Promoted Abutment-Soft Tissue Integration Around Self-Glazed Zirconia Surfaces with Nanotopography Fabricated by Additive 3D Gel Deposition.

Introduction: Improving the biological sealing around dental abutments could promote the long-term success of implants. Although titanium abutments have a wide range of clinical applications, they incur esthetic risks due to their color, especially in the esthetic zone. Currently, zirconia has been applied as an esthetic alternative material for implant abutments; however, zirconia is purported to be an inert biomaterial. How to improve the biological activities of zirconia has thus become a popular research topic. In this study, we presented a novel self-glazed zirconia (SZ) surface with nanotopography fabricated by additive 3D gel deposition and investigated its soft tissue integration capability compared to that of clinically used titanium and polished conventional zirconia surfaces. Materials and Methods: Three groups of disc samples were prepared for in vitro study and the three groups of abutment samples were prepared for in vivo study. The surface topography, roughness, wettability and chemical composition of the samples were examined. Moreover, we analyzed the effect of the three groups of samples on protein adsorption and on the biological behavior of human gingival keratinocytes (HGKs) and human gingival fibroblasts (HGFs). Furthermore, we conducted an in vivo study in which the bilateral mandibular anterior teeth of rabbits were extracted and replaced with implants and corresponding abutments. Results: The surface of SZ showed a unique nanotopography with nm range roughness and a greater ability to absorb protein. The promoted expression of adhesion molecules in both HGKs and HGFs was observed on the SZ surface compared to the surfaces of Ti and PCZ, while the cell viability and proliferation of HGKs and the number of HGFs adhesion were not significant among all groups. In vivo results showed that the SZ abutment formed strong biological sealing at the abutment-soft tissue interface and exhibited markedly more hemidesmosomes when observed with a transmission electron microscope. Conclusion: These results demonstrated that the novel SZ surface with nanotopography promoted soft tissue integration, suggesting its promising application as a zirconia surface for the dental abutment.

The Applications of Metabolic Glycoengineering.

Mammalian cell membranes are decorated by the glycocalyx, which offer versatile means of generating biochemical signals. By manipulating the set of glycans displayed on cell surface, it is vital for gaining insight into the cellular behavior modulation and medical and biotechnological adhibition. Although genetic engineering is proven to be an effective approach for cell surface modification, the technique is only suitable for natural and genetically encoded molecules. To circumvent these limitations, non-genetic approaches are developed for modifying cell surfaces with unnatural but functional groups. Here, we review latest development of metabolic glycoengineering (MGE), which enriches the chemical functions of the cell surface and is becoming an intriguing new tool for regenerative medicine and tissue engineering. Particular emphasis of this review is placed on discussing current applications and perspectives of MGE.

SPARCL1 exhibits different expressions in left- and right-sided colon cancer and is downregulated via DNA methylation.

Aim: The authors previously found that SPARCL1 functions to suppress colorectal cancer metastasis. Here, the epigenetic mechanism of SPARCL1 regulation and its relationship with clinicopathological features in colon cancer were investigated. Materials & methods: SPARCL1 expression was evaluated by immunohistochemistry staining in a tissue array containing 271 left-sided colon cancer samples and 257 right-sided colon cancer samples. In vivo and in vitro DNA methylation states were measured by biochemical sulfide potential assay. The transcription and DNA methylation states in cells were altered by siRNA or decitabine treatment, respectively. Cellular motility properties were compared through transwell assay. Results & conclusion: SPARCL1, mediated by its DNA methylation, may arrest colorectal carcinoma motility. Furthermore, SPARCL1 expression is higher and may have a specific prognostic value in left-sided colon cancer.

Lay abstract The heterogeneity of colorectal cancer is largely based on their primary tumor locations. For example, patients with left-sided colon cancer generally have better prognoses and different treatment strategies in comparison with patients with right-sided colon cancer. Research is required to uncover the mechanisms underlying these differences. The authors showed that the addition of methyl groups (DNA methylation) to DNA encoding SPARCL1 (a protein involved in cell adhesion) could inhibit regular colorectal cell motility. Furthermore, SPARCL1 protein expression was higher and positively correlated with better prognosis specifically in patients with left-sided colon cancer. The present study provides an evidential basis for the different molecular biological features between left- and right-sided colon cancer. SPARCL1 is a promising candidate for predicting colon cancer prognosis and potential therapeutic intervention. Further in-depth study of SPARCL1 would be of great value for clinical application.

Factors Affecting the Outcomes of Patients with Malignant Rhabdoid Tumors: A Population-Based Study.

Objective: Malignant rhabdoid tumor (MRT) is a rare but aggressive malignancy. It has been a long time since data on this tumor have been updated. Methods: We retrospectively reviewed patients from the SEER database who were pathologically diagnosed with MRT and analyzed incidence rates, clinical features and survival using Stata 12.0. Results: In total, 544 patients were included in the epidemiological analysis. There were two peak periods of MRT incidence: patients younger than 4 years and those older than 70 years. Further survival analysis showed that the survival of children (especially younger than 1 year) was markedly worse than that of adults (P<0.01), and different primary sites were associated with different age groups and survival outcomes. The central nervous system (CNS) was the most common primary site (50.00%), followed by the kidney (15.66%). Patients with MRTs that originated from the digestive system experienced worse survival outcomes than those with MRTs originating from other locations. Primary site surgery conferred survival benefits to patients with renal and digestive system MRTs (HR = 0.06, CI: 0.02-0.23, P<0.01; HR=0.10, CI: 0.02-0.48, P<0.01), whereas radiotherapy conferred benefits to patients with CNS, bone and soft tissue MRTs (HR=0.22, CI: 0.15-0.34, P<0.01; HR=0.44, CI: 0.21-0.90 P=0.03). Conclusions: Our results indicate that age and the primary site of MRT are critical clinical factors that affect patient survival and treatment choices. Primary site tumor resection should be considered for renal and digestive system MRTs, and systematic therapy, including surgery and radiotherapy, should be recommended for the treatment of CNS, bone and soft tissue MRTs.

Immunotherapies for well-differentiated grade 3 gastroenteropancreatic neuroendocrine tumors: A new category in the World Health Organization classification.

According to the 2019 World Health Organization (WHO) classification, well-differentiated grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a new category of cancer of the digestive system. G3 GEP-NET research and treatment are not as robust as those of lower grade (G1/2) NETs and poorly differentiated neuroendocrine carcinomas (NECs). Previously, the management of high-grade NETs was mainly based on NEC therapies, as high-grade NETs were classified as NECs under the previous WHO classification. Despite this, G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs, due to their distinct molecular pathogenesis and course of pathological grade transition. Patients with advanced G3 GEP-NETs, who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide, have limited treatment choices. Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors. Immunotherapies, either alone or in combination with other therapies, do not have a clear function in the treatment of G3 GEP-NETs. Currently, the majority of immunotherapy studies, both prospective and retrospective, do not reliably differentiate G3 GEP-NETs from NECs. By contrast, a significant number of studies include non-GEP neuroendocrine neoplasms (NENs). Therefore, there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor. The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.

A Retrospective Exploration of Targeted Maintenance Therapy in Advanced Colorectal Cancer: Based on the Background of Chinese Patient Assistance Program.

Background: Maintenance therapy with bevacizumab (Bev) in patients with colorectal cancer (CRC) provides progression-free survival (PFS) benefits. However, the role of maintenance therapy with an anti-EGFR monoclonal antibody has not been established. Methods: Eligible CRC patients were assigned to maintenance therapy with cetuximab (Cet; Cet group) or Bev (Bev group). PFS, the duration of maintenance therapy, and safety were analyzed. Cox multivariate regression analyses were performed to determine independent prognostic factors. Results: A total of 143 eligible patients were assigned to the Cet (n = 79) or Bev (n = 64) groups. In the Cet group, all patients had KRAS wild-type. The baseline characteristics were well-balanced between the two groups, except for a higher percentage of patients with a left-sided primary tumor in the Cet group than in the Bev group (86.1 vs. 62.5%, P < 0.0001). The median PFS was not significantly different between the Cet group and the Bev group: 5.9 months (95% CI 2.30-9.50) vs. 7.0 months (95% CI 3.69-10.31) (HR 1.17, 95% CI 0.77-1.79, P = 0.45). The median duration of maintenance therapy in the Cet group was shorter than that in the Bev group: 4.0 months (95% CI 1.94-5.99) vs. 4.8 months (95% CI 2.68-6.98) (HR 0.90, 95% CI 0.61-1.33; P = 0.59). The subgroup analyses showed that the median PFS for the first maintenance therapy and the second maintenance therapy were 3.2 months (95% CI 1.69-4.78) and 5.2 months (95% CI 1.58-8.83), respectively (HR 0.89, 95% CI 0.44-1.81; P = 0.75). Conclusions: This study suggests that maintenance therapy with Cet or Bev can be considered an appropriate option following induction chemotherapy for selected patients with advanced CRC. Multiple maintenance therapy seems to confer survival benefits in advanced CRC. Maintenance therapy with Cet after first-line induction chemotherapy seems to be associated with greater survival benefits.