PB1082 - Intratumoral administration of anticoagulant Protein S reduces tumor volume in nude mouse model of pancreatic cancer.

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Teagan M. Prouse

Student
Louisiana State University Health Sciences Center, Department of Interdisciplinary Oncology
Metairie, Louisiana, United States

Co-Author(s)

NK

Narender Kumar

Postdoctoral Fellow
LSUHSC
New Orleans, Louisiana, United States
KL

Kristina Larter

Graduate Student
LSUHSC, Department of Genetics
New Orleans, Louisiana, United States
SG

Sonali Ghosh

Postdoctoral Fellow
LSUHSC
New Orleans, Louisiana, United States
MM

Mohammad A. Mohammad

Post-doctoral fellow
LSUHSC
New Orleans, Louisiana, United States
SM

Samarpan Majumder

Associate Professor and Researcher
LSUHSC, Department of Genetics
New Orleans, Louisiana, United States

Presenting Author(s)

RM

Rinku Majumder

Professor
LSUHSC
New Orleans, Louisiana, United States

Background: Thrombotic complications and hypercoagulopathies are associated with the progression of pancreatic ductal adenocarcinoma (PDAC). Although the mechanistic link between the two phenomena is uncertain, it has been reported that the anticoagulant protein S (PS) is decreased during the progression of PDAC, a condition that possibly contributes to hypercoagulopathy.

Aims: To evaluate the safety and efficacy of PS administered to immunocompromised C57BL-6 black mice that had human PANC-1 induced tumors.

Methods: PANC-1 cells (5 x106) were mixed with Matrigel (1:1) and injected in the right flanks of 20 mice. Ten female and ten male mice were used to account for possible sex as biological variable. Once tumor size reached 80 mm3, the 20 mice were divided into three groups- untreated control, and treatment groups of 2 mg/kg per week of PS and 4 mg/kg per week of PS. The tumor volumes and mouse weights were measured and calculated weekly. After four weeks of treatment, the mice were sacrificed and the tumors compared.

Results: Mice treated weekly with 2 mg/kg and 4 mg/kg PS showed statistically significant reduction in tumor size compared with control (Figure 1). The greatest reduction in tumor size overall was in the 4 mg/kg PS group in both male and female mice. These results suggest a PS dose-dependent reduction in tumor size.

As shown in Figure 2, the naked tumors treated with PS are significantly smaller and less vascularized than tumors from control mice. These results support the conclusion that PS decreased the size of PANC-1 tumors in C57BL-6 black nude mice. We did not observe toxicity or weight loss during the four-week treatments.

Conclusion(s): We show that PS administration directly into PANC-1 tumors that were induced subcutaneously on the flank of C57BL-6 black mice significantly reduced tumor volume.

The project is funded by the Start Up Fund 14976036TN to RM.