Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers.

Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT. A retrospective cohort of 448 NET patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions. Of the 448 PRRT treated patients, 335 received 177Lu-DOTATATE (74.78%) and 113 were treated with 90Y-DOTATOC (25.22%). Comparing patients treated with 177Lu-DOTATATE to those treated with 90Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with 90Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with 177Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received 177Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with 90Y-DOTATOC, but there was no difference in OS. There was no significant renal, but minor hematological toxicity, in patients treated with 177Lu-DOTATATE compared with 90Y-DOTATOC. Compared to 90Y-DOTATOC, 177Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with 177Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.

被引量：- 发表：1970

Euphorbia helioscopia L. extract suppresses hepatitis B virus-related hepatocellular carcinoma via alpha serine/threonine-protein kinase and Caspase-3.

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) has poor prognosis and high mortality rate. Euphorbia helioscopia L. (EHL) is a classic Chinese medicinal herb. This study aimed to evaluate in vitro anti-HBV-HCC properties of EHL, and explore it targets in HBV-HCC based on molecular docking. The anti-tumor effect of EHL on HBV-HCC was evaluated using the cell viability, migration, invasion, and apoptosis of Hep 3B2.1-7 and HepG2.2.15 cells. Next, network pharmacological analysis was performed to predicted the key targets of EHL against HBV-HCC. Then the prognostic targets, including RAC-alpha serine/threonine-protein kinase (AKT1) and Caspase-3 (CASP3), were verified using molecular docking and rescue experiments. EHL exhibited inhibitory effects on cell proliferation/migration/invasion and induced cell apoptosis. Network pharmacological analysis proposed 12 active compounds in EHL, which targeted 22 HBV-HCC-related genes. AKT1 and CASP3 were identified to be key targets for EHL against HBV-HCC. AKT1 and CASP3 had prognostic significance in liver cancer. Overexpression of AKT1 and caspase-3 inhibitor can counteract the EHL effect. EHL can exert anticancer effects on HBV-HCC by inhibiting migration/invasion, and inducing apoptosis, which may be achieved through AKT1 and CASP3.

被引量：- 发表：1970

A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment.

High-dose methotrexate (HDMTX) is used in the treatment of a range of adult and childhood cancers. Although HDMTX can provide effective anti-tumor activity with an acceptable safety profile for most patients, delayed methotrexate elimination (DME) develops in a minority of patients receiving HDMTX and may be accompanied by renal dysfunction and potentially life-threatening toxicity. A panel of European physicians with experience in the use of HDMTX as well as of glucarpidase convened to develop a series of consensus statements to provide practical guidance on the prevention and treatment of DME, including the use of glucarpidase. Robust implementation of supportive measures including hyperhydration and urine alkalinization emerged as critical in order to reduce the risk of DME with HDMTX treatment, with leucovorin rescue critical in reducing the risk of DME complications. Early recognition of DME is important to promptly implement appropriate treatment including, intensified hydration, high-dose leucovorin and, when appropriate, glucarpidase.

被引量：- 发表：1970

Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4.

被引量：- 发表：1970

ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.

被引量：- 发表：1970