Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR‐T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.
OBJECTIVELower-grade gliomas (LGGs) are often observed within eloquent regions, which indicates that tumor resection in these areas carries a potential risk for neurological disturbances, such as motor deficit, language disorder, and/or neurocognitive impairments. Some patients with frontal tumors exhibit severe impairments of neurocognitive function, including working memory and spatial awareness, after tumor removal. The aim of this study was to investigate neurocognitive and functional outcomes of frontal LGGs in both the dominant and nondominant hemispheres after awake brain mapping.METHODSData from 50 consecutive patients with diffuse frontal LGGs in the dominant and nondominant hemispheres who underwent awake brain surgery between December 2012 and September 2018 were retrospectively analyzed. The goal was to map neurocognitive functions such as working memory by using working memory tasks, including digit span testing and N-back tasks.RESULTSDue to awake language mapping, the frontal aslant tract was frequently identified as a functional boundary in patients with left superior frontal gyrus tumors (76.5%). Furthermore, functional boundaries were identified while evaluating verbal and spatial working memory function by stimulating the dorsolateral prefrontal cortex using the digit span and visual N-back tasks in patients with right superior frontal gyrus tumors (7.1%). Comparing the preoperative and postoperative neuropsychological assessments from the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III) and Wechsler Memory Scale–Revised (WMS-R), significant improvement following awake surgery was observed in mean Perceptual Organization (Z = −2.09, p = 0.04) in WAIS-III scores. Postoperative mean WMS-R scores for Visual Memory (Z = −2.12, p = 0.03) and Delayed Recall (Z = −1.98, p = 0.04) were significantly improved compared with preoperative values for every test after awake surgery. No significant deterioration was noted with regard to neurocognitive functions in a comprehensive neuropsychological test battery. In the postoperative course, early transient speech and motor disturbances were observed in 30.0% and 28.0% of patients, respectively. In contrast, late permanent speech and motor disturbances were observed in 0% and 4.0%, respectively.CONCLUSIONSIt is noteworthy that no significant postoperative deterioration was identified compared with preoperative status in a comprehensive neuropsychological assessment. The results demonstrated that awake functional mapping enabled favorable neurocognitive and functional outcomes after surgery in patients with diffuse frontal LGGs.
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