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1.
Laura Cernat Cristina Blaj Rene Jackstadt Lydia Brandl Jutta Engel Heiko Hermeking Andreas Jung Thomas Kirchner David Horst 《PloS one》2014,9(8)
Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes. 相似文献
2.
Summary The degree of satellite association was found to be significantly higher in phytohemagglutinin (PHA)-stimulated lymphocytes from cystic fibrosis (CF) patients than from those of control individuals. PHA-stimulated lymphocytes from obligatory heterozygotes for the CF mutant allele showed an intermediate degree of satellite association. The degree of satellite association was estimated by the frequency of cells exhibiting associations, by the number of associations per cell, and by the number of chromosomes in an association. The differences in the degree of satellite association were dependent on the concentration of colchicine used for cell arrest. These findings may assist in developing a diagnostic method for the early identification of heterozygotes for the CF allele and for prenatal detection of CF homozygous fetuses.This paper is based on a portion of a dissertation to be submitted by Y. Ravia in partial fulfilment of the Ph. D. requirements in the Graduate School of Tel Aviv University 相似文献
3.
G. Renner 《Life sciences》1983,33(14):1427-1431
Studies on the biotransformation of N-acetyl-S-(pentachlorophenyl) cysteine, a mutual polar metabolite of the lipophilic fungicides pentachloronitrobenzene and hexachlorobenzene, showed metabolic conversions in rats. The rate of its metabolism, leading in return to more lipophilic and toxic products (1) was investigated by determination of pentachlorothioanisole, its major metabolite in blood and liver of rats. The metabolic rate was found to be very small. 相似文献
4.
Summary An analysis was made of the effects of different sampling and extraction techniques on the amounts and pattern of monoterpenoids isolated from needles of Norway spruce. The following isolation and analysis procedure was finally adopted: liquid nitrogen-cooled needles were pulverized by a microdismembrator, extracted with pentane overnight at 2°–3°C and concentrated to a volume not less than 3 ml/g fresh weight on a Vigreux column. The crude extract was injected splitless (with solvent split) onto a cold programmed temperature vaporized (PTV) precolumn of a gas chromatograph and the vaporizable compounds heated to a capillary column. This method was tested for production of artefacts and quantitative extraction and applied to needles of eleven 80-year-old spruce trees. 相似文献
5.
Photoautotrophic cell suspension cultures of Chenopodium rubrumrequire high concentrations of nitrate and ammonium. Duringthe growth phase total NH4+ and the greater portion of NH3were consumed. During the stationary phase nitrate uptake continuedbut at a substantially smaller rate than during the growth phase.During growth the bulk of the absorbed N was incorporated intoprotein, the amount of which was then maintained constant untilsenescence. NH3 was accumulated upon transition betweenthe growth and the stationary phase. NH3, like the freeamino acids, was deposited in the vacuole but, unlike thesecompounds, could not be remobilized upon transfer of the cellsinto N-free medium. Readdition of NH4+ to the medium, however,resulted in a mobilization of the vacuolar NH3-pool.Reutilization of both vacuolar N-storage pools must have beenaccomplished by recycling from the vacuole to the cytoplasmbecause N-metabolizing enzymes could not be detected in isolatedvacuoles. Transfer of the cells of the stationary phase intomedium containing NH3 and NH4+ resulted in an inductionof nitrate uptake by the cells, but only after a lag phase of45 days. It is conceivable that NH4+ induces NH3-translocatingsystems in the plasmalemma and in the tonoplast. (Received December 19, 1988; Accepted March 2, 1989) 相似文献
6.
Abstract Four plasmids were constructed by associating Escherichia coli and yeast selection markers and replication origins to a structural gene coding for aminoglycoside phosphotransferase (APH(3')) controlled by different flanking sequences. We used the two bacterial genes of Tn5 (APH(3')II) and Tn903 (APH(3')I) as such and the chimeric pSVneo (APH(3')II) and pNOSneo (APH(3')II) constructs, functional in mammalian and plant cells, respectively. Yeast clones resistant to G418 were obtained with all plasmids except with that bearing the bacterial APH(3')II gene. The three plasmids harbouring the functional APH genes, however, conferred different levels of G418 resistance to yeast. 相似文献
7.
Amiloride and amiloride analogs inhibit Na+/K+-transporting ATPase and Na+-coupled alanine transport in rat hepatocytes 总被引:2,自引:0,他引:2
Amiloride, a commonly used inhibitor of Na+-H+ exchange, has been shown to exhibit a variety of nonspecific effects. Recently, the more potent amiloride analogs, 5-(N,N-dimethyl)amiloride hydrochloride (DMA) and 5-(N-ethyl-N-isopropyl)amiloride (EIA), have been used to control for the nonspecific effects of the parent compound. In the present study, we have explored the effects of these analogs on Na+/K+-transporting ATPase (Na+/K+-ATPase) and Na+-coupled alanine transport in primary rat hepatocyte cultures and rat liver plasma membranes, and we have compared the effects of these analogs with the effects of amiloride and ouabain. Amiloride, DMA, and EIA increased steady-state Na+ content and inhibited ouabain-sensitive 86Rb+ uptake in a reversible, concentration-dependent, ouabain-like manner, with estimated 50% inhibitory concentrations (IC50) of 3.0.10(-3) M, 5.2.10(-4) M, and 1.2.10(-4) M, respectively. Amiloride, DMA and EIA also inhibited ouabain-sensitive ATP hydrolysis in rat liver plasma membranes with similar potency (IC50 values of 2.2.10(-3) M, 2.2.10(-3) M, and 1.7.10(-4) M, respectively). In separate experiments, amiloride (5.10(-3) M), DMA (10(-3) M), and EIA (2.5.10(-4) M) decreased the uptake into hepatocytes of alanine by 20%, 61%, and 59%, respectively, and further studies with DMA (10(-3) M) demonstrated that this inhibition was largely due to a decrease in the Na+-dependent fraction of alanine uptake. These findings indicate that amiloride, DMA, and EIA inhibit hepatic Na+/K+-ATPase directly, reversibly, and with a relative rank order potency of EIA greater than DMA greater than amiloride. All three compounds also inhibit the hepatic uptake of alanine, and presumably could indirectly inhibit other Na+-coupled transport processes as well. 相似文献
8.
A group of 13 bacterial species from the rRNA superfamily III were tested for their ability to produce the biodegradable
polyesters poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxyvalerate [P(3HB-co-3-HV)]. Screening for polyhydroxyalkanoate production was performed on cultures obtained from solid media, rolling cultures
and shaking flasks. All 13 species were able to store a poly(3-hydroxybutyrate) homopolymer, 12 species could produce P(3-HB-co-3-HV) copolymers, but only 9 species accumulated P(3-HB-co-4-HB) copolymers. Similarities in polyhydroxyalkanoate-accumulation behaviour between closely related strains were noted.
Received: 18 December 1995/Received revision: 3 April 1996/Accepted: 28 May 1996 相似文献
9.
10.
Francesca Vittoria Sbrana Benedetta Fiordi Jessica Bordini Daniela Belloni Federica Barbaglio Luca Russo Lydia Scarfò Paolo Ghia Cristina Scielzo 《Journal of cellular and molecular medicine》2023,27(4):576-586
Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy. 相似文献