scholarly journals Investigating changes in β-adrenergic gene expression (ADRB1 and ADRB2) in Takotsubo (stress) cardiomyopathy syndrome; a pilot study

2021 ◽  
Author(s):  
Serap Tutgun Onrat ◽  
İbrahim Etem Dural ◽  
Zafer Yalım ◽  
Ersel Onrat
Keyword(s):  
Gene Expression ◽  
Pilot Study ◽  
Stress Cardiomyopathy

scholarly journals An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Erica M. Stringer-Reasor ◽  
Jori E. May ◽  
Eva Olariu ◽  
Valerie Caterinicchia ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Repair ◽  
Pilot Study ◽  
Expression Analysis ◽  
Triple Negative Breast Cancer ◽  
Gene Expression Analysis ◽  
Triple Negative ◽  
Egfr Inhibition ◽  
Link Type

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014

scholarly journals Analysis of cell cycle related gene expression in Myb deficient mandible – a pilot study

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 100907
Author(s):  
Sabina Stouracova ◽  
Eva Matalova ◽  
Jon Frampton ◽  
Mary Clarke ◽  
Premysl Bartos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Pilot Study ◽  
Related Gene ◽  
Cell Cycle Related Gene

scholarly journals Systems Approaches to Treatment Response to Imatinib in Severe Asthma: A Pilot Study

2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Seung Han Baek ◽  
Dinah Foer ◽  
Katherine N. Cahill ◽  
Elliot Israel ◽  
Enrico Maiorino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Systems Biology ◽  
Pilot Study ◽  
Severe Asthma ◽  
Treated Patient ◽  
Expression Patterns ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
Imatinib Treatment

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.

scholarly journals Micro-biopsy for detection of gene expression changes in ischemic swine myocardium: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250582
Author(s):  
Arvin Chireh ◽  
Rikard Grankvist ◽  
Mikael Sandell ◽  
Abdul Kadir Mukarram ◽  
Fabian Arnberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pilot Study ◽  
Early Stage ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Balloon Occlusion ◽  
Deconvolution Analysis ◽  
Infarcted Area ◽  
Tissue Changes ◽  
Apoptosis And Inflammation

Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.

scholarly journals Effects of Non-thermal, Non-cavitational Ultrasound Exposure on Human Diabetic Ulcer Healing and Inflammatory Gene Expression in a Pilot Study

2018 ◽  
Vol 44 (9) ◽  
pp. 2043-2049 ◽  
Author(s):  
Anamika Bajpai ◽  
Sumati Nadkarni ◽  
Michael Neidrauer ◽  
Michael S. Weingarten ◽  
Peter A. Lewin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pilot Study ◽  
Ulcer Healing ◽  
Ultrasound Exposure ◽  
Diabetic Ulcer ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene
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