Search results for "C63"
showing 10 items of 58 documents
Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
2019
Background Genomic instability is a feature of multiple myeloma (MM), and impairment in DNA damaging response (DDR) has an established role in disease pathobiology. Indeed, a deregulation of DNA repair pathways may contribute to genomic instability, to the establishment of drug resistance to genotoxic agents, and to the escape from immune surveillance. On these bases, we evaluated the role of different DDR pathways in MM and investigated, for the first time, the direct and immune-mediated anti-MM activity of the nucleotide excision repair (NER)-dependent agent trabectedin. Methods Gene-expression profiling (GEP) was carried out with HTA2.0 Affymetrix array. Evaluation of apoptosis, cell cyc…
Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment l…
2019
Background Multiple myeloma (MM) is a clonal plasma cell malignancy associated with osteolytic bone disease. Recently, the role of MM-derived exosomes in the osteoclastogenesis has been demonstrated although the underlying mechanism is still unknown. Since exosomes-derived epidermal growth factor receptor ligands (EGFR) are involved in tumor-associated osteolysis, we hypothesize that the EGFR ligand amphiregulin (AREG) can be delivered by MM-derived exosomes and participate in MM-induced osteoclastogenesis. Methods Exosomes were isolated from the conditioned medium of MM1.S cell line and from bone marrow (BM) plasma samples of MM patients. The murine cell line RAW264.7 and primary human CD1…
Paroxysmal nocturnal haemoglobinuria: When delay in diagnosis and long therapy occurs
2017
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somaticmutation in PIG-A gene that results in theabsence of CD55 and CD59, two important complement regulatory proteins. In thispaper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms isdescribed, together with an adequate follow-up over a 7-years treatment period. Inthis case, the not specificity and the limited clinical relevance of the symptoms led to adelay in diagnosis. After thrombosis, Eculizumab therapy has been shown to be effec…
Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer
2017
Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their…
Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia
2020
Background. Haematological and non-haematological malignancies are able to escape the host immune by the capacity to hijack the immune check-points. Several immune check-point molecules are known, such as T cell immunoglobulin mucin-3 (TIM-3), cytotoxic T-cell antigen-4 (CTLA-4), programmed death-1 (PD-1) with its ligand PD-L1 and others.1 The function of these immune check-points is to prevent the damage resulting from an excessive activation of the immune response in the setting of chronic antigenic stimulation, thus leading to autoimmune phenomena, as proved in knock-out mice models. PD-1 is normally present on activated T lymphocytes membrane, acting as a negative costimulatory receptor…
Genotypic and Phenotypic Characteristics of Acute Promyelocytic Leukemia Translocation Variants.
2020
Acute promyelocytic leukemia (APL) is a special disease entity of acute myeloid leukemia (AML). The clinical use of all-trans retinoic acid (ATRA) has transformed APL into the most curable form of AML. The majority of APL cases are characterized by the fusion gene PML-RARA. Although the PML-RARA fusion gene can be detected in almost all APL cases, translocation variants of APL have been reported. To date, this is the most comprehensive review of these translocations, discussing 15 different variants. Reviewed genes involved in APL variants include: ZBTB16, NPM, NuMA, STAT5b, PRKAR1A, FIP1L1, BCOR, NABP1, TBLR1, GTF2I, IRF2BP2, FNDC3B, ADAMDTS17, STAT3, and TFG. The genotypic and phenotypic …
Final Results of a Phase I/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Folli…
2020
Abstract. In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m2, day 1 + 2) and Rituximab (375 mg/m2, day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment. Overall, 39 (29 MCL, 10 FL) patients were included. Median age was 71 years and median pretreatment number was 2. Grade 3/4 non-hematologic adverse events wer…
Bicausative matrices to measure structural change: Are they a good tool?
1999
The causative-matrix method to analyze temporal change assumes that a matrix transforms one Markovian transition matrix into another by a left multiplication of the first matrix; the method is demand-driven when applied to input-output economics. An extension is presented without assuming the demand-driven or supply-driven hypothesis. Starting from two flow matrices X and Y, two diagonal matrices are searched, one premultiplying and the second postmultiplying X, to obtain a result the closer as possible to Y by least squares. The paper proves that the method is deceptive because the diagonal matrices are unidentified and the interpretation of results is unclear. Keywords : Input-Output ; Ch…
Forecast Output Coincidence and Biproportion: Two Criteria to Determine the Orientation of an Economy. Comparison for France (1980-1997)
2002
International audience; The method of forecast output coincidence used to determine if sectors are demand-sided or supply-sided in an input-output framework mixes two effects, the structural effect (choosing between demand and supply side models) and the effect of an exogenous factor (final demand or added-value). The note recalls that another method is possible, the comparison of the stability of technical and allocation coefficients, generalized by the biproportional filter: if for a sector, after biproportional filtering, column coefficients are more stable than row coefficients, then this sector is declared as not supply-sided (but one cannot decide that it is demand-sided anyway), and …
About the criteria of output coincidence for forecasts to determine the orientation of the economy (application for France, 1980-1997)
2000
This note indicates that the method of output coincidence for forecasts used to determine if sectors are demand-driven or supply-driven in an input-output framework mixes two effects, the structural effect (choosing between demand and supply driven models) and the effect of an exogenous factor (final demand or added-value). The note recalls that another method is possible, the comparison of the stability of technical and allocation coefficients, generalized by the biproportional filter: if for a sector, after biproportional filtering, column coefficients are more stable than row coefficients, then this sector is declared as not supply-driven (but one cannot decide that it is demand-driven a…