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  • ||||||||||  [VIRTUAL] Integrated Cytof, Scrna-Seq and Cite-Seq Analysis of Bone Marrow Immune Microenvironment in the Mmrf Commpass Study (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_1113;    
    P=N/A
    Our preliminary results suggested good concordance of immune cell type abundance identified in CyTOF, scRNA-seq and CITE-seq as well as concordant expression of some canonical cell type markers between RNA level and protein level. This work provides the field with reference data sets and shows more detailed examination of NK and T cell subsets is needed when handling single cell sequencing with different modalities.
  • ||||||||||  azacitidine / Generic mfg., decitabine / Generic mfg.
    [VIRTUAL] Uptake of Novel Therapies into First-Line Treatment for AML Patients - EU5 Perspective (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_786;    
    Following FDA approval of venetoclax for AML, usage of venetoclax-containing low-intensity regimens has been observed in EU5. Although approved for targeted AML patient populations (i.e. CD33-mutated, FLT3-mutated patients), only approximately 10% of appropriate patients are receiving gemtuzumab ozogamicin and midostaurin in the first-line setting.
  • ||||||||||  Preclinical, Journal:  ImmunoPET, [64Cu]Cu-DOTA-anti-CD33 PET-CT, imaging of an AML Xenograft model. (Pubmed Central) -  Oct 28, 2020   
    The study is rated Class III because of the case control design and the risk of spectrum bias. We have successfully developed a novel anti-CD33 immunoPET-CT-based non-invasive modality for AML and its spatial distribution, indicating a preferential skeletal niche.
  • ||||||||||  [VIRTUAL] A rare case of de novo mast cell leukemia manifested with duodenal ulcer perforation () -  Oct 17, 2020 - Abstract #SOHOItaly2020SOHO_Italy_33;    
    Taken together, genetic predisposition, P. gingivalis infection and microglia could promote neurodegeneration typical of that reported for AD. Abstract Introduction Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis, which has poor prognosis and limited treatment choice Timely and proper MCL diagnosis plays an important role in treatment effectiveness, and remission achievement It is known that mast cells are highly aggressive, easily degranulating with realizing a significant amount of histamine, that can lead to unusual manifestation of leukemia with primary injury of different extramedullary organs There are no clear guidelines for MCL treatment, that is forcing doctors to seek new approaches for patient’s management The aim is to present a case of de novo mast cell leukemia manifested with duodenal ulcer (DU) perforation and to analyze the effectiveness of mitoxantrone plus cytarabine combination as an initial treatment Methods A 62-year old man was diagnosed with de novo MCL, which manifested with DU perforation The MCL diagnosis was made based on WHO (2016) diagnostic criteria Patient underwent 2 courses of induction chemotherapy (ICT) with 3 days of 10 mg/m2 and 7 days of 200 mg/m2 cytarabine Supportive treatment included surgery, antibiotics, double dose proton-pump inhibitors (pantoprazole), blood transfusions and standard infusion therapy Patient’s general condition, hemogram, myelogram and endoscopy data were evaluated twice: at baseline and after 2 courses of CT Results Our patient was initially admitted to surgical department of Poltava Regional Clinical Hospital with acute abdominal pain, fever up to 380C, severe weight loss of 15 kg and signs of peritonitis Patient had neither lymphadenopathy, nor hepatosplenomegaly Upper endoscopy revealed an DU perforation After its suturing and abdominal drainage, the antibiotics were prescribed But in 3 days the fever continued, leukocytosis increased, immature cells appeared in the blood The tests showed a HGB level of 95 g/l, RBC 299×1012/l, PLT 60×109/l, WBC 62×109/l, of which 45% immature cells with dense basophilic granules in the cytoplasm, sometimes with vacuolation Bone marrow (BM) aspiration showed 31% of blast cells and 50% basophils, morphologically the same as in the blood These cells were myeloperoxidase negative, nonspecific acid esterase positive Acid phosphatase was positive, diffuse-granulated Flow cytometry revealed a significant malignant cell population: 74,6% of BM cells were CD33-/+13-34-117+CD11c+CD11b+CD19-CD3-HLA-DR-, CD25+7+14- After ICT the remission was achieved: general condition improved, complete DU healing according to endoscopy In hemogram HGB level reached 137 g/l, RBC 499×1012/l, PLT 170×109/l, WBC 573×109/l, of which eos 7%, bas 0%, neutr 51%, lymph 35%, mon 7%, no immature cells BM aspiration showed normocellularity, blast cells 1%, basophils 4% Conclusions We have presented a case of a unique leukemia with rare manifestation Mitoxantrone in combination with cytarabine could be an initial treatment choice in case of MCL with high amount of immature malignant cells
  • ||||||||||  Journal:  A Novel, Five-Marker Alternative to CD16-CD14 Gating to Identify the Three Human Monocyte Subsets. (Pubmed Central) -  Oct 16, 2020   
    Finally, we found that the observed expansion of intermediate (CD14) monocytes in dengue virus-infected patients was due to up-regulated CD16 expression on classical monocytes. With our new combination of markers, we can now identify monocyte subsets without CD16 and CD14, and accurately re-examine monocyte subset perturbations in diseases.
  • ||||||||||  sirolimus / Generic mfg.
    [VIRTUAL] Drug-regulatable engineered T cells eliminate CD33+ and CD33ΔE2+ AML () -  Oct 14, 2020 - Abstract #SITC2020SITC_1142;    
    Methods We engineered DARIC-expressing lentiviral vectors containing encoding separated CD33-C2-specific antigen binding and 41BB-CD3zeta signaling chains that heterodimerize following addition of rapamycin via embedded FKBP12 and FRB* domains.4 Peripheral blood mononuclear cells were stimulated with IL-2, anti-CD3, and anti-CD28 antibodies 24h prior to transduction with DARIC33 lentiviral vector...Conclusions DARIC33 T cells appear to be potent antileukemic agents: they are activated by AML cell lines in vitro as demonstrated by cytokine release and cytotoxicity, and significantly extend survival in an aggressive xenograft model. Temporal control provided by the DARIC architecture promises to enhance safety and potentially efficacy of CAR T therapy for AML, for example by enabling hematopoietic recovery or providing T cell rest.
  • ||||||||||  sirolimus / Generic mfg.
    [VIRTUAL] Drug-regulatable engineered T cells eliminate CD33+ and CD33ΔE2+ AML () -  Oct 14, 2020 - Abstract #SITC2020SITC_407;    
    Methods We engineered DARIC-expressing lentiviral vectors containing encoding separated CD33-C2-specific antigen binding and 41BB-CD3zeta signaling chains that heterodimerize following addition of rapamycin via embedded FKBP12 and FRB* domains.4 Peripheral blood mononuclear cells were stimulated with IL-2, anti-CD3, and anti-CD28 antibodies 24h prior to transduction with DARIC33 lentiviral vector...Conclusions DARIC33 T cells appear to be potent antileukemic agents: they are activated by AML cell lines in vitro as demonstrated by cytokine release and cytotoxicity, and significantly extend survival in an aggressive xenograft model. Temporal control provided by the DARIC architecture promises to enhance safety and potentially efficacy of CAR T therapy for AML, for example by enabling hematopoietic recovery or providing T cell rest.
  • ||||||||||  [VIRTUAL] Acute Myeloid Leukemia Worsens Sepsis-Induced AKI (On-Demand) -  Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2718;    
    Leukemia intensified sepsis-induced AKI, and sepsis AKI increased the numbers of circulating AML cells. Systemic cytokines derived from the human leukemia cells correlated with tumor burden, but not with the severity of sepsis-induced AKI.
  • ||||||||||  Journal:  Diallyl disulfide induces downregulation and inactivation of cofilin 1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells. (Pubmed Central) -  Oct 8, 2020   
    The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho‑associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL‑60 cells, while 8 µM DADS enhanced the effects of the Rac1‑ROCK1‑LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL‑60 cells. These results suggest that the anticancer function of DADS on HL‑60 leukemia cells is regulated by the Rac1‑ROCK1‑LIMK1‑cofilin 1 pathway, indicating that DADS could be a promising anti‑leukemia therapeutic compound.
  • ||||||||||  [VIRTUAL] Predictors of Outcomes in AML with MLL Rearrangement () -  Sep 14, 2020 - Abstract #SOHO2020SOHO_398;    
    MLLr AML has unique molecular and phenotypic features and is associated with dismal outcomes improved only with HSCT. Given the limited progress made in treatment of this entity, novel approaches are needed.
  • ||||||||||  capecitabine / Generic mfg.
    Clinical, Journal, Myeloid-derived suppressor cells:  Intratumoral HLA-DR/CD33/CD11b Myeloid-Derived Suppressor Cells Predict Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. (Pubmed Central) -  Sep 11, 2020   
    Capecitabine-based neoadjuvant chemoradiation therapy (nCRT) is currently the mainstay of treatment for locally advanced rectal cancer (LARC), prior to surgical tumor removal...Importantly, therapy by itself, had significant differential effects on MDSC levels, leading to increased circulating MDSCs, concomitantly with decreasing intratumoral MDSCs. Our results suggest that high levels of intratumoral, but not circulating MDSCs may confer drug resistance due to immunomodulatory effects, and serve as a biomarker for patient stratification and decision-making prior to nCRT.