Case report: Concurrent intrathecal and intravenous pembrolizumab for metastatic melanoma with leptomeningeal disease.

Leptomeningeal disease (LMD) is a serious cancer complication associated with poor prognosis. Approximately 5%-25% of patients with melanoma develop LMD. Currently, no standard treatment protocol exists and very few cases have been reported. Despite ongoing advances in new therapies, treatment options for LMD remain limited. Herein, we report a case of intrathecal pembrolizumab administration in a patient with melanoma and LMD. Intrathecal pembrolizumab administration was feasible and safe at the doses tested. Drawing from this case, along with our expertise and the existing evidence on systemic immunotherapy, we propose that an immunotherapy approach involving intrathecal administration for patients with LMD from melanoma warrants additional exploration in clinical trials.

MFAP2 is a Potential Diagnostic and Prognostic Biomarker That Correlates with the Progression of Papillary Thyroid Cancer.

BACKGROUND: Microfibril-associated protein 2 (MFAP2) is a protein coding gene that exerts important phenotypic effects on cell motility, and increasing research has indicated that MFAP2 was correlated with many cancers. However, the functional and potential clinical role of MFAP2 in papillary thyroid cancer (PTC) has not yet been verified. MATERIALS AND METHODS: We performed whole transcriptome sequencing on 78 paired PTC tissues and corresponding adjacent normal tissues and found that MFAP2 was highly expressed in PTC tissues. Then, we analyzed the expression of MFAP2 and its relation with the clinicopathological features of PTC in The Cancer Genome Atlas (TCGA) PTC genomic dataset. We detected MFAP2 expression in 40 paired PTC tissues and corresponding adjacent normal tissues through RT-qPCR (real time-quantitative polymerase chain reaction) to validate the sequencing data and TCGA cohort. Cell functional assays were performed to elucidate the function of MFAP2 in PTC cells, Western blot assay was performed to explore the correlation between MFAP2 and EMT (epithelial-mesenchymal transition)-related proteins. RESULTS: Statistical analysis showed that MFAP2 was obviously upregulated in PTC tissues compared to matched normal tissues, and the expression levels of MFAP2 in PTC tissues were strongly related with lymph node metastasis (p=0.016). The results of RT-qPCR of our own tissue specimens showed the same conclusions as that in TCGA dataset. The results of functional assays in PTC cell lines showed that MFAP2 could promote proliferation, colony formation, migration and invasion abilities and decrease the apoptotic rate in PTC cells. Western Blot assay showed that MFAP2 could regulate the expression of EMT-related proteins. CONCLUSION: MFAP2 increases the proliferation, motility and decreases the apoptosis of PTC cells, and might be a potential therapeutic target for papillary thyroid cancer.

Efficacy and Safety of Multiband Mucosectomy Versus Cap-assisted Endoscopic Resection For Early Esophageal Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap). METHODS: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software. RESULTS: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs. CONCLUSIONS: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

Involvement of Spinal CCR5/PKCγ Signaling Pathway in the Maintenance of Cancer-Induced Bone Pain.

Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.