Thromb Res. 2015;13(7):1310–9. 2012;3:385. To determine the role of NETs in platelet aggregation in our cancer model, we first examined platelet activation and aggregation in mice injected with orthotopic tumor and sham injected controls. The addition of NETs to whole blood stimulated platelet activation and aggregation. 2017;157:9–15. Martinod K, Demers M, Fuchs TA, Wong SL, Brill A, Gallant M, et al. Subsequent studies have established that HCQ has direct effects on platelet activation and aggregation [48, 49]. But then there's this: Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents: Human (500 μL) and murine (300 μL) whole blood was treated with 50 to 100 μL of NET supernatant for 10 min., DOI: Ding N, Chen G, Hoffman R, Loughran PA, Sodhi CP, Hackam DJ, et al. PubMed  Additionally, the 90 day postoperative reduction in VTE occurred despite HCQ stopping at time of surgery.,,, Infection, immunity and cancer vaccines’. Chloroquine has previously been studied for prevention of perioperative VTE in orthopedic surgery patients, however these studies had mixed results and the precise mechanism was not completely understood [46, 47]. Pre-existing hypercoagulability in patients undergoing potentially curative cancer resection. Article  Swamydas M, Luo Y, Dorf ME, Lionakis MS. Hydroxychloroquine is an autophagy inhibitor. 2014;155(1):134–44. Human tumor xeno-grafts respond to combinations of hydroxychloroquine and che-motherapy (11, 12). Olsson AK, Cedervall J. NETosis in Cancer - platelet-neutrophil crosstalk promotes tumor-associated pathology. Google ScholarÂ. 2017;69(3):655–67. Tumor response rate is the percentage of patients achieving complete or partial response on treatment based on RECIST 1.0 criteria. Given its well-established use, favorable safety profile and anti-tumor effects, CQ is a suitable treatment to decrease VTE rate in patients with pancreatic cancer. Oncoimmunology. Heinmoller E, Schropp T, Kisker O, Simon B, Seitz R, Weinel RJ. Front Immunol. The NET inhibitor chloroquine reduces platelet aggregation, reduces circulating tissue factor and decreases hypercoagulability on TEG. An additional … Experimental: Hydroxychloroquine 400 mg b.i.d. We appreciate the efforts of Stacy Stull, Peter Adams and MACRO (Multidisciplinary Acute Care Research Organization) research, University of Pittsburgh, in running TEG samples. Nosal R, Jancinova V, Danihelova E. Chloroquine: a multipotent inhibitor of human platelets in vitro. Kambas K, Mitroulis I, Apostolidou E, Girod A, Chrysanthopoulou A, Pneumatikos I, et al. Abstract Background: The hypercoagulable state associated with pancreatic adenocarcinoma (PDA) results in increased risk of venous thromboembolism, leading to substantial morbidity and mortality. Springer Nature. CAS  California Privacy Statement, Furthermore, treatment of whole blood from RAGE KO mice with NET supernatant led to diminished platelet aggregation compared with WT mice (Fig. 2d). To study the effects of chloroquine inhibition of NETs and subsequent decrease in platelet aggregation and circulating tissue factor on the hypercoagulable state seen in pancreatic cancer, we performed thromboelastograms (TEG) in mice with pancreatic adenocarcinoma to assess hypercoagulability as measured by the coagulation index, which takes into account all of the TEG parameters (Additional file 5: Table S2). RPMI media with 500 nM PMA was added to whole blood for a control. Google ScholarÂ. Individual Participant Data (IPD) Sharing Statement: To determine the efficacy of single-agent hydroxychloroquine in patients with metastatic pancreatic cancer previously treated with one or two prior chemotherapy regimens as measured by progression-free survival at two months, To assess tumor response rate, biochemical response rate (i.e. We next examined the impact of hydroxychloroquine (HCQ) on circulating tissue factor in patients with pancreatic cancer using serum from our recently completed randomized clinical trial of preoperative gemcitabine/nab-paclitaxel with or without HCQ. 2014;66(9):2532–44. 2013;2(2):e22946. Of note, the lone patient who developed VTE was treated as part of the dose escalation at 800 mg per day rather than at the maximum dose of 1200 mg. 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