Nanoparticles as drug delivery systems in the treatment of oral squamous cell carcinoma: current status and recent progression.

Oral squamous cell carcinoma (OSCC) is a common human malignancy with an estimated incidence of around 377,713 new cases worldwide in 2020. Despite the advance in clinical management, some of OSCC patients still miss the opportunity of completable resection of tumor, and have to accept medical therapies, e.g., chemotherapy, radiotherapy, or immunotherapy when the disease develops into the advanced stage. However, these therapies have been reported to be far from ideal due to the low efficiency of conventional delivery approaches. To obtain a better therapeutic effect, considerable attempts have been made toward to develop an effective drug delivery system (DDS). Nanoparticles (NPs) including inorganic NPs, polymer NPs, lipid NP, extracellular vesicles and cell membrane-based NPs have been evaluated as the better DDS candidates that can specifically accumulate in the tumor microenvironment along with a large amount of blood vessels. Emerging evidence suggested that NPs formulated with anticancer drugs including chemotherapeutic drugs, radiotherapy and immunotarget antibodies could remarkably improve the release and increase concentration of these drugs at the tumor site and show a better therapeutic efficacy, suggesting that NPs might serve as promising DDSs in the treatment of OSCC. Therefore, we have conducted this review to summarize recent progression and current status of diverse NPs as DDSs in this research field.

Thermosensitive Micelles Gel to Deliver Quercetin Locally for Enhanced Antibreast Cancer Efficacy: An In Vitro Evaluation.

Although quercetin is low cytotoxicity to normal human cells, quercetin is effective against the growth of some tumors. Given the poor blood stability in vivo, insolubility, low delivery efficiency, and poor medicinal properties of quercetin, we developed a local drug delivery system comprising quercetin core's polymer micelles and F127 hydrogel stroma. In vitro evaluation revealed that quercetin core's polymer micelles have excellent antitumor activity and could inhibit the multiplication of 4T1 breast cancer cells through the apoptosis pathway. Meanwhile, a rheological study revealed that the quercetin core's micelles gel possessed excellent properties of hydrogel formation and injectability of liquid preparation as a local drug delivery system after the quercetin core's polymer micelles were loaded into the F127 hydrogel stroma. Our study findings indicated that the drug stability and stable release capacity of quercetin were vastly improved with the composite formulation of the micelles gel. This not only realized drug injectability but also drug storage in the semisolid form, which is a more comfortable and slower drug-releasing form that will eventually exert a proper therapeutic effect. In conclusion, quercetin micellar hydrogel system has better antitumor activity and excellent hydrogel properties.

Adjunctive Use of Active Compounds such as Chlorhexidine in the Nonsurgical Treatment of Peri-Implant Mucositis for Oral Health: A Systematic Review and Meta-Analysis.

Background: Peri-implant mucositis (PiM) is characterized as a reversible inflammatory change of the peri-implant soft tissues without alveolar bone loss or continuing marginal bone loss. Without proper control of PiM, the reversible inflammation may advance to peri-implantitis (PI). Mechanical debridement (MD) by the implant surface is the most common and conventional nonsurgical approach to treat PiM but with limitations in complete resolution of diseases. For more than a decade, chlorhexidine (CHX) and active compounds has been investigated in the treatment of PiM. Therefore, the aim of this systematic review and meta-analysis was to evaluate the efficacy of CHX treatment in combination with MD versus MD alone or MD+placebo in patients with PiM on their oral health problems. Methods: A search using electronic databases (Ovid MEDLINE, EMBASE, Science Direct databases, and Cochrane Central Register of Controlled Trials) and a manual search up to May 2022 were performed independently by 2 reviewers and included eligible randomized controlled trials (RCTs) comparing MD+CHX versus MD alone or MD+placebo. The assessment of quality for all the selected RCTs was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. Disease resolution of PiM (absence of BOP), IPPD reduction, IBOP% reduction, and PI% reduction after treatment as primary outcomes were selected as the primary outcomes. Weighted mean differences (WMD) and 95% confidence interval (CI) were for continuous outcomes, and odds ratio (OR) and 95% CI was for dichotomous outcomes using random effect models. This review is registered on the PROSPERO database (CRD42020221989). Results: After independent screening, nine eligible studies were included in this systematic review and meta-analysis. Meta-analysis showed OR of disease resolution between test and control groups amounted to 1.41 (95% CI (0.43, 4.65), P = 0.57, I 2 = 65%) not favoring adjunctive CHX treatment over MD alone. Through subgroup analysis, the results indicated that oral irrigation of CHX may have more benefits on the resolution of PiM. Similarly, CHX did not significantly improve IPPD reduction at both short-, medium-, and long-term follow-up. Only a short-term effect has been observed at IBOP% reduction (WMD = 13.88, 95% CI (10.94, 16.81), P < 0.00001, I 2 = 9%), IPI reduction (WMD = 0.12, 95% CI (0.09, 0.14), P < 0.00001, I 2 = 0%), and FMPPD reduction (WMD = 0.19 mm, 95% CI (0.03, 0.35), P = 0.02, I 2 = 0%) with adjunctive CHX application. Conclusion: Adjunctive CHX application may have some benefits to improve the efficacy of MD in PiM treatment by reducing IBOP%, IPI, and FMPPD in short-term. But these benefits disappeared at medium- and long-term follow-up. In order to achieve better disease resolution of PiM, adjunctive CHX irrigation with MD may be suggested and has positive potential. Well-designed large clinical trials are needed in future.

miR-30 inhibits the progression of osteosarcoma by targeting MTA1.

OBJECTIVES: MicroRNAs (miRNAs) have been considered as a new class of novel diagnostic and predictive biomarker in many diseases. However, there are few studies on miRNA in osteosarcoma (OS). This study aimed to investigate the roles of miR-30 on OS occurrence and development. METHODS: PCR was used to detect mRNA levels of miR-30 and MTA1 in cancer tissues, adjacent non-cancerous tissues from OS patients. Western blot was used to detect MTA1 protein expression in all tissues and cell lines (hFOb1.19,Saos-2, MG63, and U2OS). The correlation between miR-30 and MTA1 was predicted through bioinformatics software, and identified by a luciferase reporting experiment. In vitro, functional test detected the specific effects of miR-30 and MTA1 on the development of OS. RESULTS: miR-30 expression was significantly reduced, while the expression of MTA1 was increased in OS tissues and cells. Luciferase reporting experiment showed that miR-30 sponged MTA1 which was negatively correlated with miR-30 expression. Furthermore, rescue tests revealed that MTA1 restrained the functions of miR-30 on cell proliferation and migration of OS. CONCLUSION: Our finding showed that miR-30 modulated the proliferation and migration by targeting MTA1 in OS.

Overexpression of S100A1 in Osteosarcoma Inhibits Tumor Proliferation and Progression.

Background: Osteosarcoma is the most common primary malignant tumor of bone. Abnormal expression of S100A1 protein is closely related to the occurrence and development of malignant tumors. However, S100A1 in osteosarcoma has not been studied. Methods: All osteosarcoma tissues were collected from patients who received surgical therapy at the Affiliated Hospital of Inner Mongolia Medical University, China in 2020. QRT-PCR and western blot assays were used to detect the expression of S100A1 in osteosarcoma tissues and cells. The negative effect of S100A1 on osteosarcoma cell growth was confirmed by vitro and vivo experiments. Results: S100A1 inhibited the growth of osteosarcoma cells in vitro. Overexpression of S100A1 may inhibit the proliferation of osteosarcoma cells by preventing the activation of AKT signaling pathway by western blot assay. Finally, animal experiments confirmed that overexpression of S100A1 could inhibit the proliferation of osteosarcoma cells. Overexpression of S100A1 obtained better survival benefit in mice. Conclusion: Our findings provided a new insight to the treatment of osteosarcoma. It also raised the possibility that S100A1 could be used in targeted therapies for osteosarcoma.

Carcinoma-associated fibroblasts promote the proliferation and metastasis of osteosarcoma by transferring exosomal LncRNA SNHG17.

Cancer-associated fibroblasts (CAFs) serve as a predominant regulator in the tumor microenvironment. However, the crosstalk between CAFs and OS cells remains mostly unclear. Recent studies explored that long non-coding RNA (LncRNAs) involved in regulating osteosarcoma (OS) formation and development, but their functions in CAFs are unknown. Here, we first investigated the SNHG17 was upregulated in OS tissues and correlated with the poor prognosis through the integrating clinical data. We then evaluated the function of SNHG17 in vitro using the stable SNHG17-depleted OS cells. HOS cells with SNHG17 knocked down were performed to generate the OS xenograft model. Through immunohistochemistry assay and TUNEL apoptosis assay, the role of SNHG17 on OS development was assessed in vivo. We then examined the SNHG17 expression in exosomes derived from CAFs, normal fibroblasts (NFs), and tumor tissues from the OS clinical samples. The interaction among SNHG17, miR-2861, and MMP2 was predicted by bioinformatics analysis and identified by RIP and luciferase assays. The cell proliferation, migration, and apoptosis of SJSA-1 and HOS cells co-cultured with CAFs-derived exosomes were assessed by CCK-8 and colony formation assays. We found that SNHG17 was upregulated in the tumor tissues and presented a pro-tumorigenic effect on OS both in vitro and in vivo. It also was an essential exosomal cargo of CAFs and could affect OS cell proliferation and migration in vitro. CAFs-released exosomal SNHG17 acted as an essential molecular sponge for miR-2861 in OS cells. Moreover, MMP2 was a direct target of miR-2861 and was regulated by SNHG17. Overall, our findings identified that SNHG17 was an essential exosomal cargo of OS-related CAFs that contributes to proliferation and metastasis of OS, supporting the therapeutic potency of targeting the crosstalk between cancer cells and CAFs.

Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma.

BACKGROUND: Glycolysis was a representative hallmark in the tumor microenvironment (TME), and we aimed to explore the correlations between glycolysis with immune activity and clinical traits in bladder urothelial carcinoma (BLCA). METHODS: Our study obtained glycolysis scores for each BLCA samples from TCGA by a single-sample gene set enrichment analysis (ssGSEA) algorithm, based on a glycolytic gene set. The relationship between glycolysis with prognosis, clinical characteristics, and immune function were investigated subsequently. RESULTS: We found that enhanced glycolysis was associated with poor prognosis and metastasis in BLCA. Moreover, glycolysis had a close correlation with immune function, and enhanced glycolysis increased immune activities. In other words, glycolysis had a positive correlation with immune activities. Immune checkpoints such as IDO1, CD274, were up-regulated in high-glycolysis group as well. CONCLUSION: We speculated that in BLCA, elevated glycolysis enhanced immune function, which caused tumor cells to overexpress immune checkpoints to evade immune surveillance. Inhibition of glycolysis might be a promising assistant for immunotherapy in bladder cancer.

lncRNA TUSC7 inhibits osteosarcoma progression through the miR­181a/RASSF6 axis.

Osteosarcoma (OS) is one of the most aggressive malignancies, accompanied by an elevated incidence and a decreased rate of healing. Recently, several long non­coding RNAs (lncRNAs) have been reported to be involved in OS progression. Although tumor suppressor candidate 7 (TUSC7) was reported as a novel lncRNA, little is known about its biological functions in OS. The present study was designed to explore whether TUSC7 was involved in the pathological development of OS using various methods, including hematoxylin and eosin staining, Cell Counting Kit­8 assay, colony formation assay and Transwell assay. The present study revealed that TUSC7 expression was downregulated in OS tissues and cell lines compared with in normal tissues and cell lines. Functionally, the current results revealed that overexpression of TUSC7 inhibited OS cell proliferation, migration and invasion, while promoting apoptosis in vitro and in vivo. Next, the subcellular distribution of TUSC7 was examined by nuclear/cytoplasmic RNA fractionation and reverse transcription­quantitative PCR. Mechanistic studies revealed that TUSC7 exerted its role by sponging microRNA (miR)­181a in OS cell lines. Ras association domain family member 6 (RASSF6) was confirmed as a target gene of miR­181a, and the expression levels of RASSF6 were negatively regulated by miR­181a. Additionally, the results of rescue experiments suggested that overexpression of miR­181a neutralized the inhibitory effects of TUSC7 overexpression on OS cells. Overall, the present study demonstrated that the tumor suppressor role of TUSC7 in OS progression was mediated through the miR­181a/RASSF6 axis, which may represent a new therapeutic target for OS.

Sacral and thoracic chordoma with pulmonary metastases: A case report and review of the literature.

Chordoma is a sporadic type of cancer that affects the spine and is particularly challenging to treat due to the paucity of reported cases and scientific literature. In particular, primary chordomas affecting both the sacral and thoracic vertebrae are extremely rare. We herein report a rare case of chordoma in the sacral and thoracic vertebrae with pulmonary metastasis, along with a literature review. The objective of the present study was to explore treatment options and long-term outcomes in patients with metastatic chordoma. Posterior decompression was performed for the thoracic tumor, followed by extended resection of the sacral tumor. The symptoms of the patient were relieved after surgery, and the postoperative Nurick score decreased from grade 3 to grade 2, while the postoperative McCormick score was I. Therefore, complete chordoma excision and internal spinal fixation may effectively reduce tumor recurrence and metastasis.