The desmoplastic stroma in pancreatic cancer comprising mainly of collagen and glycosaminoglycans like hyaluronan (HA), is responsible for compression of vasculature in the tumor resulting in impaired drug delivery and poor prognosis. Minnelide, a water-soluble pro-drug of triptolide currently in Phase I clinical trial, has been very effective in multiple animal models of pancreatic cancer. However, whether Minnelide will have efficacious delivery into the tumor in spite of the desmoplastic stroma, has not been evaluated before. Experiment design Patient tumor derived xenografts (PDX) and spontaneous pancreatic cancer mice were treated with 0.42mg/kg and 0.21mg/kg body weight for 30 days. Stromal components were determined by IHC and ELISA based assays. Vascular functionality and drug delivery to the tumor were assessed following treatment with Minnelide. Result Our current study shows that treatment with Minnelide decreases of ECM components like HA and collagen in the pancreatic cancer stroma of both the spontaneous KPC mice and in PDX tumors. Further, treatment with Minnelide improved functional vasculature in the tumors resulting in more functional vessels in the treated animals compared to untreated animals. Consistent with this observation, Minnelide also resulted in increased drug delivery into the tumor compared to untreated animals. Further, Minnelide decreased viability of the stromal cells along with the tumor cells in pancreatic adenocarcinoma. Conclusion In conclusion, these results are extremely promising as they indicate that Minnelide, along with having anti-cancer effects is also able to deplete stroma in pancreatic tumors, which makes it an effective therapy for pancreatic cancer.
Pharmacology, Toxicology and Pharmaceutical Science
3
5%
Computer Science
3
5%
Agricultural and Biological Sciences
1
2%
Other
2
3%
Unknown
28
48%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2016.
All research outputs
#9,225,767
of 29,042,824 outputs
Outputs from Clinical Cancer Research
#7,791
of 14,224 outputs
Outputs of similar age
#123,929
of 414,574 outputs
Outputs of similar age from Clinical Cancer Research
#80
of 179 outputs
Altmetric has tracked 29,042,824 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 14,224 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.3. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 414,574 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 179 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
