29 april 2005: Bron: Prostaatkankersite

HIFU = High Intensity Focused Ultrasound geeft, wanneer gegeven in korte stoten een opmerkelijk positief effect op de aanwezigheid en/of bereikbaarheid van ingebrachte eiwitten (gentherapie) en andere medicijnen in de tumorcellen bij de muizen die daarvoor werden gebruikt. HIFU wordt al vaak gebruikt in plaats van operatie bij prostaatkankerpatiënten. Met deze vorm van heel gerichte verhitting van bepaalde plaatsen wordt veel tumorweefsel direct en snel gedood en laat het gezonde weefsel in tact.

Opvallend in onderstaand artikel: er wordt ook melding gemaakt van gebruik van fotosensitizerachtig eiwit gehaald uit een plant diep onder de zeespiegel. Een interessante ontwikkeling omdat anderhalf jaar geleden dr. Carmody mij vertelde dat het aansturen van radachlorin beter met geluidsgolven kan worden gedaan dan met licht gezien de betere doordringbaarheid van geluid en ook het risico op verbrandingen hierbij niet optreed, zoals wel bij lasering kan voorkomen. Achtereenvolgens het abstract van de studie met HIFU bij muizen en een artikel daarover gehaald van een website van en voor prostaatkankerpatiënten.

Radiology. 2005 Mar 29;

Pulsed High-Intensity Focused Ultrasound Enhances Systemic Administration of Naked DNA in Squamous Cell Carcinoma Model: Initial Experience.
Dittmar KM, Xie J, Hunter F, Trimble C, Bur M, Frenkel V, Li KC.
Department of Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Md. vfrenkel@cc.nih.gov.

PURPOSE: To determine whether exposures to pulsed high-intensity focused ultrasound can enhance local delivery and expression of a reporter gene, administered with systemic injection of naked DNA, in tumors in mice.

MATERIALS AND METHODS: The study was performed according to an approved animal protocol and in compliance with guidelines of the institutional animal care and use committee. Squamous cell carcinoma (SCC7) tumors were induced subcutaneously in both flanks of female C3H mice (n = 3) and allowed to grow to average size of 0.4 cm(3). In each mouse, one tumor was exposed to pulsed high-intensity focused ultrasound while a second tumor served as a control. Immediately after ultrasound exposure, a solution containing a cytomegalovirus-green fluorescent protein (GFP) reporter gene construct was injected intravenously via the tail vein. The mouse was sacrificed 24 hours later. Tissue specimens were viewed with fluorescence microscopy to determine the presence of GFP expression, and Western blot analysis was performed, at which signal intensities of expressed GFP were quantitated. A paired Student t test was used to compare mean values in controls with those in treated tumors. Histologic analyses were performed with specific techniques (hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) to determine whether tumor cells had been damaged by ultrasound exposure.

RESULTS: GFP expression was present in all sections of tumors that received ultrasound exposure but not in control tumors. Results of signal intensity measurement at Western blot analysis showed expressed GFP to be nine times greater in ultrasound-exposed tumors (160.2 +/- 24.5 [standard deviation]) than in controls (17.4 +/- 11.8) (P = .004, paired Student t test). Comparison of histologic sections from treated tumors with those from controls revealed no destructive effects from ultrasound exposure.

CONCLUSION: Local exposure to pulsed high-intensity focused ultrasound in tumors can enhance the delivery and expression of systemically injected naked DNA. (c) RSNA, 2005.

PMID: 15798154 [PubMed - as supplied by publisher]

April 26, 2005. OAK BROOK, Ill. - High-intensity focused ultrasound emitted in short pulses is a promising, non-invasive procedure for enhancing gene delivery to cancerous cells without destroying healthy tissue, according to a study in the May issue of the journal Radiology .
High-intensity focused ultrasound (HIFU) is more powerful than standard ultrasound. HIFU can destroy tumors through long and continuous exposures that raise the temperature inside cancerous cells, effectively "cooking" them.
Under a technique introduced by King C.P. Li, M.D., M.B.A., from the National Institutes of Health (NIH), short pulses of HIFU can be used to prevent exposed tissue from becoming too hot and damaged. Pulsed-HIFU instead renders tissues permeable and helps target them for taking up genes and other therapeutic substances injected into the body.
"Basically, we're using sound waves to open up the tissue by producing gaps between the cells, making it leakier and more prone to taking up various genes, agents and compounds," said Victor Frenkel, Ph.D., a staff scientist for the diagnostic radiology department at the NIH Clinical Center in Bethesda, Md.

Working with lead authors Kristin M. Dittmar, M.D., and Jianwu Xie, M.D., the researchers used pulsed-HIFU on tumors in mice, then immediately injected an easily measurable reporter gene into the vein in their tails. The reporter gene in this study—a fluorescent-green protein found in deep-sea invertebrates—was visible in all sections of the tumors exposed to pulsed-HIFU. Tumors not targeted with pulsed-HIFU showed negligible signs of the gene.

An analysis showed reporter gene levels to be nine times higher in tumors treated with pulsed-HIFU compared with tumors left unexposed.
Researchers were especially encouraged by the results because the type of cancer treated in the study—squamous cell carcinoma, found in head and neck tumors—is one of the least permeable cancers and does not respond well to chemotherapy or radiation. However, these types of tumors have responded to certain types of therapeutic genes.

"This procedure is hypothetically generic for enhancing delivery to all tissues," Dr. Frenkel said. "Previous studies by Dr. Li have shown that pulsed-HIFU increases the uptake of drugs. Now we've shown that it works for genes and we're making the case that there's a connection between the two." Other methods currently being investigated for enhancing gene delivery, such as lasers and electric current, are limited to surface lesions or require needles to be inserted in the body. Pulsed-HIFU is non-invasive and can treat any area of the body accessible by ultrasound, the exceptions being the lungs and bones. Additional advantages of pulsed-HIFU include no scarring, limited blood loss and infections, reduced risk of other complications, shortened recovery time, significant reduction in costs and the potential for many procedures to be done on an outpatient basis.

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