need not accept their literal truth in order to profit from these pictures and what they imply. Our intention is to further the cause of peace and justice in the world for all beings, not only our animal cousins but ourselves and our human sisters and brothers. We know we will be more effective in our outreach when we ourselves can deal with hostility without losing our balance--when we can encompass the destructive critic with compassion--when more and more we become the change we seek. We want to send out beautiful, loving energy rather than the muddy, out-of-control kind.
It is hardly necessary to point out how difficult this is. We may be able to react with love sometimes when we are attacked , but how are we to gain the strength to operate this way in a reliable manner? An important part of the answer, as suggested in some past editorials, is to be found in maintaining a spiritual discipline.
Holding
Spiritual disciplines vary, yet certain characteristics recur in many of them. One factor is learning to hold steadily in mind the ultimate goal. This does not mean that Five-Time Oscar Nominee George Fenton to Conduct The Berlin Philharmonic Orchestra, one of the world's foremost musical institutions, will break with tradition and record a motion picture soundtrack for the first time for the BBC Worldwide/Greenlight Media theatrical feature documentary, DEEP BLUE, it is announced today by producers Alix Tidmarsh of BBC Worldwide and Sophokles Tasioulis of Greenlight Media. Five-time Oscar nominee George Fenton (Gandhi, Cry Freedom, Dangerous Liaisons, The Fisher King) has written the score for the film and will conduct the orchestra in a recording session at the Philharmonic hall in Berlin next month. Under the artistic direction of its new musical director Sir Simon Rattle, the Berlin Philharmonic, which was founded in 1882, has been involved in a number of unusual projects expanding the repertoire of the Orchestra into new dimensions. At Cannes, BBC Worldwide and Greenlight Media will screen advance footage from DEEP BLUE, which is the feature-length version of BBC's award-winning natural history series, "The Blue Planet". Composer Fenton won Ivor Novello, BAFTA and Emmy awards for his score for the original eight-episode TV series. Tasioulis, Vice President, Production, for Greenlight Media, stated: "DEEP BLUE is a powerful and emotional film that should be seen on the big screen. George Fenton's new score represents some of the finest music composed for an epic feature and we are honoured that the Berlin Philharmonic Orchestra will record it. Such great images require extraordinary music and in George we have the best composer to interpret them. Having the Berlin Philharmonic perform his music, is the equivalent of casting the best actor possible to play a leading role in one's film." Alix Tidmarsh, Director of Factual IPM Factual, BBC Worldwide added: "The joint power of the Berlin Philharmonic and the .BBC Worldwide Press Releases
16.05.03
Berlin Philharmonic to record first movie score for Deep Blue