Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3-targeted magnetic resonance imaging, positron emission tomography, and near-infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti-GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.
Thermal ablation has been considered as an alternative for local curative intent in patients with unresectable colorectal liver metastases. The influence of primary tumor location on the prognosis of colorectal liver metastases patients who have undergone microwave ablation has yet to be determined. We reviewed 295 patients who underwent microwave ablation for colorectal liver metastases at our institution between March 2006 and March 2016. Univariate and multivariate analyses were performed to identify predictors of overall and progression-free survival. Technical success was achieved in 96.6% of patients (n = 289), with a post-procedural complication rate of 2.0% (n = 6). After a median follow-up of 24 (range, 2–86) months, comparable overall survival rates (p = 0.583) were observed in patients with different primary tumor locations. Patients with colorectal liver metastases originating from left-sided primary colon cancer exhibited a better progression-free survival than patients whose colorectal liver metastases had originated from right-sided primary colon cancer (hazard ratio: 0.67, 95.0% confidence interval: 0.48–0.94; p = 0.012), which was further confirmed in a multivariate analysis after adjustment for other potential prognostic factors. Stratification based on primary tumor location should be taken into consideration in the assessment of disease progression in patients who intend to undergo microwave ablation for colorectal liver metastases.
Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced by acute psychostimulants in rodents via GABAb receptors. This study investigated the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated methamphetamine- (METH-) induced locomotor sensitization and conditioned place preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6 consecutive days, subjected to 6 days of withdrawal, and then challenged with the same dose of METH to induce locomotor sensitization; during the withdrawal period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort of rats was treated with either METH or saline every other day for 6 days in METH-paired or saline-paired chambers, respectively, to induce CPP. These rats were also administered MEGR (180 mg/kg) prior to every METH or CPP expression test. Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH-induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR significantly inhibited the development and expression of METH-induced CPP. Furthermore, administration of a selective GABAb receptor antagonist (SCH50911) prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae Radix blocked repeated METH-induced behavioral changes via GABAb receptors.
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