Harvard and Brigham and Women’s Hospital researchers have devised a method that may allow clinicians to use higher doses of a powerful chemotherapy drug that has been limited because it is toxic not only to tumors but to patients’ kidneys.The research, conducted in laboratory animals, marries chemistry and nanotechnology to deliver toxic platinum atoms to tumors while almost entirely blocking the platinum from accumulating in the kidney, according to Shiladitya Sengupta, a Harvard assistant professor of medicine and health sciences and technology whose Laboratory for Nanomedicine at Harvard-affiliated Brigham and Women’s Hospital conducted the work.Sengupta has focused his research for three years on cisplatin, a powerful anti-cancer drug used in first-line chemotherapy. Sengupta said the drug, discovered about 40 years ago, has many positive aspects. It is relatively inexpensive and effective against many cancers. Its toxicity, however, limits its use.“Even if you can see amazing results as an anti-tumor therapy, you can’t give more,” Sengupta said.Despite several attempts, cisplatin hasn’t been improved upon, Sengupta said. Two similar drugs that also incorporate platinum are on the market, but while they are less toxic to the kidney, they are also less active against tumors.Though the chemistry involved is complex, the key to cisplatin’s effectiveness — and its toxicity — lies in how easily it releases platinum, both at the tumor site and, undesirably, in the kidneys.Manufacturers of the two alternative drugs have reduced those drugs’ toxicity by making them hold onto their platinum more tightly. Sengupta’s work took a different track, however. Understanding that particles greater than five nanometers in size would not be absorbed by the kidney, he set out to engineer a super-sized cisplatin.Understanding the chemical properties of the cisplatin molecule and the laws that govern molecular folding, his team designed a polymer that would bind to cisplatin, much as a thread runs through a bead’s central hole. By stringing together enough cisplatin, the whole molecule wrapped itself into a ball, 100 nanometers in size, too large to enter the kidney.It took a couple of tries to get the molecular design right, Sengupta said. Though the initial design proved nontoxic to kidneys, it wasn’t as effective as the original cisplatin. Sengupta and colleagues tweaked the chemical formula so the molecule didn’t hold quite so tightly to the platinum atoms.Studies conducted by Basar Bilgicer, assistant professor at the University of Notre Dame, showed that the molecule accumulated in tumor tissue, whose leaky blood vessels allowed it to pass out of the capillaries that feed the tumor. The molecule is too large to pass into other tissues, such as the kidney, lungs, liver, and spleen. Once lodged in the tumor, the higher acidity there caused the molecule to fall apart, dumping its toxic load on the cancerous tissue.“It showed absolutely minimal toxicity to the kidney,” Sengupta said.The new compound has been found to be effective against lung and breast cancers. Instructor in pathology Daniela Dinulescu at Brigham and Women’s Hospital also demonstrated that the nano-compound outperformed cisplatin in a transgenic ovarian cancer model that mimics the disease in humans.The research, which received funding from the National Institutes of Health and the Defense Department’s Breast Cancer Research Program, has not been tried in humans, and would require potentially lengthy testing before being ready for patient care.Described in this week’s Proceedings of the National Academy of Sciences, the project also included researchers at the University of Notre Dame, the Harvard-MIT Division of Health Sciences and Technology, the Dana-Farber Cancer Institute, the National Chemical Laboratory in Pune, India, and the Translational Health Science and Technology Institute in New Delhi.Sengupta praised the work and creativity of fellows Abhimanyu Paraskar and Shivani Soni on the project.
Tags: Andy Lulefufa big leagueproline fcShafick BisasoWakiso Giants Wakiso won the Elgon Group with 41 Points. (PHOTOS/FILE)FUFA Big League finalProline FC vs Wakiso GiantsStarTimes Stadium, LugogoSaturday, 18-05-2019Referee: Shamirah NabaddaLUGOGO – All good things have to come to an end and for Wakiso Giants and Proline, the day has come.The two sides have been cruising throughout the 2018/19 FUFA Big League season and either side would be forgiven for not wanting the it to end.However, it has to, and for one of them, it will end with a title in the hands as the two will contest the final on Saturday, 18th May, at the StarTimes Stadium in Lugogo.Wakiso Giants earned their finals’ spot after topping the Elgon Group following a run of 11 wins, 8 draws and only one defeat.In their maiden season, the Purple Sharks have been the envy of everyone else in the division and it would only feel right for their faithful, if it climaxed with a first ever championship.“It’s an important game for us, says Wakiso Assistant coach Andy Lule ahead of the game.“Although our main target of promotion was achieved, we would love to crown the season with a trophy.Wakiso was only given birth-to, last year after they bought off the now defunct Kamuli Park. Their target was to attain promotion at the first time of asking but with a trophy now on line, who would turn it down anyways!Going into Saturday’s encounter, Wakiso goalkeeper Yasin Mugabi is back from injury and could start in goal ahead of Ivan Mutumba. However, there is no place for Norman Ogik who is still nursing an injury. Winger Yasin Mugume is a major doubtful for the games as well.For Proline, they are also aiming to end the season on a high.After succumbing to relegation from the top tier last year, the Lugogo based side made big changes especially in management. Out stepped long serving coach Mujib Kasule and he was replaced by Shafick Bisaso.In his maiden season back at the club, Bisaso knew that promotion back to the top tier, was the primary target and he achieved that in style.With 42 points, Proline won the Rwenzori Group boosting the best record in the entire division.Proline finished the regular season with the best record in the Big League.With a Uganda Cup final against Bright Stars coming later this month, the Proline faithful couldn’t have asked for more at the start of the season.“We have had a dream season as per our standards, said Bisaso.“We won the Rwenzori Group and are into the finals of both the Big League and Uganda Cup. What more would we have asked for for God!“Everyone at the club knows we still have two games to play in the season and victories in both games will see as crowned double champions.Despite finishing ahead of Wakiso in terms of points, Bisaso is worry of the threat that the Purple Sharks possess.“Wakiso Giants is a very good side with proper management and administration.“They have very good experienced players some of whom at one point featured in the National team. But my team is also good and with God on our side, we will win the contest.Proline will feel they have a slight advantage going into the contest as it will be played at a venue on which they have been hosting their League games for the last three years.Match FactsThis will be the first ever competitive meeting between the two sides.Both side won their respective Big League Groups with Wakiso topping the Elgon Group on 41 points while Proline did likewise in the Rwenzori Group, one point better off the the Purple Sharks.In their last games, Wakiso drew 1-1 away to Dove All Stars while Proline defeated Kabale Sharpe 2-0.Comments