Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience.

From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders.

Differential inhibition of single and cluster type tumor cell migration.

For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system.

Extracellular matrix induces doxorubicin-resistance in human osteosarcoma cells by suppression of p53 function.

Background: Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. The several chemotherapy-resistant cases of osteosarcoma are at a higher risk of relapse and adverse outcome.

Objective: The aim of the current study was to determine the role of extracellular matrix in the resistance developed against chemotherapeutic treatments of human osteosarcoma cells.

Fibrinolysis in a lipid environment: modulation through release of free fatty acids.

Background: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization.

Objective: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity).

Methods And Results: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi.

[Role of syndecan-1 proteoglycan in the invasiveness of HT-1080 fibrosarcoma].

Syndecan-1 is a transmembrane heparan sulfate proteoglycan which plays pivotal role in cell-cell and cell-extracellular matrix interactions. However, its implication in the establishment of malignant phenotype is still controversial. Its expression indicates differentiated phenotype in certain tumors, while it confers invasive nature for others.

[Study of drugs against neoplastic metastasis].

Further progress in the therapy of malignant diseases is expected from the introduction of potent antimetastatic drugs. Surveying of the complex and multi-step behavior of the metastatic process, compounds showing inhibitory action against tumor cell migration may be ranked among the promising antimetastatic agents. Our present study indicate, however, that the antimigratory actions of certain antitumor drugs (doxorubicin, taxol), and inhibitors of signal transduction (PD-98059, LY-294002, SB-203580) are highly dependent on the assay applied (Boyden-chamber, 3D ECM cell culture).

Repopulation of osteosarcoma cells after treatment with doxorubicin in the presence of extracellular matrix biopolymers.

Purpose: To elucidate the role of extracellular matrix (ECM) in repopulation capacity of osteosarcoma cells after doxorubicin treatment.

Methods: OSCORT cells established in our laboratory from a human osteosarcoma, were treated with doxorubicin in monolayer for 4 h, then cells were further incubated either in monolayer or in ECM-containing three-dimensional cell-culture (3-DCC), apoptosis induction and changes in cell number were measured. Alkaline comet assay was applied to estimate DNA damage, immunoblot technique and immunocytochemistry were used to investigate p53 protein synthesis, and the repopulating capacity in monolayer culture and in ECM-based 3-DCC, after doxorubicin treatment was measured.

Invasive growth and topoisomerase-switch induced by tumorous extracellular matrix in osteosarcoma cell culture.

Osteosarcoma cells are capable of extracellular matrix (ECM) synthesis. The ability of ECM to trigger the proliferation of a novel osteosarcoma cell line (OSCORT) was tested in this study in relation to a known tumor ECM, isolated from Engelbreth-Holm-Swarm (EHS) sarcoma (EHS-ECM). OSCORT was grown in monolayer, in EHS-ECM and in ECM deposited by the cells (OSCORT-ECM).

Antiproliferative and antimigratory effects of doxorubicin in human osteosarcoma cells exposed to extracellular matrix.

Osteosarcoma cells are involved in the remodeling of the extracellular matrix (ECM) that affects their growth, invasive and metastatic activities. The tumour ECM provided effective protection against chemotherapy agents in several previously studied malignancies. The current study examined the effects of doxorubicin on cells that were migrated into a 3-dimensional extracellular matrix gel (ECM-gel) in comparison with its effects on cells remaining in the monolayer compartment.

Selective suppression of an endothelin and platelet-derived growth factor containing vesicular system in endothelium of rat saphenous vein by long-term orthostasis.

Electron-dense vesicles were observed in rat vascular endothelium. The purpose of this study was to characterize their content(s), venous-arterial distribution and response to chronic orthostatic stress in extremity vessels. Saphenous and brachial vessels - saphenous vein (SV), saphenous artery (SA), brachial vein, brachial artery - were prepared for electron microscopy to quantitate the vesicle area within the endothelium following immunohistochemical and immunocytochemical identification.

[Potentiation of 5-fluorouracil efficacy. Molecular mechanisms playing a role in the cytotoxic action of 5-fluorouracil and 5-ethyl-2'-deoxyuridine (EUdR) combination].

Unlabelled: Pharmacologic modulation of 5-fluorouracil (5-FU) metabolism provides a possibility for the enhancement of its clinical efficacy.

Aim: The purpose of the present work was to study the effect of 5-ethyl-2'-deoxyuridine (EUdR), a potent 5-FU modulator, on different molecular mechanisms, influenced by 5-FU itself, and to obtain further data about the mode of action of the combination.

Materials And Methods: SW620 cell line was used for the experiments.

Vacuole formation in the endothelium of rat extremity vessels depends on fixation techniques and vessel type.

Applying immersion fixation for electron microscopy, huge clear endothelial membrane-bound vacuoles of 0.1-3 microm diameter were noted in the extremity veins of Sprague-Dawley rats. Histological and electron microscopic histochemical methods were applied to determine whether they were the product of programmed cell death or any other kind of cell damage.

Adhesion dynamics and cytoskeletal structure of gliding human fibrosarcoma cells: a hypothetical model of cell migration.

During motility of fibroblast type cells on planar surfaces, adhesions are formed at the anterior of the protruding lamella, which remain stationary relative to the substrate and undergo a maturation process as the cell passes over them. Through these adhesions force is exerted, the orientation of which is parallel to the direction of the movement. Here we show that, during gliding-type motility of human tumor cells, characterized by a semicircular shape, adhesions were found at the outer rim of the cells, along the semicircle.

In vitro antiangiogenic effect of sandostatin (octreotide) on the proliferation of the placental vessels.

Background: The somatostatin analog octreotide (Sandostatin) exerts its antineoplastic effect through different mechanisms. There are several in vitro and in vivo studies available demonstrating an antiangiogenic activity, however, some other observations failed to reinforce these results. We investigated the potential angio-inhibiting activity of this drug in an in vitro system using human placental fragments.

Interdigitation index - a parameter for differentiating between young and older skin specimens.

BACKGROUND/AIMS: Quantitative morphometry developed rapidly during the last decade due to advances is computers and software. We wish to establish a simple baseline for the morphometric differences due to intrinsic ageing between young and old cohorts: the interdigitation index. It is an expression of the shape of the border between the epidermis and dermis.

Formaldehyde promotes and inhibits the proliferation of cultured tumour and endothelial cells.

Formaldehyde was applied in various doses (0.1-10.0 mM) to HT-29 human colon carcinoma and HUV-EC-C human endothelial cell cultures.

Role of the basement membrane in tumor cell dormancy and cytotoxic resistance.

Objectives And Methods: Tumor dormancy and resistance to cytotoxic agents are key limiting events in the treatment of malignant diseases. To determine whether both are influenced by the extracellular milieu in which tumors reside, HT1080 human fibrosarcoma, MCF-7 breast carcinoma and OSCORT osteosarcoma cell proliferation, viability, apoptosis and cytoreductive-treatment-induced death were investigated in the presence or absence of extracellular matrix (ECM).

Results: ECM-adherent, but not plastic-adherent HT1080 cells formed a multicellular network accompanied by reduced proliferation and lowered DNA synthetic capacity.

Anti-apoptotic and apoptotic action of (-)-deprenyl and its metabolites.

The mode of cytoprotective action of the monoamine oxydase B inhibitor (-)-deprenyl was studied using A-2058 human melanoma cells in culture. Serum deprivation caused apoptosis of the cultured cells, which could be decreased by administration of 10(-9) - 10(-13)M (-)-deprenyl. The known metabolites of (-)-deprenyl, (-)-desmethyl-deprenyl, (-)- and (+)-methylamphetamine failed to exert the same effect.

Modulation of 5-fluorouracil by 5-ethyl-2'-deoxyuridine on cell lines expressing different dihydropyrimidine dehydrogenase activities.

The purpose of the present study was to clarify the significance of the inhibition of dihydropyrimidine dehydrogenase (DPD) in the modulation of 5-fluorouracil (5-FU) action by 5-ethyl-2'-deoxyuridine (EUdR). Four human cell lines, which differed in their susceptibility to 5-FU and in their DPD activity, were selected as biological objects. Several other enzymes of pyrimidine metabolism, i.

Establishment and characterization of a new transplantable pancreatic cancer xenograft (PZX-5) in immunosuppressed mice.

Conclusion: A new, stable, transplantable human pancreatic cancer xenograft (PZX-5) model has been established in CBA immunosuppressed mice.

Background: Numerous human pancreatic carcinomas have been successfully transplanted into athymic nude mice. However, artificially immunosuppressed animals have rarely been used as recipients.

The antiproliferative action of a melphalan hexapeptide with collagenase-cleavable site.

Purpose: The objective of the present study was to examine the relevance of collagenase in the antitumor action of a melphalan peptide (MHP) with a collagenase-cleavable sequence. The question was addressed as to whether collagenase may act as an activator or a target in the antiproliferative mechanism of MHP.

Methods: Melphalan was inserted into peptides representing the sequence Pro-Gln-Gly-Ile-Ala.

Studies on the proliferative activity of diethylnitrosamine-induced hepatocellular carcinomas in monkeys.

In this study, synthetic phase fractions (SPFs) determined by flow cytometry and AgNOR counts were analysed in benign liver lesions (regenerative nodules and adenomas), hepatocellular carcinomas (HCCs), and lung metastases of a monkey hepatocarcinogenesis model to find out if AgNOR counts and SPFs can discriminate between malignant and non-malignant liver lesions. The average per cent SPF values and the AgNOR counts were significantly (P = 0.001) increased in regenerative liver nodules (5.

Quantitative evaluation of lysozyme- and CD68-positive Kupffer cells in diethylnitrosamine-induced hepatocellular carcinomas in monkeys.

Quantitative analysis of lysozyme- and CD68-positive Kupffer cells was carried out in connection with diethylnitrosamine-induced hepatocarcinogenesis in non-human primates. The number of Kupffer cells/mm2 was determined in 28 cases of hepatocellular carcinoma (HCC) and seven age-matched controls. The Kupffer cell counts (mean +/-SEM) gradually decreased in the following order, irrespective of the histochemical markers (lysozyme or CD 68) used: healthy control liver (101.

Modification of Acute and Chronic Liver Damage by Thiazolidine Compounds.

As high sulfhydril levels were shown to reduce the action of agents causing tissueinjury, increasing glutathion concentrations may have cytoprotective potential. In this study the hepatoprotective effects of several derivatives of 4carboxy5,5dimethyl thiazolidine, a modulator of glutathion metabolism were studied in rat liver damaged with CCl4. It was found that 4(S) carboxy 5,5dimethyl2 (5'nitro2furyl) thiazolidine (dimethylthiazolidinenitrofuran: DTNF) had the most significant hepatoprotective action; therefore it was subjected to detailed investigation in various models for acute and chronic liver injury.

Olive oil decreases liver damage in rats caused by carbon tetrachloride (CCl4).

Oral carbon tetrachloride (CCl4) poisoning of the liver of male F-344 rats was modified by dissolving CCl4 in various oils (sunflower, corn, fish and olive). After 8 weeks of CCl4 treatment (3 x 0.2 ml/kg body weight every other day, dissolved in aliquots of 0.