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Biomedical subjects

T Tanabe

Publications and source records attributed to T Tanabe.

At least 109 records · Page 6Linked to original sources
PubMed2000

Purification and characterization of a 49-kDa chitinase from Streptomyces griseus HUT 6037.

A 49-kDa chitinase (pI7.3) was purified to homogeneity from the culture supernatant of Streptomyces griseus HUT 6037 by ultrafiltration, DEAE-Sephadex A-50 and Sephadex G-100 column chromatographies, and chromatofocusing. The purified enzyme was stable up to 40 degrees C. The N-terminal amino acid sequence of the enzyme was highly homologous to the N-terminal region of the fibronectin type III-like domain of S. olivaceoviridis chitinase 01 belonging to family 18 glycosyl hydrolases. The 49-kDa chitinase hydrolyzed partially N-acetylated chitosan more easily than colloidal chitin. The hydrolyzate of 54% deacetylated chitosan by the enzyme was separated by CM-Sephadex C-25 column chromatography. The structures of the oligosaccharides obtained were determined by MALDI-TOF MS analysis combined with exo-glycosidase digestion. In addition to GlcNAc, (GlcNAc)2, and (GlcNAc)3, hetero-chitooligosaccharides with GlcNAc at the reducing end were detected. Thus, the specificity of the enzyme for the hydrolysis of the beta-1,4-glycosidic linkages in partially N-acetylated chitosan was similar to that of the family 18 chitinases.

Journal Article↗
PubMed2000

Maxizymes, novel allosterically controllable ribozymes, can be designed to cleave various substrates.

We demonstrated previously that an allosterically controllable novel ribozyme, designated the maxizyme, is a powerful tool for disruption of an abnormal chimeric RNA target [BCR-ABL (b2a2) mRNA], and we proposed that it might provide the basis for future gene therapy for the treatment of chronic myelogenous leukemia (Kuwabara et al. Mol. Cell 1998, 2, 617-627). The maxizyme has sensor arms that can recognize a specific sequence and, in the presence exclusively of such a specific sequence, it can form a cavity for capture of catalytically indispensable Mg2+ ions. Cleavage of the target RNA then occurs at a site distant from the specific sequence. Clearly, the specific sequences recognized by sensor arms should not be limited to those of the above mentioned abnormal chimeric target. Thus, to demonstrate the general applicability of maxizyme technology, we constructed maxizymes targeted to other mRNAs, such as PML-RAR alpha mRNA, sDLST mRNA, and BCR-ABL (b1a2) mRNA, that are not cleaved with high specificity by the wild-type hammerhead ribozyme. Specific and efficient cleavage in vitro of these mRNAs by the custom-designed maxizymes demonstrated clearly that maxizyme technology is not limited to a specific case but may have broad general applicability in molecular biology and, also, in a clinical setting.

Autoradiography↗
PubMed2000

Inhibition of the glioblastoma cell cycle by type I IFNs occurs at both the G1 and S phases and correlates with the upregulation of p21(WAF1/CIP1).

The antiproliferative effect of IFNalpha was tested on the human glioblastoma cell lines, U-373MG and T98G. IFNalpha significantly inhibited the growth of both cell lines, but was more effective in retarding the growth of U-373MG cells. Flow cytometry analysis indicated that synchronized IFNalpha-treated U-373MG cells showed a strong block in the progression of cells out of the S phase of the cell cycle. T98G cells, on the other hand, showed a moderate delay in the transition of cells from G1 to S phase and only a slight delay in the S phase, consistent with the decreased antiproliferative effect of IFNalpha on this cell line. IFNalpha-treated cells were then tested for the induction of the tumor suppressor gene product, p21(WAF1/CIP1). Higher levels of p21(WAF1/CIP1) were detected in lysates from IFNalpha-treated U-373MG cells as compared to media controls for as long as 18 h. In IFNalpha-treated T98G cells, p21(WAF1/CIP1) levels were slightly elevated at 4 and 6 h, but decreased to levels similar to controls thereafter, correlating with the antiproliferative effects of IFNalpha on each cell line. Immunoprecipitation studies on lysates from IFNalpha-treated U-373MG and T98G cells indicated that increased amounts of p21(WAF1/CIP1) were complexed to both cyclin D1 and cyclin E. Further, reduced cyclin-dependent kinase 2 (cdk2) activity was found in both IFNalpha-treated U-373MG and T98G cells, suggesting a mechanism by which p21(WAF1/CIP1) exerted its antiproliferative effects. Lastly, we analyzed the time-dependent production of the cyclins D1, E, and A. No differences in cyclin D1 levels were found between IFNalpha-treated and media-treated U-373MG and T98G cells. However, both IFNalpha-treated U-373MG and T98G cells showed a prolonged elevation in cyclin E, correlating with the G1 to S phase delays observed in these cell lines. Further, the duration of cyclin E production corresponded with the magnitude of the cell cycle delays seen in IFNalpha-treated U-373MG and T98G cells. Prolonged elevation of cyclin A was also seen in both IFNalpha-treated U-373MG and T98G cells, the magnitude of which correlated with the S phase delay observed in these cell lines. Thus, the data indicate that IFNalpha has significant antiproliferative activity against glioblastoma cells that is mediated, at least in part, by the tumor suppressor gene product, p21(WAF1/CIP1).

Brain Neoplasms↗
PubMed2000

Attenuation of KATP channel-opener induced shortening of repolarization time by alpha 1-adrenoceptor antagonist during ischemia in canine heart.

The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolarization time can be related to the KATP channel activity. The anterior descending branch of the left coronary artery was ligated four times for 5 minutes, separated by 15 minutes of reperfusion (stages 1-4) to test the dose-dependent effect of drugs on repolarization. Dogs received either vehicle (n = 9), Y (0.4, 2.0, and 4.0 micrograms/kg at stages 2, 3, and 4, respectively, with 0.4 microgram/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at each of stages 2-4, n = 8), or a combination of these two drugs (BN + Y, the same dose of BN and Y in groups BN and Y, respectively, n = 9). Drugs were administered into the left atrium. The monophasic action potential (MAP) and regional electrograms were recorded. The MAP90 and the duration of the slow deflections (DSD) of the regional electrogram were used as markers of repolarization. The Vmax of the MAP and the rapid deflections (DRD) of the regional electrogram were used as markers of conduction. Y augmented an ischemia-induced shortening of MAP90 and DSD in proportion to an increase in the dose given and the plasma concentration (P < .05-.01), especially at the epicardial site. BN and BN + Y blunted the ischemia-related shortening of MAP90 and DSD, causing a reduction in repolarization time dispersion between the ischemic and normal zones. There were no significant changes in the Vmax or DRD in the ischemic zone between periods before and after an increase in each drug dose in the four groups. None of the seven dogs developed ventricular tachycardia (VT)/ventricular fibrillation (VF) in the Y group, whereas two of the eight dogs in the BN group, three of the nine dogs in the BN + Y group, and three of the nine dogs in the control group developed VT/VF. These results suggest that the alpha 1-adrenergic blocker bunazosin blunts the shortening effect of KATP channel activator on repolarization time, and that the KATP channel opener Y may be antiarrhythmic, although the repolarization time dispersion during myocardial ischemia is increased.

ATP-Binding Cassette Transporters↗
PubMed2000

The behavior and effect of isopoly (S-carboxymethyl-L-cysteine) derivatives of nucleic acid bases.

Isopoly(S-carboxymethyl-L-cysteine) derivatives of nucleic acid bases were prepared as antisense compounds. These compounds in vitro have been found to form stable complex with oligo-DNA or RNA. This paper deals with effect of antisense compounds in vivo. The target in this paper is the sequence of the PSD-95 protein linked with NMDA receptor. Excess passing of calcium ions through the loss of the signal pathway without PSD-95 proteins caused by antisense compound. The cells detailing with L-cysteine derivatives showed the lowest percentage of 19.1%. The data were compared with that of phosphotioate antisense compound.

Animals↗
PubMed2000

Detection of capillary protein leakage by indocyanine green and glucose dilutions in septic patients.

OBJECTIVE: To determine whether indocyanine green (ICG) and glucose dilutions can detect generalized capillary protein leakage in septic patients without requiring repeated measurements. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Twelve consecutive patients who met the criteria of sepsis and 16 consecutive acute myocardial infarction (AMI) patients without any underlying pathology inducing generalized protein capillary leakage. INTERVENTIONS: Both ICG 25 mg and glucose 5 g were administered simultaneously, to calculate the plasma volume determined by the ICG dilution method (PV-ICG) and the initial distribution volume of glucose (IDVG), on day 1 of sepsis or on day 1 of hospitalization for the AMI patients. The relationship between these two volumes and the PV-ICG/IDVG ratio was evaluated in two patient groups. MEASUREMENTS AND MAIN RESULTS: Although the IDVG of the two patient groups was not statistically different, the PV-ICG in the septic patients was higher than that in the AMI patients (p < .01). Consequently, the PV-ICG/IDVG ratio in the septic patients was higher than that in the AMI patients (p < .01). Eight of the 12 septic patients had a PV-ICG/IDVG ratio of >0.45, which was not observed in any of the AMI patients. The PV-ICG/IDVG ratio in the septic patients correlated inversely with the total plasma protein concentration (r2 = .46, p < .025) and mean arterial pressure (r2 = .42, p < .05). CONCLUSIONS: Our results indicate that overestimation of the PV-ICG can occur in septic patients and, further, suggest that simultaneous measurement of the two distribution volumes would help predict generalized capillary protein leakage in septic patients without repeated measurement.

Adult↗
PubMed2000

Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart.

To clarify the role of the natriuretic peptide (NP) system in the myocardial protective effects of carvedilol, a beta-blocking agent, we investigated the effects of carvedilol on the NP system in the rat heart. After oral administration of carvedilol (low-dose group: 2 mg/kg/day, group C2; high-dose group: 20 mg/kg/day, group C20) for 1 week, plasma rat atrial NP (r-ANP), atrial mRNA levels of ANP, left ventricular mRNA of brain NP (BNP), NP receptor-A and NP receptor-C (NPR-C) (as a clearance receptor) were measured. Values were compared with those in vehicle-treatment rats (group V). The concentration of r-ANP was significantly higher in group C2 (135 +/- 9 pg/ml) and group C20 (161 +/- 11 pg/ml) than group V (75 +/- 6 pg/ml; both p < 0.01). ANP and BNP mRNA levels were significantly increased and NPR-C was significantly down regulated in group C2 (151 +/- 7, 120 +/- 8 and 78 +/- 7%, respectively, vs. group V) and group C20 (164 +/- 8. 133 +/- 7 and 72 +/- 8%, respectively, vs. group V) compared with group V (all p < 0.01). These results suggest that not only a high dose, but a low dose of carvedilol has the effect of increasing plasma ANP and BNP levels. This effect was closely related to the upregulation of ANP and BNP mRNA expression, and the down regulation of NPR-C mRNA expression in the heart. These mechanisms seem to account for a sizable portion of the protective effect of carvedilol for heart diseases.

Adrenergic beta-Antagonists↗
PubMed2000

[Concurrent chemoradiotherapy for locally unresectable head and neck cancer].

In patients with locally unresectable head and neck cancer with large nodal involvement, the expected five-year survival is as low as 1-2%. To improve the prognosis of these patients, we studied the usefulness of concurrent chemoradiotherapy in a phase II trial. Between September 1996 and May 1999, thirty-five patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m2 on 5 days of the week and 5FU, 150 mg/m2 as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 33 patients evaluable for response, 17 complete and 9 partial responses were noted, with an overall response rate of 79%. Oral mucostis and myelosuppression were the major side effects and mucositis was a dose limiting toxicity. This study demonstrates increase in survival among the responders (complete + partial) in the concurrent chemoradiotherapy setting. However 8 local relapses were eventually noted in the 17 complete responders. We concluded that this treatment strategy was beneficial in patients with locally unresectable head and neck cancer.

Adult↗
PubMed2000

Effects of N-(4-hydroxyphenyl) retinamide on urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in prostate adenocarcinoma cell lines.

Previous investigations have demonstrated that a synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), inhibits the invasion of prostate adenocarcinoma in vitro. Urokinase-type plasminogen activator (uPA) is a prerequisite for tumor invasion. The purpose of this study was to evaluate the effects of 4-HPR on uPA and plasminogen activator inhibitor-1 (PAI-1) in prostate cancer. Human prostate adenocarcinoma cell lines, TSU-PR1 and PC3, were grown in serum-free media containing 4-HPR. Cellular mRNA and protein were subsequently extracted. Northern blot analysis, enzyme-linked immunosorbent assay (ELISA) and chromogenic functional analysis were performed on the samples. Administration of 10(-6) M 4-HPR for 3 days resulted in an increase in uPA mRNA expression (TSU-PR1: 391%, PC3: 356%), and a simultaneous increase in PAI-1 mRNA expression (TSU-PR1: 217%, PC3: 235%) was observed. ELISA concomitantly demonstrated a significant increase (p < 0.05) in uPA protein in the conditioned media (TSU-PR1: 134%, PC3: 139%) and cell lysates (TSU-PR1: 284%, PC3: 255%). Both cell lines demonstrated a significant increase (p < 0.05) in PAI-1 protein in the conditioned media (TSU-PR1: 152%, PC3: 167%) and cell lysates (TSU-PR1: 170%, PC3: 222%). Concentrations below 10(-6) M failed to alter the protein production of either uPA or PAI-1. The functional uPA assay demonstrated a reduction of the proteolytic activity of uPA (TSU-PR1: 13%, PC3: 7%) in cell lysates of 10(-6) M 4-HPR (p < 0.05), while there was minimal uPA activity in the conditioned media. 4-HPR stimulates a paradoxical increase in uPA and PAI-1, but the anti-invasive effects of 4-HPR are consistent with the increase in both uPA and PAI-1, resulting in an overall reduction of functional uPA activities.

Adenocarcinoma↗
PubMed2000

The role of low dose cisplatin plus 5-fluorouracil for treatment of recurrent and/or advanced squamous cell carcinoma of the head and neck.

To improve survival rate in advanced head and neck cancer, we scheduled 90 patients to receive low dose cisplatin plus 5-fluorouracil regimen as neoadjuvant(NAC), concurrent(CC), adjuvant(AC), and second line chemotherapy (SC) setting. Our regimen consisted of cisplatin (CDDP 5 mg/m2/1 hr infusion on days 1-5, 8-12, 15-19, 22-26) and 5-fluorouracil (5-FU 200 mg/m2/24 hr infusion or oral administration of tegaful-uracil (UFT-E) 400 mg/body on days 1-28). The concurrent chemoradiotherapy consisted of conventional irradiation with 1.6-2.0 Gy/day on five days per week up to a total dose around 60Gy, and CDDP 3 mg/m2 by intravenous infusion over 1 hour plus 5-FU 150 mg/m2 by intravenous infusion over 24 hours per day on five days per week. For SC, 24 patients evaluable for response, 4 CR and 6 PR with RR of 42% were achieved. For NAC, 14 patients were evaluated for response, 2 CR and 7 PR were achieved. CC was indicated for locally unresectable cases. Of the 33 patients evaluable for response were 17 CR and 9 PR with RR of 79%. Dose limiting toxicities for chemotherapy were anemia and leukopenia and chemoradiotherapy was mucositis. Our treatment modality showed marginal toxicity and good response. Moreover, our regimen could be given in an outpatient setting safely so quality of life for patients was identical. We concluded that for advanced head and neck cancer, these treatment options were effective for second line and adjuvant setting. Chemoradiotherapy with this regimen also gave a impact for improving local control and survival period for locally unresectable cases.

Adult↗
PubMed2000

[Clinical usefulness of 123I-BMIPP myocardial SPECT in collagen disease].

This study was designed to evaluate the clinical usefulness of 123I-BMIPP myocardial SPECT for detecting cardiac involvement in patients with collagen disease. We studied 12 patients with systemic lupus erythematosus (SLE), 8 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM) and 3 with allergic granulomatosis and angiitis (AGA). A 111 MBq of 123I-BMIPP was intravenously injected at rest, and SPECT images were obtained at 15 min after the injection. Seven of 12 SLE, 6 of 8 PSS, 3 of 6 PM/DM and all 3 AGA patients showed an abnormal tracer uptake. The left ventricular ejection fraction was inversely correlated with a BMIPP abnormality. The regional wall motion abnormality was reduced in regions with reduced tracer uptake. These findings suggest that 123I-BMIPP imaging could be useful for assessment of cardiac involvement in patients with collagen disease.

Aged↗
PubMed2000

Biological response to expandable metallic stents implanted into the portal vein. A histomorphometric study.

BACKGROUND: This study was undertaken to investigate the biological response to an expandable metallic stent implanted in the canine portal vein with a special reference to the histomorphometric contribution of cellular and acellular elements to the intimal and medial growth. METHODS: In 11 dogs, the Gianturco Z stent was placed into the portal vein and was harvested at intervals of 4 (n=6) and 12 weeks (n=5). In 6 dogs, the normal portal vein was harvested and used as a control. The specimens were subjected to histomorphometric examination. RESULTS: Mean intimal/medial thickness and total intimal/medial area significantly increased progressively by 12 weeks. Collagen intimal/medial area also significantly increased progressively by 12 weeks, while smooth muscle intimal/medial area significantly increased at 4 weeks but did not change from 4 weeks to 12 weeks. Collagen density tended to increase at 4 weeks and significantly increased at 12 weeks, while smooth muscle density significantly decreased at 4 weeks and continued to decrease at 12 weeks. CONCLUSIONS: The total area or mean thickness of the intima and media of the stented portal vein continued to increase by 12 weeks after stent placement. This phenomenon appeared to be due to proliferation of smooth muscle cells followed by accumulation of collagen.

Animals↗
PubMed2000

Effect of age on rat aortic responses to acetylcholine and nitric oxide donor (NOC-18).

The purpose of the present study was to examine the effects of age on vascular responses to acetylcholine (ACh) and NO-releasing compound (NOC-18). The studies were performed in young (4 months old, n = 8) and old (22 months old, n = 6) male rats. Responses to ACh and NOC-18 were examined in vitro by using isolated abdominal aortic rings. The maximum relaxation response to ACh, an endothelium-dependent vasodilation, was lower in aortas from old rats. Sensitivity (mean effective concentration; EC50) of ACh in old rats was significantly less than in young rats. There were no differences in maximum NOC-18-induced relaxation, an endothelium-independent vasodilation, in aortas from young and old rats. On the other hand, the concentration-response curve for NOC-18 was shifted to the right and the sensitivity (EC50 to NOC-18) was lower in old rats. These results indicated that both endothelium-dependent vasodilation induced by ACh and endothelium-independent vasodilation induced by NOC-18 are impaired in aorta from old rats.

Acetylcholine↗
PubMed1999

Effects of macrophage colony-stimulating factor (M-CSF) on protease production from monocyte, macrophage and foam cell in vitro: a possible mechanism for anti-atherosclerotic effect of M-CSF.

M-CSF is a growth factor that stimulates proliferation and differentiation of monocyte/macrophage-lineage cells. In our previous studies, M-CSF regresses atherosclerotic lesions preformed in aorta of high cholesterol-fed rabbit. Immunohistochemical analysis indicated that extracellular matrix (ECM), such as collagen, was especially eliminated in the intima of atherosclerotic lesion. To define the collagen-lowering potential of M-CSF, we have studied the effects of M-CSF on production of collagen-degrading proteases, such as MMP-1, -9 and urokinase in vitro. Monocytes freshly isolated from human peripheral blood produced MMP-9, but not urokinase, and M-CSF enhanced MMP-9 production. Macrophages were prepared by culturing monocytes for 10 days in the presence or absence of M-CSF, and protease production was assayed. M-CSF augmented production of MMP-9 and urokinase in a dose-dependent manner. M-CSF also enhanced MMP-1 production of macrophages, but not significantly. Foam cells were prepared by culturing macrophages in the presence of acetyl LDL, and protease production from these cells were also elevated by M-CSF. These results suggest that M-CSF exogenously administered in atherosclerotic rabbits might regress the thickened intima by activating macrophages to degrade collagen accumulated in the lesion.

Animals↗
PubMed1999

Human prostacyclin synthase gene and hypertension : the Suita Study.

BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.

Adult↗
PubMed1999

Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2.

Human breast cancer cell line Hs578T was stably transfected with cDNA for cyclooxygenase-1 or -2. When the cells overexpressing cyclooxygenase-1 or -2 were stimulated with concanavalin A, the processing of matrix metalloproteinase-2 was observed with the aid of gelatin zymography. This processing was not seen in mock-transfected and original cells which did not express detectable cyclooxygenase activity. Furthermore, Northern blotting showed 8-13 fold induction of membrane-type 1 matrix metalloproteinase which processed matrix metalloproteinase-2 in the cells expressing cyclooxygenases. These findings suggest that both isoforms of cyclooxygenase mediate the processing of matrix metalloproteinase-2 through induction of membrane-type I metalloproteinase in breast cancer cells.

Breast Neoplasms↗
PubMed1999

Regulation of cyclooxygenase-2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells. Role of mitogen-activated protein kinases.

Treatment of normal human epidermal keratinocytes (NHEK) with interferon-gamma (IFN-gamma) causes a 9-fold increase in the level of cyclooxygenase-2 (COX-2) mRNA expression. Nuclear run-off assays indicate that this induction is at least partly due to increased transcription. Activation of the epidermal growth factor receptor (EGFR) signaling pathway due to the enhanced transforming growth factor alpha (TGFalpha) expression plays an important role in the induction of COX-2 by IFN-gamma. This is supported by the ability of TGFalpha to rapidly induce COX-2 and the inhibition of the IFN-gamma-mediated COX-2 mRNA induction by an EGFR antibody and EGFR-selective kinase inhibitors. Deletion and mutation analysis indicates the importance of the proximal cAMP-response element/ATF site in the transcriptional control of this gene by TGFalpha. The increase in COX-2 mRNA by TGFalpha requires activation of both the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways. Inhibition of p38 MAPK decreases the stability of COX-2 mRNA, while inhibition of MAPK/ERK kinase (MEK) does not. These results suggest that the p38 MAPK signaling pathway controls COX-2 at the level of mRNA stability, while the ERK signaling pathway regulates COX-2 at the level of transcription. In contrast to NHEK, IFN-gamma and TGFalpha are not very effective in inducing TGFalpha or COX-2 expression in several squamous carcinoma cell lines, indicating alterations in both IFN-gamma and TGFalpha response pathways.

Amphiregulin↗