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91.
92.
Hepatocyte growth factor stimulates the growth and activates mitogen-activated protein kinase in human hepatoma cells 总被引:4,自引:0,他引:4
Hsuan-Shu Lee A-Mei Huang Guan-Tarn Huang Pei-Ming Yang Pei-Jer Chen Jin-Chuan Sheu Ming-Yang Lai Sheng-Chung Lee Chen-Kung Chou Ding-Shinn Chen MD 《Journal of biomedical science》1998,5(3):180-184
Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and various epithelial cells. Unexpectedly, it has been reported to inhibit the growth of hepatoma cells in vitro. To clarify this phenomenon, we examined the effects of recombinant baculovirus-expressed HGF on the growth of 6 human hepatoma cell lines. The growth of Hep3B and HepG2 cells was markedly stimulated to 1.8- and 1.7-fold, respectively, PLC/PRF/5 to 1.4-fold, and SK-Hep-1 to 1.2-fold in a dose-dependent manner under HGF concentrations below 20 ng/ml. Neither HuH-7 nor HCC36 were affected. None of these cells were inhibited. All these cells expressed c-Met, the membrane receptor for HGF, and their c-Met would be activated to be phosphorylated upon addition of HGF. They also contained the ERK2 subgroup of mitogen-activated protein kinases (MAPKs). When HGF was added, their ERK2 would also be phosphorylated. The extent of ERK2 phosphorylation was partially correlated to their growth response to HGF. In conclusion, HGF could stimulate the growth of certain human hepatoma cells, probably through activation of c-Met and MAPKs. 相似文献
93.
Experimental vaccine strategies for cancer immunotherapy 总被引:10,自引:0,他引:10
Recently, cancer immunotherapy has emerged as a therapeutic option for the management of cancer patients. This is based on the fact that our immune system, once activated, is capable of developing specific immunity against neoplastic but not normal cells. Increasing evidence suggests that cell-mediated immunity, particularly T-cell-mediated immunity, is important for the control of tumor cells. Several experimental vaccine strategies have been developed to enhance cell-mediated immunity against tumors. Some of these tumor vaccines have generated promising results in murine tumor systems. In addition, several phase I/II clinical trials using these vaccine strategies have shown extremely encouraging results in patients. In this review, we will discuss many of these promising cancer vaccine strategies. We will pay particular attention to the strategies employing dendritic cells, the central player for tumor vaccine development. 相似文献
94.
95.
Deysi V. T. Wong Roberto C. P. Lima-Júnior Cibele B. M. Carvalho Vanessa F. Borges Carlos W. S. Wanderley Amanda X. C. Bem Caio A. V. G. Leite Maraiza A. Teixeira Gabriela L. P. Batista Rangel L. Silva Thiago M. Cunha Gerly A. C. Brito Paulo R. C. Almeida Fernando Q. Cunha Ronaldo A. Ribeiro 《PloS one》2015,10(10)
Intestinal mucositis is a common side effect of irinotecan-based anticancer regimens. Mucositis causes cell damage, bacterial/endotoxin translocation and production of cytokines including IL–1 and IL–18. These molecules and toll-like receptors (TLRs) activate a common signaling pathway that involves the Myeloid Differentiation adaptor protein, MyD88, whose role in intestinal mucositis is unknown. Then, we evaluated the involvement of TLRs and MyD88 in the pathogenesis of irinotecan-induced intestinal mucositis. MyD88-, TLR2- or TLR9-knockout mice and C57BL/6 (WT) mice were given either saline or irinotecan (75 mg/kg, i.p. for 4 days). On day 7, animal survival, diarrhea and bacteremia were assessed, and following euthanasia, samples of the ileum were obtained for morphometric analysis, myeloperoxidase (MPO) assay and measurement of pro-inflammatory markers. Irinotecan reduced the animal survival (50%) and induced a pronounced diarrhea, increased bacteremia, neutrophil accumulation in the intestinal tissue, intestinal damage and more than twofold increased expression of MyD88 (200%), TLR9 (400%), TRAF6 (236%), IL–1β (405%), IL–18 (365%), COX–2 (2,777%) and NF-κB (245%) in the WT animals when compared with saline-injected group (P<0.05). Genetic deletion of MyD88, TLR2 or TLR9 effectively controlled the signs of intestinal injury when compared with irinotecan-administered WT controls (P<0.05). In contrast to the MyD88-/- and TLR2-/- mice, the irinotecan-injected TLR9-/- mice showed a reduced survival, a marked diarrhea and an enhanced expression of IL–18 versus irinotecan-injected WT controls. Additionally, the expression of MyD88 was reduced in the TLR2-/- or TLR9-/- mice. This study shows a critical role of the MyD88-mediated TLR2 and TLR9 signaling in the pathogenesis of irinotecan-induced intestinal mucositis. 相似文献
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97.
Flávio Teles Tarcilo Machado da Silva Francisco Pessoa da Cruz Júnior Vitor Hugo Honorato Henrique de Oliveira Costa Ana Paula Fernandes Barbosa Sabrina Gomes de Oliveira Zenaldo Porfírio Alexandre Braga Libório Raquel Lerner Borges Camilla Fanelli 《PloS one》2015,10(1)
The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection. 相似文献
98.
Borges R Pereda D Beltrán B Prunell M Rodríguez M Machado JD 《Cellular and molecular neurobiology》2010,30(8):1359-1364
Chromaffin granules are similar organelles to the large dense core vesicles (LDCV) present in many secretory cell types including
neurons. LDCV accumulate solutes at high concentrations (catecholamines, 0.5–1 M; ATP, 120–300 mM; or Ca2+, 40 mM (Bulenda and Gratzl Biochemistry 24:7760–7765, 1985). Solutes seem to aggregate to a condensed matrix to elude osmotic lysis. The affinity of solutes for LDCV matrix is responsible
for the delayed release of catecholamines during exocytosis. The aggregation of solutes occurs due to a specific H+ pump denominated V-ATPase that maintains an inner acidic media (pH ≈5.5). This pH gradient against cytosol is also responsible
for the vesicular accumulation of amines and Ca2+. When this gradient is reduced by modulation of the V-ATPase activity, catecholamines and Ca2+ are moved toward the cytosol. In addition, some drugs largely accumulate inside LDCV and not only impair the accumulation
of natural solutes, but also act as false neurotransmitters when they are co-released with catecholamines. There is much experimental
evidence to conclude that the physiological modulation of vesicle pH and the manipulation of intravesicular media with drugs
affect the LDCV cargo and change the kinetics of exocytosis. Here, we will present some experimental data demonstrating the
participation of drugs in the kinetics of exocytosis through changes in the composition of vesicular media. We also offer
a model to explain the regulation of exocytosis by the intravesicular media that conciliate the experimentally obtained data. 相似文献
99.
Vinod R. Hegde Scott Borges Haiyan Pu Mahesh Patel Vincent P. Gullo Bonnie Wu Paul Kirschmeier Michael J. Williams Vincent Madison Thierry Fischmann Tze-Ming Chan 《Bioorganic & medicinal chemistry letters》2010,20(4):1384-1387
Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure–activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature. 相似文献
100.
This article serves as a brief history and review of EBM—how EBM developed, its strengths and limitations, and the need for constant improvements. Hopefully, this review will have enhanced your understanding of EBM and its importance and stimulated you to apply EBM to your own practice. As more data and therapies become available, and as clinical guidelines continue to evolve based on EBM, we should expect patient outcomes to improve. 相似文献