Syntaxin 18 Defects in Human and Zebrafish Unravel Key Roles in Early Cartilage and Bone Development.

SNARE proteins comprise a conserved protein family responsible for catalyzing membrane fusion during vesicle traffic. Syntaxin18 (STX18) is a poorly characterized endoplasmic reticulum (ER)-resident t-SNARE. Recently, together with TANGO1 and SLY1, its involvement was shown in ER to Golgi transport of collagen II during chondrogenesis. We report a fetus with a severe osteochondrodysplasia in whom we identified a homozygous substitution of the highly conserved p.Arg10 to Pro of STX18. CRISPR/Cas9-mediated Stx18 deficiency in zebrafish reveals a crucial role for Stx18 in cartilage and bone development. Furthermore, increased expression of multiple components of the Stx18 SNARE complex and of COPI and COPII proteins suggests that Stx18 deficiency impairs antero- and retrograde vesicular transport in the crispant stx18 zebrafish. Taken together, our studies highlight a new candidate gene for a recessive form of osteochondrodysplasia, thereby possibly broadening the SNAREopathy phenotypic spectrum and opening new doors toward future research avenues. © 2023 American Society for Bone and Mineral Research (ASBMR).

The role of the surgeon in the management of oligometastatic non-small cell lung cancer: a literature review.

OBJECTIVE: In this review, we aim to summarize the most recent data on the surgical management of oligometastatic non-small cell lung cancer (NSCLC). BACKGROUND: Approximately 60-70% of all patients with NSCLC initially present with advanced stages of cancer at time of diagnosis. These patients are generally treated with chemotherapy, radiation therapy, or a combination of these modalities. Patients with late-stage disease are usually not considered to be amenable for curative-intent treatments due to poor prognoses. Despite advances in systemic therapies, 5-year overall survival rates in these patients remain poor. However, technological advances in imaging modalities and new imaging strategies have substantially increased tumor detection rates and have resulted in a shift towards earlier diagnosis of NSCLC, possibly in stages in which metastatic disease is limited and still treatable. Studies in recent years have shown that there is a distinct group of patients with metastatic lesions at one or a few sites, often referred to as oligometastatic disease, that may have better survival outcomes compared to patients with more disseminated diseases. Furthermore, it is suggested that these patients may benefit from a combination of systemic treatment and local treatment aimed at the metastatic site(s). However, the role of surgery in this setting remains a controversial subject, with many unanswered questions. METHODS: The PubMed/MEDLINE database and the Cochrane database were searched to find relevant articles regarding oligometastatic NSCLC. Specifically, articles regarding definitions of oligometastatic disease, oligometastatic tumor biology, diagnosis, and the treatment of oligometastatic disease were identified. CONCLUSIONS: Oligometastatic NSCLC represents a wide spectrum of diseases and encompasses a heterogeneous patient population. Current data suggests that local ablative treatment of oligometastatic lesions with surgery or stereotactic body radiation therapy may result in improved overall survival and progression-free survival rates. However, more data from multi-center prospective trials are necessary to shed light on which therapeutic modalities are most suitable for the treatment of oligometastatic NSCLC. Integration of clinical and molecular staging data is necessary to allow for more personalized treatment approaches.