Biomedical subjects

S Akiba

Publications and source records attributed to S Akiba.

At least 19 recordsLinked to original sources

PubMed2003

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aged↗

PubMed2001

Ceramide accelerates dephosphorylation of extracellular signal-regulated kinase 1/2 to decrease prostaglandin D(2) production in RBL-2H3 cells.

In the present study, the effect of ceramide on antigen-stimulated phosphorylation of extracellular signal-regulated kinase (ERK) in the mechanism responsible for regulating production of prostaglandin (PG) D(2) was investigated in the mast cell line, RBL-2H3 cells. Cell-permeable C(6)-ceramide (N-hexanoylsphingosine) suppressed antigen-stimulated phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase. Ceramide also inhibited production of PGD(2) and an increase in the activity of cytosolic phospholipase A(2) (cPLA(2)), whereas it did not influence the tyrosine phosphorylation of major cellular proteins in response to antigen. The ceramide-induced inhibition of ERK1/2 phosphorylation and of cPLA(2) activation was suppressed by orthovanadate, a tyrosine phosphatase inhibitor, but not by okadaic acid, a serine/threonine phosphatase inhibitor. Addition of ceramide to the lysate prepared from antigen-stimulated cells reduced the phosphorylated ERK1/2, and orthovanadate effectively prevented the reduction. These results suggest that ceramide accelerates the dephosphorylation of phosphorylated ERK1/2 via activation of a protein tyrosine phosphatase, thus preventing activation of cPLA(2) and production of PGD(2).

Animals↗

PubMed2001

Expression of functional lung resistance--related protein predicts poor outcome in adult T-cell leukemia.

Chemotherapy of patients with adult T-cell leukemia (ATL) has been unsuccessful. The poor outcome is thought to be caused mainly by the drug resistance of ATL cells. Lung resistance-related protein (LRP) is a novel protein associated with drug resistance. The expression of LRP messenger RNA (mRNA) was evaluated by slot blot analysis in 55 patients with ATL. Of these patients, 36 had acute, 12 chronic, and 7 lymphoma-type ATL. The expression levels of LRP mRNA were significantly higher in chronic ATL than in lymphoma-type ATL (P =.007). The expression of LRP mRNA was higher in patients with white blood cell counts above 30,000/microL (P =.038) or with abnormal lymphocyte counts above 10,000/microL (P =.007) than in the remaining patients. The enhanced efflux of [(14)C]doxorubicin from nuclei isolated from ATL cells that expressed high levels of LRP was inhibited by a polyclonal antibody against LRP, and the accumulation of doxorubicin in the isolated nuclei was increased by the anti-LRP antibody. In acute and lymphoma-type ATL patients, high expression of LRP mRNA at diagnosis correlated with shorter survival, and a Cox proportional hazards model showed that LRP expression is an independent prognostic factor. These findings suggest that functionally active LRP is expressed in some ATL cells and that it is involved in drug resistance and poor prognosis in ATL. (Blood. 2001;98:1160-1165)

Active Transport, Cell Nucleus↗

PubMed2001

Relation between cyclooxygenase-2 expression and tumor invasiveness and patient survival in transitional cell carcinoma of the urinary bladder.

BACKGROUND: Expression of the inducible form of cyclooxygenase (COX)-2 is known to correlate with development of transitional cell carcinoma (TCC) of the human urinary bladder. However, the clinical significance of COX-2 expression with respect to clinicopathologic findings and patient survival is unknown. METHODS: COX-2 expression was examined immunohistochemically in tumor tissues obtained from 108 patients who underwent radical cystectomy for TCCs, without knowledge of clinicopathologic findings. Correlation between COX-2 expression and clinicopathologic findings and patient survival was determined. RESULTS: COX-2 expression was detected in 34 of 108 (31%) tumors but in none of 10 normal uroepithelial samples. Univariate logistic regression analysis showed a significant correlation between COX-2 expression and local invasion, infiltration pattern, lymphatic invasion, and venous invasion. However, multivariate logistic regression analysis revealed that only local invasion correlated significantly with COX-2 expression (P = 0.047). Cox proportional hazards regression analysis showed that both local invasion (P = 0.008) and lymph node metastasis (P = 0.001) were independent prognostic factors; however, COX-2 expression (P = 0.16) was not. CONCLUSIONS: The authors showed that COX-2 overexpression plays a role in development and invasion of TCCs, but not prognosis of patients with TCC. COX-2 inhibitors may be useful for chemoprevention of TCCs and treatment of invasive disease.

Adult↗

PubMed2001

Secretory phospholipase A2 mediates cooperative prostaglandin generation by growth factor and cytokine independently of preceding cytosolic phospholipase A2 expression in rat gastric epithelial cells.

Transforming growth factor (TGF)-alpha and interleukin (IL)-1beta are responsible for the healing of gastric lesions through, in part, prostaglandin (PG) generation. We examined the contribution of cytosolic and secretory phospholipase A(2)s (cPLA(2) and sPLA(2)) to the PG generation by rat gastric epithelial cells in response to both stimuli. Stimulation with TGF-alpha for 24 h increased cPLA(2) and cyclooxygenase (COX)-2 markedly, PGE(2) slightly, and type IIA sPLA(2) and COX-1 not at all, whereas IL-1beta increased sPLA(2) only. Both stimuli synergistically increased PGE(2), sPLA(2), and the two COXs but not cPLA(2). The onset of the PGE(2) generation paralleled the sPLA(2) release but was apparently preceded by increases in cPLA(2) and the two COXs. The increase in PGE(2) was impaired by inhibitors for sPLA(2) and COX-2 but not COX-1. cPLA(2) inhibitors suppressed PGE(2) generation by TGF-alpha alone but not augmentation of PGE(2) generation or sPLA(2) release by IL-1beta in combination with TGF-alpha. Furthermore, despite an increase in cPLA(2) including its phosphorylated form (phosphoserine), -induced arachidonic acid liberation was impaired in the TGF-alpha/IL-1beta-stimulated cells, in which p11, a putative cPLA(2) inhibitory molecule, was also increased and co-immunoprecipitated with cPLA(2). These results suggest that synergistic stimulation of sPLA(2) and COX-2 expression by TGF-alpha and IL-1beta results in an increase in PGE(2). Presumably, the preceding cPLA(2) expression is not involved in the PGE(2) generation, because of impairment of its hydrolytic activity in the stimulated cells.

Animals↗

PubMed2001

Epstein-Barr virus in gastric carcinoma is associated with location in the cardia and with a diffuse histology: a study in one area of Chile.

Epstein-Barr virus (EBV) has been associated with the most common form of stomach neoplasms, the gastric carcinoma (GC). The presence of EBV-encoded small RNAtype-1 (EBER-1), a marker for EBV infection was analyzed by in situ hybridization (ISH) in 185 formalin-fixed and paraffin-embedded cases of GC from a high risk region. We found 31 (16.8%) EBV-positive cases with no relationship to age. Although male predominance (19% in males and 12.5% in females) was observed, the gender difference did not achieve statistical significance. Odds ratio (OR) for cardia location was 5.4 (95% CI 1.7-17.3) when antrum was used as referent category and the effects of gender and age were taken into account. The proportion of EBV-positive cases in diffuse histology was higher than intestinal type (OR = 4.8, 95% CI = 2.0-11.1). Our findings are contrary to a previously accepted hypothesis, that high-risk countries for GC have low rates of EBV-associated GC. In addition, our findings regarding location, histology and weak male predominance are different from what has been described in Asian and European countries, but similar to those described in Mexico and Mexican descendants living in the U.S. suggesting unique characteristics of EBV-associated GC in Latin-America.

Adult↗

PubMed2001

Preoperative assessment of vascularity by color Doppler ultrasonography in human rectal carcinoma.

PURPOSE: Although angiogenesis assessed by immunostaining endothelial cells (microvessel density) is a well-known prognostic factor in a wide variety of human solid tumors, preoperative determination of microvessel density seems to be difficult in rectal carcinoma. Thus, we performed transanal color Doppler ultrasonography in 46 patients with rectal carcinoma to assess preoperative angiogenic status and compare it with microvessel density in surgical specimens. METHODS: Time-averaged maximal velocity, peak systolic velocity, number of vascular points, and vascular point index were conducted by color Doppler ultrasonography in 46 patients with rectal carcinoma. Number of vascular points was defined as the number of vessels with pulsation in the section of tumor. Vascular point index was defined as the average number of vascular points divided by the area assessed by color Doppler ultrasonography in the section of tumor. The profiles of number of vascular points were similar to those assessed by microangiography in five rectal carcinomas. RESULTS: Vascular point index significantly correlated with microvessel density (P < 0.0001). No significant correlation was found between microvessel density and time-averaged maximal velocity or peak systolic velocity. Vascular point index was also a better indicator of lymph node metastasis and venous invasion than microvessel density. In addition, 11 of 46 cases with postoperative hematogenous metastasis (23.9 percent) were observed prospectively. Vascular point index may be a best predictor for hematogenous metastasis from rectal carcinoma compared with peak systolic velocity, time-averaged maximal velocity, and microvessel density by receiver operating characteristic analysis. CONCLUSION: These results suggest that preoperative quantification of angiogenesis using color Doppler ultrasonography will provide quick and useful information in the management of rectal carcinoma.

Blood Flow Velocity↗

PubMed2001

Quantitative evaluation of skin condition in an epidemiological survey of females living in northern versus southern Japan.

Image analysis and biophysical methods were used to compare the skin condition of a group of females ranging in age from 5 to 65 years who had lived all of their lives in either Kagoshima (n=300), located in southern Japan, or Akita (n=302), located in northern Japan. Kagoshima annually receives approximately 1.5 times more solar UVB radiation than Akita. The methods used and corresponding skin parameters reported in this survey were: high resolution digital imaging followed by computer analysis of facial images for facial skin wrinkling and hyperpigmentation; silicone skin replicas followed by Moiré interferometry for facial skin surface roughness (texture); the Minolta Chromameter for skin color (L*a*b*) on sun-exposed (forehead) and sun-protected (upper inner arm) skin sites; the Corneometer for skin capacitance (hydration) on the cheek and ventral forearm; the Sebumeter for sebum excretion rate on the forehead; and the Minolta Spot Thermometer for skin temperature on the upper cheek. Compared with Japanese women living in Akita, Japanese women living in Kagoshima had significantly longer facial wrinkles, higher number of wrinkles, larger hyperpigmented spots, higher number of spots, rougher facial skin texture, more yellow foreheads and upper inner arms, darker foreheads, and less stratum corneum hydration in the cheeks and arms. When compared on an age-for-age basis, the average 40-year-old Kagoshima women has the same level of facial wrinkling as a 48-year-old Akita women, a delay of 8 years for living in the northern latitude. For facial hyperpigmentation, the delay is 16 years; the average 40-year-old Kagoshima women has the same level of facial hyperpigmentation as a 56-year-old Akita women. The results further testify to the skin damaging effects of sun exposure and may be useful in public health education to promote everyday sun protection.

Adolescent↗

PubMed2001

Patterns of pelvic invasion are prognostic in the treatment of locally recurrent rectal cancer.

BACKGROUND: Local recurrence of rectal cancer after curative resection remains a difficult clinical problem. The aim of this study was to elucidate prognostic risk factors after resection of recurrent cancer. METHODS: Between January 1983 and December 1999, 83 patients with locally recurrent rectal cancer were studied retrospectively for survival benefit by re-resection. Sixty patients underwent resection for recurrent cancer, including total pelvic exenteration in 30 patients and sacrectomy in 23 patients. The extent of locally recurrent tumour was classified by the pattern of pelvic invasion as follows: localized, sacral invasion and lateral invasion. RESULTS: Multivariate analysis showed that the pattern of pelvic invasion was a significant prognostic factor which independently influenced survival after resection of recurrent cancer (P < 0.001). The 5-year survival rates were 38 per cent in the localized type (n = 27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral invasive type (n = 17). CONCLUSION: Resection for locally recurrent rectal cancer is potentially curative in patients with localized or sacral invasive patterns of recurrence. Alternatives should be explored in patients with recurrence involving the lateral pelvic wall.

Adult↗

PubMed2001

HTLV-I proviral load correlates with progression of motor disability in HAM/TSP: analysis of 239 HAM/TSP patients including 64 patients followed up for 10 years.

To clarify clinical and laboratory findings that may be related to the pathomechanism of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we analyzed these findings in 239 patients with HAM/TSP, including 64 patients followed up for 10 years after their first examinations, with special interest in the HTLV-I proviral load in peripheral blood mononuclear cells (PBMCs). The proviral load in PBMCs did not differ in terms of modes of HTLV-I transmission. However, the proviral load in patients with age of disease onset greater than 65 years tended to be higher than those with a younger age of onset. In the 64 patients followed up for 10 years, the clinical symptoms deteriorated in 36 patients (56%), unchanged in 26 patients (41%), and improved in 2 patients (3%). HTLV-I proviral load also appeared to be related to the deterioration of motor disability in these patients. To our knowledge, the present study is the first longitudinal study concerning the relationship between the clinical course of HAM/TSP and HTLV-I proviral load. It is suggested that HTLV-I proviral load is related to the progression of motor disability and is an important factor to predict prognosis of patients with HAM/TSP.

Age of Onset↗

PubMed2001

Epstein-Barr virus-associated gastric carcinoma in Japanese Brazilians and non-Japanese Brazilians in São Paulo.

The proportion of Epstein-Barr virus-associated gastric carcinoma (EBV-GC) was examined in 149 Japanese-Brazilian and 151 non-Japanese-Brazilian gastric-carcinoma cases using in situ hybridization (ISH) assay to detect EBV-encoded small RNA (EBER), and the results were compared with our referent Japanese data. We found that 4.7% of cases in Japanese Brazilians were EBER-positive. This frequency was slightly lower than that of the referent Japanese, among whom 6.2% of 2038 gastric-carcinoma cases were EBER-positive. On the other hand, the non-Japanese-Brazilian series showed a significantly higher proportion of EBV-GC (11.2%) than the referent group did (P = 0.01). Although EBV-GC was predominant in males among non-Japanese Brazilians (M / F = 3.6, P = 0.047), as was the case in Japanese (M / F = 2.7), Japanese Brazilians did not show such a male predominance. The sex-ratio difference between the Japanese Brazilians and Japanese was statistically significant (P = 0.005). In conclusion, the present study in Japanese Brazilians and Japanese yielded no evidence suggesting any change in the frequency of EBV-GC caused by migration, except the absence of male predominance, which was observed both in Japanese and non-Japanese Brazilians.

Adenocarcinoma↗

PubMed2001

Prognostic significance of multidrug resistance protein in adult T-cell leukemia.

The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major obstacle to successful treatment is intrinsic or acquired drug resistance. To determine the clinical significance of multidrug resistance protein (MRP) 1 in ATL, we studied MRP1 expression and its association with clinical outcome. The expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was significantly higher than that in lymphoma-type ATL (P = 0.033). There was no correlation between MRP1 expression and age, gender, WBC count, LDH, hypercalcemia, blood urea nitrogen, or performance status. However, the expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1 mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with low expression of MRP1 mRNA. This uptake was almost completely inhibited by LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox regression analysis revealed that MRP1 expression was an independent prognostic factor. These findings suggest that functionally active MRP1 is expressed in some ATL cells and that it is involved in drug resistance and has a possible causal relationship with poor prognosis in ATL. Multidrug resistance-reversing agents, such as ONO-1078 and MK571, that directly interact and inhibit the transporting activity of MRP1 may be useful for treating ATL patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Acceleration by ceramide of calcium-dependent translocation of phospholipase A2 from cytosol to membranes in platelets.

The effect of ceramide on Ca2+-dependent translocation of cytosolic phospholipase A2 (cPLA2) to membranes was studied. Pretreatment of platelets with sphingomyelinase or C6-ceramide (N-hexanoylsphingosine) led to apparent enhancement of Ca2+-ionophore A23187-stimulated arachidonic acid release but did not affect the cytosolic phospholipase A2 (cPLA2) activity. Under these conditions, the cPLA2 proteins in membranes increased significantly, compared with those by A23187 alone. Sphingomyelinase and C6-ceramide, but not C6-dihydroceramide, a control analog of C6-ceramide, also facilitated the Ca2+-dependent increase in the cPLA2 protein, as well as the activity, in membranes induced by addition of Ca2+ into platelet lysate. Protein kinase Calpha, which possesses a Ca2+-dependent lipid binding domain, was increased in membranes in a Ca2+-dependent manner, but the increase was not accelerated by sphingomyelinase or C6-ceramide. These findings suggest that ceramide in membranes potentiates Ca2+-dependent cPLA2 translocation from cytosol to membranes, probably through modification of membrane phospholipid organization.

Animals↗

PubMed2000

The role of thymidine phosphorylase expression in the invasiveness of gastric carcinoma.

BACKGROUND: Thymidine phosphorylase (TP) has angiogenic activity in various cancer tissues. Gastric carcinomas are classified into two histologic groups: differentiated and undifferentiated adenocarcinomas. There are differences in the modes of development and the extent of infiltration between the two groups. The purpose of the current study was to determine whether TP is involved in the invasiveness and progression of these two types of gastric carcinoma. METHODS: To investigate the expression and localization of TP and the microvessel counts, the authors examined specimens from 149 gastric carcinoma patients. The specimens were stained using monoclonal antibody against TP and polyclonal antibody against factor VIII. To determine the cell type expressing TP, immunohistochemical staining using a monoclonal antibody against CD68 that is specific for macrophages and double staining using antibodies to both TP and CD68 were performed. RESULTS: The proportion of TP positive tumors in differentiated adenocarcinomas was higher than that in undifferentiated adenocarcinomas. The TP positive differentiated adenocarcinomas invaded more deeply than the TP negative ones, but this was not the case with undifferentiated adenocarcinomas. TP was expressed mainly in the invasive edges of tumors and was expressed more frequently in macrophages than in tumor cells. TP expression was correlated with microvessel count and CD68 expression. Patients with TP positive carcinomas had a poorer prognosis than those with TP negative differentiated adenocarcinomas. CONCLUSIONS: TP expressed in macrophages may be correlated with microvessel count and play an important role in tumor invasiveness and progression in differentiated gastric adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder.

BACKGROUND: Thymidine phosphorylase (TP), which is identical to platelet-derived endothelial cell growth factor (PD-ECGF), stimulates chemotaxis of endothelial cells and is involved in the angiogenesis of human solid tumors. METHODS: The activity and expression of TP were examined in human transitional cell carcinomas (TCCs) of the bladder, and their association with clinicopathologic findings was determined. The activity of the enzyme in 37 TCCs and 12 adjacent nonneoplastic tissues was measured spectrophotometrically. The expression of TP was also examined by immunoblotting. Immunohistochemical analysis was performed on 108 TCCs. RESULTS: TP activity in the carcinomas was higher than that in adjacent normal tissues (P = 0.002). TP activity in Grade 3 tumors or those classified as pT2-4 was higher than in Grade 1 and 2 tumors (P = 0.017) or those classified as pT1 (P = 0.007). The level of expression of TP detected by immunoblotting correlated well with TP activity. Immunohistochemical analyses showed that 62 of 108 cases (57.4%) were TP positive. There was a significant correlation between TP expression and histologic grade, infiltration pattern, local invasion, and lymph node metastasis. TP expression as a prognostic variable was studied using the Cox proportional hazards model. TP overexpression was an independent prognostic factor, as were lymph node metastasis and local invasion. CONCLUSIONS: These findings suggest that TP activity and its level of expression influence the progression of TCC and the prognoses of patients with this disease.

Adult↗

PubMed2000

Inhibitory effect of cepharanthine on fibronectin production in growth factor-stimulated rat mesangial cells.

We examined the effect of cepharanthine, a biscoclaurine alkaloid, on extracellular matrix production in rat mesangial cells in response to platelet-derived growth factor (PDGF) or transforming growth factor-beta (TGF-beta). Stimulation of the cells with PDGF increased the amounts of fibronectin, one of extracellular matrix components. Pretreatment with cepharanthine (0.1-2 microM) suppressed the PDGF-stimulated increase in fibronectin in a dose-dependent manner. At a concentration of 2 microM, the alkaloid almost completely suppressed the production. Under the conditions, the alkaloid inhibited tyrosine phosphorylation of several proteins including PDGF beta receptor in PDGF-stimulated cells, and also tyrosine kinase activity of the receptor prestimulated with PDGF in a cell-free assay system. Furthermore, cepharanthine suppressed TGF-beta-stimulated fibronectin production at the same concentration ranges. Our results suggest that cepharanthine inhibits fibronectin production induced by growth factors, probably through suppression of receptor autophosphorylation.

Alkaloids↗

PubMed2000

Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A(2) under the control of p11 in rat gastric epithelial cells.

The regulatory effects of transforming growth factor (TGF)-alpha on phospholipase A(2) (PLA(2)) isozymes contributing to prostaglandin generation in rat gastric epithelial RGM1 cells were examined. Stimulation with TGF-alpha for 24 h time-dependently induced prostaglandin E(2) generation with an increase in cyclo-oxygenase-2 protein. The TGF-alpha-induced prostaglandin E(2) generation was suppressed by NS-398, a cyclo-oxygenase-2 inhibitor. TGF-alpha stimulated the activity and the protein synthesis of cytosolic PLA(2) (cPLA(2)). A time-dependent increase in cPLA(2) protein occurred in parallel with PGE(2) generation, which was inhibited by methyl arachidonyl fluorophosphonate (MAFP), a cPLA(2) inhibitor. However, no change in activity of secretory PLA(2) or Ca(+2)-independent PLA(2) was observed in the TGF-alpha-stimulated cells. Stimulation with the Ca(2+) ionophore A23187 for 10 min induced MAFP-sensitive arachidonic acid liberation. Interestingly, preincubation with TGF-alpha for 24 h diminished A23187-stimulated arachidonic acid liberation despite the increase in cPLA(2) protein. Under the conditions, TGF-alpha was found to increase p11, an endogenous cPLA(2) suppressor, also known as annexin II light chain. The TGF-alpha-induced increase in p11 was suppressed by tyrphostin AG1478, an inhibitor of tyrosine kinase of epidermal growth factor receptor, which was also found to restore the inhibition by TGF-alpha of A23187-stimulated arachidonic acid liberation. However, TGF-alpha did not alter protein levels of annexin II heavy chain. These results suggest that TGF-alpha stimulates prostaglandin generation through an increase in cPLA(2), the hydrolytic action of which may be under the control of p11.

Animals↗

PubMed2000

Expression of the adrenomedullin gene in epithelial ovarian cancer.

Adrenomedullin (AM) gene expression was analysed in 60 cases of epithelial ovarian cancer, (29 serous, 14 mucinous, 13 endometrioid, three clear cell, and one undifferentiated) using reverse transcription-polymerase chain reaction (RT-PCR); 10 of the cases were of low malignant potential; 25 were stage I; three were stage II; 27 were stage III; and five were stage IV. The level of AM gene expression was described in terms of the relative yield of the AM gene to the beta2-microglobulin gene. AM gene expression ranged from 0.04 to 1.57 (median 0.36). The association between histological grade and AM gene expression was significant (P: = 0.027), however, the association with other clinico-pathological features, i.e. patients' age at diagnosis, stage of disease, residual tumour mass after initial surgery, and histological subtype were not significant. Survival data were available for all patients and univariate Cox regression analysis showed that the AM gene expression was significantly associated with a poor prognosis (P: = 0.019). Immunohistochemical studies showed that AM was localized in the outer cell membrane or the cytoplasm of the carcinoma cells and in the endothelial cells of the tumour stroma. The AM gene expression level may play a key role in the biology of epithelial ovarian cancer and may define a more aggressive tumour phenotype.

Adrenomedullin↗