Efficacy of antiviral therapy and host-virus interactions visualized using serial liver sampling with fine-needle aspirates
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PROVIDER: PRJNA979188 | ENA |
REPOSITORIES: ENA
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Project description:Infection-dependent transcriptional changes and the impact of antiviral therapy on viral replication can be measured in longitudinal human liver biopsies using single-cell RNA sequencing data
2023-06-07 | GSE234015 | GEO
Project description:Background & aimsNovel therapies for chronic hepatitis B (CHB), such as RNA interference, target all viral RNAs for degradation, whereas nucleoside analogues are thought to block reverse transcription with minimal impact on viral transcripts. However, limitations in technology and sampling frequency have been obstacles to measuring actual changes in HBV transcription in the liver of patients starting therapy.MethodsWe used elective liver sampling with fine-needle aspirates (FNAs) to investigate the impact of treatment on viral replication in patients with CHB. Liver FNAs were collected from patients with CHB at baseline and 12 and 24 weeks after starting tenofovir alafenamide treatment. Liver FNAs were subjected to single-cell RNA sequencing and analysed using the Viral-Track method.ResultsHBV was the only viral genome detected and was enriched within hepatocytes. The 5' sequencing technology identified protein-specific HBV transcripts and showed that tenofovir alafenamide therapy specifically reduced pre-genomic RNA transcripts with little impact on HBsAg or HBx transcripts. Infected hepatocytes displayed unique gene signatures associated with an immunological response to viral infection.ConclusionsLongitudinal liver sampling, combined with single-cell RNA sequencing, captured the dynamic impact of antiviral therapy on the replication status of HBV and revealed host-pathogen interactions at the transcriptional level in infected hepatocytes. This sequencing-based approach is applicable to early-stage clinical studies, enabling mechanistic studies of immunopathology and the effect of novel therapeutic interventions.Impact and implicationsInfection-dependent transcriptional changes and the impact of antiviral therapy on viral replication can be measured in longitudinal human liver biopsies using single-cell RNA sequencing data.
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Project description:Fine needle stimulation also known as acupuncture is a traditional Chinese medical practice which causes relief of pain. We demonstrated that it caused neovascularization and enhanced recovery of blood perfusion in a ischemic portion of skeletal muscle in rats with hindlimb ischemia. Therefore we evaluated the effect of fine needle stimulation on skeletal muscle at gene expression level Keywords: Evaluation of physical stimulation
2007-09-01 | GSE8911 | GEO
Project description:No method with low morbidity presently exists for obtaining serial hepatic gene expression measurements in humans. While hepatic fine needle aspiration (FNA) has lower morbidity than core needle biopsy, applicability is limited due to blood contamination, which confounds quantification of gene expression changes. The aim of this study was to validate FNA for assessment of hepatic gene expression. Liver needle biopsies and FNA procedures were simultaneously performed on 17 patients with chronic hepatitis C virus infection with an additional FNA procedure 1 week later. Nine patients had mild/moderate fibrosis and eight advanced fibrosis. Gene expression profiling was performed using Affymetrix microarrays and TaqMan qPCR; pathway analysis was performed using Ingenuity. We developed a novel strategy that applies liver-enriched normalization genes to determine the percentage of liver in the FNA sample, which enables accurate gene expression measurements overcoming biases derived from blood contamination. We obtained almost identical gene expression results (? = 0.99, P < 0.0001) comparing needle biopsy and FNA samples for 21 preselected genes. Gene expression results were also validated in dogs. These data suggest that liver FNA is a reliable method for serial hepatic tissue sampling with potential utility for a variety of preclinical and clinical applications.
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Project description:Ultrasound-guided fine-needle aspiration (US-FNA) biopsy is a widely used minimally invasive sampling procedure for cytological diagnosis. This study investigates the feasibility of using US-FNA samples for both cytological diagnosis and whole transcriptome RNA-sequencing analysis (RNA-Seq), with the ultimate aim of improving canine prostate cancer management. The feasibility of the US-FNA procedure was evaluated intra vitam on 43 dogs. Additionally, aspirates from 31 euthanised dogs were collected for standardising the procedure. Each aspirate was separated into two subsamples: for cytology and RNA extraction. Additional prostate tissue samples served as control for RNA quantity and quality evaluation, and differential expression analysis. The US-FNA sampling procedure was feasible in 95% of dogs. RNA isolation of US-FNA samples was successfully performed using phenol-chloroform extraction. The extracted RNA of 56% of a subset of US-FNA samples met the quality requirements for RNA-seq. Expression analysis revealed that only 153 genes were exclusively differentially expressed between non-malignant US-FNAs and tissues. Moreover, only 36 differentially expressed genes were associated with the US-FNA sampling technique and unrelated to the diagnosis. Furthermore, the gene expression profiles clearly distinguished between non-malignant and malignant samples. This proves US-FNA to be useful for molecular profiling.
2019-10-08 | GSE122916 | GEO
Project description:Fine needle stimulation also known as acupuncture is a traditional Chinese medical practice which causes relief of pain. We demonstrated that it caused neovascularization and enhanced recovery of blood perfusion in a ischemic portion of skeletal muscle in rats with hindlimb ischemia. Therefore we evaluated the effect of fine needle stimulation on skeletal muscle at gene expression level Experiment Overall Design: With 0.14mm diameter stainless steel needle, a hundred pricks were applied in a 100 square mili-meter region on addductor portion of the left rat hindlimb. Right hindlimb was left intact as control. 24 hrs after fine needle stimulation, skeletal muscle sample was resected from adductor muscle of fine needle stimulated left hindlimb and non-stimulated right hindlimbs, respectively. Then gene expression analysis with microarray was conducted on each skelatal muscle sample.
2008-06-16 | E-GEOD-8911 | biostudies-arrayexpress
Project description:Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.
2013-12-02 | E-GEOD-46141 | biostudies-arrayexpress
Project description:Paired FNA and CBX specimens were prospectively collected from 37 breast cancers before any systemic therapy during a biomarker discovery study at The University of Texas M. D. Anderson Cancer Center. We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes
2011-10-31 | GSE32518 | GEO
Project description:Paired fine needle aspiration biopsies (FNABs) of breast cancers were taken before (PRE) and after (POST) surgeries from 16 patients and compared the cDNA microarray data to determine the genes that were differentially expressed between the FNABs taken at the two time points. The timing of fine needle aspiration biopsies can be a confounding factor in microarray data analyses in breast cancer. FOS-related genes, which have been implicated in early hypoxia as well as the development of breast cancers, were differentially expressed before and after surgery. Therefore, it is important that future studies take timing of tissue acquisition into account. Keywords: Breast cancer, fine needle, biopsy timing, microarray standardization, early hypoxic genes
2008-09-09 | GSE12072 | GEO
Project description:To determine whether breast cancer molecular subtypes and tumor characteristics with demonstrated significance in a primary tumor setting can also confer clinically relevant information in breast cancer metastases. We assessed previously published gene expression modules of seven biological processes and the intrinsic subtypes (PAM50). The translational aspect of the Swedish randomized TEX trial included 112 patients with at least one biopsy from morphologically confirmed loco-regional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up and metastasis gene expression information (Affymetrix array GPL10379). We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.
2014-11-03 | E-GEOD-56493 | biostudies-arrayexpress