Biomedical subjects

N Fujimoto

Publications and source records attributed to N Fujimoto.

At least 109 records · Page 6Linked to original sources

PubMed1997

Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features.

Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.

Adenocarcinoma↗

PubMed1997

Serum hepatocyte growth factor/scatter factor levels in small cell lung cancer patients.

Serum hepatocyte growth factor/scatter factor (HGF/SF) levels were measured in 25 patients with small cell lung cancer (SCLC), 16 patients with benign lung diseases and 15 healthy subjects with an enzyme-linked immunosorbent assay. The patients with SCLC did not have bacterial or interstitial pneumonia. Patients with benign lung diseases included eight with bacterial pneumonia, three with interstitial pneumonia, and five with benign lung tumor. Serum HGF/SF levels were significantly higher in patients with SCLC (mean +/- S.D.: 0.40 +/- 0.17 ng/ml) than in healthy subjects (0.26 +/- 0.093 ng/ml) (P = 0.0083). Patients with bacterial pneumonia had significantly higher serum HGF/SF (0.52 +/- 0.19 ng/ml) than did those with benign lung tumors (0.27 +/- 0.058 ng/ml) and healthy subjects (P = 0.013 and P = 0.0019, respectively). By clinical stage of SCLC, HGF/SF levels were 0.34 +/- 0.12 and 0.47 +/- 0.20 ng/ml in patients with limited disease and extensive disease, respectively; this difference was not significant (P = 0.080). Although serum HGF/SF levels were increased in patients with SCLC, this increase might not have been related to tumor burden.

Adult↗

PubMed1997

Measurement of serum p53 protein in patients with small cell lung cancer and results of its clinicopathological evaluation.

Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.

Age Factors↗

PubMed1997

Up-regulation of the estrogen receptor by triiodothyronine in rat pituitary cell lines.

The effects of thyroid hormones on estrogen receptor (ER) levels in four different rat pituitary clonal cell lines designated as MtT/Se, SM, S and E, were investigated. When T3 was added at 10(-7) M, a significant increase in ER was evident after 9 h with maximum levels reached after 24-48 h in MtT/Se (270% of control), MtT/SM (160%) and MtT/S (140%). No significant increase was noted in MtT/E cells in which the T3 receptor (T3R) level was only one-tenth of that in the other cells, suggesting a direct link between ER expression and T3R binding. ER levels began to increase at 10(-10) M and reached maxima at 10(-8) M in MtT/Se, SM and S cells. Up to 10(-5) M of retinoic acid (RA) did not change ER levels in any of the cell lines. When Se cells were treated with cycloheximide before T3 administration, the increase in ER was completely blocked. Northern blot analysis of total RNA isolated from T3-treated MtT/Se cells revealed a limited 1.4-fold increase in ER mRNA at 10(-7) M. In conclusion, thyroid hormones (but not RA) increase ER levels in pituitary cells by a process requiring protein synthesis, and which is accompanied by an increase in the mRNA.

Animals↗

PubMed1997

The production of tissue inhibitors of metalloproteinases (TIMPs) in megakaryopoiesis: possible role of platelet- and megakaryocyte-derived TIMPs in bone marrow fibrosis.

We quantified tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in serum and plasma in normal control subjects and patients with a low or high platelet count, using one-step sandwich enzyme immunoassays. The serum levels of TIMP-1 and TIMP-2 were 101.1 +/- 13.3 ng/ml, and 82.7 +/- 26.3 ng/ml, respectively, in normal subjects. In patients with an elevated platelet count, such as in essential thrombocytosis, polycythaemia vera, and myelofibrosis, serum levels of TIMP-1 and TIMP-2 were 351.6 +/- 200.9 ng/ml and 148.9 +/- 84.0 ng/ml, respectively. Serum levels of TIMP-1 and TIMP-2 in patients with a low platelet count, such as in aplastic anaemia and idiopathic thrombocytopenic purpura, were 57.2 +/- 25.8 ng/ml and 19.7 +/- 7.68 ng/ml, respectively. The serum level of TIMP-1 was significantly correlated with the platelet count in all subjects. The correlation between the serum level of TIMP-2 and the platelet count was not as strong. The level of TIMP-1 in platelet-depleted plasma was not correlated with the platelet count. Immunohistochemical staining using monoclonal antibodies against TIMP-1 and TIMP-2 showed that megakaryocytes and platelets were positive for both TIMP-1 and TIMP-2, confirming that they are rich sources of TIMPs. TIMP-1 and TIMP-2 stimulated the proliferation of bone marrow fibroblasts, although their effect was less potent than that of TGF-beta and PDGF. Erythroleukaemia and megakaryoblastic cell lines showed the highest secretion of TIMP-1 among the leukaemia cell lines examined. There was no lineage specificity for TIMP-2 secretion. These results suggest that TIMPs released from megakaryocytes or from local platelet coagulation may be important in the development of bone marrow fibrosis.

Blood Platelet Disorders↗

PubMed1997

Serum levels of tissue inhibitor of metalloproteinases-2 and of precursor form of matrix metalloproteinase-2 in patients with liver disease.

Serum levels of tissue inhibitor of metalloproteinases-2 (TIMP2) and of precursor form of matrix metalloproteinase-2 (proMMP2) were determined in patients with chronic hepatitis and hepatocellular carcinoma by a one-step sandwich enzyme immunoassay. Serum levels of TIMP2 and proMMP2 were significantly higher in patients with chronic liver disease, than in normal controls. Serum levels of TIMP2 showed a weak negative correlation with the serum albumin level and prothrombin time (PT). Serum levels of proMMP2 in patients with chronic hepatitis were strongly correlated with those of type IV collagen and were negatively correlated with PT and serum albumin levels. Serum proMMP2 levels were also significantly correlated with histological stages. These data indicate that serum levels of proMMP2 might be useful in the follow-up of patients with chronic hepatitis.

Adult↗

PubMed1997

Biodegradabilities of ethylenediamine-N,N'-disuccinic acid (EDDS) and other chelating agents.

Biodegradabilities of chelating agents were tested with activated sludge. Ethylenediaminetetraacetic acid (EDTA) remained intact in the effluent even after acclimation for 100 days, but propanediamine-N,N'-disuccinic acid (PDDS) and nitrilotriacetic acid (NTA) were biodegraded after acclimation for 5 and 23 days, respectively. Optical isomers of ethylenediamine-N,N'-disuccinic acid (EDDS) had different biodegradabilities: SS- and RS-isomers were susceptible to biodegradation, but the RR-isomer was resistant. SS-isomer was degraded even by activated sludge without acclimation.

Biodegradation, Environmental↗

PubMed1997

Keratinocytes cultured under hyperthermal conditions secrete factor(s) which can modulate dermal fibroblast proliferation and extracellular matrix production.

We have studied how keratinocytes cultured under hyperthermal conditions modulate skin fibroblast growth potential and their biosynthetic phenotypes in vitro. When keratinocytes were cultured at 30, 34, 37 or 39 degrees C, the conditioned medium of the keratinocytes cultured at 39 degrees C showed a greater inhibitory activity for fibroblast proliferation and greater synthetic activities of collagen and glycosaminoglycans than those incubated at 30, 34, or 37 degrees C. Transforming growth factor (TGF) beta 1 production in skin fibroblasts was also stimulated by the keratinocyte conditioned medium cultured at 39 degrees C. The stimulating activity of collagen and glycosaminoglycan syntheses of keratinocyte conditioned medium may be explained at least partly by enhanced TGF beta 1 production. The results indicate that keratinocytes cultured at a higher temperature (39 degrees C) may secrete factor(s) which modulate both fibroblast growth and matrix synthesis. This may provide evidence that under hyperthermal conditions epidermis can influence the functions of skin fibroblasts.

Cell Division↗

PubMed1997

[Preoperative localization of enlarged parathyroid glands by 99mTc-MIBI scintigraphy].

BACKGROUND: Recent studies have shown that 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), a new agent for myocardial perfusion imaging, can be successfully applied to parathyroid imaging. We evaluated the efficacy of 99mTc-MIBI scintigraphy for preoperative localization of enlarged parathyroid glands in patients with hyperparathyroidism. PATIENTS AND METHODS: From June 1994 to September 1996, 24 patients with biochemical confirmation of hyperparathyroidism were studied with 99mTc-MIBI scintigraphy prior to operation. Eleven patients had primary hyperparathyroidism (PHPT) and 13 had secondary hyperparathyroidism (SHPT) associated with chronic renal failure, including one patient with recurrent disease after subtotal parathyroidectomy. A positive 99mTc-MIBI scan for an enlarged gland was defined as an area of persistent focal uptake on the delayed image acquired at 150 min after intravenous injection of 600 MBq of 99mTc-MIBI. RESULTS: Of 11 patients with PHPT, 10, were found to have solitary parathyroid adenomas at surgery and one patient had primary hyperplasia. 99mTc-MIBI scintigraphy accurately detected 9 of 10 adenomas and 2 of 3 hyperplastic glands with no false positive results. Both of the two glands that were not detected by 99mTc-MIBI weighed 200 mg. The mean weight of the 11 glands that were visualized was 1264 mg (range 300 approximately 4300 mg). The sensitivity and predictive value positive for PHPT were 84.6% and 100%, respectively. In 13 patients with SHPT, all of 49 parathyroid glands were identified during surgery, with 43 hyperplastic glands and 6 normal-size glands. Of 43 hyperplastic glands, 28 were detected by 99mTc-MIBI and there was significant difference between the mean weight of these 28 glands (999 mg, range 290 approximately 2630 mg) and that of the 15 nonimaged hyperplastic glands (283 mg, range 90 approximately 540 mg). None of the six normal glands were imaged with 99mTc-MIBI. One patient had a false positive scan caused by a thyroid nodule. The sensitivity and predictive value positive for SHPT were 65.1% and 96.6%, respectively. CONCLUSION: 99mTc-MIBI scintigraphy is an excellent imaging method for localization of enlarged parathyroid glands in patients with hyperparathyroidism, especially with PHPT. However, it has the difficulty to demonstrate enlarged glands smaller than 300 mg in weight.

Adult↗

PubMed1997

Plasma concentration of matrix metalloproteinase 9 in gastric cancer.

BACKGROUND: The clinical significance of plasma concentration of matrix metalloproteinase 9 (MMP-9) was investigated in patients with gastric cancer. METHODS: Plasma was obtained from 138 healthy individuals and 70 patients who underwent gastrectomy for gastric cancer at Aichi Cancer Centre between August 1994 and July 1995. Plasma concentrations of MMP-9 were measured using a one-step sandwich enzyme immunoassay employing monoclonal antibodies. RESULTS: Patients with gastric cancer had plasma higher concentrations of MMP-9 than normal subjects. Postoperative concentrations of MMP-9 were lower than preoperative levels. In addition to patients with advanced cancer, those with early gastric cancer also exhibited higher mean values of and positivity rates for MMP-9 than healthy individuals. Preoperative plasma MMP-9 concentration correlated closely with Union Internacional Contra la Cancrum tumour node metastasis (pTNM) stage, severity of T, N and M classification, and tumour size. CONCLUSION: Plasma MMP-9 concentration can be used for detection of primary or recurrent gastric cancer, and for estimation of tumour extent.

Adult↗

PubMed1997

Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis.

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.

Adult↗

PubMed1997

Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage.

Matrix metalloproteinases (MMPs) are expressed in osteoarthritic (OA) cartilage and are thought to be involved in the degradation of cartilage extracellular matrix (ECM). Among these proteinases, MMP-2 (gelatinase A) demonstrates a wide range of substrate specificity against the ECM present in cartilage. Although MMP-2 expression increases in OA cartilage, the activation mechanism of the corresponding zymogen (pro-MMP-2) in cartilage is unknown. In this study, we examined the expression pattern of membrane-type 1 MMP (MT1-MMP) in human OA articular cartilage and its correlation with the activation of pro-MMP-2. Immunohistochemical studies demonstrate that MT1-MMP localizes to the chondrocytes in the superficial and transitional zones in all of the samples examined directly correlating with cartilage degradation. Reverse transcription polymerase chain reaction confirmed the predominant expression of MT1-MMP mRNA in the OA cartilage. In situ hybridization revealed the site of expression of MT1-MMP in OA cartilage to be the chondrocytes. Through gelatin zymography and a sandwich enzyme immunoassay it was demonstrated that OA cartilage explants secrete significantly higher levels of pro-MMP-2 than normal samples. Pro-MMP-2 activation was enhanced in the OA cartilage samples and correlated with MT1-MMP expression in the cartilage. Plasma membranes prepared from cultured chondrocytes with MT1-MMP expression and those directly isolated from OA cartilage could activate pro-MMP-2. MT1-MMP gene expression in cultured chondrocytes was induced by treatment with interleukin-1 alpha and/or tumor necrosis factor-alpha. These data suggest that cytokine-induced MT1-MMP in the chondrocytes may play a key role in the activation of pro-MMP-2 in the OA articular cartilage, leading to cartilage destruction through ECM degradation.

Aged↗

PubMed1997

[Sensitivity loss of short wavelength sensitive cones in myopic eyes by blue-on-yellow perimetry].

A decrease of the short wavelength sensitive cone (S-cone) sensitivity has been reported in myopic eyes in addition to glaucoma and retinal diseases such as retinal detachment and diabetic retinopathy. In order to investigate early changes of visual function in myopic eyes, blue-on-yellow perimetry (B on Y) which could detect S-cone sensitivity and white-on-white perimetry (W on W) were measured with a computed perimeter program. Young subjects with good visual acuity, normal color vision, and normal intraocular pressure were selected. They had no other ophthalmoscopic abnormalities except for tigroid fundus. Mean deviations of W on W were reduced in mild and high myopic groups. In both tests, the sensitivities decreased as the refractive errors increased in all the tested areas (p < 0.0001). The sensitivity in B on Y decreased more remarkably than in W on W with an increase of refractive error (p < 0.05). We concluded that B on Y perimetry was significantly sensitive to identify early changes of visual function in myopic eyes.

Contrast Sensitivity↗

PubMed1997

Effect of 17 beta-estradiol, retinoic acid and tamoxifen upon primary and transplanted thyroid tumor in B6C3F1 mice fed an iodine deficient diet.

This study was aimed to establish TSH dependent, transplantable thyroid tumor (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its growth in mice given 17 beta-estradiol (E2), retinoic acid (RA), tamoxifen (TAM), T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p. injection of radioactive iodine (131I) once at a dose of 60 mu Ci/head and/or given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was individually dissected aseptically and s.c. grafted under the fat pad of one site of the neck in the same strain of mice at 5 weeks of age. All mice were sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the experiments. The transplantability of both pituitary and thyroid tumor was 100% in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid gland was significantly promoted by the oral administration of RA in both sexes, whereas the growth of transplanted TT was significantly increased by RA in the female, but not in the male. Oral administration of TAM proved inhibitory upon in in situ and transplanted TT in the male, but not in the female. Thyroid tumor induced by IDD could grow only in mice with IDD and was partially regulated of its growth by RA and TAM.

Animals↗

PubMed1996

[Clinical study of occupational uroepithelial cancer].

We studied 438 persons who were engaged in the production and use of aromatic amines (benzidine sulfate, beta-naphthylamine, alpha-naphthylamine and dianisidine). Among these 438 persons, 88 new cases of occupational uroepithelial cancer had occurred from 1949 to 1995. The incident rate of occupational uroepithelial cancer was 20.1%. The average exposure period of these 88 cases to the aromatic amines was 7.40 years (range, 0.75-26.75), and the incidence rate of tumors increased with the length of exposure to aromatic amines. The average latent period was 26.79 years (range, 1.33-48.50), and the average age of first onset was 52.59 (range, 24-79). Recently it has been determined that the longer the latent period, the older the age of first onset. Of these 88 cases, the tumor sites were bladder in 67 cases (76.1%) and upper urinary tract (renal pelvis and/or ureter) in 5 cases (5.7%). The other 16 cases (18.2%) were the bladder and upper urinary tract. The screening examination for chemical workers using urinary cytology was begun in 1962. In our cases, urine cytology was a useful method for diagnosing occupational uroepithelial cancer. As for initial treatment of the 88 cases, transurethral surgery was most frequently performed, that is on 58 cases (65.9%). However, eight cases (9.1%) had to undergo a total nephroureterectomy, and six cases (6.8%) had a total cystectomy. Recurrence was observed in 61 cases (69.3%) out of the 88 patients with an average of 1.81 times. The other organic cancers developed in 39 cases (8.9%) out of 438 workers who were exposed to aromatic amines and in 8 cases out of 88 patients (9.1%). Prognosis of the 88 patients is that, the number of alive and dead is 51 (58.0%) and 37 (42.0%) respectively on December 31, 1995. Twenty-eight patients (31.8%) died of uroepithelial cancer, and five patients (5.7%) died of other organic cancers. The survival rates of 5, 10, 15 and 20 years was 87.9%, 74.0%, 65.9% and 56.3%, respectively. From these results, patients with occupational uroepithelial cancer and workers who are exposed to aromatic amines should undergo long term observation.

2-Naphthylamine↗

PubMed1996

Elevation of serum levels of matrix metalloproteinase-2 and -3 as new predictors of recurrence in patients with urothelial carcinoma.

BACKGROUND: The relationship between serum levels of matrix metalloproteinase-2 (MMP-2) and MMP-3 and recurrence in patients with urothelial carcinoma after complete resection was studied to determine whether the enzymes could be a new predictor of recurrence. METHODS: Serum levels of MMP-2 and MMP-3 in 146 healthy controls, 52 patients with superficial (noninvasive) and 35 patients with advanced (invasive or metastatic) bladder carcinoma, and 30 patients with advanced upper urothelial carcinoma (renal pelvis and ureter) were measured by a one-step sandwich enzyme assay. RESULTS: Among the 53 patients with advanced urothelial carcinoma who underwent complete resection, the 1- and 3-year disease free survival rates of patients with elevated serum levels of either or both of the enzymes were 51% and 19%, respectively, whereas those of patients with normal serum levels of these enzymes were much higher, 86% and 79%, respectively (P < 0.005). In pT2N0M0 and pT3N0M0 patients who underwent complete resection, the recurrence rate in those with preoperative elevated serum levels of either or both of the enzymes was significantly higher than that in patients with normal levels (75% vs. 8%; P < 0.001). The 1- and 3-year disease free survival rates of pT2N0M0 and pT3N0M0 patients with elevated serum levels of either or both of the enzymes were 55% and 21%, respectively, which was significantly lower than that of patients with normal levels (92%; P < 0.001). CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.

Adult↗

PubMed1996

Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection.

The relationship between the serum matrix metalloproteinase-2 (MMP-2):tissue inhibitor of metalloproteinases-2 (TIMP-2) ratio and disease recurrence was examined in 53 urothelial cancer patients with muscular invasion or with lymph node metastasis who underwent complete resection. The mean MMP-2:TIMP-2 ratio in 31 patients with recurrence was significantly higher than that in 22 patients without recurrence (P < 0.05). Disease-free survival of patients with high MMP-2:TIMP-2 ratios was extremely poor compared with that of patients with lower ratios (P < 0.01). Cox's multivariate analysis suggests that the serum MMP-2:TIMP-2 ratio would be a new independent prognostic indicator of urothelial cancer recurrence.

Female↗

PubMed1996

Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas.

We examined the production and tissue localization of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gastric carcinoma tissues. MMP-1 (tissue collagenase), MMP-9 (gelatinase B) and TIMP-2 were immunolocalized in carcinoma cells and MMP-2 (gelatinase A) on tumor cell membranes, whereas no or little immunostaining for MMP-3 (stromelysin-1) and TIMP-1 was seen in carcinoma cells. Stromal cells in carcinoma tissue were also positively stained for these MMPs and TIMPs. MMP-2 immunostaining was observed exclusively on advanced gastric carcinoma cells and correlated with vascular invasion by tumor cells. Sandwich enzyme immunoassays revealed enhanced production of MMP-1, MMP-2, MMP-3, MMP-9 and TIMP-1 by carcinoma tissues. Gelatinolytic activities were significantly higher in carcinoma samples than in normal controls. Using gelatin zymography, active forms of MMP-2 and MMP-9 were more frequently detected in carcinoma tissue, and the activation rate of the zymogen of MMP-2 (proMMP-2), but not that of proMMP-9, correlated well with degree of local invasion and lymphatic permeation. Our data indicate an enhanced production of 4 MMPs in gastric carcinoma tissue and suggest that activation of pro-MMP-2 may be a key step for spreading of gastric carcinoma cells.

Enzyme Activation↗