HIFU-Induced Gene Activation in a Cell-Embedded Tissue Mimicking Phantom

2007 ◽  
Author(s):  
Fang Yuan ◽  
Chris Pua ◽  
Pei Zhong ◽  
Yunbo Liu
Keyword(s):  
Gene Expression ◽  
Focused Ultrasound ◽  
Gene Activation ◽  
Tumor Model ◽  
High Intensity Focused Ultrasound ◽  
Specific Gene ◽  
A Cell ◽  
Transparent Cell

The synergistic integration of high intensity focused ultrasound (HIFU) thermal ablation and HIFU-induced gene therapy represents a promising approach in improving the overall efficacy and quality of cancer therapy. Previous studies have demonstrated that HIFU can induce GFP gene activation under the control of hsp70B promoter in a murine tumor model [1]. Thermal stress has been identified as the primary mechanism to regulate the gene expression. However, the natural heterogeneity and opacity of solid tumors has hindered direct correlation of site-specific gene expression level with in situ thermal dosimetry. We have developed a homogeneous and transparent cell-embedded tissue mimicking phantom as an alternative for simultaneous assessment of temperature distribution, HIFU lesion formation, and gene expression.

scholarly journals Aspergillus nidulans wetA activates spore-specific gene expression.

1991 ◽  
Vol 11 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M A Marshall ◽  
W E Timberlake
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Aspergillus Nidulans ◽  
Gene Activation ◽  
Regulatory Function ◽  
Specific Gene ◽  
Coding Region ◽  
Vegetative Cells ◽  
Mutant Strains ◽  
Late Stages

The Aspergillus nidulans wetA gene is required for synthesis of cell wall layers that make asexual spores (conidia) impermeable. In wetA mutant strains, conidia take up water and autolyze rather than undergoing the final stages of maturation. wetA is activated during conidiogenesis by sequential expression of the brlA and abaA regulatory genes. To determine whether wetA regulates expression of other sporulation-specific genes, its coding region was fused to a nutritionally regulated promoter that permits gene activation in vegetative cells (hyphae) under conditions that suppress conidiation. Expression of wetA in hyphae inhibited growth and caused excessive branching. It did not lead to activation of brlA or abaA but did cause accumulation of transcripts from genes that are normally expressed specifically during the late stages of conidiation and whose mRNAs are stored in mature spores. Thus, wetA directly or indirectly regulates expression of some spore-specific genes. At least one gene (wA), whose mRNA does not occur in spores but rather accumulates in the sporogenous phialide cells, was activated by wetA, suggesting that wetA may have a regulatory function in these cells as well as in spores. We propose that wetA is responsible for activating a set of genes whose products make up the final two conidial wall layers or direct their assembly and through this activity is responsible for acquisition of spore dormancy.

In Situ Gene Expression in Mixed-Culture Biofilms: Evidence of Metabolic Interactions between Community Members

1998 ◽  
Vol 64 (2) ◽  
pp. 721-732 ◽  
Author(s):  
Søren Møller ◽  
Claus Sternberg ◽  
Jens Bo Andersen ◽  
Bjarke Bak Christensen ◽  
Juan Luis Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Pure Culture ◽  
Fluorescent Protein ◽  
Confocal Laser ◽  
Specific Gene ◽  
Community Members ◽  
Metabolic Interactions ◽  
Green Fluorescent

ABSTRACT Microbial communities growing in laboratory-based flow chambers were investigated in order to study compartmentalization of specific gene expression. Among the community members studied, the focus was in particular on Pseudomonas putida and a strain of anAcinetobacter sp., and the genes studied are involved in the biodegradation of toluene and related aromatic compounds. The upper-pathway promoter (Pu) and themeta-pathway promoter (Pm) from the TOL plasmid were fused independently to the gene coding for the green fluorescent protein (GFP), and expression from these promoters was studied inP. putida, which was a dominant community member. Biofilms were cultured in flow chambers, which in combination with scanning confocal laser microscopy allowed direct monitoring of promoter activity with single-cell spatial resolution. Expression from thePu promoter was homogeneously induced by benzyl alcohol in both community and pure-culture biofilms, while the Pmpromoter was induced in the mixed community but not in a pure-culture biofilm. By sequentially adding community members, induction ofPm was shown to be a consequence of direct metabolic interactions between an Acinetobacter species and P. putida. Furthermore, in fixed biofilm samples organism identity was determined and gene expression was visualized at the same time by combining GFP expression with in situ hybridization with fluorescence-labeled 16S rRNA targeting probes. This combination of techniques is a powerful approach for investigating structure-function relationships in microbial communities.

scholarly journals Distinct CoREST complexes act in a cell-type-specific manner

2019 ◽  
Author(s):  
Igor Mačinković ◽  
Ina Theofel ◽  
Tim Hundertmark ◽  
Kristina Kovač ◽  
Stephan Awe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Line ◽  
Protein Complexes ◽  
Specific Gene ◽  
S2 Cells ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific

Abstract CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.

scholarly journals Advanced Pancreatic Cancer: High-Intensity Focused Ultrasound (HIFU) and Other Local Ablative Therapies

2019 ◽  
Vol 191 (03) ◽  
pp. 216-227 ◽  
Author(s):  
Milka Marinova ◽  
Timo Wilhelm-Buchstab ◽  
Holger Strunk
Keyword(s):  
Pancreatic Cancer ◽  
Focused Ultrasound ◽  
Advanced Pancreatic Cancer ◽  
High Intensity Focused Ultrasound ◽  
Treatment Modalities ◽  
Mass Reduction ◽  
Local Tumor ◽  
Tumor Mass ◽  
Ablative Therapies

Background Locally advanced pancreatic cancer is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer-associated pain. Several local ablative therapies with both thermal and non-thermal sources have recently received significant attention as modern treatment options for local tumor control and symptomatic improvement. The following review article provides an overview of currently available techniques and their outcomes including our own experience with high-intensity focused ultrasound (HIFU) being one of the most exciting and innovative modalities. Method Our experiences with HIFU treatment are based on 89 pancreatic cancer patients (UICC III-IV). Outcomes such as treatment-related changes in symptoms particularly in cancer pain and quality of life as well as local tumor response, safety and survival were compared to reported studies concerning HIFU, radiofrequency and microwave ablation, cryoablation, irreversible electroporation and stereotactic body radiation therapy. Results Even though all strategies appeared to be feasible, the unique feature of noninvasiveness represents a substantial advantage of the HIFU procedure. In 85 % of HIFU-treated patients, long-lasting pain relief was achieved. 50 % of patients did not require any analgesic treatment 6 weeks post-ablation. Unfortunately, pain palliation and quality-of-life outcomes are only rarely reported for other local treatment modalities. Tumor mass reduction could be achieved with all ablative therapies, with a mean tumor volume reduction of 60 % after 6 months in HIFU-treated pancreatic tumors. Differences in treatment-associated morbidity were reported. However, they are only partially comparable due to unbalanced study populations. Conclusion Various local ablative treatment modalities are available and feasible for tumor mass reduction of advanced pancreatic cancer but with different symptomatic benefit for patients. An effective and long-lasting reduction of cancer-related pain was observed following HIFU without insertion of needles or electrodes. Randomized controlled studies for head-to-head comparison of these modalities are warranted in the near future. Key points:  Citation Format

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