aprepitant and Carcinoma--Hepatocellular

Tumor microenvironment (TME) plays a vital role in the development of hepatocellular carcinoma (HCC). Mounting evidence indicates that peripheral nerves could induce a shift from quiescent hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) by secreting substance P (SP). The anti-tumor strategy by targeting "SP-HSCs-HCC" axis might be an effective therapy to inhibit tumor growth and metastasis.. In this study, we prepared novel liposomes (CUR-APR/HA&GA-LPs) modified with hyaluronic acid (HA) and glycyrrhetinic acid (GA) for co-delivery aprepitant (APR) and curcumin (CUR), in which APR was chosen to inhibit the activation of HSCs by blocking SP/neurokinin-1 receptor (NK-1R), and CUR was used to induce apoptosis of tumor cells.. To mimic the TME, we established "SP+HSCs+HCC" co-cultured cell model in vitro. The results showed that CUR-APR/HA&GA-LPs could be taken up by CAFs and HCC simultaneously, and inhibit tumor cell migration. Meanwhile, the "SP+m-HSCs+HCC" co-implanted mice model was established to evaluate the anti-tumor effect in vivo. The results showed that CUR-APR/HA&GA-LPs could inhibit tumor proliferation and metastasis, and reduce extracellular matrix (ECM) deposition and tumor angiogenesis, indicating a superior anti-HCC effect.. Overall, the combination therapy based on HA&GA-LPs could be a potential nano-sized formulation for anti-HCC therapy.

Topics: Animals; Aprepitant; Carcinoma, Hepatocellular; Cell Line, Tumor; Curcumin; Glycyrrhetinic Acid; Hyaluronic Acid; Lipopolysaccharides; Liposomes; Liver Neoplasms; Mice; Tumor Microenvironment

Combination therapy using multiple antiemetic drugs is recommended for intravenous administration of cisplatin, a highly emetogenic agent, whereas a 5-HT3 receptor antagonist alone is commonly used in hepatic arterial infusion chemotherapy using cisplatin for hepatocellular carcinoma owing to its less toxicity than that in the intravenous administration. Given that optimal antiemetic therapy is not yet established, we retrospectively investigated the efficacy of antiemetic drugs for hepatic arterial infusion chemotherapy using cisplatin. This study enrolled 72 patients with hepatocellular carcinoma who received hepatic arterial infusion chemotherapy using cisplatin at Kurashiki Central Hospital between January 2011 and May 2019. A 5-HT3 receptor antagonist was used in all cases, while aprepitant and/or dexamethasone were used concomitantly in 6 cases. After chemotherapy, a complete response rate for 5 days was achieved in 73.6% of the patients; however, complete control could be achieved only in 29.2%. During these 5 days, both rates were lower on days 2-5 than on day 1. In addition, younger age was associated with worse control rates. Our findings suggest that more effective antiemetic therapy is needed for hepatic arterial infusion chemotherapy using cisplatin, especially in non-elderly patients.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Carcinoma, Hepatocellular; Cisplatin; Dexamethasone; Drug Therapy, Combination; Humans; Liver Neoplasms; Middle Aged; Morpholines; Nausea; Palonosetron; Receptors, Serotonin, 5-HT3; Retrospective Studies; Vomiting

This study investigated the prevalence of chemotherapy-induced nausea and vomiting (CINV) in patients with hepatobiliary-pancreatic (HBP) cancer in a prospective nationwide survey.. One hundred patients with HBP cancer (biliary tract cancer; n=70, hepatocellular carcinoma; n=20, and pancreatic cancer; n=10) who received chemotherapy for the first time were analyzed. Medical personnel were surveyed to examine the accuracy of their predicted frequency of CINV.. The compliance rate with the Japanese guideline with highly emetogenic chemotherapy was 36/89 (40%). Although the prevalence of CINV in patients with HBP cancer was significantly lower than that of the total 1,910 patients with cancer, the prevalence of delayed CINV in patients with HBP cancer was as high as 28%. The survey results suggested that the medical staff tended to overestimate the incidence of CINV.. CINV appears to be controlled under management according to the guidelines, but delayed nausea remains prevalent and requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Biliary Tract Neoplasms; Carcinoma, Hepatocellular; Dexamethasone; Female; Humans; Liver Neoplasms; Male; Middle Aged; Morpholines; Nausea; Pancreatic Neoplasms; Serotonin 5-HT3 Receptor Antagonists; Vomiting