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S Lang

Publications and source records attributed to S Lang.

At least 73 records · Page 4Linked to original sources
PubMed2001

Expression of insulin-like growth factor-I (IGF-I) in aneurysmal bone cyst.

The effects of insulin-like growth factor-I on bone tissue and its role in bone development have been extensively investigated, but there is little information on its role in the pathogenesis of aneurysmal bone cyst. Therefore, using the techniques of immunohistochemistry and in situ hybridization, the authors studied the expression of insulin-like growth factor-I in 19 specimens of aneurysmal bone cyst. Insulin-like growth factor-I or specific mRNA sequences encoding for insulin-like growth factor-I were detectable in all specimens tested and were mainly localized in multinucleate giant cells. In contrast, only insignificant levels of insulin-like growth factor-I expression were detectable in normal human bone tissue. Taken together with the previously reported role of insulin-like growth factor-I in the pathogenesis of giant cell tumor, the findings of this study suggest that insulin-like growth factor-I may play a role in the pathogenesis of aneurysmal bone cyst.

Adolescent↗
PubMed2001

Recurrence of curetted and bone-grafted giant-cell tumours with and without adjuvant phenol therapy.

AIMS: Giant-cell tumour of bone (GCT) represents 5% of all primary bone tumours. The aim of this study was to compare the outcome of GCT treated with or without phenol. METHODS: Out of 53 patients primarily treated for a giant-cell tumour, 47 were followed, with a median follow-up of 11 (range 4-43) years. All patients were disease-free at the latest follow-up. Of the 40 tumours (85%) located in long bones, 14 (35%) were treated by curettage and bone grafting and 12 (30%) by additional adjuvant phenol treatment. Fourteen patients (35%) received different therapies, including en-bloc resection, endoprosthesis, cement packing or other therapy. RESULTS: There were seven (17.5%) recurrences in long bones after a median of 12 (range 4-60) months, three (3/14, 21%) in the group treated without phenol and three (3/12, 25%) in the group with phenol. Of the seven tumours located in the axial skeleton, two patients died within the first year after surgery. The remaining five patients were followed, with a median follow-up of 12 (range 8-23) years. No patients had metastases or a multicentric tumour. CONCLUSIONS: Despite the different rates of recurrence reported in literature, this study suggests that local recurrence rate of giant-cell tumours located in long bones treated with or without phenol is similar. Adequate removal of the tumour seems to be a more important predictive factor for the outcome of surgery than the use of phenol as an adjuvant therapy.

Adolescent↗
PubMed2001

A long-term review of the treatment of patients with Ewing's sarcoma in one institution.

AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over the last three decades. We report the analyses, significant prognostic factors, interdisciplinary approach and development of therapy in one institution in Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six patients were treated between 1949 and 1980 (group 1), and 86 patients between 1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy. Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32 patients had a definitive operation, 48 patients received either radiation therapy only or additional radiation therapy compared with in group 2: 6, 80 and 44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from 27% to 57%. Significant prognostic factors for OS were pre-operative metastases (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION: The most effective treatment of Ewing's sarcoma is chemotherapy.

Adolescent↗
PubMed2001

Rapid serodiagnosis of gram-positive bacterial endocarditis.

OBJECTIVES: To characterize a serological test for diagnosing endocarditis caused by Gram-positive cocci. METHODS: We have developed an indirect enzyme-linked immunosorbent assay (ELISA) for the serological detection of Gram-positive infections. The test measures serum IgG directed towards lipid S, a recently identified exocellular glycolipid antigen which is related to lipoteichoic acid. We have previously shown the test to be of value in serodiagnosis of central venous catheter-associated sepsis and infection of orthopaedic prostheses caused by coagulase-negative staphylococci. We now describe the application of this test in endocarditis. RESULTS: Serum IgG levels to lipid S were significantly elevated in 34 patients with Gram-positive bacterial endocarditis confirmed as 'definite' by the Duke criteria as compared to 50 control patients. The test had a sensitivity of 88% and a specificity of 88%. CONCLUSIONS: The assay is independent of culture results or endocardial imaging, making it complementary to currently used investigations. It may therefore be possible to refine the current Duke criteria for diagnosing endocarditis. We describe an algorithm which incorporates lipid S serology into a positive diagnostic strategy.

Algorithms↗
PubMed2001

[IL-2 gene therapy in ENT carcinomas].

Suppressed cellular immunity is common in patients with squamous cell carcinoma of the head and neck (HNSCC). It was demonstrated in previous studies that administration of interleukin 2 (IL-2) results in enhanced antitumoral immunity in vitro as well as in vivo. Since the serum half-life of IL-2 is relatively short, repeated applications are necessary to achieve therapeutically effective serum concentrations, but this strategy might cause severe side effects. Therefore, methods that provide high local cytokine levels over a prolonged period of time without the need for repeated injections are desirable. Gene therapy as an innovative treatment approach using tumor cells stably transduced to produce IL-2 might meet these criteria. In vitro manipulated tumor cells, if readministered in the vicinity of non-manipulated tumor cells, may enhance a specific anti-tumor response in vivo without systemic side effects. The present manuscript reviews the current literature dealing with IL-2-protein and -gene therapy with special emphasis on head and neck cancer. Our own in vitro results with IL-2 gene therapy in conjunction with published data from other authors argue in favour of an in vivo approach for this therapeutic strategy that is currently in progress in our department.

Animals↗
PubMed2001

p16(INK4a) alterations in chronic pancreatitis-indicator for high-risk lesions for pancreatic cancer.

BACKGROUND: p16(INK4a) alterations are considered to be an early event in pancreatic tumorigenesis and have been described in duct lesions adjacent to pancreatic cancers. This study evaluates whether duct lesions in chronic pancreatitis tissues of patients without pancreatic cancer also harbor genetic alterations in the p16(INK4a) tumor-suppressor gene, and thus represent high-risk precursors for pancreatic cancer. METHODS: Tissues were obtained from 20 pancreatic specimens taken from patients operated on for histologically verified chronic pancreatitis. Pancreatic intraductal neoplasias (PanIN) were identified in hematoxylin-and-eosin-stained slides. p16 protein expression was investigated immunohistochemically in all specimens. DNA from PanIN and non-PanIN tissue was analyzed genetically for p16(INK4a) mutations by single-strand conformation variation analysis and direct sequencing of the encoding region. Additionally, p16(INK4a) promoter methylation was analyzed by a methylation specific polymerase test. RESULTS: PanIN-1a lesions were identified in 10 of the 20 chronic pancreatitis specimens. Four of these 10 PanIN specimens (40%), but none of the 20 non-PanIN tissues, revealed a loss of p16 expression in immunohistochemistry. The mutational analysis of the p16(INK4a) gene showed 1 known polymorphism (c.442G > A; A148T) but no mutations. Two of the 10 specimens with PanIN revealed an inactivating hypermethylation of the p16(INK4a) promoter. CONCLUSIONS: This study shows for the first time that p16(INK4a) alterations can be observed in a considerable number of PanIN1 in chronic pancreatitis tissues not associated with pancreatic cancer. Therefore, p16(INK4a) alterations, especially promoter methylation, might indicate high-risk precursors in chronic pancreatitis that might progress to cancer.

Adult↗
PubMed2001

Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome.

Bone cells are important targets of platelet-derived growth factors (PDGFs) because they stimulate proliferation of osteoblasts and chondrocytes. In this study we wanted to determine the expression of PDGF-AA and PDGF-alpha receptor in conventional chondrosarcomas and to compare the results with those obtained from benign enchondromas and non-neoplastic cartilage tissue. Sixty-seven chondrosarcomas, 20 enchondromas, and 5 specimens of healthy cartilage as well as 7 specimens of hypertrophic callus cartilage were immunohistochemically analyzed for the expression of PDGF-AA and PDGF-alpha receptor, respectively. Additionally, the proliferation activity was examined with the MIB-1 antibody. Clinical follow-up data were available from 53 patients. A significant overexpression of receptor and factor was found in chondrosarcomas as compared with enchondromas (PDGF-AA p = 0.013, PDGF-alpha receptor p <0.001). MIB-1 values were significantly higher in chondrosarcomas (p <0.001). In healthy joint cartilage no staining was detectable, whereas reactive cartilage of callus formation showed high expression levels. PDGF-alpha receptor expression was significantly higher in grade 3 chondrosarcomas compared with grade 2 (p = 0.022) and grade 1 tumors (p = 0.002). Survival analysis documented a significantly shorter overall survival for patients with high PDGF-alpha receptor expression (p = 0.0172, log-rank test). Because PDGF-alpha receptor expression positively correlates with the aggressiveness of chondrosarcoma, it may be considered as a possible target for novel therapeutic strategies.

Adolescent↗
PubMed2001

The role of surgery and resection margins in the treatment of Ewing's sarcoma.

Because of the enormous progress in surgery in the treatment of patients with tumors, the current study analyzed the influence of wide surgical resection margins on the outcome of patients with Ewing's sarcoma. Between 1980 and 1994, 86 patients were treated with systemic therapy and surgery (biopsy in six patients, tumor resection in 80 patients). Forty-four patients also had radiation therapy. The 5-year overall survival was 56.8% (5-year disease-free survival, 59.4%). The 5-year overall survival after radical or wide resection was 60.2% (5-year disease-free survival, 58.2%), in comparison with 40.1% (46.7%) after marginal or intralesional resection. Two patients with inadequate resection margins had local recurrences. In addition to the influence of neoadjuvant chemotherapy for higher survival rates (5-year overall survival with a good response was 80.2% versus 41.7% with a poor response), adequate surgical margins significantly affect the outcome for patients with Ewing's sarcoma.

Adolescent↗
PubMed2001

In vitro models to study cellular differentiation and function in human prostate cancers.

In Vitro Models to Study Cellular Differentiation and Function in Human Prostate Cancers. To augment the currently available models of human prostate cancer in vitro, we have established extended life-span epithelial cultures from biopsies of well-differentiated prostate cancers. The genetic identity of the target cells was assessed by allelotyping, using microsatellites located on chromosome 8p, and microdissection of tissues and primary cell cultures. Cells with an extended life span (PxE6) were derived by recombinant retrovirus infection to introduce the human papilloma virus E6 gene (epithelial cells). Immunophenotyping of the resultant cell strains confirmed retention of differentiated cell functions, and the genotype of the E6-expressing epithelial cells was stable, while SV40-immortalized cultures were more unstable, leading to tetraploidy. All PxE6 cells eventually senesced, but an immortalized epithelial culture, P4E6, was derived from one of the epithelial cultures. The properties of this cell line, which remains close to diploid, are similar to those of early prostate cancer cells, and it retains expression of many prostate-associated antigens, such as prostate-specific antigen (PSA).

Allelic Imbalance↗
PubMed2001

Effects of mobile phone radiation on X-ray-induced tumorigenesis in mice.

The increased use of mobile phones has raised the question of possible health effects of such devices, particularly the risk of cancer. It seems unlikely that the low-level radiofrequency (RF) radiation emitted by them would damage DNA directly, but its ability to act as a tumor promoter is less well characterized. In the current study, we evaluated the effect of low-level RF radiation on the development of cancer initiated in mice by ionizing radiation. Two hundred female CBA/S mice were randomized into four equal groups at the age of 3 to 5 weeks. The mice in all groups except the cage-control group were exposed to ionizing radiation at the beginning of the study and then to RF radiation for 1.5 h per day, 5 days a week for 78 weeks. One group was exposed to continuous NMT (Nordic Mobile Telephones)-type frequency-modulated RF radiation at a frequency of 902.5 MHz and a nominal average specific absorption rate (SAR) of 1.5 W/kg. Another group was exposed to pulsed GSM (Global System for Mobile)-type RF radiation (carrier-wave frequency 902.4 MHz, pulse frequency 217 Hz) at a nominal average SAR of 0.35 W/kg. The control animals were sham-exposed. Body weight, clinical signs, and food and water consumption were recorded regularly. Hematological examinations and histopathological analyses of all lesions and major tissues were performed on all animals. The RF-radiation exposures did not increase the incidence of any neoplastic lesion significantly. We conclude that the results do not provide evidence for cancer promotion by RF radiation emitted by mobile phones.

Animals↗
PubMed2000

Analysis of antibody A6 binding to the extracellular interferon gamma receptor alpha-chain by alanine-scanning mutagenesis and random mutagenesis with phage display.

The monoclonal antibody A6 binds a conformational epitope comprising mainly the CC' surface loop on the N-terminal fibronectin type-III domain of the extracellular interferon gamma receptor (IFNgammaR). The crystal structure of an A6 Fab-IFNgammaR complex revealed an interface rich in the aromatic side chains of Trp, Tyr, and His residues. These aromatic side chains appear to interact with both polar and hydrophobic groups at the interface, a property which, in general, may be advantageous for ligand binding. To analyze these interactions in more detail, the affinities of 19 A6 alanine-scanning mutants for the IFNgammaR have been measured, using engineered A6 single chain variable region fragments, and a surface plasmon resonance biosensor. Energetically important side chains (DeltaG(mutant) - DeltaG(wt) > 2.4 kcal/mol), that form distinct hot spots in the binding interface, have been identified on both proteins. These include V(L)W92 in A6, whose benzenoid ring appears well situated for a pi-cation (or pi-amine) interaction with the side chain of receptor residue K47 and simultaneously for T-stacking onto the indole ring of W82 in the receptor. At another site, energetically important residues V(H)W52 and V(H)W53, as well as V(H)D54 and V(H)D56, surround the aliphatic side chain of the hot receptor residue K52. Taken together, the results show that side chains distributed across the interface, including many aromatic ones, make key energetic contributions to binding. In addition, the receptor CC' loop has been subjected to random mutagenesis, and receptor mutants with high affinity for A6 have been selected by phage display. Residues previously identified as important for receptor binding to A6 were conserved in the clones isolated. Some mutants, however, showed a much improved affinity for A6, due to changes at Glu55, a residue that appeared to be energetically unimportant for binding the antibody by alanine-scanning mutagenesis. An E55P receptor mutant bound A6 with a 600-fold increase in affinity (K(D) approximately 20 pM), which is one of the largest improvements in affinity from a single point mutation reported so far at any protein-protein interface.

Alanine↗
PubMed2000

Learning effects on event-related brain potentials.

This study investigates whether learning can manifest itself in EEG changes without explicit awareness of the acquired knowledge and without any motor requirement (to rule out acquisition of motor skills). Subjects passively heard particular stimulus combinations interspersed with random combinations. Immediately after this, stimulus combinations were presented which contained violations of the previously learned regular sequences. These violations elicited two frontally distributed negative waves peaked at about 250 ms and 500 ms, respectively. None of the participants could detect any regularity of the stimulation. No significant difference between regular vs random stimulus combinations was found during acquisition. These findings indicate that learning without explicit knowledge does not require motor activity (i.e. is independent of learning response sequences) and does not depend on stimulus probabilities.

Adult↗
PubMed2000

New Syntheses with Oils and Fats as Renewable Raw Materials for the Chemical Industry.

Oils and fats are the most important renewable raw materials for the chemical industry. Hitherto, industrial oleochemistry has concentrated predominantly on the carboxy functionality of fatty acids but, more recently, modern synthetic methods have been applied extensively to fatty compounds for the selective functionalization of the alkyl chain. Radical, electrophilic, nucleophilic, and pericyclic as well as transition metal catalyzed additions to the C-C double bond of, for example, oleic acid as the prototype of a readily accessible, unsaturated fatty acid have led to a large number of novel fatty compounds from which interesting properties are expected. Functionalization of C-H bonds in the alkyl chain is also feasible with remarkable selectivity. Effective and highly versatile catalysts for the metathesis of esters of unsaturated fatty acids have been developed, which lead to new and interesting omega-unsaturated fatty acids. The epoxidation of unsaturated fatty acids has been developed extensively. Enzymatic reactions allow syntheses with high selectivity and yield of mono- and diglycerides and esters of carbohydrates with a variety of surfactant properties. Regio- and enantioselective microbial hydrations and hydroxylations widen the spectrum of selective reactions. Of considerable significance is that, with the use of gene technology, natural oils and fats have been improved significantly and will be improved still further, insofar as they show a more uniform and often unusual fatty acid spectrum. Numerous fatty acids are now available in a purity which makes them attractive for synthesis and as raw materials for the chemical industry.

Journal Article↗
PubMed2000

Prostatic luminal cell differentiation and prostatic steroid-binding protein (PBP) gene expression are differentially affected by neonatal castration.

BACKGROUND: Although normal prostatic development is androgen-dependent, the prostate continues to grow in the neonate despite castration. However, the manner in which neonatal growth of the prostate occurs, in the absence of the testis, remains largely unknown. The purpose of this study was to examine the differentiation of prostatic epithelial cells after neonatal castration. METHODS: Immunohistochemistry was utilized to detect the expression of differentiation products: basal-cell cytokeratin (CK 5), luminal-cell cytokeratin (CK 18), and prostatic steroid-binding protein (PBP), a ventral prostate-specific marker indicative of secretory function in luminal cells. The reverse transcription-polymerase chain reaction was used to detect transcription products of the three polypeptide subunits of PBP, designated C1, C2, and C3. Rats were castrated on day 5 after birth, and ventral prostates were collected on day 14. Dihydrotestosterone was injected (100 microg/animal every 2 days) in castrated animals to determine if PBP expression could be initiated by androgen. RESULTS: Although no major effects of castration were detected on the differentiation of stromal or basal cells (which differentiate prior to day 5), castration had a pronounced effect on luminal-cell differentiation. Castration inhibited PBP protein expression, but did not affect the expression of luminal-cell cytokeratin (CK 18) protein. Furthermore, castration reduced C1, C2, and C3 transcription. Androgen replacement to castrated animals allowed for the initiation of PBP expression, although its onset was delayed. CONCLUSIONS: These observations indicate that the testis is not necessary for prostatic luminal-cell differentiation, but is necessary for full expression of luminal-cell secretory phenotype. Furthermore, our study suggests that factors of testicular origin, in addition to androgen, are needed for proper timing of PBP expression. This investigation establishes that the cytological and the physiological differentiation of the rat prostate are differentially regulated.

Androgen-Binding Protein↗
PubMed2000

Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)-TGF-beta type II dominant negative receptor.

BACKGROUND: Prostatic epithelial cells are sensitive to the inhibitory effects of TGF-beta. However, TGF-beta signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF-beta from that of androgen on the prostate. METHODS: The objective of the present study was to create and verify a transgenic mouse system in which epithelial cells of the ventral prostate are insensitive to the actions of TGF-beta. By using a modified prostate-specific promoter, C3(1), the TGF-beta dominant negative receptor is only expressed in the epithelial cells of the ventral prostate, and these cells are resistant to TGF-beta. Morphology of transgenic animal prostates was compared to wild-type animal prostates by immunohistochemistry and microscopy. RESULTS: The prostate of transgenic mice exhibited an abnormal morphology with multiple layers of epithelial cells lining the proximal ducts, in contrast to the simple cuboidal monolayer of cells seen in the normal prostate. This observation was accompanied by a loss of apoptosis in this region, as seen by TUNEL assay. There was no significant difference in serum levels of testosterone between the wild-type and transgenic animals. CONCLUSIONS: These results demonstrated that a loss of sensitivity to TGF-beta results in the accumulation of multiple layers of epithelial cells in the proximal region of the ventral prostate. This abnormal growth illustrates that TGF-beta plays an important role in regulating prostate growth. The current transgenic system can be used as an experimental model to study the functional role of TGF-beta in prostatic growth and function.

Activin Receptors, Type I↗
PubMed2000

B7.1 on human carcinomas: costimulation of T cells and enhanced tumor-induced T-cell death.

Human squamous cell carcinomas of the head and neck (SCCHN) do not express the costimulatory molecules B7.1 or B7.2 in situ or in culture. Transduction of B7.1(-) SCCHN cells with the retroviral B7. 1 and neo(r) genes resulted in the expression of high levels of the transgene in these tumor cells. When B7.1(+) SCCHN cells were used as stimulators of autologous or allogeneic PBL in mixed lymphocyte-tumor cultures (MLTC), T-cell proliferation and generation of antitumor effector T cells as well as levels of their lytic activity were significantly increased. At the same time, a proportion of activated T cells seen to undergo apoptosis was found to be significantly higher upon coincubation with B7.1(+) SCCHN than with B7.1(-) SCCHN. Both B7.1(+) and B7.1(-) SCCHN cells were found to express FasL on the cell surface and in the cytoplasm, as well as mRNA for FasL and mRNA for TRAIL. However, expression of the B7.1 transgene did not lead to increased expression of FasL protein on tumor cells. Yet, up to 50% of activated CD28(+) allogeneic T cells, which were CD95(+), showed evidence of DNA fragmentation in JAM and TUNEL assays upon incubation with an excess of B7.1(+) SCCHN for 24 h. Tumor-induced T-cell death was equally and only in part blocked by anti-Fas antibodies in both B7.1(+) and B7.1(-) MLTC. While surface expression of B7.1 molecules on SCCHN cells enhanced T-cell costimulation via B7.1-CD28 interactions, it did not rescue activated T cells from tumor-induced apoptosis. The outcome of MLTC under these conditions was dependent on the ratio of tumor to T cells. Thus, in the presence of an excess of B7.1(+) tumor cells, activated T cells showed increased sensitivity to apoptosis which did not appear to be Fas/FasL mediated. These data are important for the development of B7.1 gene therapy and efforts directed at the generation of effector cells in MLTC.

Apoptosis↗