Biomedical subjects

M Streit

Publications and source records attributed to M Streit.

At least 37 records · Page 2Linked to original sources

PubMed2000

Expression of vascular endothelial growth factor induces an invasive phenotype in human squamous cell carcinomas.

Inhibition of the vascular endothelial growth factor (VEGF) receptor Flk-1 has been shown to prevent invasion of experimental squamous cell carcinomas (SCC). To directly investigate the role of VEGF in tumor invasion, we stably transfected human SCC-13 cells, which are characterized by a noninvasive phenotype in vivo, with expression vectors containing murine VEGF(164) in sense (SCC/VEGF+) or antisense (SCC/VEGF-) orientation or with vector alone (SCC/vec). SCC/vec cells formed slowly growing, well-differentiated tumors with well-defined borders between tumor and stroma, after intradermal or subcutaneous injection. In contrast, SCC/VEGF+ tumors were characterized by rapid tumor growth, with small cell groups and single cells invading into the surrounding tissue, and by admixture of blood vessels and tumor cells in areas of tumor invasion. We detected an increase in tumor vessel density and size in VEGF-overexpressing tumors, resulting in a more than fourfold increase in total vascular areas. In contrast, SCC/VEGF- clones formed noninvasive, sharply circumscribed tumors with reduced vascular density. These findings demonstrate that selective VEGF overexpression was sufficient to induce tumor invasiveness, and they provide further evidence for an active role of the tumor stroma in cancer progression.

Animals↗

PubMed2000

Typical features of calciphylaxis in a patient with end-stage renal failure, diabetes mellitus and oral anticoagulation.

We report a multimorbid patient with end-stage renal failure showing a large necrosis and livedo racemosa on the right thigh. Histology revealed medial calcification of the small arteries typical of calciphylaxis. We found the typical features of the disease with different risk factors like elevated calcium-phosphate product, diabetes mellitus and oral anticoagulation. On account of the location of the skin lesions, a bad prognosis was expected. In spite of therapeutical measures with lowering of the calcium and phosphate levels, the patient died 1 month after the diagnosis had been made.

Administration, Oral↗

PubMed2000

Coupling of regional activations in a human brain during an object and face affect recognition task.

Magnetic field tomography (MFT) was used to extract estimates for distributed source activity from average and single trial MEG signals recorded while subjects identified objects (including faces) and facial expressions of emotion. Regions of interest (ROIs) were automatically identified from the MFT solutions of the average signal for each subject. For one subject the entire set of MFT estimates obtained from unaveraged data was also used to compute simultaneous time series for the single trial activity in different ROIs. Three pairs of homologous areas in each hemisphere were selected for further analysis: posterior calcarine sulcus (PCS), fusiform gyrus (FM), and the amygdaloid complex (AM). Mutual information (MI) between each pair of the areas was computed from all single trial time series and contrasted for different tasks (object or emotion recognition) and categories within each task. The MI analysis shows that through feed-forward and feedback linkages, the "computation" load associated with the task of identifying objects and emotions is spread across both space (different ROIs and hemispheres) and time (different latencies and delays in couplings between areas)-well within 200 ms, different objects separate first in the right hemisphere PCS and FG coupling while different emotions separate in the right hemisphere FG and AM coupling, particularly at latencies after 200 ms.

Brain↗

PubMed2000

Apligraf--a living human skin equivalent for the treatment of chronic wounds.

Apligraf, a manufactured living human skin equivalent, was the first true composite tissue analog to become commercially available. It has been approved by the FDA for the treatment of venous leg ulcers and diabetic foot ulcers. The tissue engineered bi-layered skin equivalent has both an epidermis and a dermis, which consist of keratinocytes and fibroblasts derived from neonatal foreskin and bovine collagen. The skin equivalent produces a great number of cytokines and growth factors and is immunologically well tolerated. The product is easy to handle in clinical use and can be applied in an outpatient setting.

Collagen↗

PubMed1999

Thrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis.

Recent evidence suggests a potential role for thrombospondin-2 (TSP-2), a matricellular glycoprotein, in the regulation of primary angiogenesis. To directly examine the biological effect of TSP-2 expression on tumor growth and angiogenesis, human A431 squamous cell carcinoma cells, which do not express TSP-2, were stably transfected with a murine TSP-2 expression vector or with vector alone. A431 cells expressing TSP-2 did not show an altered growth rate, colony-forming ability, or susceptibility to induction of apoptosis in vitro. However, injection of TSP-2-transfected clones into the dermis of nude mice resulted in pronounced inhibition of tumor growth that was significantly stronger than the inhibition observed in A431 clones stably transfected with a thrombospondin-1 (TSP-1) expression vector, and combined overexpression of TSP-1 and TSP-2 completely prevented tumor formation. Extensive areas of necrosis were observed in TSP-2-expressing tumors, and both the density and the size of tumor vessels were significantly reduced, although tumor cell expression of the major tumor angiogenesis factor, vascular endothelial growth factor, was maintained at high levels. These findings establish TSP-2 as a potent endogenous inhibitor of tumor growth and angiogenesis.

Angiogenesis Inhibitors↗

PubMed1999

Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas.

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in epithelial tumor development has remained controversial. We studied the in vitro growth characteristics and the in vivo tumor xenograft growth of the human squamous cell carcinoma cell lines A431 and SCC-13, stably transfected to overexpress human TSP-1. Overexpression of TSP-1 inhibited tumor growth of A431 xenotransplants, and completely abolished tumor formation by SCC-13 cells. TSP-1 overexpressing A431 tumors were characterized by extensive areas of necrosis and by decreased tumor vessel number and size. The effects of TSP-1 on tumor cell growth were indirect since tumor cell proliferation rates in vivo and in vitro, anchorage-dependent and -independent growth in vitro, and susceptibility to induction of apoptosis by serum withdrawal were unchanged in TSP-1 overexpressing tumor cells. However, TSP-1 overexpression up-regulated the TSP-1 receptor CD36, leading to enhanced adhesion of A431 cells to TSP-1. These findings establish TSP-1 as a potent inhibitor of angiogenesis and tumor growth in carcinomas of the skin.

Animals↗

PubMed1999

Neurophysiological correlates of the recognition of facial expressions of emotion as revealed by magnetoencephalography.

MEG correlates of the recognition of facial expressions of emotion were studied in four healthy volunteers. Subjects performed a facial emotion recognition task and a control task involving recognition of complex objects including faces. Facial emotion recognition activated inferior frontal cortex, amygdala and different parts of temporal cortex in a relatively consistent time sequence. The characteristics of these activations were clearly different from those recorded during the control task. Most interesting was the fact that faces evoked different MEG responses as a function of task demands, i.e., the activations recorded during facial emotion recognition were different from those recorded during simple face recognition in the control task. These findings support the assumption that MEG is able to specifically identify the activation pattern of the brain when recognition of the emotional expression of a face is performed.

Adult↗

PubMed1999

Pharmacokinetic and pharmacodynamic comparison of two doses of calcium folinate combined with continuous fluorouracil infusion in patients with advanced colorectal cancer.

The optimum dose of calcium folinate (leucovorin) as modulator of fluorouracil has not been defined yet. We conducted a randomized trial to compare the pharmacokinetics/pharmacodynamics of two doses of calcium folinate. 16 patients with advanced colorectal cancer were treated with 650 mg/m2/d fluorouracil as 5 day continuous infusion and randomized to receive either 20 mg/m2 or 100 mg/m2 calcium folinate as short infusion twice daily. The two diastereoisomers of calcium folinate were analyzed separately by chiral HPLC to account for differences in their pharmacokinetics. The pharmacokinetics of fluorouracil was not affected by folinate dosing. Total clearance of the active (6S)-diastereoisomer was found to be lower after the higher dose of folinate which can be explained by nonlinear metabolism. The incidence of treatment-induced mucositis significantly increased with (6S)-folinate exposure, whereas fluorouracil exposure was not related to this type of toxicity. In conclusion, exposure to folinate is more important for toxicity in this regimen than fluorouracil pharmacokinetics. Therefore, monitoring of fluorouracil plasma levels is not useful in this combination. Our results show that folinate dose should be carefully selected. Lower doses of folinate might be preferred because of less toxicity compared to higher doses.

Aged↗

PubMed1999

Single trial analysis of neurophysiological correlates of the recognition of complex objects and facial expressions of emotion.

In an earlier experiment, we have used the BTi twin MAGNES system (2 x 37 channels) to record the evoked magnetic field from five healthy right-handed male volunteers using two tasks: visual recognition of complex objects including faces and facial expressions of emotion. We have repeated the experiment with one of the five subjects using the BTi whole head system (148 channels). Magnetic field tomography (MFT) was used to extract 3D estimates of brain activity millisecond by millisecond from the recorded magnetoencephalographic (MEG) signals. Results from the MFT analysis of the average signals of the five subjects have been reported elsewhere (Streit et al. 1997; Streit et al. 1999). In this paper, we present results of the detailed single trial analysis for the subject recorded from the whole head system. We found activations in areas extending from the occipital pole to anterior areas. Regions of interest (ROIs) were defined entirely on functional criteria and confirmed independently by the location of the maximum activity on the MRI. Activation curves for each ROI were computed and objective statistical measures (Kolmogorov-Smirnov test) were then used to identify time segments for which the ROI activity showed significant differences both within the same and across different object/emotion categories. Emphasis is placed on the quantification of the activity from two ROIs, fusiform gyrus (FG) and amygdala (AM), which have been best studied in the context of processing of faces and facial expressions of emotion, respectively. We found no face-specific area as such, but instead areas like the FG was activated by all complex objects at roughly similar latencies and varying strengths. The amygdala activity was significantly different between 150 and 180 ms for fearful expression, and even earlier for happy expression.

Animals↗

PubMed1999

[Soft tissue augmentation for treatment of wrinkles and scars of the face].

Facial wrinkles and scars can be corrected by injecting implants into the dermal connective tissue. Today, several substances can be used for this purpose. Injectable bovine collagen (Zyderm and Zyplast) has been used successfully for more than twenty years in some hundred thousand patients. Due to the xenogenity of the product a skin testing is required before augmentation. As the implant is degraded by the body's own mechanisms periodic maintenance injections are necessary. Gelatin matrix (Fibrel) was developed as an alternative to injectable collagen. It is mainly used for the correction of scars. The long term-correction seems to be better compared to collagen but a skin test must be performed as well. The most promising material for soft tissue augmentation today is hyaluronic acid and its derivatives. The substance is easy to handle and requires no previous skin testing. The efficacy is comparable to collagen. Apart from the biomaterials synthetic implants are still of interest. The augmentation with expanded polytetrafluorothylene (Gore-tex) requires a surgical procedure because a tubular implant is inserted undermeath the wrinkles. The correction is permanent, but scars and an asymmetrie of the face may be complications.

Animals↗

PubMed1998

De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on fibronectin.

Changes in integrin expression during malignant transformation have been observed in many tumors. Colon-carcinoma cells show reduced expression or even loss of the alpha5beta1 integrin compared to normal or adenoma cells. To determine the significance of absent alpha5beta1 integrin signaling, we transfected the cDNA coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line HT29, which constitutively lacks this subunit but does express the beta1 subunit. We show here that the newly expressed fibronectin receptor alpha5beta1 generates multiple signals, causing marked changes in cytoskeletal arrangements within a few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin exhibit the formation of actin stress fibers and focal adhesions, as well as the induction of tyrosine phosphorylation of several proteins, within 10 min. We identified the focal adhesion kinase pp125FAK and the cytoskeletal protein paxillin as major phosphorylation substrates in these cells. These proteins remained hypophosphorylated when alpha5-negative control cells were plated on fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation of cellular proliferation and constitutively over-expressed in HT29 and in colon-carcinoma cells, showed reduced intrinsic kinase activity in unstimulated HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1 increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor during malignant transformation may contribute to tumor-cell autonomy, while reduced activity of pp60c-src in HT29alpha5-cells may participate directly in growth control.

Cell Adhesion↗

PubMed1998

Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis.

The integrin alpha5beta1 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin alpha5beta1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin alpha5beta1. Similar to other reports, expression of the integrin alpha5beta1 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin alpha5beta1 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin alpha5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injection into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 +/- 2.6 to 22.0 +/- 6.6 (mean colony number +/- SEM), mice inoculated with HT-29 cell clones expressing the integrin alpha5beta1 were almost completely free of lung colonies (ranging from 0.0 +/- 0 to 0.2 +/- 0.1). Our results imply that integrin alpha5beta1 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model.

Animals↗

PubMed1997

Facial-affect recognition and visual scanning behaviour in the course of schizophrenia.

The performance of schizophrenic in-patients in facial expression identification was assessed in an acute phase and in a partly remitted phase of the illness. During visual exploration of the face stimuli, the patient's eye movements were recorded using an infrared-corneal-reflection technique. Compared to healthy controls, patients demonstrated a significant deficit in facial-affect recognition. In addition, schizophrenics differed from controls in several eye movement parameters such as length of mean scan path and mean duration of fixation. Both the facial-affect recognition deficit and the eye movement abnormalities remained stable over time. However, performance in facial-affect recognition and eye movement abnormalities were not correlated. Patients with flattened affect showed relatively selective scan pattern characteristics. In contrast, affective flattening was not correlated with performance in facial-affect recognition. Dosage of neuroleptic medication did not affect the results. The main findings of the study suggest that schizophrenia is associated with disturbances in primarily unrelated neurocognitive operations mediating visuomotor processing and facial expression analysis. Given their time stability, the disturbances might have a trait-like character.

Adult↗

PubMed1997

Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: an effective second-line regimen.

OBJECTIVE: A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks. PATIENTS AND METHODS: From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial. RESULTS: In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months. CONCLUSION: This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.

Adult↗

PubMed1996

Current treatment modalities in advanced colorectal carcinoma.

Several biochemical and immunological substances are currently being tested for their efficacy in the treatment of advanced colorectal cancer, the second-most malignant disease in the western world. Presently, a combination of 5-fluorouracil (FU) and the biochemical modulator folinic acid is considered to be the standard treatment for this malignancy, with a median response rate of 30%. A recent multi-analysis of phase III trials with methotrexate and FU versus FU alone has demonstrated a statistically significant doubling of the response rate as well as a significant survival advantage for the combination. So far, other biochemical or immunological modulators of FU have not shown a significant advantage regarding response or survival. Several new drugs such as tegafur, thymidilate synthase inhibitors, trimetrexate, or topoisomerase-I-inhibitors have been tested with promising results in preclinical and early clinical settings. While local treatment such as hepatic artery infusion has become safer, it is still more toxic than systemic treatment and showed a significant improvement of response but no survival advantage. Since all treatment strategies in advanced colorectal cancer are still palliative, quality of life is a more important endpoint in clinical trials.

Colorectal Neoplasms↗

PubMed1996

Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors.

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.

Animals↗

PubMed1996

Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors.

Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.

Cell Transformation, Neoplastic↗

PubMed1996

Facial affect recognition in the course of schizophrenia.

Deficits in facial affect recognition have been shown repeatedly in schizophrenia. However, the stability of this deficit over time remains to be clarified. A total of 36 remitted, 32 acutely ill schizophrenic patients and 21 healthy volunteers participated in a cross-sectional and longitudinal study. All subjects were assessed twice within 4 weeks (acute schizophrenics and normal controls), or 12 weeks, respectively (remitted schizophrenics). Subjects had to identify six basic emotions from corresponding facial expressions shown as photographs on a video screen. Both acute and remitted schizophrenics demonstrated a stable deficit over time in facial affect recognition unrelated to psychopathology and medication. This suggests that deficits in facial affect recognition in schizophrenia reflect a trait-like, rather than a state-dependent, characteristic.

Acute Disease↗