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R Liu

Publications and source records attributed to R Liu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury.

STUDY DESIGN: Experimental laboratory investigation of the role and pathways of reactive oxygen species (ROS)-mediated motor neuron cell death in a mouse model of compression spinal cord injury. OBJECTIVES: To analyze ROS-mediated oxidative stress propagation and signal transduction leading to motor neuron apoptosis induced by compression spinal cord injury. SETTING: University of Louisville Health Science Center. METHODS: Adult C57BL/6J mice and transgenic mice overexpressing SOD1 were severely lesioned at the lumbar region by compression spinal cord injury approach. Fluorescent oxidation, oxidative response gene expression and oxidative stress damage markers were used to assay spinal cord injury-mediated ROS generation and oxidative stress propagation. Biochemical and immunohistochemical analyses were applied to define the ROS-mediated motor neuron apoptosis resulted from compression spinal cord injury. RESULTS: ROS production was shown to be elevated in the lesioned spinal cord as detected by fluorescent oxidation assays. The early oxidative stress response markers, NF-kappaB transcriptional activation and c-Fos gene expression, were significantly increased after spinal cord injury. Lipid peroxidation and nucleic acid oxidation were also elevated in the lesioned spinal cord and motor neurons. Cytochrome c release, caspase-3 activation and apoptotic cell death were increased in the spinal cord motor neuron cells after spinal cord injury. On the other hand, transgenic mice overexpressing SOD1 showed lower levels of steady-state ROS production and reduction of motor neuron apoptosis compared to that of control mice after spinal cord injury. CONCLUSION: These data together provide direct evidence to demonstrate that the increased production of ROS is an early and likely causal event that contributes to the spinal cord motor neuron death following spinal cord injury. Thus, antioxidants/antioxidant enzyme intervention combined with other therapy may provide an effective approach to alleviate spinal cord injury-induced motor neuron damage and motor dysfunction.

Animals↗
PubMed2005

Radioprotection by fullerenols of Stylonychia mytilus exposed to gamma-rays.

The aim was to study the protective effects of fullerenols, C60(OH)x, on Stylonychia mytilus cells exposed to 60Co gamma-rays and the probable mechanisms of fullerenols protection. Ciliated protozoans Smytilus, kept in solutions of fullerenols at different concentrations, were irradiated with 60Co gamma-rays to various dose levels. Surviving cells were counted each day over 5 days after irradiation, and the surviving fraction was calculated. The relations of the surviving fraction to radiation dose and to fullerenols concentration were studied. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and lipofusion (LIP) levels in S. mytilus were also measured. The surviving fraction of S. mytilus decreased with increasing gamma-ray doses from 100 to 2000 Gy. Fullerenols enhanced the surviving fraction, except for the highest gamma-ray dose level. The maximum protection by fullernols occurred at a concentration of 0.10 mg ml(-1). However, fullerenols at concentration of 0.25 mg ml(-1) yielded a surviving fraction lower than that for the control sample. Fullerenols at a concentration of 0.10 mg ml(-1) increased the SOD and CAT activities in the gamma-ray plus fullerenols (gamma + F) group compared with the levels in both the gamma-ray (gamma) group (p < 0.01) and the control group (p < 0.01). The MDA and LIP levels in the gamma + F groups (p < 0.01) were significantly lower than that in both the control group (p < 0.05) and the gamma group (p < 0.01). At a concentration of 0.25 mg ml(-1), fullerenols reduced the SOD and CAT activities, but increased the MDA and LIP level compared with the control. There was no significant difference in SOD and CAT activities between the gamma + F group and gamma group. While the MDA and LIP level in the gamma + F and gamma groups were similar at a dose of 500 Gy, the LIP level in the gamma + F group was significantly higher than that in the gamma group (p < 0.01) at a dose of 2000 Gy. Fullerenols are good radiation protectors for the protozoan S. mytilus exposed to gamma-rays. The effectiveness of radioprotection depends on both fullerenols concentration and gamma-ray dose. The protective effect of fullerenols on damage induced by gamma-rays seems to be mediated, at least in part, through their anti-oxidative and radical scavenging activities.

Animals↗
PubMed2005

Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries.

We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating 'one-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

Alkaline Phosphatase↗
PubMed2004

Microwave-assisted extraction followed by gas chromatography-mass spectrometry for the determination of endocrine disrupting chemicals in river sediments.

In this study, microwave-assisted extraction (MAE) followed by gas chromatography (GC)-mass spectrometry (MS) analysis has been successfully developed for the simultaneous extraction and determination of contrasting endocrine disrupting chemicals (EDCs) including 17beta-estradiol, estrone, 17(alpha-ethynylestradiol, 16alpha-hydroxyestrone, 4-nonylphenol, 4-tert-octylphenol and bisphenol A in river sediments. For MAE, the effects of various parameters on the extraction efficiency were investigated. It is shown that the most efficient extraction (recovery > 74%) of the target compounds was achieved by using methanol as the solvent, an extraction temperature of 110 degrees C and 15 min of holding time. The cleanup of extracts was carried out by passage through a non-deactivated silica gel column, and a satisfactory elution efficiency of all compounds was achieved using a solvent mixture of ethyl acetate-hexane (4:6, v/v). The spiking experiments show that the mean recovery of the target compounds exceeded 61% at a spiking level of 5 ng/g dry mass, and 73% at 10, 40 and 100 ng/g dry mass with a good reproducibility. The method developed was applied to the determination of target EDCs in river sediments collected from rivers Uck and Ouse, UK, and results revealed the presence of the chosen compounds at low ng/g level.

Endocrine Glands↗
PubMed2004

Effect of re-expansion after short-period lung collapse on pulmonary capillary permeability and pro-inflammatory cytokine gene expression in isolated rabbit lungs.

BACKGROUND: Re-expansion pulmonary oedema is a rare complication caused by rapid re-expansion of a chronically collapsed lung. Several cases of pulmonary oedema associated with one-lung ventilation (OLV) have been reported recently. Elevated levels of pro-inflammatory cytokines in pulmonary oedema fluid are suggested to play important roles in its development. Activation of cytokines after re-expansion of collapsed lung during OLV has not been thoroughly investigated. Here we investigated the effects of re-expansion of the collapsed lung on pulmonary oedema formation and pro-inflammatory cytokine expression. METHODS: Lungs isolated from female white Japanese rabbits were perfused and divided into a basal (BAS) group (n=7, baseline measurement alone), a control (CONT) group (n=9, ventilated without lung collapse for 120 min) and an atelectasis (ATEL) group (n=9, lung collapsed for 55 min followed by re-expansion and ventilation for 65 min). Pulmonary vascular resistance (PVR) and the coefficient of filtration (Kfc) were measured at baseline and 60 and 120 min. At the end of perfusion, bronchoalveolar lavage fluid/plasma protein ratio (B/P), wet/dry lung weight ratio (W/D) and mRNA expressions of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and myeloperoxidase (MPO) were determined. RESULTS: TNF-alpha and IL-1beta mRNA were significantly up-regulated in lungs of the ATEL group compared with BAS and CONT, though no significant differences were noted in PVR, Kfc, B/P and W/D within and between groups. MPO increased at 120 min in CONT and ATEL groups. CONCLUSION: Pro-inflammatory cytokines were up-regulated upon re-expansion and ventilation after short-period lung collapse, though no changes were noted in pulmonary capillary permeability.

Animals↗
PubMed2004

Simultaneous determination of endocrine disrupting phenolic compounds and steroids in water by solid-phase extraction-gas chromatography-mass spectrometry.

A solid-phase extraction (SPE)-gas chromatography (GC)-mass spectrometry (MS) analytical method for the simultaneous separation and determination of endocrine disrupting chemicals (EDCs) from water samples is described in detail. Important and contrasting EDCs including estrone, 17beta-estradiol, 17beta-ethynylestradiol, 16beta-hydroxyestrone, 4-nonylphenol, bisphenol A and 4-tert-octylphenol were selected as the target compounds. The SPE technique, followed by the derivatisation with bis (trimethylsilyl) trifluoroacetamide was used for the extraction recoveries of target compounds from water samples. A number of parameters that may affect the recovery of EDCs, such as the type of SPE cartridges, eluents, as well as water properties including pH value, and concentration of salts and humic substances were investigated. It is shown that the Oasis cartridges produced the best recoveries of target EDCs while ethyl acetate was efficient in eluting EDCs from SPE cartridges. The recovery of some EDCs was enhanced by the addition of salt, but reduced by the increase in pH value and humic acid concentration. The optimised method was further verified by performing spiking experiments in natural river water and seawater matrices, with good recovery and reproducibility for all the selected compounds. The established method was successfully applied to environmental water samples from East and West Sussex, UK, for the determination of the target EDCs.

Calibration↗
PubMed2004

Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea.

Chronic intermittent hypoxia (CIH), as occurs in obstructive sleep apnea (SA), is associated with substantial cortico-hippocampal damage leading to impairments of neurocognitive, respiratory and cardiovascular functions. Previous studies in a rat model have shown that CIH increases brain cortical neuronal cell death. However, the molecular events leading to CIH-mediated neuronal cell death remain largely undefined. The oscillation of O2 concentrations during CIH remarkably mimics the processes of ischemia/re-oxygenation and could therefore increase cellular production of reactive oxygen species (ROS). We extended the CIH paradigm to a mouse model of SA to identify the molecular mechanisms underlying cortical neuronal cell death. A significant increase of ROS production in mouse brain cortex and cortical neuronal cells was detected by fluorescent oxidation assays upon exposure of mice to CIH, followed by increased expression of oxidative stress response markers, c-Fos, c-Jun and NF-kappaB in mouse brain cortex, as revealed by immunohistochemical and LacZ reporter assays respectively. Long-term exposure of mice to CIH increased the levels of protein oxidation, lipid peroxidation and nucleic acid oxidation in mouse brain cortex. Furthermore, exposure of mice to CIH induced caspase-3 activation and increased some cortical neuronal cell apoptosis. On the other hand, transgenic mice overexpressing Cu,Zn-superoxide dismutase exposed to CIH conditions had a lower level of steady-state ROS production and reduced neuronal apoptosis in brain cortex compared with that of normal control mice. Taken together, these findings suggest that the increased ROS production and oxidative stress propagation contribute, at least partially, to CIH-mediated cortical neuronal apoptosis and neurocognitive dysfunction.

Animals↗
PubMed2004

Astrocytes in injured adult rat spinal cord may acquire the potential of neural stem cells.

It has been well documented that in adult rats astrocytes in the subventricular zone and subgranular layer of the dentate gyrus are neural stem cells. Elsewhere in the CNS astrocytes are not generally recognized as stem cells. Here we describe nestin expression in a population of astrocytes in the spinal cord of adult rat following cord injury. In either hemitransectioned or longitudinally cut spinal cord, there was widespread nestin expression in astrocytes of both the gray and white matters. Isolation of the lateral part of the spinal cord from the central canal region, where stem cells may reside, could not block the appearance of nestin-immunoreactive astrocytes in the lateral cord, and none of them showed Fast DiI labeling after the central canal ependyma had been labeled by the dye, indicating that the nestin-immunoreactive astrocytes can evolve locally in the lateral cord. They were found to be undergoing a process of de-differentiation. Culture of the nestin-immunoreactive astrocytes of the lateral cord generated neurospheres, the cells of which had the ability of self-renewal, and were able to differentiate into neurons, astrocytes, or oligodendrocytes. Taken together, the results indicate that the astrocytes in injured adult rat spinal cord may acquire the potential of neural stem cells.

Animals↗
PubMed2004

Mechanisms for macula densa cell release of renin.

The juxtaglomerular apparatus in the kidney is important in controlling extracellular fluid volume and renin release. The fluid load to the distal tubule is first sensed at the macula densa site via the entry of NaCl, through a Na, K, 2Cl co-transport mechanism. The next step is unclear, but there is recent evidence of an increased macula densa cell calcium concentration with a reduction in fluid load to the macula densa. An increase in macula densa cell calcium could activate phospholipase A2 to release arachidonic acid, the rate-limiting step in the formation of prostaglandins. Recent evidence suggests that the prostaglandin formed is PGE2, a potent stimulator for renin release. Recent evidence has also shown that adenosine has an important function in the juxtaglomerular apparatus. It stimulates calcium release in afferent arteriolar smooth muscle cells, leading to contraction of the afferent arteriole as part of the tubuloglomerular feedback mechanism, and inhibits renin release. Thus, renin release from the afferent arteriole is mediated partly through formation of PGE2, and partly through the reduction of adenosine formation that inhibits renin production.

Animals↗
PubMed2003

Ciliary neurotrophic factor improves diabetic parameters and hepatic steatosis and increases basal metabolic rate in db/db mice.

Obesity plays a central role in the development of insulin resistance and type 2 diabetes. We therefore examined the effects of a modified form of ciliary neurotrophic factor [Axokine, which is hereafter referred to as ciliary neurotrophic factor (CNTF)Ax15], which uses a leptin-like mechanism to reduce body weight, in the db/db murine model of type 2 diabetes. In previous studies, weight loss produced by CNTF treatment could largely be attributed to its effects on food intake. In contrast, CNTFAx15 treatment of db/db mice caused significantly greater weight loss and marked improvements in diabetic parameters (e.g., levels of glucose, insulin, triglyceride, cholesterol, and nonesterified free fatty acids) than could be accounted for by reduced caloric intake alone. These beneficial effects, above and beyond those seen in animals controlled for either food restriction or body weight, correlated with the ability of CNTFAx15 to increase metabolic rate and energy expenditure and reduce hepatic steatosis while enhancing hepatic responsiveness to insulin. The hepatic effects were linked to rapid alterations in hepatic gene expression, most notably reduced expression of stearoyl-CoA desaturase 1, a rate-limiting enzyme in the synthesis of complex lipids that is also markedly suppressed by leptin in ob/ob mice. These observations further link the mechanisms of CNTF and leptin action, and they suggest important, beneficial effects for CNTF in diabetes that may be distinct from its ability to decrease food intake; instead, these effects may be more related to its influence on energy expenditure and hepatic gene expression.

Animals↗
PubMed2003

Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats.

Tau hyperphosphorylation leads to formation of paired helical filament/neurofibrillary tangles, the hallmark lesion seen in Alzheimer's disease (AD) brain. An imbalanced regulation in protein kinases and protein phosphatases in the affected neurons is proposed to be a reasonable causative factor to the disease process. To verify the hypothesis, we have injected in the present study calyculin A, a potent and specific inhibitor of protein phosphatase (PP) 2A and PP1, into rat hippocampus bilaterally, thus reproduced an Alzheimer's-like deficiency in dephosphorylation system. It was found that calyculin A-injected rats developed lesions in spatial memory retention in Morris water maze test. At mean time, tau was hyperphosphorylated at Ser396/Ser404 (PHF-1) and Ser-262/Ser-356 (12E8) sites determined both by immunohistochemistry and Western blot. It is implicated that (1) PP2A and PP1 participate in the in vivo regulation of tau phosphorylation, and down-regulation of the two phosphatases will result in tau hyperphosphorylation; (2) hyperphosphorylation of tau at PHF-1 and 12E8 sites might be crucial to affect spatial memory in AD.

Animals↗
PubMed2003

Visualization of nitric oxide production and intracellular calcium in juxtamedullary afferent arteriolar endothelial cells.

AIM: Nitric oxide (NO) is an important signal transmitter with multiple haemodynamic functions in the kidney. Study of these is complicated by the difficulty in measuring NO directly or visualizing its production. Recently the synthesis of a group of new NO-sensitive fluorescent dyes, diaminofluoresceins (DAF), suitable for imaging applications has been reported. We attempted to use one DAF (DAF-2 DA) to investigate the relationship between endothelial calcium, NO production and afferent arteriolar reactivity. METHODS: We used the isolated, perfused juxtamedullary nephron preparation (JMN) and loaded the afferent arteriolar endothelium with Fura-2 AM and DAF-2 DA (4,5-diaminofluorescein-2-diacetyl). After in vitro calibration of the imaging system, we measured Fura-2 and DAF-2 fluorescence in single endothelial cells of afferent arterioles (AA) perfused at a pressure of 100 mmHg. RESULTS: Carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO) (10-3 m), a specific NO scavenger, decreased DAF-2 fluorescence in the endothelium by 16.1% and the mid-afferent arteriolar diameter by 10.2%, and increased endothelial calcium by 17.8%. Nomega-nitro-l-arginine methyl ester (l-NAME) (10-4 m) decreased fluorescence intensity of DAF-2 by 18.6%, increased cellular calcium level by 19.7% and constricted the vessels by 11.6%. Addition of carbachol (10-4 m) increased average DAF-2 fluorescence by 22.8% and endothelial calcium concentration by 28.9%, whereas the arteriolar diameter remained essentially unchanged. Carbachol failed to increase DAF-2 fluorescence when administered after l-NAME pre-treatment. CONCLUSION: We conclude that endothelial NO homeostasis is an important determinant of AA reactivity and suggest that DAF are suitable for real-time imaging of afferent arteriolar NO production in the isolated, perfused JMN and may be used in combination with calcium-sensitive fluorophores. We have found that NO reduction by carboxy-PTIO or l-NAME increases endothelial calcium, suggesting involvement of calcium signalling in an autocrine NO production feedback in the endothelium. This method should help to further clarify the role of endothelial NO in renal haemodynamics.

Animals↗
PubMed2003

Analysis of complement-bound hepatitis B virus complexes by an immuno-capture polymerase chain reaction method.

Hepatitis B Virus (HBV) can be present in the circulating blood either as a free virus or as a virion-immunoglobulin (Ig) complex with or without complement. However, information regarding the complement-bound HBV circulating immune complexes (CIC) in HBV-infected patients is currently not available. In the present study, we have combined immuno-capture and polymerase chain reaction (PCR) and developed a quick method of high specificity for the detection of complement-bound HBV CIC. We found that the frequency of HBV-factor B was associated with clinical types of hepatitis B (HB) but not with that of HBV-C1q. Moreover, increased frequency at P < 0.05 were found for HBV/C1q-CIC in the group with normal total bilirubin (TBIL) and for HBV/factor B-CIC in the group with positive hepatitis B e antigen (HBeAg). These findings suggest that the immuno-capture PCR (iPCR) for the detection of HBV-bound CIC is a valuable method for analysis of the composition of the immune complexes and for the understanding of host immune response and immune pathogenesis in HBV-infected individuals. In summary, iPCR is a valuable method for analysis of the composition of the immune complexes, which may provide new and valuable insights into HBV pathogenesis.

Adolescent↗
PubMed2003

Development and characterization of potent and specific peptide inhibitors of p60c-src protein tyrosine kinase using pseudosubstrate-based inhibitor design approach.

The cytoplasmic protein p60c-src, an ubiquitous non-receptor protein tyrosine kinase (PTK) is a potential anticancer target as it is over-expressed and/or constitutively active in several cancer types. In addition, the phenotype of c-src knock-out mice is consistent with osteopetrosis, which suggests that inhibitors against this enzyme may also be therapeutic for osteoporosis. Using a known peptide substrate for c-src, MIYKYYF, as a template, we have developed a series of pseudosubstrate-based peptide inhibitors. Structure-activity relationship studies have been performed on one of these inhibitors, CIYKYYF. In a kinase assay using YIYGSFK as the substrate, CIYKYY has been demonstrated to inhibit p60c-src, with an IC50 of 0.6 microm. Further truncation has led to the determination that even the smaller peptide, CIYK, is a moderately potent inhibitor with IC50 of 15 microm. Some improvement in inhibitory potency (IC50 = 11.8 microm) has been observed with the replacement of Tyr3 in CIYK with beta-phenylalanine (beta-Phe). The tetrapeptide CI(beta-Phe)K will be used as a lead compound for future development of peptidomimetics and small molecule inhibitors that have the capacity to penetrate the plasma membrane of intact cells.

Amino Acid Sequence↗
PubMed2002

Genetic transformation of two species of orchid by biolistic bombardment.

We report here the transformation of two species of orchid, Dendrobium phalaenopsis and D. nobile,by biolistic bombardment. Calli or protocorm-like bodies (PLBs) were used as target explants. Gold particles (1.0 microm) coated with plasmid DNA (pCAMBIA1301) encoding an intron-containing beta-glucuronidase gene (gus-int) and a hygromycin phosphotransferase (hpt) gene were introduced into the PLBs or calli using the Bio-Rad PDS-1000/He Biolistic Particle Delivery System. Calli and PLBs were then chopped up and pre-cultured in 1/2-strength MS medium supplemented with 0.4 M mannitol for a 1-h osmoticum treatment before bombardment. Immediately after bombardment, the calli and PLBs were transferred to 1/2-strength MS medium without mannitol for recovery. Putatively transformed plantlets were obtained by selection and regeneration on medium supplemented with 30 mg/l hygromycin. The highest efficiency of transformation was obtained when selection was conducted at 2 days post-bombardment. For D. phalaenopsis and D. nobile, respectively, about 12% and 2% of the bombarded calli or PLBs produced independent transgenic plants. Integration and expression of the transgenes were confirmed by Southern hybridization and Northern hybridization. No nontransformed plants were regenerated, indicating a tight selection scheme. However, separate incorporation of the gus gene and the hpt gene was observed, and in one transgenic line the gus gene was integrated into the genome of the transgenic plant, but not expressed.

Biolistics↗
PubMed2002

Nitric oxide modulates and adenosine mediates the tubuloglomerular feedback mechanism.

The tubuloglomerular feedback (TGF) mechanism is an important regulator of the glomerular filtration rate (GFR) and urine excretion rate. It operates by sensing the distal delivery of fluid at the macula densa site and adjusting the tone of the glomerular arterioles to control GFR. We found evidence that nitric oxide is an important modulator of the setting of the sensitivity of the TGF mechanism. Studies on adenosine A1 receptor deficient mice have shown that these animals lack the TGF response and have an increased renin release. These findings show the important role of adenosine as a mediator of the signal for the TGF mechanism and as an inhibitor of renin release.

Adenosine↗
PubMed2001

Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells.

Signal transducers and activators of transcription (STATs) are transcription factors activated in response to cytokines and growth factors. Constitutively active Stat3 has been shown to mediate oncogenic transformation in cultured cells and induce tumor formation in mice. An increasing number of tumor-derived cell lines as well as samples from human cancer have been reported to express constitutively active Stat3 protein. We previously demonstrated that ovarian cancer cell lines express high levels of constitutively active Stat3. In this study, we show that inhibition of the Stat3 signaling pathway using the Janus Kinase-selective inhibitor, AG490, and a dominant negative Stat3 (Stat3beta) significantly suppresses the growth of ovarian and breast cancer cell lines harboring constitutively active Stat3. In the ovarian cancer cell lines, AG490 also diminished the phosphorylation of Stat3, Stat3 DNA binding activity, and the expression of Bcl-x(L). Further, AG490 induced significant apoptosis in ovarian and breast cancer cell lines expressing high levels of constitutively active Stat3 but had a less profound effect on normal cells lacking constitutively active Stat3. AG490 also enhanced apoptosis induced by cisplatin in ovarian cancer cells. These results suggest that inhibition of Stat3 signaling may provide a potential therapeutic approach for treating ovarian and breast cancers.

Apoptosis↗