scholarly journals IBD-like Lesions in a Secukinumab-treated Patient

Author(s):  
Kozue Kakizoe ◽  
Shin Fujioka ◽  
Mayaka Noda ◽  
Takehiro Torisu
Keyword(s):  
Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  

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.


2020 ◽  
Vol 58 (9) ◽  
pp. 1461-1468 ◽  
Author(s):  
Jean-Claude Alvarez ◽  
Pierre Moine ◽  
Isabelle Etting ◽  
Djillali Annane ◽  
Islam Amine Larabi

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.


2009 ◽  
Vol 27 (23) ◽  
pp. 3786-3793 ◽  
Author(s):  
Naureen Starling ◽  
Sheela Rao ◽  
David Cunningham ◽  
Timothy Iveson ◽  
Marianne Nicolson ◽  
...  

PurposeData concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited.Patients and MethodsThis was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses.ResultsThe incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043).ConclusionThis analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.


2007 ◽  
Vol 4 (12) ◽  
pp. 722-725 ◽  
Author(s):  
Stelvio Ballanti ◽  
Elena Mastrodicasa ◽  
Niccolò Bolli ◽  
Flavia Lotti ◽  
Ilaria Capolsini ◽  
...  

2005 ◽  
Vol 39 (7-8) ◽  
pp. 1368-1369 ◽  
Author(s):  
Enes Murat Atasoyu ◽  
T Rifki Evrenkaya ◽  
Emrullah Solmazgul
Keyword(s):  

2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Seung Han Baek ◽  
Dinah Foer ◽  
Katherine N. Cahill ◽  
Elliot Israel ◽  
Enrico Maiorino ◽  
...  

There is an acute need for advances in pharmacologic therapies and a better understanding of novel drug targets for severe asthma. Imatinib, a tyrosine kinase inhibitor, has been shown to improve forced expiratory volume in 1 s (FEV1) in a clinical trial of patients with severe asthma. In a pilot study, we applied systems biology approaches to epithelium gene expression from these clinical trial patients treated with imatinib to better understand lung function response with imatinib treatment. Bronchial brushings from ten imatinib-treated patient samples and 14 placebo-treated patient samples were analyzed. We used personalized perturbation profiles (PEEPs) to characterize gene expression patterns at the individual patient level. We found that strong responders—patients with greater than 20% increase in FEV1—uniquely shared multiple downregulated mitochondrial-related pathways. In comparison, weak responders (5–10% FEV1 increase), and non-responders to imatinib shared none of these pathways. The use of PEEP highlights its potential for application as a systems biology tool to develop individual-level approaches to predicting disease phenotypes and response to treatment in populations needing innovative therapies. These results support a role for mitochondrial pathways in airflow limitation in severe asthma and as potential therapeutic targets in larger clinical trials.


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