Skin involvement of medication-related osteonecrosis of jaws in an immunocompromised, bisphosphonate-treated patient

Background:PDGF is a potential important factor in the pathogenesis of scleroderma. PDGF is almost undetectable in healthy skin or lung. Immunohistochemical studies have revealed increased presence of PDGFαand PDGFβreceptors in scleroderma skin biopsies.Objectives:The aim of this study was to determine the mRNA level ofIFNα1,IL-4, TGFβ1,TGFβ2,PDGFα,PDGFβ,TNFαin whole blood in SSc patients in the aspect of clinicalMethods:A group of 14 patients (50% were women) with systemic sclerosis based on EULAR / ACR 2013 criteria was included in the study. The modified Rodnan Skin Score (mRSS) was evaluated by same assistant at the beginning of the study and six months later. DLCO, HRCT, echocardiography and NFC were measured.Gene expression was determined using validated TaqMan probes in qPCR. Constitutive mRNA level of selected genes was analyzed using ΔCt method. Comparison between different groups of patients was determined using non-parametric Mann-Whitney U test. Correlation was analyzed using non-parametric Spearman test.Results:The mean age of the patients was 60 ± 15.66. 100% of patients had organ involvement as pulmonary fibrosis. 78% - had active changes -features of ground glass.64% of patients had mild mRSS-1-10 skin involvement, 36% had moderate to severe skin involvement. In SSc patientsTGFβ1andIFNα1revealed the highest level of expression in comparison to other analyzed genes. Additionally, very high and significant correlation betweenTNFαandTGFβ1(r=0.7 p=0.004) has been noted. High and significant correlation between mRNAPDGFβandTNFαlevels have been observed. We did not reveal significant differences in analyzed genes expression when compare limited and diffuse SSc. Nevertheless, patients with dSSc were characterized by higher level ofIFNα1(almost 2 times) andTGFβ1. On the border of significance higherPDGFαmRNA level was observed in dSSc patients when compared to lSSc. AveragePDGFαexpression is higher in SSc patients with Scl70 positive than than in patients without Scl70 (p=0.04).In the aspect of clinical parameters, patients with ESR ≤12 mm/h revealed almost 6 times higher level ofIFNα1(p=0.01) in comparison to the patient with ESR>12mm/h.Patients with mRSS above10 points revealed significantly higher ofPDGFαexpression in comparison to patients with mRSS ≤10 (p=0.04). In these group of patients CRP and ESR were not different significantly.In the case of patients with active fibrosis (ground glass) in HRCTIFNα1expression was almost 2.5-times higher than in patients with HRCT non-active. Significantly higherPDGFα has been revealed in patients with active HRCT when compared with patient with non-active HRCT. Nevertheless these two groups did not differ in ESR or OB parameter.SSc patients in active phase of NFC revealed almost 3 times higher level ofIFNα1expression in comparison with the patient in late phase.Conclusion:The mRNA level ofPDGFαmay be a potential blood marker to predict worse prognosis in sclerodermaReferences:[1]Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v2-4. doi: 10.1093/rheumatology/ken265.Role of PDGF in fibrotic diseases and systemic sclerosis.Trojanowska M1.Acknowledgments:NoDisclosure of Interests:None declared

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Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽

10.3233/tub-200072 ◽

2021 ◽

Vol 43 (1) ◽

pp. 11-26

Author(s):

Maike Busch ◽

Natalia Miroschnikov ◽

Jaroslaw Thomas Dankert ◽

Marc Wiesehöfer ◽

Klaus Metz ◽

...

Keyword(s):

Cell Viability ◽

Cell Lines ◽

Cancer Progression ◽

Treated Patient ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

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Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0612 ◽

2020 ◽

Vol 58 (9) ◽

pp. 1461-1468 ◽

Cited By ~ 2

Author(s):

Jean-Claude Alvarez ◽

Pierre Moine ◽

Isabelle Etting ◽

Djillali Annane ◽

Islam Amine Larabi

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Half Life ◽

Limit Of Detection ◽

Treated Patient ◽

Internal Standard ◽

Therapeutic Drug ◽

Active Metabolites ◽

Limit Of Quantification ◽

Positive Mode

AbstractObjectivesA method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 µL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524.MethodsA simple protein precipitation was carried out using 75 µL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 µL ZnSO4 1 M. After separation on Kinetex® 2.6 µm Polar C18 100A LC column (100 × 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 → m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 → m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 → m/z 206.0 for remdesivir-13C6.ResultsCalibration curves were linear in the 1–5000 μg/L range for remdesivir and 5–2500 for GS-441524, with limit of detection set at 0.5 and 2 μg/L and limit of quantification at 1 and 5 μg/L, respectively. Precisions evaluated at 2.5, 400 and 4000 μg/L for remdesivir and 12.5, 125, 2000 μg/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6–110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h.ConclusionsThis method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.

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Skin Involvement in Multiple Myeloma Demonstrated on FDG PET/CT

Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) ◽

10.1016/j.remnie.2021.03.017 ◽

2021 ◽

Author(s):

Selin Kesim ◽

Kevser Oksuzoglu ◽

Salih Ozguven ◽

Tunc Ones ◽

Leyla Cinel ◽

...

Keyword(s):

Multiple Myeloma ◽

Fdg Pet ◽

Skin Involvement ◽

Pet Ct ◽

Fdg Pet Ct

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Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases

International Journal of Molecular Sciences ◽

10.3390/ijms22137072 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7072

Author(s):

Andrea Toniato ◽

Chiara Gamba ◽

Jan Walter Schroeder ◽

Valeria Fabbri ◽

Scarlett Valeria Bernal Ortiz ◽

...

Keyword(s):

Risk Factors ◽

Drug Reaction ◽

Retrospective Study ◽

Clinical Severity ◽

Severe Reaction ◽

Skin Involvement ◽

Inflammatory State ◽

Reaction Severity ◽

Clinical Conditions

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p=0.0067) and an age of at least 68 years (p=0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

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