| 21. |
- Oohashi, T, et al.
(författare)
-
Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
- 1999
-
Ingår i: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577
-
Tidskriftsartikel (refereegranskat)abstract
- The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
|
|
| 22. |
- Wängberg, Bo, 1953, et al.
(författare)
-
Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction.
- 1996
-
Ingår i: World journal of surgery. - 0364-2313. ; 20:7
-
Tidskriftsartikel (refereegranskat)abstract
- Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.
|
|
| 23. |
- Kölby, Lars, 1963, et al.
(författare)
-
Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.
- 1998
-
Ingår i: World journal of surgery. - 0364-2313. ; 22:7, s. 679-83
-
Tidskriftsartikel (refereegranskat)abstract
- Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.
|
|
| 24. |
- Ahlman, Håkan, 1947, et al.
(författare)
-
Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.
- 1994
-
Ingår i: The British journal of surgery. - 0007-1323. ; 81:8, s. 1144-9
-
Tidskriftsartikel (refereegranskat)abstract
- 111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.
|
|
| 25. |
- af Klinteberg, C, et al.
(författare)
-
Laser-induced fluorescence diagnostics of basal cell carcinomas of the skin following topical ALA application
- 1996
-
Ingår i: Optical Biopsies and Microscopic Techniques, Proceedings of. - : SPIE. - 0819423289 ; 2926, s. 32-40
-
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.
|
|
| 26. |
- Garkavij, Michael
(författare)
-
Improving radioimmunotargeting of tumors : the impact of extracorporeal immunoadsorption and preload in rats
- 1996
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In radioimmunotherapy of tumors, uptake of the monoclonal antibody (MAb) used is often too low in relation to its uptake in normal tissues. The purpose of these studies was to improve experimental tumor radioimmunotargeting with (a) extracorporeal immunoadsorption (ECIA), where excess of radiolabeled MAbs circulating in blood is removed, (b) or by preload with unlabeled MAb prior to injection of radiolabeled MAb, (c) or by a combination of these. ECIA based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from blood and increases the tumor-to-normal tissue (T/N) uptake ratio by reducing background radioactivity in radiosensitive organs. 267 rats (athymic or Brown Norwegian) grafted with human adenocarcinoma or rat colon adenocarcinoma tumors intramuscularly, and beneath the kidney or liver capsule were included in the studies. Of these rats, 82 were subjected to ECIA. Two radioiodinated and biotinylated MAbs, murine L6 or chimeric BR96, were used and evaluated. (I) Using 50 µg dosage of L6, ECIA reduced whole body and plasma activity as well as improved the detectability of subrenal capsule tumors. T/N uptake ratios were increased on average 3 times. (II) The efficacy of ECIA in removing different injected amounts of L6 from plasma was similar. The highest T/N ratios persisting 24h after start of the ECIA were obtained by using 10 µg of 125I-L6-biotin. (III) The efficacy of preload in enhancing tumor uptake and simultaneously decreasing uptake in normal tissues was obtained with 250µg of 125I-L6 preceded by a preload of 50µg unlabeled L6 only. (IV) The effects on radioimmunotargeting of preload and ECIA in combination were synergistic and improved T/N uptake ratios up to 17 times. (V) As compared with ECIA, a new method of whole blood immunoadsorption (WBIA) was technically easier to perform, safer and more reliable, but of approx. comparable efficiency. (VI) WBIA was even applicable on the internalizing and highly tumor selective 125I-BR96-biotin MAb, resulting in manifestly improved T/N ratios.
|
|
| 27. |
- Isacsson, Ulf
(författare)
-
Comparative treatment planning in external radiotherapy of malignant tumours : Potential gains using protons
- 1998
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well known that protons have physical characteristics superior to conventional radiation qualities in external beam radiotherapy. The primary aim of this work is to determine if the physical advantages also may lead to clinical advantages. A second aim is to evaluate the treatment planning algorithms incorporated into a 3D treatment planning system, used in the prediction, Helax-TMSTM. The potential benefits of using protons instead of conventional radiation qualities is evaluated by comparing treatment plans. Dose-response models of tumour control probability (TCP) and normal tissue complication probability (NTCP) were used to predict the treatment outcome for the different plans. Uncertainties in the results were studied in sensitivity analyses.Comparative studies were performed in four different tumour types, locally advanced rectal cancer, a paraspinal tumour, oesophageal cancer and left-sided node-positive breast cancer. Advantages with protons were seen in all cases, but the advantages were of different size.Proton therapy in patients with oesophageal carcinoma increases the TCP from 6 to 49% if a risk of 1% in the spinal cord and a total NTCP for the two lungs equivalent to a one-sided pulmectomy is allowed. This gain is relatively insensitive to variations, within reasonable limits, in the dose-response parameters.Proton therapy reduces the risk for cardiac mortality and radiation pneumonitis to almost zero when treating node-positive left-sided breast cancer after breast-conserving surgery.The evaluation of the treatment planning algorithms shows that pencil kernel algorithms are required in order to accurately calculate dose distributions in heterogeneous patient volumes. The scattering phenomenon in the vicinity of interfaces between different materials is modelled. The magnitude of the effect is underestimated (less than 1%) due to the inherent approximations.
|
|
| 28. |
- Johannsson, Oskar Thor
(författare)
-
Hereditary Breast Cancer in South Sweden. Early findings from studies on the role of BRCA1
- 1997
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis presents the results from investigations into the role of BRCA1 in hereditary cancer in South Sweden. Loss of heterozygosity (LOH) studies found loss of the wildtype allele of BRCA1 to be common in BRCA1 associated breast cancer, but due to the high degree of LOH on chr. 17q in sporadic breast cancer not to be indicative of the presence of a BRCA1 mutation. Seventeen different germline BRCA1 mutations have been found in 34 separate breast and breast-ovarian cancer families. Five founder mutations were identified. If silent and suspected polymorphism mutations are excluded, frameshift, nonsense and splice mutations account for 93% in our material. mRNA in situ hybridization of BRCA1 was found to be able to identify BRCA1 and sporadic tumors with 95% specificity and sensitivity. The histology and tumor biological features of BRCA1 associated breast cancers was found to be predominantly of the ductal type, histological grade III, non-diploid with a high S-phase, predominantly TP53 positive and E
|
|
| 29. |
- Hellquist, Henrik B., et al.
(författare)
-
Salivary duct carcinoma : a highly aggressive salivary gland tumour with overexpression of c-erbB-2
- 1994
-
Ingår i: Journal of Pathology. - West Sussex, United Kingdom : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 172:1, s. 35-44
-
Tidskriftsartikel (refereegranskat)abstract
- The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.
|
|
| 30. |
- Ding, W Q, et al.
(författare)
-
Effects of ethanol on muscarinic receptor-stimulated c-fos expression in human neuroblastoma cells
- 1997
-
Ingår i: Brain Research. Molecular Brain Research. - 0169-328X. ; 46:1-2, s. 77-84
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of ethanol exposure on muscarinic receptor-stimulated expression of c-fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced carbachol-stimulated c-fos mRNA expression, analyzed with Northern blot, and Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre-incubation with muscarinic antagonists or the protein kinase C inhibitor GF109203X demonstrated that, in both control and ethanol-treated cells, carbachol-induced c-fos expression was mediated via muscarinic M1 receptors and to a large extent through protein kinase C. However, phorbol ester-induced c-fos expression was unaffected in ethanol-treated cells. Acute exposure to ethanol caused a suppression of both carbachol- and phorbol ester-stimulated c-fos expression. These results demonstrate that muscarinic receptor-stimulated gene expression is sensitive to both acute and long-term ethanol exposure.
|
|
