Maackia amurensis seed lectin

Podoplanin (PDPN) has emerged as a functionally relevant biomarker and chemotherapeutic target expressed by OSCC cells. PDPN signaling can directly increase tumor cell invasion and metastasis, and also inhibit host lymphocyte activation and immune response. Accordingly, antibodies and Maackia amurensis seed lectin (MASL) can target the PDPN receptor to inhibit OSCC cell migration and viability. However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported.

We conducted a Phase 1 human clinical trial to examine the effects of a single 100 mg oral dose of MASL on OSCC cell morphology, PDPN expression, and immune cell infiltration in lesions in oral cancer patients. We also examined the effects of MASL on the PDPN expression, motility, and viability of cells cultured from these patient lesions. In addition, we examined the ability of antibodies to target PDPN and kill OSCC cells by near-infrared photoimmunotherapy.

MASL administration was found to be safe and did not produce any adverse effects in any patients. While this single dose did not affect OSCC cell morphology in lesions in situ, it did appear to increase lymphocyte infiltration into tumor fields in one patient by over 5 fold (p < 0.01). In addition, MASL inhibited the growth and motility of all OSCC cells cultured from these patient lesions in a dose responsive manner in vitro (p < 0.05 in all cases) We also report that antibodies can target PDPN on OSCC cells obtained from these patients to destroy them by near-infrared photoimmunotherapy (NIR-PIT).

These results suggest that protocols using MASL and photoimmunotherapies that target PDPN can be developed to effectively treat OSCC lesions in oral cancer patients.

We assessed in vivo rates of hepatic mitochondrial oxidation, gluconeogenesis, and β-hydroxybutyrate (β-OHB) turnover by positional isotopomer NMR tracer analysis (PINTA) in individuals with metabolic-dysfunction-associated steatotic liver (MASL) (fatty liver) and MASL disease (MASLD) (steatohepatitis) compared with BMI-matched control participants with no hepatic steatosis. Hepatic fat content was quantified by localized ¹H magnetic resonance spectroscopy (MRS). We found that in vivo rates of hepatic mitochondrial oxidation were unaltered in the MASL and MASLD groups compared with the control group. A physiological increase in plasma glucagon concentrations increased in vivo rates of hepatic mitochondrial oxidation by 50%-75% in individuals with and without MASL and increased rates of glucose production by ∼50% in the MASL group, which could be attributed in part to an ∼30% increase in rates of mitochondrial pyruvate carboxylase flux. These results demonstrate that (1) rates of hepatic mitochondrial oxidation are not substantially altered in individuals with MASL and MASLD and (2) glucagon increases rates of hepatic mitochondrial oxidation.