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101.
Kijima T Maulik G Ma PC Madhiwala P Schaefer E Salgia R 《Journal of cellular and molecular medicine》2003,7(2):157-164
Small cell lung cancer (SCLC) is a rapidly progressive disease with ultimate poor outcome. SCLC has been shown to interact closely with the stromal and extracellular matrix (ECM) components of the diseased host. ECM consists of type I/IV collagen, laminin, vitronectin, and fibronectin (FN) among others. Herein, we investigated the behavior of a SCLC cell line (NCI-H446) on FN-coated surface. Over a course of 72 h, FN (10 micro g/ml) caused both increased survival and proliferation of NCI-H446 cells. Survival under serum-starved conditions increased 1.44-fold and proliferation in the presence of fetal calf serum increased by 1.30-fold. The phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 reduced both survival and proliferation of NCI-H446 cells (0.48- and 0.27-fold, respectively), even on FN-coated surface. We next determined the effects of FN on cytoskeletal function such as cell motility/morphology and adhesion. Over a course of 24 h, FN reduced aggregation of NCI-H446 cells and induced flattened cellular morphology with neurite-like projections after 1 h, however, in the presence of LY294002, the cells rounded up. Adhesion of NCI-H446 cells also increased with FN (4.47-fold) which was abrogated with LY294002 treatment. This correlated with phosphorylation of the cytoskeletal protein p125FAK, on Tyr397, Tyr861 and Ser843 residues with FN. Even in the presence of LY294002, these serine/tyrosine residues were still phosphorylated on FN-coated surface. In contrast, the focal adhesion protein paxillin was not phosphorylated at Tyr31 with FN. In summary, FN stimulation of SCLC cells leads to enhancement of viability and changes in cytoskeletal function that are partially mediated through the PI3-K pathway. 相似文献
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In human spermatozoa, Ca(2+) entry is stimulated by progesterone or prostaglandin E(1) (PGE(1)). The regulation of cation currents by progestins involves sigma receptors, and sigma binding sites are abundant in testis. We examined the effects of sigma ligands on human spermatozoa. Ca(2+) entry induced by progesterone or PGE(1) was not altered by the sigma ligands haloperidol and ditolylguanidine. However, the steroidal sigma ligands RU 3117 and RU 1968 had distinct effects. Stimulation by RU 3117 resulted in activation and homologous desensitization of the sperm progesterone receptor but not of the PGE(1) receptor. Because haloperidol and ditolylguanidine did not affect RU 3117 and progesterone actions in spermatozoa, we conclude that sigma receptors are not involved. However, RU 1968 potently inhibited both the progesterone- and PGE(1)-induced Ca(2+) entry and acrosome reaction. At higher concentrations, RU 1968 also inhibited hormonal Ca(2+) signaling in fibroblasts. Despite suppression of Ca(2+) mobilization, inhibition of phospholipase C by RU 1968 was not observed. Furthermore, RU 1968 did not impair the binding of inositol-1,4,5-trisphosphate to its endoplasmic reticulum receptor. Because RU 1968 preferentially inhibits signaling pathways in spermatozoa, the future development of more selective drugs structurally related to RU 1968 may be a novel approach for pharmacological contraception. 相似文献
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The purpose of this paper was to study the effect of the isopropyl myristic acid ester (IPM) on the physicochemical characteristics
of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on the size and drug loading
of the microspheres, the polymer matrix and surface morphology, and the release of etoposide from the microspheres. The experiment
was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no IPM) at 2 different etoposide-loading percentages
(10% and 5%). The microspheres were prepared using a single-emulsion solvent-extraction procedure. Samples from each batch
of microspheres were then analyzed for size distribution. drug-loading efficiency, surface characteristics, in vitro release,
and in vitro microsphere degradation. The incorporation of 50% IPM significantly increased (P<05) the size of the microspheres when compared with the control and 25% IPM microspheres. However, incorporation of 25% or
50% IPM did not change (P>.05) the drug-loading efficiency in comparison with the microspheres prepared without IPM. The microspheres containing 50%
IPM were shown to significantly increase (P<.05) the release of etoposide from the microspheres at both etoposide concentrations. The microspheres prepared incorporating
25% IPM and 5% etoposide increased the in vitro release (P<.05) in comparison with the microspheres prepared without IPM. The 5% etoposide-PLGA microspheres showed a smooth, nonporous
surface that changed to a dimpled. nonporous surface after addition of 25% IPM. During the in vitro degradation study, the
IPM-containing microspheres slowly became porous but retained their structural integrity throughout the experiment. 相似文献
108.
A method has been developed to monitor the cell growth of aggregated human embryonic kidney 293 (HEK293) suspension cultures by measuring cumulative particle volume and the particle size distribution. This method employs a particle size analyzer that determines the size of individual particles by detecting their light obscuration (blockage) or scattering. Cell counts derived from the cumulative volume of the cell particle correlate well with manual cell counts from a hemacytometer at different stages of growth. This correlation was further confirmed by quantifying total cellular protein of the samples. Simultaneously, the aggregation state of the samples can also be monitored and mathematically described. Results from this study demonstrate that this simple and reproducible method allows the direct measurement of cumulative cell volume and the degree of cell aggregation, as well as an indirect assessment of cell counts. 相似文献
109.
Morphology of the postotic laterosensory canal was surveyed across loricarioid and outgroup catfishes in order to resolve conflicting statements regarding homology and phylogenetic significance of intrinsic character variation. A pterotic branch is widespread among catfishes and has been identified as a synapomorphy for siluriforms, but its presence in loricarioid catfishes has been disputed. In contrast to previous statements that absence of a pterotic branch is synapomorphic for loricarioids, we confirm the presence of a pterotic branch in Nematogenys inermis and other trichomycterids, callichthyids, and loricariids. The pterotic branch is secondarily absent in scoloplacids and astroblepids. We present criteria for establishing homology of the pterotic branch and review character state optimization schemes on the currently accepted phylogeny. The postotic region of loricariids is further specialized in having an expanded swimbladder capsule that incorporates the trunk lateral line canal and has a lateral opening covered by a greatly expanded pterotic complex. The trunk lateral line enters the swimbladder capsule mesial to the pterotic lateral wall and passes anteromedially as a fleshy tube before forming the postotic canal in the pterotic, a morphology reported previously for a single loricariid representative. Variation in the relative extent and topographic position of postotic canal branches and other morphologies is diagnostic of certain loricariid taxa, suggesting a rich character complex of potential utility in phylogeny reconstruction. 相似文献
110.
Trueblood NA Ramasamy R Wang LF Schaefer S 《American journal of physiology. Heart and circulatory physiology》2000,279(2):H764-H771
Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD(+) ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD(+), would lower the NADH/NAD(+) ratio, increase glycolysis, and limit ischemic injury and 2) these cardioprotective benefits of niacin would be limited in conditions that block lactate removal. Isolated rat hearts were perfused without (Ctl) or with 1 microM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine the effects of limiting lactate efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero-flow ischemia and 2) the Nia group treated with the lactate-H(+) cotransport inhibitor alpha-cyano-4-hydroxycinnamate under LF conditions. Measured variables included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD(+)), lactate efflux rate, and creatine kinase release. The lactate-to-pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline and ischemic conditions (P < 0.001 and P < 0.01, respectively), with concurrent lower creatine kinase release than Ctl hearts (P < 0.05). Nia-LF hearts had significantly greater lactate release during ischemia (P < 0.05 vs. Ctl hearts) as well as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with alpha-cyano-4-hydroxycinnamate and blocking lactate washout with zero flow negated some of the beneficial effects of niacin. During LF, niacin lowered the cytosolic redox state and increased lactate efflux, consistent with redox regulation of glycolysis. Niacin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeutic agent in patients with ischemic heart disease. 相似文献