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: https://www.mdanderson.org/last_img read more

Researchers map drink consumption around the world

first_imgBy Dr. Ananya Mandal, MDJun 9 2019Researchers, in one of the most comprehensive global studies, have mapped the type and quantities of drinks consumed around the world. They explain that a major portion of the daily calorie and nutrition intake comes from the beverages consumed. The results of the study were presented at Nutrition 2019, the American Society for Nutrition annual meeting, held June 8-11, 2019 in Baltimore. In their study the team looked at beverage consumption habits from 185 countries around the world. Lead study author Laura Lara-Castor, a doctoral student in the Friedman School of Nutrition Science and Policy at Tufts University spoke about her “Global Dietary Database project,” saying that, “These preliminary data derived from the Global Dietary Database project can help inform nutrition transitions over time, the impacts of these beverages on global health, and targeted dietary policy to improve diet and health.”The team looked at 2015 data by compiling results from 1,100 surveys that were taken by 6.78 billion people around the world. The surveys looked at various dietary and beverage consuming habits.According to Lara-Castor and her team some patterns emerged from their study. She said, “Notably, sugar-sweetened beverage and fruit juice intake was highest in the Latin American region, where both commercial and homemade sugar-sweetened beverages and fruit drinks are widely consumed. Milk intake was highest in the high-income region (including countries such as Sweden, Iceland and Finland) where dairy farming is more widespread and dairy consumption has been traditionally a major part of the diet.” Youngsters living in urban areas and those with higher education levels consumed more beverages than otherwise, the team noted. Milk intake was high among those below 12 years of age as well as those above 72 years of age, found the study.Results revealed that in Mexico, sugar-sweetened beverage consumption was at its highest with an average adult consuming over 19 ounces or 2.5 cups per day. Suriname and Jamaica came next with an average of around 15 ounces per day. China, Indonesia and Burkina Faso showed lowest consumption of these beverages. Fruit juice consumption was highest in nations such as Colombia and the Dominican Republic at around 10 to 11 or 1.4 cups per day. China, Portugal and Japan consumed lowest amounts of fruit juices, the team noted. Nations such as Sweden, Iceland and Finland consumed more milk than other nations at 9 or 10 ounces or 1.3 cups per day average. China, Togo and Sudan consumed least amount of milk on an average.Related StoriesHealthy high-fiber diet could reduce preeclampsia riskDiet and nutrition influence microbiome in colonic mucosaJAMA commentary: Nutrition knowledge essential for today’s physiciansThe researchers explain that Mexico with its highest consumption of sugary beverages is also a place where rates of obesity are one of the highest. Reports show that over 70 percent of the population in the nation is overweight or obese and over 70 percent of their sugar consumption comes from these sugary beverages with Coca-Cola being the most favourite. To curb use, the Mexican government has added sugar taxes. After the first year of this taxing there has been a 5.5 percent drop in sugar consumption of the nation. In the second year after the taxes were in place, there was a 9.7 percent drop in sugar consumption. This study also noted that sugary drink consumption as well a s fruit juice consumption was high not only for commercially available packaged drinks but also home-made sugary drinks.According to Lara-Castor, “For sugar-sweetened beverages, fruit juice and milk, these data reflect updated and expanded estimates of the 2010 GDD, while for coffee and tea these constitute the first global quantitative estimates to be ever reported.” She said, “These data highlight gaps in dietary surveillance, further helping inform nutrition transitions over time, the impacts of these beverages on global health, and targeted dietary policy to improve diet and health.”The team adds that there were some limitations in the study. They write that the beverage consumption data came for only certain beverages, within a certain time period in the country. Lara-Castor said, “In particular, more intake data were available in 2015 than in 1990, and relatively few intake data were available in most Sub-Saharan African nations. [Nevertheless,] our findings represent the best available, yet still imperfect, data on global intakes of key foods.” She explained, “In ongoing work, we are updating our searches, data collection and modelling, to overcome each of these prior limitations.”Overall the study gives a fair idea of what the world is drinking, said Lara-Castor. This may help develop nutritional policies that could be beneficial to public health she concluded. Paket / Shutterstocklast_img read more

Delhi power tussle A timeline

first_imgRELATED Delhi Chief Minister Arvind Kejriwal   –  PTI COMMENT Published on justice and rights New Delhi SHARE ‘Centre egging on Delhi officials against Kejriwal’ Kejriwal calls off nine day sit-in center_img Following is the chronology of events in the case related to the power tussle between the Centre and Delhi government in which a five-judge bench of the Supreme Court today unanimously held that Lieutenant Governor Anil Baijal does not have independent decision making powers and is bound to act on the aid and advice of the Council of Ministers.It had started with lodging of an FIR in 2014 by the then Arvind Kejriwal regime against Reliance Industries Ltd (RIL), Mukesh Ambani and others including UPA ministers M Veerappa Moily and Murli Deora (since dead), accusing them of “fixing” gas prices.2014 May 2 RIL moves the Delhi High Court for quashing of FIR and challenging a 1993 notification of the Centre giving power to Delhi government’s Anti-Corruption Branch (ACB) to probe union government employees.May 8 Centre moves HC opposing FIR against the ministers contending that ACB has no powers or jurisdiction to probe.May 9 HC issues notice to Delhi government on the plea to quash FIR against the ministers. HC allowed ACB to continue with its probe.May 20 HC asks Centre, RIL to cooperate with ACB probe.August 9 ACB tells HC that it has powers to lodge FIR in gas pricing case.August 19 ACB tells HC it cannot probe the gas pricing case against RIL and a former UPA minister as a July 23, 2014 notification of Centre has taken away its jurisdiction to investigate central government employees.October 16 Delhi government tells HC its ACB can prosecute RIL and ministers.October 28 Delhi HC gives time to Centre to clarify on ACB’s powers.December 4 RIL argues in HC that State probing Centre’s decision on gas pricing is absurd.2015May 25 HC says ACB has jurisdiction to arrest policemen who come under Centre. It says the Centre’s May 21 notification limiting ACB’s powers was “suspect”.May 26 PIL in HC against Centre’s May 21 notification giving powers to the Lieutenant Governor (LG) to appoint bureaucrats in Delhi.May 28 Delhi government moves HC on Centre’s notification on LG’s powers. Centre moves the Supreme Court against Delhi HC’s May 25 order terming as “suspect” its notification.May 29 HC asks LG to consider Delhi government’s proposals on shifting of nine bureaucrats from one post to another.June 10 HC refuses to stay MHA notification on ACB power.June 27 Delhi government moves HC to restrain LG appointee ACB chief M K Meena from entering anti-graft body’s office.2016January 27 Union government tells HC that Delhi is under Centre’s control and not full-fledged state.April 5 AAP government asks HC to refer to larger bench petitions on powers of LG on the governance of Delhi.April 6 Delhi government tells HC it was competent to set up a commission to probe allegations of corruption in awarding licence to conduct CNG fitness tests.April 19 AAP government withdraws from SC its plea seeking setting up of a larger bench in HC.May 24 HC reserves order on AAP government’s plea for a stay on proceedings on the petitions arising out of its stand-off with LG over powers to appoint bureaucrats in the national capital and other issues.May 30 HC turns down AAP government’s request to first decide its stay application. July 1 SC agrees to hear AAP government’s plea seeking a direction that HC be restrained from delivering judgement on issues, including the scope of powers of the city government to exercise its authority in performing public functions.July 4 Justice J S Khehar of SC recuses from hearing AAP govt’s plea on declaration of powers of Delhi as a state.July 5 Justice L Nageshwar Rao of SC also recuses from hearing Delhi government’s plea.July 8 SC refuses to entertain Delhi government plea to first decide the preliminary issue as to whether it has the jurisdiction over disputes between the Centre and the state or is it “exclusively” triable by the apex court.August 4 HC says LG is administrative head of National Capital Territory and AAP government’s contention that he is bound to act on the advice of Council of Ministers was “without substance”.2017February 15 SC refers to constitution bench the pleas on Delhi-Centre row over governance.November 2 Constitution bench of SC commences hearing.November 8 SC observes that responsibilities conferred upon LG are not absolute.November 14 SC raises a question if constitutional scheme on division of executive powers between the Centre and the states can be made applicable to the union territory of Delhi.November 21 Centre opposes AAP government’s submissions in the SC, says Delhi has been accorded “special status” among union territories but that does not make it a state.December 6 SC reserves judgement on a batch of pleas on Delhi-Centre power tussle after hearing arguments for 15 days. 2018July 4 SC says LG does not have independent decision making powers, and is bound to act on the aid and advice of the Council of Ministers. July 04, 2018 What is Kejriwal’s issue with L-G, whose role is clearly defined: Sheila SHARE SHARE EMAIL Delhi power tussle: A big win for Kejriwal as SC says LG doesn’t have independent powers politics COMMENTSlast_img read more

Alternative to Lakshman Jhula to be built soon says Uttarakhand CM Trivendra

first_img Press Trust of India DehradunJuly 13, 2019UPDATED: July 13, 2019 20:38 IST Lakshman JhulaHIGHLIGHTSLakshman Jhula is in a dilapidated conditionThe bridge was closed on Friday on the recommendation of a team of experts from IIT RoorkeeThey recommended immediate closure of the bridge to all traffic and pedestrian movementThe Uttarakhand government has decided to build a bridge across the Ganga in Rishikesh as an alternative to the iconic Lakshman Jhula which was closed due to safety reasons, Chief Minister Trivendra Singh Rawat said on Saturday.The bridge was in a dilapidated condition and not capable of sustaining the load of traffic, Rawat said, adding that its closure was the only option left.Keeping the bridge open to traffic could have been risky, especially in view of the upcoming Kanwar mela during which thousands of devotees cross it daily, he told reporters.The bridge was closed on Friday on the recommendation of a team of experts from IIT Roorkee. They had recommended immediate closure of the bridge to all traffic and pedestrian movement.”A decision has been taken to construct a bridge over the Ganga in Rishikesh soon as an alternative to Lakshman Jhula,” the chief minister said.The opinion of experts will be taken on how to preserve the Lakshman Jhula as a cultural heritage site, he said.Built in 1923 over the Ganga, Lakshman Jhula is located five km northeast of the town and connects the two villages of Tapovan in Tehri district on the western bank of the river and Jonk in Pauri district.One of the main attractions for tourists and devotees coming to Rishikesh, the pedestrian bridge was also used by two wheelers.It was named after Hindu mythological character Lakshman as it stands where he was said to have crossed the river with the help of jute ropes.Parts of many successful Hindi movies and serials were shot at the Lakshman Jhula including Ganga Ki Saugandh, Sanyasi and popular detective serial CID.Closure of the bridge could also affect tourism as it was used by visitors bound for Tapovan and the famous Neelkanth temple near Rishikesh.ALSO READ: Rishikesh’s iconic Lakshman Jhula shut FOREVER after experts call it beyond repairALSO WATCH: CST bridge collapse case: Structural auditor’s bail plea rejectedFor the latest World Cup news, live scores and fixtures for World Cup 2019, log on to indiatoday.in/sports. Like us on Facebook or follow us on Twitter for World Cup news, scores and updates.Get real-time alerts and all the news on your phone with the all-new India Today app. Download from Post your comment Do You Like This Story? Awesome! Now share the story Too bad. Tell us what you didn’t like in the comments Posted bySanjay Nirala Next Alternative to Lakshman Jhula to be built soon, says Uttarakhand CM Trivendra Singh RawatUttarakhand government decided to build a bridge across the Ganga in Rishikesh as an alternative to the iconic Lakshman Jhula which was closed due to safety reasons.advertisementlast_img read more