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Yoshitaka Fujii

Publications and source records attributed to Yoshitaka Fujii.

At least 73 records · Page 4Linked to original sources
PubMed2004

Dominant-negative Stat5 inhibits growth and induces apoptosis in T47D-derived tumors in nude mice.

Signal transducer and activator of transcription 5 (Stat5) regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. In this study, we have analyzed the role of Stat5 in progression of the estrogen receptor-positive T47D human breast cancer cell line, in which Stat5b is constitutively activated. Expression of Stat5-regulated genes, such as cyclin D1 and bcl-xL, was strongly suppressed in T47D cells infected with the dominant-negative Stat5 adenovirus, AdStat5aDelta740. We also determined the phenotypic effects of introduction of dominant-negative Stat5 on T47D-derived tumors in nude mice. Tumors injected with AdStat5aDelta740 showed a 60% reduction in size, which was associated with the induction of apoptosis. Our results indicate the possibility of using dominant-negative Stat5 to induce apoptosis in certain Stat5-activated breast cancers.

Adenoviridae↗
PubMed2004

The recovery profile of reduced diaphragmatic contractility induced by propofol in dogs.

Propofol decreases contractility of the diaphragm, but no data are available for its effects on recovery. We studied the recovery profile of reduced diaphragmatic contractility induced by propofol in dogs. Animals were divided into 4 groups of 7 each. Group I, without fatigue, received only maintenance fluid; Group II, without fatigue, was infused with propofol; Group III, with fatigue, received no study drug; Group IV, with fatigue, was infused propofol. Propofol at an anesthetic dose (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1)) was administered for 60 min. In Groups III and IV, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at 20-Hz for 30 min. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). In group II, Pdi at low-frequency (20-Hz) stimulation decreased to less than baseline (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. At 10 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to baseline. When fatigue was established, in Groups III and IV, Pdi at 20-Hz stimulation decreased to less than baseline (P < 0.05), whereas Pdi at 100-Hz stimulation did not change. After administering propofol in Group IV, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). At 20 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to fatigued values. We conclude that reduced contractility in nonfatigued and fatigued canine diaphragm induced by propofol recovers within 20 min after the cessation of administration.

Anesthetics, Intravenous↗
PubMed2004

Expression of Smac/DIABLO is a novel prognostic marker in lung cancer.

Recently Smac/DIABLO (second mitochondria-derived activator of caspase) has been identified as a proapoptotic protein that inhibits IAPs (inhibitors of apoptosis proteins). Smac is expressed ubiquitously in many organs, including the lung. Here we evaluated the expression of Smac mRNA with real-time reverse-transcription PCR in 88 primary lung cancers and matched normal tissues. Smac mRNA expression in tumor tissues was significantly lower than that in normal tissues (p<0.0001). In squamous cell carcinomas, Smac mRNA expression was significantly lower than that in adenocarcinomas (p=0.0072). Smac mRNA expression in T2-T4 tumors was significantly lower than that in T1 tumors (p=0.0006). The expression of Smac in the tumors of smokers was lower than that in the tumors of non-smokers (p=0.0011). The prognosis of patients with a tumor exhibiting a low expression of Smac mRNA was worse than that in those with a tumor exhibiting high Smac mRNA expression (log-rank test, p=0.047). These results indicate that Smac expression may play a role in the carcinogenesis, progression, and prognosis of primary lung cancer.

Apoptosis Regulatory Proteins↗
PubMed2004

Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in colorectal cancers.

Through analysis of genome-wide expression profiles on a cDNA microarray consisting of 23,040 human genes, we have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of colorectal carcinoma (CRC). Among the genes that were frequently transactivated in colorectal tumors, we identified a novel gene termed LEMD1 (LEM domain-containing 1) whose expression was elevated in 17 of 18 CRCs compared with their corresponding non-cancerous mucosae. Northern blotting revealed that LEMD1 was expressed only in testis among the 16 normal adult tissues examined. Subsequent analysis identified six alternatively spliced forms of the transcript in normal testis, but only one of them (656 nucleotides) was expressed in CRCs. Since the LEMD1 protein appears to fall in the category of cancer-testis antigens (CTAs), it may represent a promising target antigen for immunotherapy of CRCs.

Alternative Splicing↗
PubMed2004

Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.

Aged↗
PubMed2003

Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks.

It is poorly understood how apoptotic signals arising from DNA damage are transmitted to mitochondria, which release apoptogenic factors into the cytoplasm that activate downstream destruction programs. Here, we identify histone H1.2 as a cytochrome c-releasing factor that appears in the cytoplasm after exposure to X-ray irradiation. While all nuclear histone H1 forms are released into the cytoplasm in a p53-dependent manner after irradiation, only H1.2, but not other H1 forms, induced cytochrome c release from isolated mitochondria in a Bak-dependent manner. Reducing H1.2 expression enhanced cellular resistance to apoptosis induced by X-ray irradiation or etoposide, but not that induced by other stimuli including TNF-alpha and UV irradiation. H1.2-deficient mice exhibited increased cellular resistance in thymocytes and the small intestine to X-ray-induced apoptosis. These results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks.

Animals↗
PubMed2003

Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells.

Signal transducer and activator of transcription (Stat) 5 regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. We detected for the first time that Stat5b is constitutively activated in human breast cancer cell lines, and analysed the role of Stat5 in estrogen receptor(ER)-positive breast cancer cell lines using dominant-negative variants of Stat5. Two distinct carboxyl-truncated Stat5a derivatives were generated. Stat5aDelta740 corresponded to a naturally occurring alternative splice variant, and Stat5aDelta713 was analogous to an 80 kDa Stat5a product of a nuclear protease. Stat5aDelta740 and Stat5aDelta713 displayed comparable dominant-negative properties and suppressed transcriptional activity of wild-type Stat5a and Stat5b equally well. Cotransfection experiments revealed that Stat5aDelta740 completely blocked transcriptional activity of endogenous estrogen receptor in T47D and MCF7 cells, and of both ER alpha and ER beta in COS-7 cells. Stat5aDelta740 was selected for adenoviral delivery, and high-efficiency expression of tyrosine phosphorylated Stat5aDelta740 was achieved in infected cells. Adenoviral-mediated Stat5aDelta740 induced apoptosis in T47D cells but not in caspase-3-negative MCF7 cells. The present study indicates that overexpression of a dominant-negative variant of Stat5 suppresses ER transcriptional activity and induces apoptosis in estrogen-responsive breast cancer tissue culture cells.

Adenoviridae↗
PubMed2003

Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer.

Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear. In 25 (28%) of the 90 paired samples of human breast cancer and the matched, adjacent non-cancerous tissues examined here, reduced mRNA expression of Syk in the breast cancer tissues was observed by real-time quantitative reverse transcription-polymerase chain reaction. Eight (32%) of the 25 cases showing reduced Syk mRNA expression demonstrated distant metastasis of breast cancer, while only 4 (6%) of the 65 cases who did not show reduced Syk expression had distant metastasis. Kaplan-Meier curves demonstrated that patients with reduced Syk expression were at significantly increased risk for distant metastasis (P=0.0003). Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.

Breast Neoplasms↗
PubMed2003

Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs.

BACKGROUND: Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta(1) blocker, landiolol, and milrinone in halothane-anesthetized dogs. METHODS: Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothane. Hemodynamic measurements were made at baseline, 30 min after starting the milrinone (0.5 micro g x kg(-1) x min(-1)) or normal saline infusion (n = 9 in each), then 30 min after each change in the dose of landiolol infusion. The tested doses of landiolol were 10, 100, and 1000 micro g x kg(-1) x min(-1). RESULTS: Landiolol (>/= 10 micro g x kg(-1) x min(-1)) has significant and comparable negative chronotropic effects in both groups of dogs. While it also has significant negative inotropic effects in both groups, such effects are significantly attenuated in the dogs treated with milrinone. CONCLUSION: Milrinone is effective to attenuate the negative inotropic effects of landiolol in halothane-anesthetized dogs.

Adrenergic beta-Antagonists↗
PubMed2003

Real-time energy metabolism of intestine during arterial versus venous occlusion in the rat.

BACKGROUND: Although it is less frequently encountered, mesenteric vein occlusion poses as important a problem as mesenteric artery occlusion. The energy metabolism of intestinal tissue during venous occlusion and reperfusion was studied. METHODS: Male Wistar rats were studied in four groups of 17 animals each. Intestinal ischemia was induced by clamping the superior mesenteric artery ([SMA] occlusion [O]) or vein (SMVO) for 30 or 60 min, followed by reperfusion. Magnetic resonance spectroscopy was employed to continuously monitor the energy metabolism. Additionally, intestinal motility was monitored and histological examination was performed on resected specimens. RESULTS: Energy metabolism in SMVO during ischemia was reduced more slowly than in SMAO, but recovery after reperfusion was poorer in SMVO. During ischemia, the contractive response of the intestine lasted longer in SMVO than in SMAO. Histologically, mucosal and subserosal hemorrhage was more severe in SMVO. CONCLUSIONS: In contrast to SMAO, SMVO caused less severe reduction of energy metabolism, at the expense of hemorrhage and tissue damage.

Animals↗
PubMed2003

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in thymoma.

PURPOSE: Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma. METHODS: To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. RESULTS: In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors. CONCLUSIONS: The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.

Adult↗
PubMed2003

Flow-cytometric diagnosis of thymoma using needle biopsy specimens.

INTRODUCTION: Thymoma is a neoplasm of thymic epithelial cells which is characteristically associated with a large number of non-neoplastic T lymphocytes. These T cells are induced by epithelial cells and show a unique phenotype of CD4(+)8(+) double positive (DP), when studied by flow cytometry. This DP phenotype can be used as one of the diagnostic criteria to indicate a thymoma. The preoperative diagnosis of thymoma and other thymic tumors is an important problem because the treatment differs according to the diagnosis. METHODS: A flow-cytometric analysis of needle biopsy specimens was performed on ten thymic tumors. The results were then compared with the findings of a histological diagnosis using conventional hematoxylin-eosin (H&E) staining. RESULTS: Six cases with high frequencies of DP cells were diagnosed as thymoma by a flow-cytometric analysis, and were confirmed by a histological analysis of the resected specimen. Flow cytometry did not suggest a thymoma in the other four cases with few DP cells. The final diagnoses of the resected specimen of these four cases were: one thymic carcinoma, one malignant lymphoma, and two germ-cell tumors. The accuracy and specificity of diagnosis of thymoma using a fluorescence-activated cell sorting analysis from needle biopsy specimens were 6/6 (100%). On the other hand, the specificity of H&E staining from needle biopsy specimens for the diagnosis of thymoma was 6/6 (100%), but the accuracy was only 6/9 (66.7%). DISCUSSION: Flow cytometry can be applied to needle biopsy specimens and thus is considered to offer useful information for the preoperative diagnosis of thymic tumors.

Adult↗
PubMed2003

Multicystic mesothelial cyst of the mediastinum: report of a case.

We report the rare case of a multicystic mesothelial cyst of the mediastinum. A 43-year-old man was referred to our department after a routine chest X-ray showed an anterior mediastinum mass. The lesion was resected by thoracoscopy, which revealed multicystic, thin-walled tense masses arising in the anterior mediastinum. The cysts were not adherent to the pericardium or to the thymus of the right lobe. Immunohistochemistry revealed that the cyst was lined with a layer of mesothelial cells and there were no malignant foci. The lining cells were positive for keratin and negative for the lymphocyte marker. These findings were consistent with a diagnosis of multicystic mesothelial cyst.

Adult↗
PubMed2003

Biweekly paclitaxel in patients with metastatic breast cancer.

BACKGROUND: This study was conducted to evaluate the efficacy and the toxicity of paclitaxel administered as a biweekly 1-h infusion (120 mg/m2). METHODS: Twenty patients with metastatic breast cancer were enrolled in this study. Paclitaxel was administered at a dose of 120 mg/m2 by an intravenous 1-h infusion every 2 weeks. The primary objectives of the study were the response rate and toxicity. Pharmacokinetic analysis was conducted in 7 of the 20 patients treated with paclitaxel. RESULTS: Four of the 20 patients had grade 3 or 4 neutropenia. Arthralgia or myalgia was observed in 8 of the 20 patients. Grade 2 or 3 neurotoxicity was observed in 6 of the 20 patients. In the 20 assessable patients, there was one complete response and eight partial responses. The overall response rate was 45%. The mean time to progression was 5.4 months. CONCLUSIONS: Biweekly paclitaxel may be suitable for patients receiving paclitaxel for palliative therapy, as tolerance was similar to that with the weekly schedule, but with the advantage of increased convenience.

Adult↗
PubMed2003

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer.

BACKGROUND: Using an enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as predictors of the development and extent of lung cancer. METHODS: The study included 106 lung cancer patients and 16 patients with nonmalignant thoracic disease. Serum samples were collected before clinical treatment. RESULTS: There was no difference between serum EGFR levels in patients with lung cancer (21.275 +/- 22.035 fm/ml) in comparison with those in nonmalignant-disease controls (22.630 +/- 7.330 fm/ml; P = 0.8083). However, lung cancer patients with lymph node metastasis (23.515 +/- 20.065 fm/ml) had significantly higher EGFR levels compared with those in patients without lymph node metastasis (16.390 +/- 10.970 fm/ml; P = 0.0228). The serum EGFR levels were similar in samples from lung cancer patients with various pathological subtypes. There was no difference in the prognosis between the lung cancer group with normal EGFR levels (<850 ng/ml) and the group with elevated EGFR levels (>850 ng/ml). CONCLUSION: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer. However, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EGFR levels was of limited value in the detection of lung cancer.

Aged↗
PubMed2003

Hrad17 expression in thymoma.

OBJECTIVES: We used palindromic polymerase chain reaction-driven complementary deoxyribonucleic acid differential display to identify and isolate a gene, the human homolog of the Schizosaccharomyces pombe checkpoint gene rad17 (Hrad17), from colon cancer tissue. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes--events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in thymoma, especially in invasive thymoma. We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with thymoma who had undergone surgery. METHODS: Expression of Hrad17 messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction using a LightCycler in 38 thymomas and 10 adjacent histologically normal thymus samples from patients for whom follow-up data was available. RESULTS: Hrad17 transcripts were detected in all 38 tumor samples (8.789 +/- 7.337) at levels significantly higher than those in normal thymus samples (1.908 +/- 2.267, p < 0.0001). No relationship was seen between Hrad17 gene expression and age, gender, or pathological thymoma subtypes. Hrad17 mRNA expression in invasive thymomas (stage II-IV, 10.067 +/- 5.293) was significantly higher than that in stage I thymomas (5.193 +/- 4.485, p = 0.0168). Immunohistochemistry showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue. CONCLUSIONS: Hrad17 was highly expressed in invasive thymoma.

Cell Cycle Proteins↗
PubMed2003

Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organization classification subtype and clinical stage of thymic epithelial tumors.

To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)-MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by immunohistochemistry and in selected 15 cases by in situ hybridization. The tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and 9 type C thymomas according to the World Health Organization histologic classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage IV thymomas according to the Masaoka staging system. In the positive cases, MMPs and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular localization of MMPs detected by immunohistochemistry was almost identical with that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were predominantly expressed in type B3 thymoma and type C thymoma, respectively. Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma. Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical stage. The present study suggests that certain MMPs may play an important role in the tumor progression of different subtypes of thymic epithelial tumors and that MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.

Adult↗