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- Lark, Michael W., et al.
(författare)
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Aggrecan degradation in human cartilage : Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints
- 1997
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 100:1, s. 93-106
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Tidskriftsartikel (refereegranskat)abstract
- To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP- generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE-neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and 'aggrecanase'.
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| 3. |
- Svanberg, Katarina, et al.
(författare)
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Clinical multi-colour fluorescence imaging of malignant tumours - Initial experience
- 1998
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Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 39:1, s. 2-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. Material and Methods: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant rumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and Famine levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. Results: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. Conclusions: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.
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| 4. |
- af Klinteberg, C, et al.
(författare)
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Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas
- 1999
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Ingår i: Journal of Photochemistry and Photobiology, B: Biology. - 1011-1344. ; 49:2-3, s. 120-128
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Tidskriftsartikel (refereegranskat)abstract
- Laser-induced fluorescence (LIF) investigations have been performed in connection with photodynamic therapy (PDT) of basal cell carcinomas and adjacent normal skin following topical application of 5-aminolaevulinic acid (ALA) in order to study the kinetics of the protoporphyrin TX (PpIX) build-up. Five superficial and 10 nodular lesions in 15 patients are included in the study. Fluorescence measurements are performed prior to the application of ALA, 2, 4 and 6 h port ALA application, immediately post PDT (60 J cm(-2) at 635 nm), and 2 h after the treatment. Hence, the build-up, photobleaching and re-accumulation of PpIX can be followed. Superficial lesions show a maximum PpIX fluorescence 6 h post ALA application, whereas the intensity is already the highest 2-4 h after the application in nodular lesions. Immediately post PDT, the fluorescence contribution at 670 Mm from the photoproducts is about 2% of the pre-PDT PpIX fluorescence at 635 nm. Two hours after the treatment, a uniform distribution of PpIX is found in the lesion and surrounding normal tissue. During the whole procedure, the autofluorescence of the lesions and the normal skin does not vary significantly from the values recorded before the application of ALA. (C) 1999 Elsevier Science S.A. All rights reserved.
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| 5. |
- af Klinteberg, C, et al.
(författare)
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Laser-induced fluorescence diagnostics of basal cell carcinomas of the skin following topical ALA application
- 1996
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Ingår i: Optical Biopsies and Microscopic Techniques, Proceedings of. - : SPIE. - 0819423289 ; 2926, s. 32-40
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Konferensbidrag (refereegranskat)abstract
- Fourteen patients with superficial basal cell carcinomas (BCCs) and fifteen patients with nodular BCCs were investigated by means of laser-induced fluorescence (LIF) in connection with photodynamic therapy (PDT). Topical application of delta-amino levulinic acid (ALA) was performed six hours prior to the treatment session. Fluorescence spectra were recorded, using a point-monitoring system with an excitation wavelength of 405 nm. The measurements were performed in scans over the lesion and the surrounding normal skin before application of ALA, and immediately before and after the laser treatment. The selective uptake of the photosensitiser resulted in a fluorescence intensity ratio of 2.4:1 for superficial BCCs and 2.5:1 for nodular BCCs. If the fluorescence intensity was divided by the autofluorescence, this resulted in a contrast enhancement of about a factor 6 for tumour tissue. In seven patients (five with nodular BCC and two with superficial BCC), additional fluorescence measurements were performed two and four hours following the ALA application, and two hours after the PDT procedure. Thus, the kinetics of the transformation of ACA to protoporphyrin IX (PpIX) could be followed, which indicated that the synthesis of PpIX was more rapid in the tumour than in the normal tissue. After four hours, the PpIX level inside the tumour was saturated, while there still was an accumulation in the surrounding skin. The highest contrast between tumour and normal skin was reached within two hours after the ALA application.
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| 8. |
- Heyerdahl, H, et al.
(författare)
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Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues
- 1997
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Ingår i: Cancer Letters. - 1872-7980. ; 112:2, s. 225-231
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Tidskriftsartikel (refereegranskat)abstract
- Laser-induced fluorescence (LIF) for in vivo point monitoring and fluorescence microscopy incorporating a CCD camera were used to study the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in tumours. Fluorescence in a chemically induced adenocarcinoma in the liver of rats and in an aggressive basal cell carcinoma in a patient were studied after intravenous injection of ALA at a dose of 30 mg/kg body weight. The LIF technique demonstrated slightly more ALA-induced PpIX fluorescence in the tumour than in the surrounding normal liver and abdominal muscle of rats. The visible parts of the human basal cell carcinoma exhibited strong ALA-induced fluorescence, while this fluorescence was much weaker in the necrotic areas of the tumour and in the surrounding normal skin. (C) 1997 Elsevier Science ireland Ltd.
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| 9. |
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| 10. |
- Liu, D. L, et al.
(författare)
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Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours
- 1995
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 7:11, s. 1073-1080
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the effect of photodynamic therapy (PDT) on experimental liver tumours in rats. Design: An experimental liver tumour model was used. Each of a group of Fats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic robe was used for PDT, and the other one, in the median lobe, as a control. The haem precursor delta-amino laevulinic acid (ALA), at a dose of 30 mg/kg body weight, was injected 60 min before laser irradiation. Rats in group I received ALA through a femoral vein. Those in group II received ALA through the portal vein. Group III had an injection of ALA solution through the portal vein plus hepatic inflow occlusion. Three and 6 days after the treatment, the rats were killed, and the tumours were measured, and ultrastructural changes were examined using scanning electron microscopy. Setting: Lund University Medical Laser Centre, Lund, Sweden. Results: The mean tumour volume of the treated tumours increased by factors of 1.9, 1.5 and 1.7 in groups I, II and III, respectively, compared with the pretreatment baseline value. However, the mean tumour volume in the control tumours increased by factors of 9.5, 4.3 and 4.8 in the respective groups. Under the light microscope, marked necrosis of the treated tumour and the surrounding liver tissue was observed. Scanning electron microscopy revealed heavy damage to the cells and vessels in the treated tumour. Conclusion: PDT with ALA is an effective treatment modality for rat liver tumours.
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