Uncategorized

Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

By July 23, 2019February 8th, 2021No Comments
2019 Jul 23;9:660. doi: 10.3389/fonc.2019.00660. eCollection 2019.

Author information

1
Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
2
Department of Physics, University of Massachusetts Lowell, Lowell, MA, United States.
3
Department of Biology, University of Massachusetts Boston, Boston, MA, United States.
4
Department of CaNCURE Program, Northeastern University, Boston, MA, United States.
5
Flavocure Biotech Inc., Baltimore, MD, United States.

Abstract

Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.

KEYWORDS: cannabis, flavonoids, metastasis, pancreatic cancer, radiotherapy, smart biomaterials

PMID: 31396485
PMCID: PMC6663976
DOI: 10.3389/fonc.2019.00660

Corrigendum: Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer

Associated Data

Supplementary Materials

In the original article, there was a mistake in Figures 4E, 4F, and and5C5C as published. This was due to errors during use of analysis software. The survival data in Figures 4E,F has been combined into one Figure 4E. The figure legend of Figure 4 has been updated to reflect the correction made in the figure. The corrected Figures 4 and and55 appear below.

An external file that holds a picture, illustration, etc.
Object name is fonc-10-01434-g0001.jpg

In-vivo treatment of C57BL/6 mice. Mice were inoculated with 50 μL of KPC cells in PBS suspension at concentrations of 5 × 104 pancreatic cancer cells, on each left and right flank of mouse using a 22-Gauge syringe. When right side tumors reached palpable size, mice were randomized and treatments were administered. Mice were observed at least twice per week and tumor measurements were performed using precision calipers at least once per week. The abscopal effect was examined by monitoring the non-treated tumor. Smart radiotherapy biomaterials (SRB) loaded with FBL-03G (100 μg) significantly boosts the abscopal effect in pancreatic cancer slowing down tumor growth for both treated and untreated tumors. Two experiments were conducted simultaneously: Study 1 results are shown in graphs (A–D) and combined survival results for study 1 and study 2 results are displayed in (E)(A) Volumes of non-treated tumors over time without SRB (n = 3 for each cohort). (B) Volumes of treated tumors over time (n = 3 for each cohort). (C) Volume of non-treated tumors over time with SRB and FBL-03G (n = 3 for control and 6Gy cohorts respectively; n = 4 for SRB loaded with FBL-03G with/without radiotherapy cohorts respectively). (D) Volume of treated tumors over time for cohorts treated with SRB and FBL-03G (n = 3 for control and 6 Gy cohorts respectively; n = 4 for SRB loaded with FBL-03G with/without radiotherapy cohorts respectively). (E) Survival results show significant increase in survival for cohorts treated with SRB loaded with FBL-03G (each n = 9) compared to control (n = 6), 6Gy/FBL-03G/FBL-03G_6Gy (each n = 3). For Statistical Analyses (*P < 0.05; **P < 0.01) Student’s T-Test was used for comparing the volumes of tumors for each treatment group versus those of the control group with no additional corrections, and Log-rank (Mantel-Cox) was used for the survival graphs.

An external file that holds a picture, illustration, etc.
Object name is fonc-10-01434-g0002.jpg

Investigating the optimal concentration of FBL-03G loaded in SRB to enhance the abscopal effect. Smart radiotherapy biomaterial (SRB) loaded, respectively, with FBL-03G (100, 200, or 300 μg). C57BL/6 mice were inoculated with pancreatic cancer cells (KPC) on both flanks. Tumor volume and survival (n = 10 for each cohort) were assessed. (A) Volumes of non-treated tumors 2-weeks post treatment (n = 10 for each cohort); (B) volumes of treated tumors 2-weeks post treatment (n = 10 for each cohort). This study investigated using different concentrations of FBL-03G with/without 6Gy to determine its potential effect on mice survival over time. (C) Represents a Log-rank (Mantel-Cox) survival graph (n = 10) (****p < 0.0001). (C) Survival results show no difference in survival for cohorts treated with different concentrations of SRB loaded with FBL-03G.

The data for the tumor volume and survival results has also now been published as Supplementary Material.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2020.01434/full#supplementary-material

The authors apologize for this error and state that these do not change the scientific conclusions of the article in any way. The original article has been updated.


Articles from Frontiers in Oncology are provided here courtesy of Frontiers Media SA


Leave a Reply

en English
X