scholarly journals Lack of effect of metofluthrin and sodium phenobarbital on replicative DNA synthesis and Ki-67 mRNA expression in cultured human hepatocytes

2015 ◽  
Vol 4 (4) ◽  
pp. 901-913 ◽  
Author(s):  
Tomoya Yamada ◽  
Hiroko Kikumoto ◽  
Brian G. Lake ◽  
Satoshi Kawamura

High doses of metofluthrin have been shown to produce hepatocellular tumours in rats.

Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.


1975 ◽  
Vol 21 (11) ◽  
pp. 1849-1854 ◽  
Author(s):  
C. L. Kemp ◽  
K. M. Malloy

Caffeine and the acridine dyes, acridine orange and acriflavine, were used to examine the repair potential in Eudorina elegans following ultraviolet irradiation. Acridines blocked photoreactivation primarily as a result of absorption of photoreactivating wavelengths, but acridines did not influence dark survival. Therefore, an acridine-sensitive excision–resynthesis–repair process is absent in Eudorina.Caffeine decreased both dark and light survival, the latter only after relatively high doses of ultraviolet light were used for inactivation. The caffeine-sensitive repair process appears to function most actively when the organisms are engaged in DNA synthesis, indicating that a postreplication–repair system exists in Eudorina. However, the data suggest that a repair system not associated with the DNA synthetic phases may also exist.


2002 ◽  
Vol 12 (5-6) ◽  
pp. 325-334 ◽  
Author(s):  
Narayanan Parameswaran ◽  
Carolyn Hall ◽  
Barbara Boeck ◽  
Harvey Sparks ◽  
Kathleen Gallo ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Li Jia ◽  
Kuijin Xue ◽  
Junheng Liu ◽  
Ola A. Habotta ◽  
Lianhai Hu ◽  
...  

Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.


2018 ◽  
Vol 6 (2) ◽  
pp. e00386 ◽  
Author(s):  
Brandon T. Gufford ◽  
Jason D. Robarge ◽  
Michael T. Eadon ◽  
Hongyu Gao ◽  
Hai Lin ◽  
...  

1997 ◽  
Vol 15 (10) ◽  
pp. 3249-3257 ◽  
Author(s):  
E A Levine ◽  
T Holzmayer ◽  
S Bacus ◽  
E Mechetner ◽  
R Mera ◽  
...  

PURPOSE In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS. PATIENTS AND METHODS Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay. RESULTS P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival. CONCLUSION P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.


1999 ◽  
Vol 73 (8-9) ◽  
pp. 451-456 ◽  
Author(s):  
Susan C. Hasmall ◽  
Neil H. James ◽  
Neil Macdonald ◽  
Douglas West ◽  
Stephan Chevalier ◽  
...  

2013 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
R C S van Adrichem ◽  
L J Hofland ◽  
R A Feelders ◽  
M C De Martino ◽  
P M van Koetsveld ◽  
...  

Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied. Tumoral mRNA expression of IGF-related genes (IGFs: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.


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