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Chidamide shows synergistic cytotoxicity with cytarabine via inducing G0/G1 arrest and apoptosis in myelodysplastic syndromes.

In this study, the combination of chidamide (50 nM) with cytarabine (50 nM) showed synergistic inhibition on cell growth.The mean combination index values were 0.068, 0.158, and 0.226 in SKM-1, MUTZ-1, and KG-1 MDS cell lines, respectively. The combination increased the acetylation levels of histone H3 and decreased HDAC activity in MDS cells.A low concentration (25 and 50 nM) of chidamide combined with low-dose cytarabine (50 nM) inhibited cell proliferation and arrested the cell cycle in the G0/G1 phasevia down-regulating CDK2 and up-regulating p21. Furthermore, the combined treatment induced cell apoptosis via down-regulating Bcl-2 and up-regulating cleaved caspase-3 protein. These results demonstrate the potential utility of combining chidamide and cytarabine in the treatment of MDS. PMID: 29312515 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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Abstract The metabolism of posaconazole is mediated mainly by uridine 5' -diphospho-glucuronosyltransferase (UGT) enzymes, especially the UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the posaconazole plasma concentration (PPC). This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three times daily for fungal prophylaxis. The multi-drug resistance gene 1 3435C>T and 2677G>T/A variations, and UGT1A4*3 were examined by dir...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
We report a case of delayed diagnosis of SDS in a family with another child with aplastic anemia, and review reported cases of SDS in Asia. This highlights the gap in identifying inherited bone marrow failure syndromes in adults with hematologic malignancies.
Source: Leukemia Research Reports - Category: Hematology Source Type: research
Abstract Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method...
Source: Acta Bio-Medica : Atenei Parmensis - Category: General Medicine Authors: Tags: Acta Biomed Source Type: research
Rationale: The current therapy for elderly patients with high-risk myelodysplastic syndromes (MDSs) remains unsatisfactory. Decitabine, which has been approved to treat MDS, cannot eliminate malignant clones of MDS. Patient concerns: A 68-year-old woman presented with multiple divergent bleeding points in the subcutaneous tissue of the limb. Two years earlier, she had been diagnosed with invasive ductal carcinoma of the left breast and had undergone left modified radical mastectomy and local radiation therapy. Diagnoses: The patient was diagnosed with MDS refractory anemia with excess of blast II and was classified...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionsThe novel t(7;13)(p14;q12)/PAN3–PSMA2 in the neoplastic bone marrow cells could affect two key protein complex: (a) the PAN2/PAN3 complex (PAN3 rearrangement) which is responsible for deadenylation, the process of removing the poly(A) tail from RNA, and (b) the proteasome (PSMA2 rearrangement) which is responsible for degradation of intracellular proteins. The patient showed a favorable response to decitabine after treatment with 5-azacitidine and conventional intensive chemotherapy had failed. Whether this might represent a consistent feature of MDS/AML with this particular gene fusion, remains unknown.
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 8 February 2018 Source:Clinical Lymphoma Myeloma and Leukemia Author(s): Jill A. Bell, Aaron Galaznik, Rachel Huelin, Michael Stokes, Yelan Guo, Robert J. Fram, Douglas V. Faller High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to ev...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionDe novo myeloid sarcoma mostly presented isolated. Lesions were often localized at skin and lymph nodes. Genetic aberrations frequently involved coreā€binding factor rearrangements in de novo cases and a complex karyotype in secondary cases.This article is protected by copyright. All rights reserved.
Source: European Journal of Haematology - Category: Hematology Authors: Tags: Original Article Source Type: research
DISCUSSION: Treatment with chemotherapy plus G-CSF appears to provide better survival and treatment responses compared with chemotherapy alone, particularly for patients with previously untreated AML. ABBREVIATIONS: AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission; DFS, disease-free survival; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; HR, hazard ratio; MDS, myelodysplastic syndrome; OR, odds ratio; OS, overall survival; RCTs, randomized control trials; RR, relative risk. PMID: 29516766 [PubMed - as supplied by publisher]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
Conclusion: The prevalence of PHD after PRRT with 177Lu-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Clinical Source Type: research
CONCLUSIONS:  Treatment with glasdegib in combination with standard chemotherapy was generally well-tolerated and consistent with prior findings, warranting further evaluation of glasdegib-based combinations in patients with AML or high-risk MDS. PMID: 29463550 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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