AIM:To characterize the receptor binding affinity and cytotoxicity of insulin-methotrexate (MTX) for the potential utilization of insulin as carriers for carcinoma target drugs.
METHODS:MTX was covalently linked to insulin. Insulin-MTX conjugate was purified by Sephadex G-25 column and analyzed by high performance liquid chromatography. Hepatocellular carcinoma cell membrane fractions were isolated by sucrose density gradient centrifugation. Competitive displacement of 125 I-insulin with insulin and insulin-MTX binding to insulin receptors were carried out. Cytoreductive effect of insulin-MTX on human hepatoma BEL7402 cells and human hepatocyte cell line HL7702 was evaluated using the MTT assay.
RESULTS:Insulin-MTX competed as effectively as insulin with 125 I-insulin for insulin receptors. The values of Kd for insulin-MTX and insulin were 93.82±19.32 nmol/L and 5.01±1.24 nmol/L, respectively. The value of Kd for insulin-MTX was significantly increased in comparison with insulin (t=7.2532, n=4, P<0.005). Insulin-MTX inhibited the growth of human hepatoma cells (BEL7402) almost as potently as MTX. The inhibitory effect reached a peak on the 5 th day when the growth of cells was inhibited by 79% at a concentration of 5.0 µg/mL insulin-MTX. Treatment with 5.0 µg/mL of MTX and 5.0 µg/mL of insulin-MTX merely resulted in inhibition of HL7702 cells by 31.5% and 7.8% on the 5 th day.
CONCLUSION:Insulin-MTX specifically recognizes insulin receptors and inhibits the growth of BEL7402 cells. These results suggest that insulin can be used as a carrier in receptor mediated carcinoma-targeting therapy.Ou XH, Kuang AR, Liang ZL, Peng X, Zhong YG. Receptor binding characteristics and cytotoxicity of insulin-methotrexate.
Background: To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients.Methods: A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs).Results: During a median follow-up of 23 months, 95 clinical outcomes were observed, with a one-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including Neutrophil-to-Lymphocyte Ratio (NLR), Neutrophil×Monocyte-to-Lymphocyte Ratio (SIRI), Albumin-to-Globulin Ratio (AGR) and Platelet-to-Lymphocytes Ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI: 0.32-0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making.Conclusions: Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.