Allogeneic Stem Cell Transplantation for Solid Tumors: Which Way Forward?

AbstractThe patients presenting with metastatic solid tumors remains with poor prognosis. Despite advances in treatment and better understanding of the biological pathway during the past two decades, outcome remains often very poor. On the other hand, allogeneic stem cell transplantation has been established as a potent antitumoral immunotherapy in various hematological malignancies. Preliminary results confirm that graft versus tumor effect does exist. The main challenge is now to transform this biological and clinical effect into a real clinical benefit in term of curability and survival

formulas of revised mrp

Information sharing among supply chain echelons is now an acquired result. As a consequence, most of the traditional techniques and procedures in production management must be revised and updated, exploiting the opportunities provided by new technologies. This paper presents an improved version of Material Requirement Planning procedure, which assumes information sharing capabilities and permits the creation of new business opportunities. In Orlickyʹs MRP, orders are computed considering the parent items gross requirements. On the contrary, here the order release procedure related to a certain item is computed both by exploiting all the information sharing advantages and by introducing a drastic innovation to the main process functioning. As a result, the proposed algorithm copes better with demand uncertainty, lowers the system nervousness and also removes the need for continuous forecast adjustments, thereby improving the ease in managing the material flow, allowing the development of new forms of collaboration among different supply chain partners and the creation of new business networks. The algorithm is presented in formulas to describe in detail each procedure step and calculations

Is adoptive T-cell therapy for solid tumors coming of age

Among the novel biological therapeutics that will increase our ability to cure human cancer in years to come, adoptive cellular therapy is one of the most promising approaches. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. The results obtained with tumor-infiltrating lymphocytes therapy for melanoma, and virus-specific CTLs for EBV-associated malignancies are encouraging in terms of both ability to obtain clinical benefit and limited toxicity profile. In both settings, objective responses were obtained in at least 50% of treated patients. However, improvements to the clinical protocols, in terms of better patient selection and timing of administration, as well as cell product quality and availability, are clearly necessary to further ameliorate outcome, and logistical solutions are warranted to extend T-cell therapy beyond academic centers. In particular, there is a need to simplify cell production, in order to decrease costs and ease preparation. Promising implementations are underway, including harnessing the therapeutic potential of T cells transduced with TCRs directed against shared tumor antigens, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells

SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub

SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations. Gene ontology analysis of deregulated SETBP1 target genes indicates that they are also key controllers of visceral organ development and brain morphogenesis. In line with these findings, in utero brain electroporation of mutated SETBP1 causes impairment of mouse neurogenesis with a profound delay in neuronal migration. In summary, this work unveils a SETBP1 function that directly affects gene transcription and clarifies the mechanism operating in myeloid malignancies and in the Schinzel- Giedion syndrome caused by SETBP1 mutations.Peer reviewe

Adjuvant High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for High-Risk Primary Breast Cancer: Results from the Italian National Registry

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