Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications. 相似文献
Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.
Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.
Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors. 相似文献
AbstractGaining a better grasp on factors related to changes in alcohol use is of particular interest for clinicians. Past research has highlighted a negative link between future time perspective (i.e. a disposition guiding how individuals consider and act regarding their future) and alcohol misuse. However, much remains at stake in the understanding of this association. The objective of this research was to explore bidirectional relationships between future time perspective and severity of alcohol-related problems, in a clinical setting. The sample includes 79 patients followed up in an outpatient alcohol treatment centre. Two measurement times were planned: at entry into care and 6 months later. Multiple linear regression analyses were carried out, controlling for sociodemographic variables. We found that baseline future time perspective predicted level of alcohol-related problems after 6 months in treatment, even when effects of baseline alcohol-related problems and sociodemographic variables were controlled. This study shows that the way patients see and position themselves regarding their future can affect level of alcohol-related problems. It may be useful for clinicians to identify patients with low future time perspective to offer tailored interventions and consider this dimension as a resource for change. 相似文献
The “Centre Hospitalier Francois Dunan” is located on an isolated island and ensures patients care in hemodialysis thanks to telemedicine support. Many research studies have demonstrated the importance of hemodialysis fluids composition to reduce morbidity in patients on chronic hemodialysis. The aim of this study was to identify the risks inherent in the production of dialysis fluids in a particular context, in order to set up an improvement action plan to improve risk control on the production of dialysis fluids.
Methods
The risk analysis was conducted with the FMECA methodology (Failure Mode, Effects and Criticality Analysis) by a multi professional work group. Three types of risk have been reviewed: technical risks that may impact the production of hemodialysis fluids, health risks linked with chemical composition and health risks due to microbiological contamination of hemodialysis fluids.
Results
The work group, in close cooperation with the expert staff of the dialysis center providing telemedicine assistance, has developed an action plan in order to improve the control of the main risks brought to light by the risk analysis.
Conclusion
The exhaustive analysis of the risks and their prioritisation have permitted to establish a relevant action plan in this improving quality of dialysis fluids approach. The risk control of dialysis fluids is necessary for the security of dialysis sessions for patients, even more when these sessions are realized by telemedicine in Saint-Pierre-et-Miquelon. 相似文献