Glaucarubinone Combined with Gemcitabine Improves Pancreatic Cancer Survival in an Immunocompetent Orthotopic Murine Model.

J Invest Surg 2016 Dec 30;29(6):366-372. Epub 2016 Mar 30.

a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.

Background: Pancreatic cancer continues to have a poor survival rate with an urgent need for improved treatments. Glaucarubinone, a natural product first isolated from the seeds of the tree Simarouba glauca, has recently been recognized as having anti-cancer properties that may be particularly applicable to pancreatic cancer.

Methods: The effect of glaucarubinone on the growth and migration of murine pancreatic cancer cells was assessed by H-thymidine incorporation assay. The survival impact of glaucarubinone alone and in combination with gemcitabine chemotherapy was assessed using an immunocompetent orthotopic murine model of pancreatic cancer.

Results: Glaucarubinone inhibited the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment with either glaucarubinone or gemcitabine reduced proliferation in vitro and the combination was synergistic. The combination treatment improved survival two-fold compared to gemcitabine treatment alone (p = 0.046) in PAN02 cells.

Conclusions: The synergistic inhibition by glaucarubinone and gemcitabine observed in vitro and the improved survival in vivo suggest that glaucarubinone may be a useful adjunct to current chemotherapy regimens.

Download full-text PDF

Source
http://dx.doi.org/10.3109/08941939.2016.1160167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757120PMC
December 2016
Save 15% Survey

Similar Publications

Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer.

J Trace Elem Med Biol 2021 Feb 17;65:126734. Epub 2021 Feb 17.

School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, PR China; School of Life Sciences, Nanjing University, Nanjing 210023, PR China; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, PR China. Electronic address:

Introduction: Zinc homeostasis is regulated by SLC39A/ZIP, SLC30A/ZnT, and metallothionein (MT) families in human cells. Zinc dyshomeostasis may affect or be affected by the abnormal behavior of cancer cells. Although decreased serum zinc levels are observed in patients with pancreatic adenocarcinoma (PAAD), limited information is available regarding the expression pattern and prognostic roles of zinc homeostasis-related genes in PAAD. Read More

View Article and Full-Text PDF
February 2021

Thromboembolism, mortality, and bleeding in 2,435,541 atrial fibrillation patients with and without cancer: A nationwide cohort study.

Cancer 2021 Feb 25. Epub 2021 Feb 25.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et EA7505, Faculté de Médecine, Université François Rabelais, Tours, France.

Background: The number of patients with atrial fibrillation (AF) and cancer is rapidly increasing in clinical practice. The impact of cancer on clinical outcomes in this patient population is unclear, as is the performance of the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) and CHA DS -VASc (Congestive Heart Failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Stroke or Transient Ischemic Attack, Vascular Disease, Age 65 to 74 Years, Sex Category) scores.

Methods: This was an observational, retrospective cohort study including 2,435,541 adults hospitalized with AF. Read More

View Article and Full-Text PDF
February 2021

The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration.

PLoS Biol 2021 Feb 25;19(2):e3001122. Epub 2021 Feb 25.

MOE Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.

The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. Read More

View Article and Full-Text PDF
February 2021

Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the Imaging of Pancreatic Cancer With Liver Metastases.

Clin Nucl Med 2021 Feb 20. Epub 2021 Feb 20.

From the Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou; and Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.

Abstract: A 65-year-old man with suspected pancreatic cancer underwent 18F-FDG PET/CT for initial staging. Mild FDG uptake was observed in the pancreatic mass and bone destruction in the 10th rib on the right. No significant FDG uptake was seen with the multiple hypodense or isodense nodules in the liver. Read More

View Article and Full-Text PDF
February 2021

A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects with Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer.

Ann Surg 2020 Dec 22. Epub 2020 Dec 22.

*Thomas Jefferson University Hospital and The Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, PA †Cedars Sinai Medical Center, Los Angeles, CA ‡University of Oklahoma, Oklahoma City, OK §Baylor College of Medicine, Houston, TX ¶Virginia Piper Cancer Institute, Minneapolis, MN ||University of Washington-Seattle Cancer Care, Seattle, WA **University of Kansas Cancer Center, Westwood, KS ††H. Lee Moffitt Cancer Center, Tampa, FL ‡‡Oregon Health and Science University, Portland, OR §§University of Wisconsin, Madison, WI ¶¶University of Florida, Gainesville, FL ||||Boca Raton Hospital, Boca Raton, FL ***University of California at Irvine, Irvine, CA †††NewLink Genetics Corporation, Ames, IA ‡‡‡Lumos Pharma Inc, Ames, IA.

Objectives: To compare the efficacy and safety of algenpantucel-L (HAPa; IND# 12311) immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data: To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. Read More

View Article and Full-Text PDF
December 2020