Bulletin du cancer最新文献

First-line treatments of autoimmune systemic diseases (ARD) are based on the use of various types of immunosuppressive or immunomodulatory drugs, either alone or in association, according to standardized reference protocols. Prolonged use of these drugs in severe or refractory ARD is associated with high morbidity and increased mortality. Innovative cell therapies represent a new promising approach for patients with ARDs, with the recent clinical use of: a) mesenchymal stromal cells (MSCs), based on their immunomodulatory, antifibrotic and pro-angiogenic properties and b) Chimeric Antigen Receptors (CAR) T cell therapies T lymphocytes, where genetically modified expression of a chimeric antigen receptor (CAR-T cells). Therapeutic use of MSC or CAR-T cells, remains indications of exception in patients with severe ARDs resistant to prior standard therapies with new prerequisite and organisation of health-care pathways as compared to traditional drugs, not only for the Cell and Gene Therapy (CGT) product definition and delivery process, but also for the patient clinical management before and after administration of the CGT product. The aim of this workshop under the auspices of the French Speaking Society of Bone Marrow and Cell transplantation (SFGM-TC) working group on autoimmune diseases (MATHEC) is to describe: a) the prerequisite for French hospitals to set-up the specific health-care pathways for MSC or CART therapy in ARDs patients, in accordance with regulatory and safety needs to perform academic or industry sponsored clinical trials, and b) the care-pathway for ARD patients treated with CGT, highlighting the importance of working in tandem between the ARD and the CAR-T cell specialist all along the indication, procedures and follow-up of ARDs. Patient safety considerations are central to guidance on patient selection to be validated collectively at the multidisciplinary team meeting (MDTM) based on recent (less than 3 months) thorough patient evaluation. MSC and CAR-T procedural aspects and follow-up are then carried out within appropriately experienced and SFGM-TC accredited centres in close collaboration with the ADs specialist.

Practice of pediatric aphereses - in particular when caring for low-weight children - differs from the practice of adult aphereses, since pediatric aphereses represent low numbers of procedures, which has practical implications in terms of practical training and retraining for involved healthcare personnel, as needed for habilitation and validation of ongoing competencies. A specific training is mandatory in order to ensure both the child and the staff safety during and after collection, as well as ensure high quality of the collected cell product and that its meets predefined specifications that depend on its intended use. Low and very low-weight children deserve a particular attention for a number of procedural and clinical aspects: the nature and quality of venous accesses to ensure proper operation of the cell separator, management of hemodynamic fluctuations in relation with the relative importance of the extracorporeal blood volume as compared to the total blood volume of the child, risks and clinical manifestations of citrate toxicity, minimization of stress during the procedure that may include but is not limited to pharmacological sedation. The full spectrum of competencies needed to deal with these aspects is rarely present within a single team of healthcare professionals; it most often requires the tight combination of expertise drawing from the collection facility, the pediatric department and possibly the pediatric intensive care unit ward, whether from the same or from different institutions. Interactions must be formalized in a document that accurately describes which category of actors is responsible for each category of acts (prescriptions, decisions), depending on their initial qualifications, specific competencies, and affiliations.

Conditioning regimen prior to hematopoietic stem cell transplantation have an impact on patient fertility through the use of gonadal irradiation and/or bifunctional alkylating agents. Their impact on fertility depends mainly on the dose used and, in women, on age at the time of treatment. All patients should benefit before treatment from a consultation informing them of the potential impact on fertility and of fertility preservation techniques. In the absence of contraindications, the major toxicity of myeloablative conditioning regimen justifies fertility preservation. There are few data concerning fertility after reduced-intensity conditioning. Despite lower theoretical gonadotoxicity, we also recommend fertility preservation, if possible before transplantation. The fertility preservation techniques used depend on the patient's age, pathology and conditioning. In the event of subsequent use of harvested gonadal tissue in the context of acute leukemia or aggressive lymphoma, it is advisable to assess the risk of reintroduction of tumor cells. Finally, it is recommended to assess gonadal function after transplant, especially after reduced conditioning. If there is persistent residual gonadal function, post-treatment fertility preservation should be discuss.

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT. Planning post-transplant maintenance treatment as part of a prophylaxis strategy is now feasible. Monitoring biomarkers of residual disease and post-transplant chimerism after allo-HCT allows a preemptive strategy. Within the frame of the 14th annual workshops of the Francophone Society for Bone Marrow Transplantation and Cell Therapy, the working group reviewed the literature and discussed novel strategies and therapies used to prevent relapse post-allo-HCT. Innovative drugs have been developed recently. Their toxicity profile allows their use post-allo-HCT, albeit with precaution. We reviewed the use of FLT3 inhibitors for AML, BCR::ABL inhibitors for Philadelphia chromosome for ALL, hypomethylating agents and Bcl-2 inhibitors for AML and MDS. The indications of immunomodulation and infusion of donor lymphocytes have been reviewed. Finally, we outlined methods of follow-up and support for patients receiving these prophylactic treatments.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, these transplants are complicated by a high rate of relapse in very high cytogenetic risk or refractory diseases. The benefit of this therapeutic strategy for these serious malignant hemopathies could therefore be reassessed. As part of the 14th workshop for the harmonization of allograft practices organized by the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC) (SFGM-TC) in Lille in September 2023, the role of allograft for very high risk or refractory AML and MDS was challenged after analysis of published studies.

Artificial intelligence (AI) is addressing many expectations for healthcare practitioners and patients in oncology. It has the potential to deeply transform medical practices as we know them today: improving early diagnosis by analysing large quantities of medical data, refining personalised treatment plans and optimising patient follow-up. AI also makes it easier to identify new biomarkers and predict responses to therapies, reducing margins of error and speeding up clinical decisions. Among the most popular types of AI to revolutionise clinical practice are language models. In a perfect world, the integration of AI would promote more precise, personalised and efficient care, while relieving healthcare providers of tedious or repetitive tasks, allowing them to concentrate more on providing human support to patients, and all this with a low energy consumption. However, the large-scale deployment of AI currently raises fundamental questions about fairness, safety of use and how to assess the results obtained from AI longitudinally. This article explores how the many applications are evaluated for our practice (spoiler alert: they are currently limited), potential clinical benefits and challenges currently encountered when dealing with the integration of AI into routine oncology care. We will focus on language models whose development has been exploding since 2021.

Haematopoietic stem cell collection from paediatric donors is a common and life-saving practice, as evidenced by the fact that there is a growing annual number of cases of transplants from minor donors among SFGM-TC centers over the last decade. Still, medical use of human tissue from a healthy and underage donor requires proper regulations and medical management. The guidelines below aim at underlining the importance of pondering the legal, medical and ethical aspects of using stem cells from healthy paediatric donors and stress out the importance of obtaining informed consent at the time of assessing HLA compatibility. Combined medical and psychological assessments are required before the donation, as well as one month later and one year later to ensure of the child's physical and mental wellbeing. Bone marrow harvest under general anaesthetics remains the preferred method of collection for children. Peripheral blood stem cell collection should only be considered for children who will not require a central venous access for collection. We aim at offering guidelines centered on the healthy child donating stem cells and his/her wellbeing, and these should be regularly reviewed as medical practices evolve.

Background: Anaplastic thyroid cancer (ATC) is a highly lethal form of thyroid cancer. lysine acetyltransferase 5 (KAT5) has been found to promote ATC development via c-Myc stabilization by previous study. We thus designed experiments to confirm the anti-tumor effect of a KAT5 inhibitor (MG149) in ATC.

Methods: Western blotting assessed the level of KAT5, c-Myc, and epithelial-mesenchymal transition (EMT)-related proteins in ATC cells and xenograft tumor tissues. Cell counting kit-8, flow cytometry, wound healing, and transwell assays revealed the effect of MG149 on cell proliferation, apoptosis, migration, and invasion in ATC cell lines. Immunofluorescence detected the level of E-cadherin and N-cadherin in ATC cell lines. The effect of MG149 on KAT5-mediated c-Myc stabilization was detected using co-immunoprecipitation assay. Tumor volume and tumor weight in ATC xenograft models were evaluated. H&E staining showed the effect of MG149 on lung metastasis in vivo. We further investigated whether MG149 can enhance the sensitivity of ATC to cisplatin (CDDP).

Results: MG149 inhibited cell proliferation and increased the apoptosis of cells. MG149 suppressed the migratory and invasive ability of ATC cells. The EMT in CAL-62 and 8505C cells was significantly inhibited by MG149. MG149 suppressed the KAT5-mediated c-Myc acetylation. MG149 inhibited tumor growth and lung metastasis in vivo. Additionally, MG149 potentiated the sensitivity to CDDP in ATC cells in vitro and in vivo.

Conclusion: MG149 suppresses ATC progression and metastasis by inhibiting the acetylation of c-Myc mediated by KAT5.