The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible initiated cells,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm3 were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 224 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules. 相似文献
Neurosurgical Review - The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications... 相似文献
The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 M dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer. 相似文献
We examined the presence of cell surface aminopeptidase on culturedporcine granuiosa cells by employing the aminopeptidase assayusing alanine-p-nitroanilide and histochemical staining usingL-leucyl-β-naphthylamide. Porcine granuiosa cells obtainedfrom follicles 4–5 mm in diameter were cultured for 7days. The aminopeptidase assay showed that the porcine granuiosacell culture had aminopeptidase activity and that this activitywas inhibited in a dose-dependent manner by bestatin which bindsto cell surfaces and inhibits cell surface aminopeptidases.Histochemical staining also indicated that cultured granuiosacells had aminopeptidase activity. Porcine granuiosa cells werecultured in the presence or absence of porcine follicle stimulatinghormone (FSH, 3.125 nmol/1) and/or bestatin (0.4, 4.0 and 40.0µ/ml) for 7 days, and the production of progesterone andoestradiol was measured. In the presence of porcine FSH, theproduction of progesterone and oestradiol by granuiosa cellswas increased significantly by 5- and 2-fold respectively. Theseincreases were enhanced further by bestatin (40.0 (µg/ml).In the absence of porcine FSH, progesterone production was enhancedby bestatin (40.0 µg/ml), whereas no significant effectof bestatin on oestradiol secretion was observed. These findingsindicate that the inhibition of membrane-bound amino-peptidase(s)on the cell surfaces affects the steroidogenesis of granuiosacells, and that these aminopeptidase(s) are important regulatorsof granuiosa cell differentiation. 相似文献
Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.
Objective. The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA).Methods. The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17–87) years; median (range) disease duration, 8 (0.6–48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2–16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group).Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM.Results. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group.Conclusions. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX. 相似文献
The main mechanism of restenosis after directional coronary atherectomy (DCA) remains obscure. We investigated mechanisms of restenosis after DCA in different coronary artery remodeling patterns. DCA was performed in 51 de novo lesions. The lesions were evaluated by intravascular ultrasound (IVUS) before, immediately after, and 6 months after the procedure. According to the IVUS findings before DCA, we classified the lesions into the following 3 groups: (1) positive (n = 10), (2) intermediate (n = 25), and (3) negative (n = 16) remodeling. We measured lumen area, vessel area, and plaque area using IVUS before DCA, immediately after DCA, and at follow-up. Lumen area increase after DCA was mainly due to plaque area reduction in the positive and intermediate remodeling groups (90 plus minus 15% and 80 plus minus 25% increase in lumen area, respectively), whereas that in the negative remodeling group was due to both plaque area reduction (57 plus minus 22% increase in lumen area) and vessel area enlargement (43 plus minus 33% increase in lumen area). The plaque area increase correlated strongly with late lumen area loss in the positive and intermediate remodeling groups (r = 0.884, p <0.001; r = 0.626, p <0.001, respectively), but the decrease in vessel area was not correlated with lumen area loss. In contrast, both an increase in plaque area and a decrease in vessel area were correlated with late lumen area loss (r = 0.632, p = 0.009; r = 0.515, p = 0.041) in the negative remodeling group. Coronary artery restenosis after atherectomy was primarily due to an increase in plaque in the positive and/or intermediate remodeling groups. However, in the negative remodeling group, late lumen loss might have been caused by both an increase in plaque and vessel shrinkage. 相似文献