FRI0439 The Role of the Myeloid Inflammatory Bone Marrow Compartment in Onset and Progression of Myocardial Fibrosis in Systemic Sclerosis

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 586.1-586
Author(s):  
V. Haunerdinger ◽  
E. Pachera ◽  
R. Dobrota ◽  
P. Blyszczuk ◽  
O. Distler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Systemic Sclerosis ◽  
Myocardial Fibrosis

scholarly journals Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement

2021 ◽  
Vol 12 ◽  
Author(s):  
Giacomo De Luca ◽  
Giulio Cavalli ◽  
Corrado Campochiaro ◽  
Cosimo Bruni ◽  
Alessandro Tomelleri ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Myocardial Fibrosis ◽  
Cardiac Involvement ◽  
Interleukin 1 ◽  
Inflammasome Activation ◽  
High Morbidity ◽  
Prognostic Features ◽  
Heart Involvement ◽  
Targeted Inhibition

Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.

The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Oxidative Damage ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
Normal Cells ◽  
Treatment And Prevention

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

Systematic Review of the Role of Microparticles in Systemic Sclerosis

2014 ◽  
Vol 9 (4) ◽  
pp. 279-300 ◽  
Author(s):  
James Dunne ◽  
Julius Bankole ◽  
Kevin Keen
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis

Impaired Angiogenesis in Systemic Sclerosis: The Emerging Role of the Antiangiogenic VEGF165b Splice Variant

2011 ◽  
Vol 21 (7) ◽  
pp. 204-210 ◽  
Author(s):  
Mirko Manetti ◽  
Serena Guiducci ◽  
Lidia Ibba-Manneschi ◽  
Marco Matucci-Cerinic
Keyword(s):  
Systemic Sclerosis ◽  
Splice Variant ◽  
Impaired Angiogenesis

Role of the microRNA-29 family in myocardial fibrosis

2021 ◽  
Author(s):  
Changyan Li ◽  
Nan Wang ◽  
Peng Rao ◽  
Limeiting Wang ◽  
Di Lu ◽  
...  
Keyword(s):  
Myocardial Fibrosis

scholarly journals AB0440 CLINICAL AND IMMUNOLOGICAL FEATURES OF THE SYSTEMIC SCLEROSIS-OVERLAP SYNDROMES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1248.2-1248
Author(s):  
O. Desinova ◽  
M. Starovoytova ◽  
L. P. Ananyeva ◽  
O. Koneva ◽  
L. Garzanova ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pathological Process ◽  
Point Of View ◽  
Joint Involvement ◽  
Laboratory Findings ◽  
Overlap Syndromes ◽  
Digital Ischemia ◽  
Immune Alterations ◽  
Clinical Variants

Background:Systemic Sclerosis (SSc) overlap syndromes (SSc with polymyositis / dermatomyositis (PM/DM), rheumatoid arthritis (RA), etc.) still remain a group of very heterogenous and not very well studied clinical variants of SSc that are characterized by certain clinical and immunological features.Objectives:Identify clinical and immunological features of the SSc-overlap syndromesMethods:80 pts with SSc-PM/DM and 35 pts with SSc-RA undergoing standard clinical examination and laboratory immunological evaluation.Results:ANA Hep2 was positive in 98% of SSc-PM/DM pts; a-Scl-70 was in 34%, a - PM-Scl and RF were in 20%. ACA (6%), a-RNP (9%), and a - Jo-1 (5%) were significantly less common. Correlation analysis showed significant prevalence of conduction abnormalities in pts with a-Scl-70- (p<0.03); PM-Scl was rarely associated with cardiac arrhythmia (p<0.02) and pericarditis (p<0.03), but there was an association between ACA and presence of digital ischemia (p<0.04). Three pts with limited skin had Scl-70 and PM-Scl antibodies, two of them manifested clinical features of DM. A-Jo-1 was found in 3 pts with a longstanding disease (14,10 and 7 years), and one of these pts was also positive for a-Scl-70. All pts had limited skin and two had interstitial lung disease with FVC values of 79% and 74.8%.ANA Hep2 was positive in 96% of SSc-RA pts; a-Scl-70 – in 28%, and a-RNP - in 30%. RF-positivity was in 72% of pts, and Anti-CCP - in 27%. Simultaneous Anti-CCP and a-Scl-70 was found in one case, and Anti-CCP - anti-RNP – in another, both were associated with low RF titers. All pts had early joint involvement which became prevailing in subsequent years, and onset of the disease between 30 and 36 years. There was a correlation between laboratory signs of inflammatory activity and immunological disorders: ESR and a-Scl-70 (p<0.03). Anti-CCP and a-Scl-70 co-positivity was a significantly less frequent phenomenon (p<0.04). There was a remarkable 28% proportion of a-Scl-70 cases in SSc-RA with limited cutaneous which is usually characterized by ACA-positivity.Conclusion:SSc-PM/DM and SSc-RA appear to be an active disease from the immunological point of view, confirming therefore an important role of immune alterations in disease progression. Laboratory findings display specific pathogenetic features of SSc-overlap syndromes; laboratory abnormalities can be used to measure the activity and specify characteristics of the pathological process.Disclosure of Interests:None declared

scholarly journals The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1575
Author(s):  
Lucia Zanoni ◽  
Riccardo Mei ◽  
Lorenzo Bianchi ◽  
Francesca Giunchi ◽  
Lorenzo Maltoni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Malignant Lesion ◽  
Lesion Detection ◽  
Histopathological Analysis ◽  
Choline Pet ◽  
Primary Prostate Cancer ◽  
Pet Ct

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

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