The treatment of liver injuries or hepatocellular carcinoma (HCC) with has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system (RES). As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic MRIactive contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MRI imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNPloaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP–loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.

BACKGROUNDGastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies.AIMTo evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE.METHODSA retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTSA total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score [≥ 3 points] (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1).CONCLUSIONRivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.

SMI assessment at L1 is achievable in patients with NSCLC receiving routine chest CT, with 96% having acceptable quality evaluations. Similar to results previously reported at L3, BMI showed poor correlation and low sensitivity to detect muscle mass loss. The use of CT at L1 is reliable and presents the opportunity for easier patient evaluation of sarcopenia in patients with lung cancer without the need for additional testing or radiation exposure.

ABSTRACT

Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1 st , 2 nd , and 3 rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC, hence it is considered a promising therapeutic target. Areas covered:We comprehensively reviewed the evidence from preclinical and phase I and II clinical trials, based on the authors'clinical experience and a pubmed, Chochrane library, Embase, and Google Scholar search everolimus + pancreatic cancer. Expert opinion:Everolimus has not demonstrated efficacy in PDAC; however, an mTOR inhibitor in combination with stroma-targeted therapies may be a promising area to explore in clinical trials.