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- Ahlén, J, et al.
(författare)
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Malignant Fibrous Histiocytoma, Aggressive Fibromatosis and Benign Fibrous Tumors Express mRNA for the Metalloproteinase Inducer EMMPRIN and the Metalloproteinases MMP-2 and MT1-MMP
- 2001
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 5:3, s. 143-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to stimulate fibroblasts to production of matrix metalloproteinases (MMPs). MMPs comprise a family of proteolytic enzymes implicated in the degradation of extracellular matrix which has been proposed to be one of the essential steps in tumor invasion and metastases. In the present study we investigated the expression and location of mRNAs forEMMPRIN, matrix metalloproteinase-2 (MMP-2), and membrane-type 1 matrix metalloproteinase (MT1-MMP) in mesenchymal tumors with different tendencies to recur or metastasize.Subjects:Eight malignant fibrous histiocytomas (MFH), seven aggressive fibromatosis (AF), and six benign fibrous tumors (BF).Method:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPwere studied using mRNAin situhybridization technique.Results:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPrespectively were found at varying frequency and level in all tumor types. The mRNAs corresponding toEMMPRINandMMP-2were seen in neoplastic cells as well as in endothelial cells both inside and outside the tumor pseudo-capsule, whereasMT1-MMPwas seen only within the tumors. The estimated mRNA levels ofEMMPRINandMMP-2covariated significantly. Overall, the highest expression was found in the MFH tumors and the lowest levels in the BF tumors.Discussion:These findings suggest that the MMP-inducerEMMPRINand the extracellular matrix degrading system involving the metalloproteinasesMMP-2andMT1-MMPis frequently activated in mesenchymal tumors. The covariation betweenEMMPRINandMMP-2support previous findings that EMMPRIN may be an inducer of MMP-2. The high levels ofMMP-2mRNA in MFH indicate a relationship between the proteolytic activity ofMMP-2and the tumor aggressiveness.
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- Harmenberg, JG, et al.
(författare)
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ME-609: a treatment for recurrent herpes simplex virus infections
- 2003
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Ingår i: Antiviral chemistry & chemotherapy. - : SAGE Publications. - 0956-3202 .- 2040-2066. ; 14:4, s. 205-15
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Tidskriftsartikel (refereegranskat)abstract
- Studies in conventional murine models of HSV infection use immunologically naive animals. These models thus mimic primary infections rather than recurrent infections in humans. We have, therefore, used a newly developed mouse model that more closely mimics recurrent HSV infection in humans. In this model, the mice are infected, and zosteriform HSV-1 infection develops in the presence of a primed immune response using adoptive transfer of immunity (ATI) as we have described previously. Using the ATI mouse model, it has been shown that a more beneficial therapy for recurrent mucocutaneous HSV infection could be achieved by controlling both the viral replication and the inflammatory response to the virus. Topical treatment was initiated in this model at the time of first occurrence of symptoms and was given three times daily for 4 days. Topical treatment with ME-609 (which contains 5% acyclovir and 1% hydrocortisone) in the ATI mouse model was substantially more efficacious than 5% Zovirax® cream, 1% hydrocortisone or no treatment, respectively. The beneficial properties of ME-609 were also found to be superior to those of Zovirax cream when tested in the standard guinea pig model, representing a primary HSV infection. ME-609 represents a novel treatment principle of recurrent HSV infections and the present paper summarizes the preclinical and early clinical experience of ME-609.
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- Larsson, A, et al.
(författare)
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Regional cerebral blood flow in normal individuals aged 40, 75 and 88 years studied by 99Tc(m)-d,l-HMPAO SPET.
- 2001
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Ingår i: Nuclear medicine communications. - 0143-3636. ; 22:7, s. 741-6
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in cerebral blood flow (CBF) were examined with [99Tc(m)]-d,l-hexamethylpropylene amine oxime (HMPAO), using a single photon emission tomography (SPET) gamma camera system equipped with a high resolution collimator, in 33 normal individuals in three age groups: 40 years old (n = 11), 75 years old (n = 9) and 88 years old (n = 13). A standard activity of 1000 MBq [99Tc(m)]-d,l-HMPAO was administered. Regional CBF (rCBF) (relative to cerebellar counts) was quantified in 28 grey and white matter regions. The mean rCBF of all the regions was 0.80 (95% confidence interval [CI] 0.77-0.83) in 40 year olds, 0.77 (0.74-0.80) in 75 year olds and 0.76 (0.73-0.78) in 88 year olds. rCBF in the hippocampus, angular and cingular gyri, and frontal association and motor cortices was 5-10% lower in the 75 and 88 year olds than in the middle-aged subjects (P < 0.05). The annual reduction in rCBF was 0.10% between the ages of 40 and 75 years and 0.13% between the ages of 75 and 88 years. The reduction in rCBF in the hippocampus rose from 0.14% between the ages of 40 and 75 years to 0.33% between the ages of 75 and 88 years. The mean rCBF in all 33 individuals showed no sex-related differences.
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| 8. |
- Larsson, Marcus, et al.
(författare)
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A solid state transition in the tetragonal lipid bilayer structure at the lung alveolar surface
- 2003
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Ingår i: Solid State Sciences. - 1873-3085. ; 5:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- According to our recent results the alveolar surface is formed by a coherent phase, not a monolayer as has been assumed earlier. This surface phase is a tetragonal organization of the lipid bilayer which seems to follow the CLP minimal surface structure. As lipid bilayers at cooling will undergo a transition from the liquid-crystalline type of structure into a solid state structure, we have followed the changes in the X-ray scattering curves versus temperature of a sample of lung lavage from rabbit. There are significant changes in the range 15-25 degreesC indicating a solid/liquid bilayer transition. The size of the X-ray scattering changes indicate that only parts of the bilayers are involved. As indicated by similar studies of lung surfactant extracts, there are cholesterol-rich regions that remain in the liquid-like disordered conformation at cooling through this transition. The bilayer-embedded proteins in the alveolar CLP; structure are proposed to be located in the "corners" of the CLP-structure. This surface-phase structure was also examined by conventional electron microscopy with fixation at room temperature, and it was found to exhibit quite planar bilayer regions. On the other side, the same-sample seen in cryo-transmission electron microscopy vitrified from 40 degreesC was more disordered. These observations are consistent with a partial solid state transition of the bilayer on cooling, with segregation of lipids within the bilayers into cholesterol-rich regions remaining in a liquid-like disordered state and cholesterol-poor regions crystallizing in the range 25-15 degreesC. Physiological consequences-of such a partial solidification are finally discussed.
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- Panagopoulos, I, et al.
(författare)
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Clinical impact of molecular and cytogenetic findings in synovial sarcoma
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 31:4, s. 72-362
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Tidskriftsartikel (refereegranskat)abstract
- Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).
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