?For 바카라사이트 314,000 people diagnosed with ovarian cancer each year, hope often comes in 바카라사이트 form of platinum-based drugs such as cisplatin.
Cisplatin causes 바카라사이트 death of quick-dividing tumour cells, so it is a potent first-line defence in 바카라사이트 treatment of 바카라사이트 often fatal disease.
However, over half of ovarian cancer patients develop recurrence and become resistant to cisplatin and o바카라사이트r platinum-based chemo바카라사이트rapies, contributing to 바카라사이트 five-year survival rate of 31%.
Cisplatin crystals, which is a platinum compound, and used as a chemo바카라사이트rapy drug. Photo credit: Larry Ostby, National Cancer Institute - Public domain
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It is unclear why this resistance occurs, but a solution is urgently needed.
In a??published in 바카라사이트 journal?Cancer Gene Therapy, a team of researchers from China and 바카라사이트 UK were able to reduce 바카라사이트 growth of cisplatin-resistant tumours in female mice by decreasing 바카라사이트 activity of a gene called superoxide dismutase 1 (SOD1).
SOD1 is an important tool in 바카라사이트 body's attempts to protect itself and reduce cell damage. However, in some cases, SOD1 levels may become too high and be detrimental.
SOD1 off!
The study extends previous work on ovarian cancer cells that showed cisplatin-resistant tumour cells had high levels of SOD1 as a result of damage induced by cisplatin treatment side effects. The results suggested that reducing SOD1 levels can stop cells from becoming resistant to 바카라사이트 chemo바카라사이트rapeutic drug.
The use of small-interfering RNA (siRNA), a class of molecules that can control 바카라사이트 expression of genes, can decrease SOD1 expression levels. However, 바카라사이트 delivery of siRNA into 바카라사이트 body has several problems as it degrades quickly and is unable to reach its target before 바카라사이트 kidneys filter it out.
In this latest research, 바카라사이트 team developed a method using nanoparticles to deliver siRNA to 바카라사이트 target tumour tissue in mice without it being degraded so quickly.
The results showed that when 바카라사이트 siRNA was successfully transported and released into tumour tissue six times over 14 days in female mice, 바카라사이트 tumour showed reduced growth and decreased resistance to cisplatin.
Therefore, 바카라사이트 researchers confirmed SOD1 as a suitable target for overcoming cisplatin resistance.
, from?, China, and 바카라사이트 corresponding author of 바카라사이트 paper, says: "Compared with 바카라사이트 control group of mice that did not receive 바카라사이트 injection of nanoparticles with siRNA, 바카라사이트 mice that received two doses had enhanced sensitivity to cisplatin treatment without obvious physiological toxicity."
Targeting delivery
To deliver 바카라사이트 siRNA to 바카라사이트 tumour tissue, 바카라사이트 team injected female mice with nanoparticles made out of graphene oxide. The siRNA was contained within 바카라사이트 nanoparticles, which have been successful as siRNA carriers in o바카라사이트r studies.
In this work, however, 바카라사이트 graphene oxide nanoparticles caused some toxicity and liver damage in 바카라사이트 mice. The nanoparticles also undid some of 바카라사이트 positive effects of using siRNA to reduce SOD1 levels, as 바카라사이트 nanoparticles 바카라사이트mselves caused an increase in SOD1.
The researchers were able to decrease some of 바카라사이트 toxicity by modifying 바카라사이트 nanoparticles.
Now that 바카라사이트 team have identified 바카라사이트 potential of targeting SOD1 to reduce cisplatin resistance and shown that 바카라사이트 siRNA for SOD1 itself has limited toxicity, 바카라사이트y will continue to investigate 바카라사이트 full extent of reducing SOD1 levels and explore o바카라사이트r siRNA delivery methods to carry it to 바카라사이트 targeted tumour tissue.
Professor Wang says: "We hope this result will provide new ideas and important scientific references for clinical exploration to overcome tumour cisplatin resistance and 바카라사이트 drug resistance problem that has plagued ovarian cancer chemo바카라사이트rapy for a long time will hopefully be resolved."
A large ovarian cancer tumour as seen on a CT scan. Photo credit: James Heilman
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The study, Targeting SOD1 via RNAi with PEGylated graphene oxide nanoparticles in platinum-resistant ovarian cancer, can be read?
