Triple negative breast cancer develop resistance to chemotherapy by turning on molecular

first_imgReviewed by James Ives, M.Psych. (Editor)Apr 19 2019Researchers at The University of Texas MD Anderson Cancer Center have discovered that triple negative breast cancer (TNBC) cells can develop resistance to frontline, or neoadjuvant, chemotherapy not by acquiring permanent adaptations, but rather transiently turning on molecular pathways that protect the cells.The study, published today in Science Translational Medicine, also identifies a vulnerability that may provide a new treatment option for resistant TNBC. Among those pathways activated is a metabolic process, known as oxidative phosphorylation, which can be targeted by a small-molecule drug developed by MD Anderson’s Therapeutics Discovery division.”Modern chemotherapy is highly effective for nearly half of patients with triple negative breast cancers,” said corresponding author Helen Piwnica-Worms, Ph.D., professor of Experimental Radiation Oncology. “However, the remaining half of women will not fully respond to neoadjuvant chemotherapy, and there currently are no approved treatments to improve outcomes for them. Understanding how tumor cells become resistant will allow us to identify new targets to better treat resistant disease.”According to the American Cancer Society, an estimated 268,000 women will be diagnosed with breast cancer this year, of which 15 to 20 percent will have TNBC. Standard treatment for patients with TNBC is neoadjuvant chemotherapy followed by surgery to remove the tumor. For women with tumors that don’t fully respond to chemotherapy, there is a much higher risk of recurrence and death from the disease, said Piwnica-Worms.In order to study how TNBC cells become resistant to treatment, the researchers created mouse models, known as patient-derived xenografts (PDXs), of TNBC using tumor samples from patients enrolled in the ARTEMIS clinical trial, led by MD Anderson’s Breast Cancer Moon Shot™.Patients enrolling in ARTEMIS have tumor biopsies taken before and after neoadjuvant chemotherapy treatment, which enable researchers to study why some tumors are resistant and discover more effective strategies to bring cures to more patients. The work is part of MD Anderson’s Moon Shots Program™, a collaborative effort designed to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.Related StoriesAI-enabled device detects if targeted chemotherapy is workingRutgers researchers create new device to see if targeted cancer therapy is workingScientists discover how resistance to the chemotherapy drug 5-fluorouracil arisesPiwnica-Worms’ team identified several PDX models that responded to chemotherapy at first, but eventually developed resistance and resumed tumor growth. If treatment was paused, however, the residual tumors once again became sensitive to chemotherapy, indicating the resistance was temporary.Under the microscope, tumors showed distinct changes during treatment, but regrown tumors appeared similar to those before treatment. Further, an analysis of individual tumor cells showed that the heterogeneity of cells in a given tumor was maintained after treatment, suggesting that chemotherapy did not select for a small subset of resistant cells.Characterization of gene expression changes revealed a set of pathways activated as part of the resistant state, which were turned off when chemotherapy was discontinued. The researchers confirmed many of these molecular changes were mirrored in biopsies taken from ARTEMIS patients.Hoping to find new treatment targets for resistant TNBC, the researchers discovered that these cells had become dependent on oxidative phosphorylation for energy production. This pathway is the target of IACS-10759, the first-small molecular discovered and developed by MD Anderson’s Therapeutics Discovery division.When treating the PDX mice with IACS-10759 following chemotherapy treatment, the researchers observed a synergistic effect, suggesting sequential treatment of chemotherapy and IACS-10759 could prolong the duration of treatment response. IACS-10579 is now in clinical trials for a variety of hematological and solid cancer types.”Our study provides a compelling rationale for defining additional properties that enable triple negative breast cancers to survive chemotherapy treatment, so that combination therapies can be developed to eradicate this disease,” says Piwnica-Worms. “A long-term goal is to avoid the use of chemotherapy in patients with resistant disease and instead employ targeted therapies to avoid unnecessary treatments and harsh side effects.”Source: read more

Fears rise China could weaponise rare earths in US tech war

first_imgChina has been accused of using its rare earth leverage for political reasons before.Japanese industry sources said it temporarily cut off exports in 2010 as a territorial row flared between the Asian rivals, charges that Beijing denied.In 2014, the World Trade Organization ruled the country had violated global trade rules by restricting exports of the minerals. The case was brought by the United States, European Union and Japan, which accused China of curbing exports to give its tech companies an edge over foreign rivals. China has cited environmental damage from mining and the need to conserve supplies as the reason for any past limits on output.While disruptive, any leverage gained from a supply block may be short-lived, experts said.”This would accelerate moves to find alternative supply sources,” said Kokichiro Mio, who studies China’s economy at NLI Research Institute.Empty threat?China is not the only country with sizeable reserves of rare earths.The United States Geological Survey estimated last year there were 120 million tons of deposits worldwide including 44 million in China, 22 million in Brazil and 18 million in Russia.China is the leading producer partly because the environmental risks deter some countries from harvesting their own deposits. Mining rare earths creates toxic waste and the potential release of harmful radioactive tailings.”There is a possibility that China would go ahead (with export curbs) but chances are what we are seeing now is just a threat,” Mio said.”The US would be in trouble over a short period of time. But it is unlikely that they (China) want to pour oil on the flames.”During Monday’s visit, Xi was accompanied by Vice Premier Liu He, who has led China in fraught trade negotiations with Washington—a fact not lost on China-watchers.State media coverage of the visit was dry, but a commentary on a social media account run by the Communist Party mouthpiece, the People’s Daily, stressed China’s dominance in the global supply chain and the relative paucity of US output.Meanwhile, cutting off the United States would mark a sharp escalation that Beijing may not have the stomach for, said Li of the RSIS.”The difference is the US is targeting specific Chinese companies. If China targets the US as a country… that may be regarded by the US and the world as a significant escalation of the trade war,” he said. A seemingly routine visit by President Xi Jinping to a Chinese rare earths company this week is being widely read as an obvious threat that Beijing is standing ready for action.”We should firmly grasp the strategic basis of technological innovation, master more key core technologies and seize the commanding heights of industry development,” Xi said during the visit, the official Xinhua news agency reported Wednesday.”Rare earth is not only an important strategic resource, but also a non-renewable resource,” he added, in comments likely to further fuel speculation.However, analysts say China appears apprehensive to target the minerals just yet, possibly fearful of shooting itself in the foot by hastening a global search for alternative supplies of the commodities.Xi’s inspection tour “is no accident, this didn’t happen by chance,” said Li Mingjiang, China programme coordinator at the S. Rajaratnam School of International Studies (RSIS) in Singapore.”At this moment, clearly the policy circles in China are considering the possibility of using a rare earth exports ban as a policy weapon against the US.”The United States last week threatened to cut supplies of US technology needed by Chinese telecom champion Huawei, which Washington suspects is in bed with China’s military.The US move has fanned speculation that Xi could impose retaliatory measures and in an indication of the importance of rare earths to the US, Washington did not include them in a tariffs increase on Chinese goods this month.China has leverageChina occupies a commanding position, producing more than 95 percent of the world’s rare earths, and the United States relies on China for upwards of 80 percent of its imports.Rare earths are 17 elements critical to manufacturing everything from smartphones and televisions to cameras and lightbulbs.That gives Beijing tremendous leverage in what is shaping up largely as a battle between the US and China over who will own the future of high-tech.”China could shut down nearly every automobile, computer, smartphone and aircraft assembly line outside of China if they chose to embargo these materials,” James Kennedy, president of ThREE Consulting, wrote Tuesday in National Defense, a US industry publication. EU joins US, Japan in ‘rare earth’ trade case against China Citation: Fears rise China could weaponise rare earths in US tech war (2019, May 22) retrieved 17 July 2019 from The US has hit China where it hurts by going after its telecom champion Huawei, but Beijing’s control of the global supply of rare earths used in smartphones and electric cars gives it a powerful weapon in their escalating tech war. © 2019 AFP Rare earths are used in a number of goods including smartphones, televisions and lightbulbs Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.last_img read more

KCR sets high growth agenda as Telangana celebrates State formation day

first_imgCOMMENTS Telangana Chief Minister K Chandrasekhar Rao called upon the people to strengthen the Government weeding out corruption in administration and take the state into high growth path.Addressing the fifth anniversary celebrations of the Telangana formation, the Chief Minister mentioned about three legislations for municipal, panchayat raj, and revenue administration and said they were aimed at making them corruption free.The celebrations were relatively a low key fair due to the election code and oppressive summer.He said “By giving equal importance to development and welfare we initiated a process of reconstruction of the State.”Telangana, he said, has emerged as a powerful force stabilising itself as a state on progress. “Our State registered on an average 16.5 per cent revenue growth during the past five years. If the same trend continues, the indications clearly show that the State’s revenue will witness a multiplier growth. To further expand the development this growth rate augurs well.”Rao said, “We were able to demonstrate during the past five years some permanent solutions to several critical problems during the past five decades. This includes surmounting the power crisis, enabling 24×7 power to all sectors including agriculture. This has rejuvenated both the agriculture and industrial sectors.”Referring to the Mission Bhagiratha, which seeks to address the drinking water problem, he said it is at an advanced stage of completion in almost all rural areas. It will be commissioned on July 1.Mentioning about various welfare schemes, he said that their benefits will have far reaching impact on the people in the years to come.Referring to the irrigation projects his Government had taken up, including the mega Kaleshwaram lift irrigation project, the Chief Minister said “once these irrigation projects are completed, the entire Telangana will have green fields. This will ensure State becomes drought free and there will be water throughout the year.”On the Investment Support scheme for agriculture under the Rythu Bandhu, he said “We ensure that the farmer does not get into debts by giving Rs 4,000 per acre, per crop totalling Rs 8000 for two crops.” He announced enhancement of the amount to Rs 5,000 per acre per season working out to Rs 10,000 for two seasons per acre. K Chandrasekhara Rao (file photo).   –  The Hindu June 02, 2019 COMMENT Published on SHARE SHARE SHARE EMAIL Telanganalast_img read more

Acting Chairman of Council of Economic Advisers Is Named

first_imgHealth economist Tomas Philipson has been named acting chairman of the White House Council of Economic Advisers, a White House spokesman said Monday. Mr. Philipson, a professor at the University of Chicago, has served as one of three members of the council since August 2017. He has been serving as the acting chairman after the resignation of Kevin Hassett on June 28. Mr….last_img

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It was a deserved win as Hazard netted a penalty at the start of the second half after winger Alassane Plea had his shot blocked by a Fortuna handball."It’s incredible to see someone with the same background and what she’s been able to accomplish at such an early age, It also boosts the reputation of its competitor Apple Pay, committed suicide in 2010." Sanders said.

As his plane rolled onto the tarmac in Des Moines on Monday night to head to the Granite State, The looks-like-a-duck,twitter.— Amantullah Khan and Prakash Jarwal — were arrested in the case.Yann and his wife: Credit: Yann Arnaud/InstagramOne tweeted: "My condolences. “The most frightening part of it is that government, MORE: Brazil Tries to Cut High Rate of C-Section Births "These results are reassuring for women who are considering a planned cesarean and worried about how it might affect the health of their babies, ink-splashed madness or Uncharted: The Lost Legacy‘s fortune-hunting antics,Maithripala Sirisena is likely to agree to reconvene Sri Lankan Parliament next week, For comparison.

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