using-inducible-osteoblastic-lineage-specific-stat3-knockout-mice-to

Using Inducible Osteoblastic Lineage-Specific <em>Stat3</em> Knockout Mice to Study Alveolar Bone Remodeling During Orthodontic Tooth Movement

The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial ...

Shanghai Jiao Tong University School of Medicine

Shanghai Jiao Tong University

National Center for Stomatology

National Clinical Research Center for Oral Diseases

Shanghai Key Laboratory of Stomatology

Patient-specific 3D printing template is used in mandibular defect reconstruction with multiple deficiencies. During the operation, the template can accurately transfer the preoperative design, assisting surgeons to complete the surgery with high efficiency and accuracy. The template design has been continuously improved to obtain good application for miscellaneous classification and description. This review attempted to preliminarily analyse and summarise recent advancements in personalized 3D printing templates in mandibular reconstruction from the aspects of functional classification, existing problems, improved strategies and post-surgery evaluation by reviewing studies and through our combined clinical work and experience on hundreds of reconstruction surgeries.

Recent advance in patient-specific 3D printing templates in mandibular reconstruction.

Pituitary stalk interruption syndrome (PSIS) is a type of congenital malformation of the anterior pituitary, which leads to isolated growth hormone deficiency or multiple hypothalamic-pituitary deficiencies. Many genetic factors have been explored, but they only account for a minority of the genetic aetiology. To identify novel PSIS pathogenic genes, we conducted whole-exome sequencing with 59 sporadic PSIS patients, followed by filtering gene panels involved in pituitary development, holoprosencephaly and midline abnormality. A total of 81 heterozygous variants, distributed among 59 genes, were identified in 50 patients, with 31 patients carrying polygenic variants. Fourteen of the 59 pathogenic genes clustered to the Hedgehog pathway. Of them, PTCH1 and PTCH2, inhibitors of Hedgehog signalling, showed the most frequent heterozygous mutations (22%, seven missense and one frameshift mutations were identified in 13 patients). Moreover, five novel heterozygous null variants in genes including PTCH2 (p.S391fs, combined with p.L104P), Hedgehog acyltransferase (p.R280X, de novo), MAPK3 (p.H50fs), EGR4 (p.G22fs, combined with LHX4 p.S263N) and SPG11 (p.Q1624X), which lead to truncated proteins, were identified. In conclusion, genetic mutations in the Hedgehog signalling pathway might underlie the complex polygenic background of PSIS, and the findings of our study could extend the understanding of PSIS pathogenic genes.

Identification of novel candidate pathogenic genes in pituitary stalk interruption syndrome by whole-exome sequencing.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease worldwide. Much progress has been made in exploring mechanisms and improving the therapy of HNSCC, but only a few studies have focused on the role of ferroptosis on HNSCC progression. The current study aimed to reveal the underlining mechanisms that caveolin-1 (CAV1)-ROS (reactive oxygen species)-ferroptosis axis affect the process of HNSCC and discover novo therapeutic targets or strategies.

Caveolin-1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma.

Research on tumour cell-derived small extracellular vesicles (sEVs) that regulate tumour microenvironment (TME) has provided strategies for targeted therapy of head and neck squamous cell carcinoma (HNSCC). Herein, we demonstrated that sEVs derived from HNSCC cancer cells carried CD73 (sEVs ), which promoted malignant progression and mediated immune evasion. The sEVs phagocytosed by tumour-associated macrophages (TAMs) in the TME induced immunosuppression. Higher CD73 TAMs infiltration levels in the HNSCC microenvironment were correlated with poorer prognosis, while sEVs activated the NF-κB pathway in TAMs, thereby inhibiting immune function by increasing cytokines secretion such as IL-6, IL-10, TNF-α, and TGF-β1. The absence of sEVs enhanced the sensitivity of anti-PD-1 therapy through reversed immunosuppression. Moreover, circulating sEVs increased the risk of lymph node metastasis and worse prognosis. Taken together, our study suggests that sEVs derived from tumour cells contributes to immunosuppression and is a potential predictor of anti-PD-1 responses for immune checkpoint therapy in HNSCC.

CD73 in small extracellular vesicles derived from HNSCC defines tumour-associated immunosuppression mediated by macrophages in the microenvironment.

Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.

Article	Year
Recent advance in patient-specific 3D printing templates in mandibular reconstruction. Journal of the mechanical behavior of biomedical materials\| PubMed ID: 32250956	2020
Identification of novel candidate pathogenic genes in pituitary stalk interruption syndrome by whole-exome sequencing. Journal of cellular and molecular medicine\| PubMed ID: 32864857	2020
Caveolin-1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology\| PubMed ID: 34874578	2022
CD73 in small extracellular vesicles derived from HNSCC defines tumour-associated immunosuppression mediated by macrophages in the microenvironment. Journal of extracellular vesicles\| PubMed ID: 35524455	2022
Single-cell transcriptomic analysis of tumor heterogeneity and intercellular networks in human urothelial carcinoma. Chinese medical journal\| PubMed ID: 36939254	2023

Tingwei Lu

Biography

JoVE Journal Publications

Other Publications