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T Böhling

Publications and source records attributed to T Böhling.

At least 19 recordsLinked to original sources
PubMed2006

DNA copy number amplification profiling of human neoplasms.

DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-of-origin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.

DNA Damage↗
PubMed2006

Gene copy number changes in dermatofibrosarcoma protuberans - a fine-resolution study using array comparative genomic hybridization.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, low-grade dermal tumor. Cytogenetic and FISH studies have revealed that the chromosomal rearrangements characteristic of DFSP tumors involve both translocations and the formation of a supernumerary ring derived from chromosomes 17 and 22. The t(17;22) (q22;q13.1) translocation generates a gene fusion between COL1A1 and PDGFB, which serves as a diagnostic marker of DFSP. In the present study we performed array-CGH (aCGH) analysis on ten DFSP tumors. The COL1A1 region at 17q was gained in 71% (5/7) of the samples and the PDGFB region at 22q was gained in 43% (3/7) of the individual samples. In addition to the 17q and 22q gains, altogether 17 minimal common regions of gain and one region of loss were detected.

Adult↗
PubMed2005

A novel bioabsorbable composite membrane of Polyactive 70/30 and bioactive glass number 13--93 in repair of experimental maxillary alveolar cleft defects.

A novel bioabsorbable composite membrane of polyethylene oxide terephthalate and polybutylene terephthalate copolymer (Polyactive 70/30) combined with bioactive glass No. 13--93 was tested in the repair of experimental maxillary alveolar cleft defects. In this pilot study, the possible ability of the membrane to promote bone formation by guided tissue regeneration was investigated. Standard alveolar defects were made bilaterally in the maxilla of 12 growing rabbits and were filled with autogenous bone grafts. The test defect was covered with the composite membrane and the other defect was left uncovered to serve as a control. The follow-up time was 10 weeks. Radiological, histological, and histomorphometric evaluations were performed. Radiologically, no statistically significant differences between test and control defects at 10 weeks were found. Histologically, the membrane enhanced osteogenic activity locally at the membrane-bone interface. Swelling of the membrane was observed. Histomorphometrically, no significant promotion of bone formation by the membrane was observed. The composite membrane was found to be biocompatible and surgically easy to use, but its osteopromotive effect was limited in this experimental cleft model. Further studies are necessary to assess its suitability for reconstructive surgical applications.

Alveolar Process↗
PubMed2005

Tenascin-C in primary Merkel cell carcinoma.

BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour that mostly affects the elderly. It shows rapid progression of the primary tumour, together with a vertical growth pattern into the underlying subcutaneous tissue. Metastatic dissemination to regional lymph nodes is early and frequent. Tenascin-C (Tn-C) is a large extracellular matrix glycoprotein that is expressed in various benign and malignant processes. Expression of Tn-C is also associated with invasion and cellular proliferation, and is often downregulated in fully evolved advanced carcinomas. In previous studies, Tn-C expression correlated with prognosis in tumours of different origin. METHODS: Immunohistochemistry was used to investigate the expression of Tn-C in 25 MCC specimens and to evaluate the prognostic importance of this glycoprotein. RESULTS: Seventeen samples expressed Tn-C. Staining was mainly seen in the invasion borders and within the connective tissue septae inside the tumours. The expression of Tn-C correlated significantly with large tumour size. There was also frequent expression of Tn-C in primary tumours with metastatic dissemination. Most of the Tn-C negative samples were of small size. CONCLUSIONS: Tn-C expression seems to increase with tumour size and malignant behaviour. Expression was slightly enhanced in tumours with high proliferative indices. Expression is seen mainly in areas of invasive growth and, in this respect, resembles that of other invasive tumours.

Aged↗
PubMed2003

Plasminogen activation in neurofibromatosis 2-associated and sporadic schwannomas.

BACKGROUND: Schwannomas are usually benign tumours which occur sporadically or in association with neurofibromatosis 2 (NF2), an autosomal dominant disorder. Invasiveness and higher proliferative potential compared to sporadic tumours are features of NF2-associated schwannomas. METHOD: We studied urokinase (uPA), tissue-type plasminogen activator (tPA), urokinase receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) expression by in situ hybridization and by immunohistochemistry in 14 NF2 and 15 sporadic patients with 34 schwannomas. uPAR and vitronectin immunohistochemistry were also studied. Three sural nerve specimens were included as Schwann cell controls. FINDINGS: Both schwannoma groups expressed prominent levels of uPA and tPA. Semiquantitative analysis of the in situ hybridization and immunoreactivity demonstrated that NF2 schwannomas expressed less PAI-1 at the mRNA level than sporadic schwannomas (score 1.63+/-0.41 vs. 2.05+/-0.75) and less total PAI-1 at the antigen level (score 1.55+/-0.66 vs. 2.07+/-0.56). PAI-1 was mostly in a free form in NF2 schwannomas compared to the sporadic counterparts (score 1.85+/-0.73 vs. 1.46+/-0.58), whereas there was less uPAR antigen in NF2 schwannomas than in the sporadic counterparts (score 1.18+/-0.49 vs. 1.68+/-0.56). Sural nerve Schwann cells did not express detectable level of PAI-1 and at the most a minor amount of tPA. CONCLUSIONS: Schwann cells of tumour cell origin, both in sporadic and NF2 schwannomas, expressed elevated levels of plasminogen activators and PAI-1 compared to normal suralic nerve Schwann cells. Furthermore, there seemed to be an imbalance in the PA-PAI-1 system in NF2-associated schwannomas. Although our methods are more descriptive than quantitative, we suggest that the somewhat more aggressive behavior of NF2-associated schwannomas compared to sporadic schwannomas may be based on the local proteolytic activity.

Antibodies, Monoclonal↗
PubMed2003

Merkel cell carcinoma: a clinicopathological study of 34 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignant tumour. Its natural course is fast progression of the primary tumour and rapid regional metastasis. METHODS: The pathological archives of Helsinki University Hospital and Vaasa Central Hospital were reviewed from 1987 to 2001. Specimens were re-evaluated by two pathologists and size was measured from primary tumours. Multivariate analysis was performed for age, sex, primary tumour size, and method of initial surgery, development of metastatic disease and development of local recurrence. Overall survival (OS) was calculated by the Kaplan-Meier method. RESULTS: Of 34 patients, 12 male and 22 female patients, are reported. Their median age was 76.4 years. Half of the primaries were located in the head and neck region. All patients were treated surgically. The mean OS was 2.7 years by the Kaplan-Meier method. The 2-year survival rate was 65% and 5-year rate was 50%. The mean OS for tumour size >2 cm was 1.7 years and for tumour size 2 cm) and metastatic dissemination. A favourable prognosis seemed to correlate to more aggressive surgical management as use of primary excision with split skin graft or reconstruction with a local flap. CONCLUSION: MCC affects the elderly patients. In this study, female patients predominated. Primary tumour size >2 cm predicts poorer outcome of the disease. A wide surgical excision is recommended for the primary treatment of MCC.

Aged↗
PubMed2003

Soft tissue sarcoma of the trunk and extremities.

The diagnostic methods and treatment modalities of soft tissue sarcomas have evolved with the multidisciplinary approach. The soft tissue sarcoma team must have specialists capable of using and combining modern methods of radiology and pathology, cytogenetics, tumour surgery, tissue transfer techniques, radiotherapy and chemotherapy for optimal local and systemic treatment. Limb sparing surgery combined with radiotherapy has lowered the amputation rate and maintained low rates of local recurrence. Reconstructive surgery facilitates treatment of patients with soft tissue sarcoma by permitting tumour resection with adequate margins, protects vital structures, enables early postoperative radiation therapy, maintains extremity length, and if necessary assists in palliative procedures. The ability to maintain function and aesthetics after tumour resection, and effective palliation improves the quality of life for these patients. Early recognition and appropriate referral to a tumour centre improve the outcome.

Extremities↗
PubMed2001

Cysteine proteinases in chondrosarcomas.

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathepsin mRNAs by Northern hybridisation, and for immunohistochemical localisation of the proteins. Northern analysis demonstrated the highest levels of cathepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, while cathepsin K was predominantly localised in large multinucleated osteoclastic cells and in some hypertrophic chondrocytes. These results suggest that chondrosarcoma can be included in the growing list of tumours, where cathepsins may well be involved in tumour progression. The simultaneous upregulation of cathepsins B and L, together with matrix metalloproteinase-13, and the association of cathepsin K with negative prognostic parameters suggests that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolytic enzymes. If this turns out to be the case, cathepsin inhibitors could provide the much needed adjuvant therapy for chondrosarcomas.

Adult↗
PubMed2001

Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation.

Fetal development and tumor progression both require a complex system of extracellular matrix (ECM) synthesis and breakdown, which is mediated by, for instance, the matrix metalloproteinases (MMPs). Human metalloelastase (MMP-12) is an MMP, the expression of which has so far been documented in macrophages associated with atherosclerosis, wound repair, and certain cancers. In this study we first examined the expression of MMP-12 during human fetal development. By in situ hybridization MMP-12 transcripts were detected in chondrocytes of hypertrophic cartilage in vertebrae of the spinal column, in ribs, and in extremities undergoing ossification, beginning at the gestational age of 8 weeks. Also, periosteal cells expressed MMP-12 at 11 weeks. No expression of MMP-12 mRNA could be noted in other fetal tissues, including the skin, lungs, intestine, kidney, and liver. Expression of MMP-12 mRNA could not be detected in adult normal cartilage or osteosarcomas, but in chondrosarcomas both macrophages (8 of 19 samples) (identified by CD68 immunostaining) and chondrosarcoma cells (8 of 19) were positive. MMP-12 was also demonstrated in the tumors by western blotting and it was expressed in the same regions as MMP-13 mRNA. By immunostaining, MMP-12 mRNA colocalized with the protein in both fetal and chondrosarcoma specimens. Unlike basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) induced MMP-12 mRNA production in chondrosarcoma-derived HTB-94 cells. Our results suggest that MMP-12 plays an important role in ECM remodeling during fetal bone development and is induced when chondrocytes undergo malignant transformation.

Bone Neoplasms↗
PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas.

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.

Adolescent↗
PubMed2001

SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types.

Mutated alleles of the SLC26A2 (diastrophic dysplasia sulfate transporter or DTDST) gene cause each of the four recessive chondrodysplasias, i.e., diastrophic dysplasia (DTD), multiple epiphyseal dysplasia (MED), atelosteogenesis Type II (AO2), and achondrogenesis Type IB (ACG1B). SLC26A2 acts as an Na(+)-independent sulfate/chloride antiporter and belongs to the SLC26 anion transporter gene family, currently consisting of six homologous human members. Although Northern analysis has indicated some expression in all tissues studied, the only tissue known to be affected by SLC26A2 mutations is cartilage. Abundant SLC26A2 expression has previously been detected in normal human colon by in situ hybridization. We have used in situ hybridization and immunohistochemistry to examine multiple normal tissues for the expression of human SLC26A2. As expected, a strong signal for SLC26A2 mRNA and protein immunostaining were detected in developing fetal hyaline cartilage, while bronchial cartilage showed mRNA expression in adult tissues. SLC26A2 expression could also be detected in eccrine sweat glands, in bronchial glands, and in placental villi. In addition, immunoreactivity for the SLC26A2 protein was observed in exocrine pancreas. Our results suggest a more limited expression pattern for SLC26A2 than that found by Northern analysis. However, SLC26A2 expression is also detected in tissues not affected in chondrodysplasias caused by SLC26A2 mutations.

Anion Transport Proteins↗
PubMed2000

Natural coral as bone-defect-filling material.

Natural coral (NC) has been studied experimentally and clinically as a bone substitute, but its resorption rate and possible replacement by bone still need to be defined in humans. In this study bicortical bone was harvested from the iliac crest of 10 patients. The defect was filled with a NC block, and changes were monitored by X-rays and quantitative CT scans for a mean of 2.1 years. A biopsy was taken at 1 year. The purpose of the study was to investigate the resorption rate and pattern of NC (Porites) implants and the replacement, if any, of the implant by new bone. The blocks underwent centripetal resorption, but all the blocks still could be detected by X-rays and CT scans at the end of the follow-up period. The density of the remaining block did not change. Seven of the 10 implants were smaller than 50% of their original size at the end of the study. Bone ingrowth could be observed only in two of seven biopsies. One implant had to be removed after 1.7 years due to infection. The study shows that resorption of natural coral proceeds centripetally and apparently more rapidly when accompanied by tissue ingrowth. None of the blocks resorbed completely, and the defect at the iliac crest had not been restored by the end of the study.

Adolescent↗
PubMed2000

Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Immunohistochemical evaluation of failed vessel anastomoses in clinical microsurgery.

Failed vessel anastomoses collected from 12 patients during elective free flap surgery, and from one patient after failed mid-hand replantation were subjected to immunohistochemical analysis. The anastomotic failure was due to an obvious thrombosis, poor flow, an excessively sharp pulse or some other reason causing a non-functioning anastomosis. A total of 17 samples were obtained, 13 of them arterial, three between the artery and vein graft, and one venous. The majority of samples were resected during primary surgery and four of them at reoperation. Variables of coagulation and fibrinolysis were analysed repeatedly during the operation in 7/13 patients. Total occlusion was seen in 6/17 samples and a non-occlusive thrombus in 4/17; two of these were due to suture error. Immunohistochemistry showed that, overall, the endothelial cells (PECAM-l, CD 31) were absent and that the staining pattern for platelets (CD 42b and CD 31) and fibrin (fibrin II, T2G1) correlated. In the absence of a thrombus, however, adherent platelets were positive only for CD 42b, not for PECAM-1. Vessel inflammation was a prominent feature at reoperations. Analysis of coagulation and fibrinolytic markers (thrombin-antithrombin III complex, prothrombin fragment 1 + 2 and D-dimer) confirmed the occurrence of thrombosis in three patients undergoing breast reconstruction with clinically obvious thrombosis during primary surgery or at reoperation. Moreover, the patients with active cancer (2/7) were clearly hypercoagulable compared with the other patients. In short, the primary anastomotic failure was associated with loss of endothelial cells, and with co-localised platelet recruitment and fibrin formation at these sites. At reoperation, inflammation was a prominent feature at the vessel site of thrombi.

Adult↗