Yichen Lu

Multiple myeloma (MM), a plasma cell-derived malignant hematological disease, is often treated with bortezomib, a highly effective first-generation proteasome inhibitor. However, resistance to bortezomib is a common occurrence. Profilin 1 (PFN1), a cytoskeleton-related gene known to promote autophagy in MM, induces this resistance to bortezomib, but it is unclear why. The aim of this study was to uncover the molecular mechanisms involved in bortezomib resistance, considering not only PFN1, but also CD138, a transmembrane proteoglycan that is a hallmark of plasma and MM cells. We detected CD138 and PFN1 in the bone marrow of patients with MM immunohistochemically. We also studied the Gene Expression Omnibus (GEO) data and found that CD138 was associated with PFN1 and autophagy. We then evaluated their expression in an MM cell line via western blot analysis, immunofluorescence assay, and flow cytometry; constructed PFN1-overexpressing and -knockdown cell lines; and detected ubiquitinated CD138 in the cells of both cell lines. Overexpression of PFN1 or PFN1-induced autophagy downregulated CD138 expression. Owing to the stemness and resistance of CD138⁻ MM cells, inhibition of autophagy or CD138 overexpression reversed the resistance of PFN1-overexpressing MM cells to bortezomib, as indicated in our clonogenic, apoptosis, and CCK-8 assays. These results indicated that CD138 plays an important role in the resistance of MM cells to bortezomib. Targeting PFN1, CD138, or autophagic pathways may provide a promising therapeutic strategy for overcoming PFN1-induced drug resistance in MM.

Lymphoplasmacyte-rich meningioma (LPRM) is a rare subtype of meningioma, the specific pathogenesis of which remains unclear. Herein, we report the case of a 48-year-old Asian man who experienced progressive deafness and limb weakness. Magnetic resonance imaging revealed extramedullary masses diffusely growing, wrapping, and compressing the cervical spinal cord. The dural lesion was partially excised by surgery, and postoperative pathological examination confirmed the diagnosis of LPRM. Diffuse LPRM is extremely rare, and its treatment is challenging owing to difficulties associated with surgery and the uncertain efficacy of traditional therapies. Therefore, further clinical practice and basic research are needed to improve the prognosis of diffuse LPRM.

Background: Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma is poor. Pyroptosis is a newly discovered inflammatory programmed cell death. However, the expression of pyroptosis-related genes (PRGs) in glioma and its correlation with prognosis are unclear. Methods: 27 pyroptosis genes differentially expressed between glioma and adjacent normal tissues were identified. All glioma cases could be stratified into 2 subtypes based on these differentially expressed PRGs. The prognostic value of each PRG was evaluated to construct a prognostic model. Results: A novel 16-gene signature was constructed by using the least absolute shrinkage and selection operator Cox regression method. Then, patients with glioma were divided into low- and high-risk groups in the TCGA cohort. The survival rate of patients in the low-risk group was significantly higher than that in the high-risk group (P = .001). Patients with glioma from the Gene Expression Omnibus (GEO) cohort were stratified into 2 risk groups by using the median risk score. The overall survival (OS) of the low-risk group was longer than that of the high-risk group (P = .001). The risk score was considered an independent prognostic factor of the OS of patients with glioma. Gene ontology and Kyoto Encylopedia of Genes and Genomes analysis showed that the differentially expressed PRGs were mainly related to neutrophil activation involved in immune responses, focal adhesion, cell cycle, and p53 signaling pathway. Conclusion: PRGs could predict the prognosis of glioma and play significant roles in a tumor immune microenvironment.

Combination therapy is a promising and prevalent strategy for osteosarcoma treatment. Curcumin (CUR), as a chemosensitizer, improves the antitumor effect of first‑line chemotherapy drugs. However, due to its poor solubility and instability in physiological conditions, the bioavailability of CUR is limited. In order to improve the physicochemical properties of natural CUR, β‑cyclodextrin was adopted to generate a β‑cyclodextrin curcumin (CD‑CUR) inclusion complex. A thermosensitive hydrogel, poly(D,L‑lactide‑co‑glycolide)-poly(ethylene‑glycol)‑poly(D,L‑lactide‑co‑glycolide), was selected and synthesized to co‑deliver doxorubicin (DOX) and CD‑CUR to tumor sites. The dual‑drug delivery system (gel+DOX+CD‑CUR) was prepared by mixing drugs with hydrogels and had a perfect sol‑gel phase transition temperature (18.3˚C for 20% concentration). Both DOX and CUR were released from hydrogels in a sustained manner in PBS (pH 7.4) medium. The combination therapy based on DOX+CD‑CUR exhibited higher antitumor activity than monotherapies in vitro. Combined CD‑CUR therapy significantly downregulated Bcl‑2 expression and upregulated caspase‑3 expression, suggesting that DOX combined with CD‑CUR treatment has a higher apoptosis‑inducing efficiency. The antitumor efficiency of the gel+DOX+CD‑CUR strategy was evaluated in K‑7 tumor‑bearing mice, and this localized combination therapy demonstrated a higher antitumor efficiency compared with free DOX+CD‑CUR or single‑drug strategies. There were no significant differences in body weight and histological changes of major organs in each group. Therefore, the present combination treatment based on hydrogel may be a feasible approach to co‑deliver DOX and CD‑CUR to osteosarcoma tumor sites in clinical practice.