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Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are 相似文献
References
- 1.Valcarcel D, Verma A, Platzbecker U, et al. Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes. Blood. 2015;126:1669.
- 2.Suragani RN, Cawley SM, Li R, Wallner S, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014 Jun 19;123(25):3864-72.
- 3.Dussiot M, Maciel TT, Fricot A, et al. Nat Med. 2014 Apr;20(4):398-407.
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C. Banella M. Ginevrino G. Catalano E. Fabiani G. Falconi M. Divona P. Curzi P. Panetta M.T. Voso N.I. Noguera 《Hematology/oncology and stem cell therapy》2021,14(2):163-168
FGFR–TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR–TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3–TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended. 相似文献
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《Clinical Lymphoma, Myeloma & Leukemia》2020,20(8):e461-e467
IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed. 相似文献
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Vahid MoazedElham JafariBita RashidiNezhadBehjat Kalantari-KhandaniAli NematiAhmad Naghibzadeh TahamiForoogh Mangeli 《Asian Pacific journal of cancer prevention》2020,21(1):239-241
Background: Myelodysplastic syndrome (MDS) is a heterogeneous hematological disease and certain serum factors are assumed to be involved in its pathogenesis and progression. Given this, our aim was to comparatively investigate the copper, zinc, and iron levels in MDS patients and healthy individuals. Methods: This case-control study was conducted on 31 patients with MDS (according to the WHO criteria after investigating laboratory tests such as peripheral blood smear and bone marrow aspiration) attending Bahonar Hospital, Kerman, Iran, and 31 healthy subjects from 2016 to 2018. The levels of copper, ceruloplasmin, zinc, ferritin, and iron were compared between the two groups. Results: Among the MDS patients, five individuals (16.13%) had low serum copper level (mean: 67.8 ± 4.35 µg/dl). Serum copper level was 111.3 ± 27.7 and 138.3 ± 26.6 in case and control groups, respectively (P = 0.0001). The serum zinc level and bone marrow iron level were also significantly different between the two groups (P < 0.05). Conclusion: Overall, it can be concluded that because only a small proportion of the MDS patients enrolled in this study were found to have lower copper levels compared with the MDS patients population, further studies with a larger sample size and also clinical trials in MDS patients with serum zinc, and copper deficiency are recommended, and post-treatment hematological reassessment would also be beneficial to achieving more definitive results. 相似文献
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《Journal of thoracic oncology》2021,16(3):381-394
Immune checkpoint inhibitors (ICIs) have transformed the prognosis of cancers previously considered lethal. The spectrum of therapeutic indications is rapidly expanding, including the vast majority of thoracic malignancies. By enhancing the immune responses against cancer, the ICI treatments lead to the development of immune-related adverse events (irAEs) that may affect any organ. Severity varies from mild to fatal clinical manifestations. Neurologic involvement is relatively rare and highly heterogeneous, including central and peripheral nervous system diseases associated with neural-specific autoantibodies or not, central nervous system vasculitis, and granulomatous and demyelinating disorders. Symptoms often manifest within the first four cycles of treatment and can develop regardless of the class of ICI used. An unfavorable outcome is found in up to one-third of patients and is generally associated with the patients’ clinical characteristics (e.g., age, coexistence of systemic adverse events), cancer type (e.g., lung cancer versus other), and specific clinical setting (e.g., ICI treatment in patients with preexisting paraneoplastic neurologic autoimmunity, ICI rechallenge after a first neurologic irAE). Diagnosis should be suspected in patients with new-onset neurologic symptoms while on ICI treatment which are not explained by metastatic disease or other metabolic/infectious disorders. Recommended treatment is based on clinical severity and consists of ICI discontinuation with or without immunosuppressive/immunomodulatory therapy, although alternative approaches are reasonable depending on cancer status (e.g., aggressive immunosuppression without discontinuing ICI in patients with initial cancer response). Early recognition and appropriate treatment of these neurologic irAEs are crucial for improved patient outcomes and therapeutic planning. 相似文献
8.
Johannes Brettschneider Axel Petzold Sigurd D Süssmuth Georg B Landwehrmeyer Albert C Ludolph Jan Kassubek Hayrettin Tumani 《Movement disorders》2006,21(12):2224-2227
We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each). They were also significantly higher in MSA than in PD and controls (P < 0.05 each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory-supported differential diagnosis of atypical parkinsonian syndromes. 相似文献
9.
足部骨筋膜室综合征早期诊断与治疗 总被引:2,自引:0,他引:2
目的:探讨足部骨筋膜室综合征早期诊断与治疗结果。方法:1998年1月-2003年12月收治15例足骨筋膜室综合征患者(均为男性:年龄15~55岁,平均32岁),行足背双切口减压4例,足底内侧减压9例,足内外两侧减压2例。1周后行减张缝合或植皮术。结果:15例随访9~24个月,12例恢复佳,足运动感觉正常;2例有足底感觉减退、足趾麻木;1例遗留前足挛缩、无力,足趾麻木。无爪形趾及功能障碍者。结论:足损伤后,Whiteside法测定组织间隙压力是诊断足骨筋膜室综合征的可靠方法。治疗时足部如有骨折、血肿者,骨筋膜室减张切口,宜选择足底内侧切开效果较好。 相似文献
10.
李松林副主任医师将肾小球肾炎的病机概括为湿、热、毒、瘀、虚等方面,在中医辨证的基础上,结合现代医学对其病因和发病机理的认识及中草药药理作用,针对不同的病理机制和临床表现,提出清热解毒法,活血化瘀法,调补脾肾法,扶正固本法,并视症有机结合,恰当治疗,疗效显著。 相似文献