BackgroundOrgan site-specific metastasis is an ominous feature for most poor-prognostic hepatocellular carcinoma (HCC) patients. Cancer cell lines and animal models are indispensable for investigating the molecular mechanisms of organ specific tropism. However, till now, little is known about the drivers in HCC metastatic tropism, and also no effective way has been developed to block the process of tropistic metastasis.MethodsIn this study, we established several monoclonal HCC cell lines from HCCLM3-RFP together with their xenograft models, and then analyzed their metastatic potentials and tropisms using in-vitro and in-vivo assays, and finally elucidated the driving forces of HCC tropistic metastases.ResultsSix monoclonal cell lines with different organ site-specific tropism were established successfully. SPARC, VCAM1 and ANGPTL4 were found positively correlated with the potentials of lung metastasis, while ITGA1 had a positive relation to lymph node metastasis of enterocoelia.ConclusionsBy our powerful platforms, HCC metastatic tropisms in clinic could be easily mimicked and recapitulated for exploring the bilateral interactions between tumor and its microenvironment, elucidating the drivers of HCC metastatic tropisms, and testing anti-cancer effects of newly developed agent in pre-clinical stage.

BackgroundMarkers of systemic inflammation are correlated with patient survival in various cancers. The prognostic value of neutrophil-to-lymphocyte ratio (NLR) was compared with that of platelet-to-lymphocyte ratio (PLR) in patients with glioblastoma. The association of NLR with neutrophil and T- cell infiltration was also explored.MethodsA total of 152 patients with glioblastoma were retrospectively analyzed. Clinical information was obtained from electronic medical records. Kaplan-Meier analysis and the Cox proportional hazards models were used to examine the survival function of pre-treatment NLR and PLR in these glioblastoma patients. Neutrophil and CD3+ T-cell infiltration was assessed by immunohistochemical staining of tissue microarray cores from glioblastomas.ResultsPre-treatment NLR levels were significantly correlated with overall survival (OS) in glioblastoma patients (multivariate hazard ratio =1.050; 95 % confidence interval, 1.003–1.100; P = 0.037). Despite the correlation between NLR and PLR (R = 0.509, P < 0.001), NLR was superior to PLR as a prognostic factor. High pre-treatment NLR (≥4 versus < 4) was significantly associated with high neutrophil infiltration and low CD3+ T-cell infiltration into tumors, and predicted poor OS (mean, 10.6 vs. 17.9 months, P < 0.001).ConclusionsPre-treatment NLR is of prognostic significance independent of MGMT status and is superior to PLR as a prognostic factor. Our results demonstrate a correlation between elevated peripheral blood NLR levels and increased tumor neutrophil infiltration/decreased CD3+ T-cell infiltration.

BackgroundPrimary care providers do not routinely follow guidelines for the care of patients with chronic kidney disease (CKD). Multidisciplinary efforts may improve care for patients with chronic disease. Pharmacist based interventions have effectively improved management of hypertension. We performed a pragmatic, randomized, controlled trial to evaluate the effect of a pharmacist based quality improvement program on 1) outcomes for patients with CKD and 2) adherence to CKD guidelines in the primary care setting.MethodsPatients with moderate to severe CKD receiving primary care services at one of thirteen community-based Veterans Affairs outpatient clinics were randomized to a multifactorial intervention that included a phone-based pharmacist intervention, pharmacist-physician collaboration, patient education, and a CKD registry (n = 1070) or usual care (n = 1129). The primary process outcome was measurement of parathyroid hormone (PTH) during the one year study period. The primary clinical outcome was blood pressure (BP) control in subjects with poorly controlled hypertension at baseline.ResultsAmong those with poorly controlled baseline BP, there was no difference in the last recorded BP or the percent at goal BP during the study period (42.0% vs. 41.2% in the control arm). Subjects in the intervention arm were more likely to have a PTH measured during the study period (46.9% vs. 16.1% in the control arm, P <0.001) and were on more classes of antihypertensive medications at the end of the study (P = 0.02).ConclusionsA one-time pharmacist based intervention proved feasible in patients with CKD. While the intervention did not improve BP control, it did improve guideline adherence and increased the number of antihypertensive medications prescribed to subjects with poorly controlled BP. These findings can inform the design of quality improvement programs and future studies which are needed to improve care of patients with CKD.Trial registrationClinicalTrials.gov: NCT01290614.