Search PubMed⌕ Search

Biomedical subjects

M Mori

Publications and source records attributed to M Mori.

At least 379 records · Page 21Linked to original sources
PubMed2000

A novel class of antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), that releases 5-fluorouracil upon hypoxic irradiation.

We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2'-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding sigma * orbital of the C(1')-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O(2) into superoxide anion radicals (O(2).(-)) under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G-value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9 x 10(-7) mol / J following hypoxic irradiation, while the G-value for 5-FU release was 1.0 x 10(-8) mol/J following aerobic irradiation. However, the G-values for decomposition of OFU001 were almost the same, i.e., 3.4 x 10(-7) mol/J following hypoxic irradiation and 2. 5 x 10(-7) mol / J following aerobic irradiation. When hypoxically irradiated (7.5 - 30 Gy) OFU001 was added to murine SCCVII cells for 1 - 24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents.

Animals↗
PubMed2000

Photodynamic therapy for experimental tumors using ATX-S10(Na), a hydrophilic chlorin photosensitizer, and diode laser.

ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second-generation photosensitizer for use in photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using ATX-S10(Na) and a diode laser for experimental tumors was evaluated in vitro and in vivo. In-vitro PDT using ATX-S10(Na) and the diode laser showed drug concentration-, laser dose- and drug exposure time-dependent cytotoxicity to various human and mouse tumor cell lines. In Meth-A sarcoma-implanted mice, optimal PDT conditions were found where tumors were completely eliminated without any toxicity. Against human tumor xenografts in nude mice, the combined use of 5 mg / kg ATX-S10(Na) and 200 J / cm(2) laser irradiation 3 h after ATX-S10(Na) administration showed excellent anti-tumor activity, and its efficacy was almost the same as that of PDT using 20 mg / kg porfimer sodium and a 100 J / cm(2) excimer dye laser 48 h after porfimer sodium injection. Microscopic observation of tumor tissues revealed that PDT using ATX-S10(Na) and the diode laser induced congestion, thrombus and degeneration of endothelial cells in tumor vessels, indicating that a vascular shutdown effect plays an important role in the anti-tumor activity of PDT using ATX-S10(Na) and the diode laser.

Animals↗
PubMed2000

In vitro plasma protein binding and cellular uptake of ATX-S10(Na), a hydrophilic chlorin photosensitizer.

ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second-generation photosensitizer for photodynamic therapy (PDT) for cancer treatment. In this study, we examined plasma protein binding, cellular uptake and subcellular targets of ATX-S10(Na) in vitro. Protein binding ratios of 50 microg / ml ATX-S10(Na) in rat, dog and human plasma were 73.0%, 87.2% and 97.7%, respectively. Gel filtration chromatography revealed that 1 mg / ml ATX-S10(Na) bound mainly to high-density lipoprotein (HDL) and serum albumin at the protein concentration of 0.4%, with binding ratios of 46% and 36%, respectively. The free form of ATX-S10(Na) was mostly incorporated into T.Tn cells, and its cellular uptake was partially but significantly inhibited by endocytosis inhibitors such as phenylarsine oxide, chloroquine, monensin and phenylglyoxal, and by chilling the cells to 4 degrees C. However, ouabain, harmaline, sodium cyanide, probenecid and aspartic acid did not influence the uptake of ATX-S10(Na), suggesting that cellular uptake of ATX-S10(Na) was not related to sodium-potassium pump activity, sodium-dependent transporter activity, mitochondrial oxidative respiration, organic anion transporter activity or aspartic acid transporter activity. By fluorescence microscopy, lysosomal localization of ATX-S10(Na) was observed in T.Tn cells. However, electron microscopic observation revealed that many subcellular organelles such as mitochondria, endoplasmic reticulum, ribosomes, Golgi complex and plasma membrane were damaged by PDT using 25 microg / ml ATX-S10(Na) soon after laser irradiation at 50 J / cm(2), and tumor necrosis was rapidly induced. This result indicated that ATX-S10(Na) was widely distributed within the cell.

Animals↗
PubMed2000

Interleukin-8 and SDF1-alpha mRNA expression in colonic biopsies from patients with inflammatory bowel disease.

OBJECTIVES: Interleukin-8 (IL-8) as an alpha-chemokine recruits and activates neutrophils, which are abundant in the intestinal lesions of ulcerative colitis (UC) and Crohn's disease (CD). Stromal cell-derived factor 1 (SDF1-alpha) is a new chemokine that is chemotactic to neutrophils. The aims of this study were to assess the relative expression of SDF1-alpha and IL-8 mRNA in different colonic regions and patients with inflammatory bowel disease with varied degrees of inflammation in the colon. METHODS: Colon biopsy samples were obtained from 19 patients with UC, 12 with CD, and 5 with irritable bowel syndrome (IBS) who underwent colonoscopy. Levels of IL-8 and SDF1-alpha mRNA expression were measured semiquantitatively by reverse-transcription and polymerase chain reaction amplification. The cytokine mRNA levels were corrected for glyceraldelyde-3-phosphate dehydrogenase mRNA expression. RESULTS: IL-8 mRNA expression was significantly correlated with SDF1-alpha expression in normal biopsies from IBS patients (r = 0.58, p < 0.01). There was no significant difference in cytokine mRNA expression (IL-8 or SDF1-alpha) across different regions of the colon or rectum in uninflamed normal biopsies. The IL-8 mRNA expression ratios in UC (mean +/- SD, 1.03 +/- 0.52) and CD (0.90 +/- 0.38) patients were significantly higher than in IBS (0.52 +/- 0.17) (p < 0.01, p < 0.05, respectively). The SDF1-alpha mRNA expression ratio in UC (0.30 +/- 0.52) was higher than in both CD (0.21 +/- 0.10) and IBS patients (0.22 +/- 0.11) (p < 0.01, <0.05, respectively). A statistically significant correlation was found between the IL-8 mRNA expression and the colonic inflammation in UC patients (r = 0.44, p < 0.05) but not for SDF1-alpha expression in UC patients. CONCLUSIONS: IL-8 but not SDF1-alpha mRNA expression was associated with inflammation in UC. This suggests that IL-8 may play a more important role in inflammatory bowel disease than does SDF1-alpha.

Adult↗
PubMed2000

Differences between features of adenoma in the rectum versus sigmoid colon.

OBJECTIVE: Although the prevalence of cancer in the rectosigmoid is high compared with that in the more proximal colon, the features of cancer developing from an adenoma have yet to be elucidated. The aim of this study is to examine the clinicopathological relationship between cancer and adenoma in the rectosigmoid. METHODS: A total of 340 adenomas located in the rectosigmoid in 255 patients were retrospectively examined regarding such clinicopathological factors as location and the grade of dysplasia. RESULTS: The prevalence of adenoma was 102 in the rectum and 238 in the sigmoid colon, respectively, whereas the prevalence of adenoma with high-grade dysplasia was 39 in the rectum and 48 in the sigmoid colon, respectively. This prevalence of adenoma with high-grade dysplasia was thus significantly higher in the rectum than in the sigmoid colon (p < 0.02). CONCLUSIONS: These findings suggest the possibility of different types of cancer development between adenoma of the rectum and sigmoid colon.

Adenocarcinoma↗
PubMed2000

Cooperation of pituitary hormone prolactin with interleukin-2 and interleukin-12 on production of interferon-gamma by natural killer and T cells.

The pituitary hormone prolactin (PRL) is also produced by cells of the immune system and participates in early and late T cell activating events. We have previously shown a modulatory role of PRL during maturation of dendritic cells (DC). Production of IL-12 by T cell receptor (TCR)-activated DC is necessary for T cells to acquire the Th1 cytokine (i.e., IFN-gamma secreting) profile, which is associated with activation of cellular response. In a separate work, PRL has been shown to increase IFN-gamma synthesis by natural killer (NK) cells. We have extended that study by exploring the ability of PRL to induce IFN-gamma production by T and NK cells in the presence of the specific stimuli IL-12 and IL-2. The individual effect of PRL, IL-12, and IL-2 was specific for NK cells, and IL-2 and IL-12 were much more efficient than PRL. Cooperation of IL-2 and PRL was observed on NK cells. IL-2-induced synthesis of IFN-gamma was increased by physiological concentrations of PRL but was unaffected or inhibited by high concentrations. By contrast, optimal enhancement of IL-12-induced IFN-gamma release was observed with T cells but not with NK cells. Unexpectedly, interaction between PRL and IL-12 occurred only at high concentrations of PRL. These data indicate a complex role of PRL in the cytokine network and point to a revaluation of the proposed immunosuppression by stress-related hyperprolactinemia.

Cells, Cultured↗
PubMed2000

[Why there were few isolations of tubercle bacilli in young children with pulmonary tuberculosis?].

We retrospectively evaluated the factors influencing the isolation of tubercle bacilli in 51 children under 14 years of age with pulmonary tuberculosis who were admitted to Yokohama City University Hospital from 1975 to 1998. Young children (0-6 years of age) with pulmonary tuberculosis were significantly less positive by smear and culture than elder children (7-14 years of age) with pulmonary tuberculosis. According to the Japanese Society for Tuberculosis classification of finding on chest X-ray film for pulmonary tuberculosis, the culture-positive patients with type II (cavitary lesions) were found in all, the culture-positive patients with type III (non-cavitary lesions) in 39.3%, and the culture-positive patients with type H (hilar and mediastinal lymphadenopathys) in 35.3%. Patients with cavitary lesions (type II) were significantly more positive by smear and culture than patients with non-cavitary lesions (type III + type H). Only 15.8% of the young children with pulmonary tuberculosis had received BCG vaccine and all had non-cavitary lesions (type III and type H). But, 84.6% out of the older children had received BCG vaccine and half had cavitary lesions. Taken together, the result was that there were few isolation of tubercle bacilli in young children with pulmonary tuberculosis because they had non-cavitary tuberculosis without delayed-type hypersensitivity to tubercle bacilli.

Adolescent↗
PubMed2000

Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by hepatitis C virus core protein.

The effects of hepatitis C virus (HCV) proteins on several signal transduction pathways in human nonneoplastic hepatocyte PH5CH8 cells were investigated using expression vectors encoding HCV proteins derived from HCV-infected human nonneoplastic cultured T-lymphocyte and hepatocyte cells (MT-2C and PH5CH7), which could support HCV replication. The amino acid sequences of HCV proteins obtained from HCV-infected human cells were identical or very close to the consensus sequences of the proteins derived from the original inoculum used for HCV infection. During the course of the study, we found that HCV core protein specifically activated the 40/46-kDa 2'-5'-oligoadenylate synthetase (2'-5'-OAS) gene promoter in a dose-dependent manner in different human hepatocyte cell lines (PH5CH8, HepG2, and PLC/PRF/5). We also found that the activation by core protein was further enhanced in the cells treated with alpha interferon. The expression of E1 or E2 envelope protein or nonstructural NS5A protein did not activate the 2'-5'-OAS gene promoter. We demonstrated that the activation by core protein in the hepatocyte cells was suppressed by antisense RNA complementary to core-encoding RNA. Deletion mutant analysis of core protein and deletion analysis of the 2'-5'-OAS gene promoter have been performed. Finally, we demonstrated that the activation of the 2'-5'-OAS gene occurred at the transcriptional level and furthermore demonstrated that the endogenous 2'-5'-OAS gene was also activated by core protein. This is the first report to show that a viral protein activated the 2'-5'-OAS gene.

2',5'-Oligoadenylate Synthetase↗
PubMed2000

Identification and functional analysis of human Tom22 for protein import into mitochondria.

Mitochondria have a receptor complex in the outer membrane which recognizes and translocates mitochondrial proteins synthesized in the cytosol. We report here the identification and functional analysis of human Tom22 (hTom22). hTom22 has an N-terminal negatively charged region exposed to the cytosol, a putative transmembrane region, and a C-terminal intermembrane space region with little negative charge. Tom22 forms a complex with Tom20, and its cytosolic domain functions as an import receptor as in fungi. An import inhibition assay, using pre-ornithine transcarbamylase (pOTC) derivatives and a series of hTom22 deletion mutants, showed that the C-terminal segment of the cytosolic domain is important for presequence binding, whereas the N-terminal domain is important for binding to the mature portion of pOTC. No evidence for pOTC interaction with the Tom22 intermembrane space domain was obtained. Binding studies revealed that the presequence is critical for pOTC binding to Tom20, whereas both the presequence and mature portion are important for binding to Tom22. A cell-free immunoprecipitation assay indicated that an internal segment of the Tom22 cytosolic domain is important for interaction with Tom20.

Amino Acid Sequence↗
PubMed2000

Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness.

BACKGROUND: Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with broad substrate specificity which can be activated by membrane type 1 (MT1) matrix metalloproteinase in vitro. These may play a critical role in cancer aggressiveness. AIMS: To examine the clinical significance of collagenase-3 expression and the cooperative role of MT1-MMP in human oesophageal carcinomas. PATIENTS: Forty five individuals with oesophageal carcinoma who underwent surgery without preoperative treatment. METHODS: The tumour/normal (T/N) ratios of collagenase-3 and MT1-MMP mRNA expression in 45 human oesophageal carcinomas were determined by northern blot analysis. The production and localisation of collagenase-3 and MT1-MMP proteins were investigated by immunohistochemistry, western blot analysis, and zymography. RESULTS: The mean T/N ratio of collagenase-3 mRNA was 3.5 and that of MT1-MMP 2.1. There was a significant correlation between collagenase-3 and MT1-MMP mRNA expression (p<0.001). Twenty two cases with a collagenase-3 T/N ratio >3.5 showed a significantly higher frequency of vascular involvement and lymph node metastasis, and tended to be at a more advanced stage than 23 cases with a T/N ratio < or =3.5 (p<0.05). Western blot analysis and zymography demonstrated production of collagenase-3 protein in tumour tissues but not in normal tissues. Immunohistochemical studies revealed that collagenase-3 was localised predominantly in tumour cells and MT1-MMP was detected in the same collagenase-3 positive cells; there was a significant association between collagenase-3 and MT1-MMP protein expression (p<0.05). With regard to prognosis, the survival time for subjects in the high collagenase-3 group (T/N ratio >3.5) was significantly worse (p<0.05). CONCLUSIONS: These data suggest that production of collagenase-3 together with MT1-MMP is implicated in tumour aggressiveness and prognosis in human oesophageal carcinomas.

Adult↗
PubMed2000

Isolated absence of F waves and proximal axonal dysfunction in Guillain-Barré syndrome with antiganglioside antibodies.

OBJECTIVES: To investigate the pathophysiology of selective absence of F waves and its relation with antiganglioside antibodies in Guillain-Barré syndrome (GBS). Some patients with GBS show the absence of F waves as an isolated conduction abnormality, which has been interpreted as demyelination in the proximal nerve segments. METHODS: In 62 consecutive patients with GBS, sequential nerve conduction and F wave studies were reviewed, and antibodies against ganglioside GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, and GQ1b were measured by an enzyme linked immunosorbent assay. RESULTS: In the first electrophysiological studies, isolated absence of F waves was found in 12 (19%) patients. Sequential studies in 10 of these patients showed two electrophysiological sequel patterns; rapid restoration of F waves (six patients), and persistent absence of F waves with distal motor nerve degeneration (acute motor axonal neuropathy, four patients). None of the 10 patients showed evidence of demyelination in the proximal, intermediate, or distal nerve segments throughout the course. Of the 62 patients, IgG antibodies against GM1, GM1b, GalNAc-GD1a, or GD1b were significantly associated with the electrodiagnosis of acute motor axonal neuropathy, and patients with these antibodies more often had isolated absence of F waves than patients without them (11 of 36 (31%) v one of 26 (4%); p<0.01). Eleven of the 12 patients with isolated absence of F waves had positive serology for one or more antiganglioside antibodies. CONCLUSIONS: In GBS with antiganglioside antibodies, isolated absence of F waves is a frequent conduction abnormality especially in the early phase of the disease, and may be caused by axonal dysfunction, such as physiological conduction block or axonal degeneration at the nerve roots.

Adolescent↗
PubMed2000

Expression of GFRalpha-1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB.

It is well known that the blood-brain barrier (BBB) matures at approximately 2 wk after birth in the rat. Recently, we showed that glial cell line-derived neurotrophic factor (GDNF) enhances the barrier function of porcine endothelial cells forming the BBB in culture. In the present study, we examined the relation between permeability of the BBB, using Evans blue as a tracer, and expression of the GDNF family receptor (GFRalpha-1) during postnatal development of the BBB. Morphometric analysis showed that exudation of Evans blue from capillaries of the cerebral cortex progressively decreased until postnatal day 21. Inversely, immunohistochemical examinations showed expression of GFRalpha-1 in the capillaries at postnatal day 3 and expression that reached the same levels as observed in adult rats by postnatal day 10. However, c-ret, which is thought to mediate a signal evoked by binding of GDNF to GFRalpha-1, was not expressed in the capillaries of the brain cortex in 3-mo-old rats. On the other hand, the tight junction proteins occludin and ZO-1 appeared to be fully expressed at birth. The reciprocal relation between GFRalpha-1 expression and the permeability of the BBB strongly suggests active participation of GDNF in postnatal development of the BBB, although the mechanism(s) involved is still veiled.

Animals↗
PubMed2000

Tom20-mediated mitochondrial protein import in muscle cells during differentiation.

Mitochondrial biogenesis is accompanied by an increased expression of components of the protein import machinery, as well as increased import of proteins destined for the matrix. We evaluated the role of the outer membrane receptor Tom20 by varying its expression and measuring changes in the import of malate dehydrogenase (MDH) in differentiating C2C12 muscle cells. Cells transfected with Tom20 had levels that were twofold higher than in control cells. Labeling of cells followed by immunoprecipitation of MDH revealed equivalent increases in MDH import. This parallelism between import rate and Tom20 levels was also evident as a result of thyroid hormone treatment. Using antisense oligodeoxynucleotides, we inhibited Tom20 expression by 40%, resulting in 40-60% reductions in MDH import. In vitro assays also revealed that import into the matrix was more sensitive to Tom20 inhibition than import into the outer membrane. These data indicate a close relationship between induced changes in Tom20 and the import of a matrix protein, suggesting that Tom20 is involved in determining the kinetics of import. However, this relationship was dissociated during normal differentiation, since the expression of Tom20 remained relatively constant, whereas imported MDH increased 12-fold. Thus Tom20 is important in determining import during organelle biogenesis, but other mechanisms (e.g., intramitochondrial protein degradation or nuclear transcription) likely also play a role in establishing the final mitochondrial phenotype during normal muscle differentiation.

Cell Differentiation↗
PubMed2000

Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo.

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day -3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-beta-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.

Animals↗
PubMed2000

Regulation of diaphragmatic nitric oxide synthase expression during hypobaric hypoxia.

Nitric oxide (NO) is normally synthesized inside skeletal muscle fibers by both endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases. In this study, we evaluated the influence of hypobaric hypoxia on the expression of NOS isoforms, argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and manganese superoxide dismutase (Mn SOD) in the ventilatory muscles. Rats were exposed to hypobaric hypoxia ( approximately 95 mmHg) from birth for 60 days or 9-11 mo. Age-matched control groups of rats also were examined. Sixty days of hypoxia elicited approximately two- and ninefold increases in diaphragmatic eNOS and nNOS protein expression (evaluated by immunoblotting), respectively, and about a 50% rise in diaphragmatic NOS activity. In contrast, NOS activity and the expression of these proteins declined significantly in response to 9 mo of hypoxia. Hypoxia elicited no significant alterations in AS, AL and Mn SOD protein expression. Moreover, the inducible NOS (iNOS) was not detected in normoxic and hypoxic diaphragmatic samples. We conclude that diaphragmatic NOS expression and activity undergo significant adaptations to hypobaric hypoxia and that iNOS does not participate in this response.

Animals↗
PubMed2000

Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs.

BACKGROUND/AIMS: Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO). METHODS: Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time. RESULTS: CCK-8 decreased the phasic wave amplitude of the choledochal sphincter, and increased NO release. N(G)-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, increased the spontaneous motility and converted the CCK-induced inhibitory response into an excitatory response. L-NAME also reduced NO release and abolished the increase of NO that had been caused by CCK-8. These effects were reduced by treatment with L-arginine (L-Arg). L-Arg application enhanced NO release, and recovered the increase of NO by CCK-8. CONCLUSION: These studies demonstrate that CCK relaxes the choledochal sphincter and this relaxant response is mediated by NO.

Animals↗
PubMed2000

Reduced expression of manganese superoxide dismutase mRNA may correlate with invasiveness in esophageal carcinoma.

Little is known about the expression and antioxidant function of manganese superoxide dismutase (Mn-SOD) in esophageal squamous cell carcinoma. To determine the significance of Mn-SOD in esophageal squamous cell carcinomas, Mn-SOD mRNA expression was examined in 45 esophageal squamous cell carcinomas and the corresponding normal mucosal tissues by reverse transcription-polymerase chain reaction. The tumor/normal (T/N) ratio of 45 patients with esophageal carcinoma was calculated, and the data were clinicopathologically analyzed. The T/N ratio of Mn-SOD mRNA expression was less than 0.5 in 11 (32.4%) of 34 esophageal carcinoma cases without any preoperative treatments, while none of 11 cases who underwent preoperative chemotherapy showed a T/N ratio of <0.5 (p < 0.05). There was an inverse correlation between the Mn-SOD expression level and the degree of venous invasion (p < 0.05) as well as lymphatic invasion (p < 0.05). Furthermore, poorly differentiated squamous cell carcinoma showed significantly lower Mn-SOD mRNA expression levels than well differentiated carcinoma (p < 0.05). Our results suggest that Mn-SOD mRNA was frequently reduced in esophageal carcinoma when compared to the normal mucosa and the reduced expression levels of Mn-SOD mRNA may lead to an accumulation of superoxide radicals in conjunction with the increased invasiveness of esophageal carcinoma.

Carcinoma, Squamous Cell↗