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C Kremer

Publications and source records attributed to C Kremer.

25 records · Page 2Linked to original sources
PubMed1997

Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system.

Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR) are key mediators of physiological and pathological angiogenesis. They are expressed in most tissues during embryonic development but are down-regulated in the adult, when angiogenesis ceases. Up-regulation of VEGFR-2 and of VEGF are observed in many pathological conditions under which angiogenesis is reinduced. A major regulator of VEGF expression is hypoxia. Although the temporal expression pattern of VEGFR-2 parallels VEGF expression to a high extent, little is known about its regulation. Here, we show that VEGFR-2 is highly expressed in early postnatal mouse brain but is down-regulated commencing at postnatal day 15 (P15) of mouse brain development and is hardly detectable in P30 mouse brain. Using P30 mouse brain slices, we observed that hypoxia up-regulates VEGFR-2 in the slices but not in human umbilical vein endothelial cells, suggesting the presence of a hypoxia-inducible factor in the murine neuroectoderm that up-regulates VEGFR-2. To identify the factors involved, normoxic P30 cerebral slices were cultured with growth factors that are either hypoxia-inducible (e.g., PDGF-BB, erythropoietin, and VEGF) and/or are known to act on endothelial cells (e.g., PDGF-BB, VEGF, and PIGF). Exogenously added recombinant VEGF led to an up-regulation of VEGFR-2 expression, which could be inhibited by preincubation with a neutralizing anti-VEGF antibody. Addition of PDGF-BB, PIGF, and erythropoietin had no effect on VEGFR-2 expression. Our results suggest a differential but synergistic regulation by hypoxia of VEGF and VEGFR-2: a direct induction of VEGF that subsequently up-regulates VEGFR-2 in endothelial cells. This autoenhancing system may represent an important mechanism of tumor angiogenesis.

Animals↗
PubMed1996

Labelling, control and radiopharmacological evaluation of 99mTc-adenosine 5'-diphosphate (99mTc-ADP) as tumour seeking agent.

A study of 99mTc-adenosine-5'-diphosphate (99mTc-ADP) as a radiopharmaceutical for tumour diagnosis is presented. Two different labelling methods, using SnCl2 in alkaline solution and Zn as reducing agents, were developed. Reduction with Sn(II) alkaline solution was the selected method because a lower concentration of ADP (0.5 mg/mL) could be used and a higher radiochemical yield was achieved. A labelled molecule with a radiochemical purity higher than 95%, in vitro stability of at least 6 hours and an over all negative charge was obtained Biodistribution studies carried out in normal mice and rats revealed rapid urinary excretion and no specific accumulation of activity in any other particular organ. This behaviour was similar to that reported for 99mTc-adenosine-5'-triphosphate (99mTc-ATP). Rapid blood clearance, that could be fitted to a bicompartimental model, was also verified. No evidence of in vivo instability was observed. Studies in mice and rats bearing spontaneous mammary adenocarcinomas were performed and the results were compared to those from the 99mTc-ATP studies. Although the tumour models used were not the same, the incorporation of both labelled compounds was very similar. Radioactivity uptake in the tumour and the tumour-to-blood ratio were not notably high. However, a significant increment was observed in the tumour-to-muscle ratio (1.0 +/- 0.2 at 30 minutes to 2.7 +/- 0.4 at 240 minutes). Whole-body autoradiography enabled tumour visualization. Further investigations, including scintigraphic imaging, must be carried to complete the clinical evaluation of 99mTc-ADP as a tumour seeking agent.

Adenocarcinoma↗
PubMed1994

Response of multicellular tumor spheroids to liposomes containing TNF-alpha.

This publication describes a new model to investigate the influence of tumor necrosis factor-alpha (TNF-alpha) on a three-dimensional glial cell aggregate under defined, standardized, reproducible conditions using the glioma cell line A 172. The cells are initially grown as normal monolayer culture until they reach a cell density of up to 1 x 10(6). Subsequently they are grown as spheroids by the liquid overlay technique. Spheroids grown in this way were divided into ten groups of more than 50 cell aggregates. Three groups were coincubated with free TNF-alpha in increasing dosages (100 ng/ml, 200 ng/ml and 1000 ng/ml); three groups were incubated with empty liposomes (0.2 mg/ml, 0.4 mg/ml and 2 mg/ml); three groups received liposomes which had been loaded with TNF-alpha, and one group, which received no treatment, served as control. The diameter of the spheroids ranged from 80 microns to 350 microns. There was no significant difference in growth between the 3 groups treated with 'free' TNF-alpha. Comparing spheroids treated with TNF-alpha with those which had been coincubated with empty liposomes, there was a significant difference (p < 0.001) in growth, which correlated with the amount of liposomes. Similarly, free TNF-alpha had a significantly (P < 0.001) stronger growth-inhibiting effect as compared to liposomes loaded with TNF-alpha. Comparing the groups treated with liposomes only to those treated with liposomes loaded with TNF-alpha, the latter exhibited a more marked (although not significantly) growth-inhibiting effect. The preliminary conclusion is that the major growth-inhibiting effect seems to be mediated by the liposomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Aggregation↗
PubMed1993

Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers.

Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in two sibs and we suggest Usher syndrome type I could be a primary ciliary disorder.

Abnormalities, Multiple↗
PubMed1993

[Infections during the hospitalization of patients with liver cirrhosis].

We studied retrospectively the clinical records of 291 hospital patients with liver cirrhosis, 95% of which was alcohol related. Within this group, 114 patients presented 155 episodes of infection in 144 separate hospital admissions. In a previous communication, we pointed out that although infection was the fourth cause of admission, it was the main cause of death in this group. The main incidence of infection was among the female group. The most common infections episodes were respiratory and bacterial spontaneous peritonitis (BSP). On admission, 57% of the patients were diagnosed as belonging to the C Child group; 38% presented sepsis and 22% were hospitalary infections. The most frequent infections were respiratory and BSP. We obtained bacteriologic documentation in 55% of the episodes with prevalence of Gram negative bacilli (E. coli), with high relative frequency of neumoccocus. The most frequent complications were related to hepatic insufficiency. Global death rate was 27.1%, while nosocomial death rates were 42.1% and 40.9% for patients with Child C. We observed the highest incidence of mortality in patients with SBP and non localized bacteriemia. Survival rates were 42% for 2 years and 18% for 5 years. In summary, we stress the relevancy of checking the presence of infection systematically in every cirrhotic patient with encephalopathy and/or renal insufficiency without justifiable cause.

Adult↗
PubMedDate not supplied

Integrated optical density and entropiefluss (current of entropy) in bronchial carcinoma.

Histological sections of formalin-fixed, paraffin-embedded bronchial carcinomas comprising 241 surgical specimens (lobes and lungs) were Feulgen stained. The integrated optical density of the nuclei (IOD) and the minimum distance between their centers of gravity (DG) was measured with an automated image analyzing system consisting of a TV camera connected to a personal computer via a frame grapper. Intratumorous lymphocytes served as DNA standard (2C peak), and 300 nuclei were measured at minimum. The entropy of the IOD, the percentage of S-phases (PS) of tumor cells with an IOD > 3C and > 5C, and the 2CV mean standard deviation were measured. According the theory of thermodynamically open systems, the entropiefluss (current of entropy) was defined by the gradient IOD/time through the surface of the tumors which can be approximated by the formula IOD*PS*DG/tumor volume. The following results were obtained: a) IOD of bronchial carcinoma is not associated with tumor size or lymph node infiltration (pT and pN stage). b) The minimum distance between tumor cells decreases with increasing tumor stage and increasing lymph node stage (pT, pN stage). c) The entropiefluss is low in limited and advanced tumor stages, and highest in tumors at moderately progressive tumor stages (pT2, pT3, pN1, pN2). Thus, in accordance with the theory of thermodynamically open systems, the entropiefluss reflects the "biological activity" of bronchial carcinoma.

Bronchial Neoplasms↗