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Yoshitaka Fujii

Publications and source records attributed to Yoshitaka Fujii.

At least 109 records · Page 6Linked to original sources
PubMed2002

Gene expression analysis of human thymoma correlates with tumor stage.

Thymoma is one of the most common solid tumors in the mediastinum. The recent development of high-density oligonucleotide arrays provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in actual neoplastic tissues. We used oligonucleotide arrays to monitor in vivo gene expression levels in early- (stage I or II) and late- (stage IVa) stage thymoma tissues in 36 patients. These in vivo gene expression profiles were verified by real-time quantitative RT-PCR using LightCycler. Using both methods, 2 candidate genes were identified that were more highly expressed in advanced-stage thymomas. One was a well-known gene, c-JUN, and another was an unknown gene, AL050002. AL050002 expression, but not c-JUN expression, was also correlated with the WHO classification (type B3 vs. type B1, B2 or AB). The combined use of oligonucleotide microarray and real-time RT-PCR analyses provides a powerful new approach to elucidate the in vivo molecular events correlated with tumor stage of thymoma.

DNA, Complementary↗
PubMed2002

Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas.

To investigate the mechanisms of colorectal carcinogenesis, we searched for genes regulated by adenomatous polyposis coli gene product (APC) and identified a novel gene, termed HELAD1 (helicase, APC down-regulated 1). A recombinant polypeptide representing the ATPases associated with cellular activities (AAA) domain of the HELAD1 product showed 3' to 5' helicase activity and exonuclease activity in vitro. HELAD1 was abundantly expressed in 16 of 20 colon cancers examined but hardly detectable in corresponding non-cancerous mucosae. Treatment of colon-cancer cells with antisense oligonucleotides suppressed its expression and induced apoptosis. These data revealed an importance of HELAD1 in colorectal carcinogenesis and suggest that suppression of HELAD1 may be a promising therapeutic strategy.

Colorectal Neoplasms↗
PubMed2002

The expression of Bcl-2 family proteins (Bcl-2, Bcl-x, Bax, Bak and Bim) in human lymphocytes.

Bcl-2 family proteins regulate programmed cell death, and may play an important role in the selection of lymphocytes. We investigated the expression of Bcl-2, Bcl-x, Bax, Bak and Bim in human lymphocytes using flow-cytometry. Bcl-2 was down-regulated in CD4(+)8(+) (DP) thymocytes and CD19(+)38(+) tonsillar lymphocytes (GC B cells). Among DP thymocytes, cells co-expressing CD69 up-regulated Bcl-2, suggesting that the role of Bcl-2 is promoting survival of positively selected DP cells. Unexpectedly, the expression level of Bcl-x was higher in DP cells than in Single Positive (SP) cells and in CD69(+) DP thymocytes it was lower than in CD69(+) DP thymocytes. Expression of Bim was low in DP thymocytes but high in a subset of GC B cells. Bim and Bax were expressed more highly in SP than in DP thymocytes. Among peripheral blood lymphocytes (PBL), CD8(+) T cells expressed an approximately ten-fold higher level of Bcl-x than CD4(+) T cells while both subsets expressed similar levels of Bcl-2. Bak expression was low and Bim expression was absent in PBL. These results suggest that not only Bcl-2 but other members of the Bcl-2 family are involved in T cell development in the thymus and affinity maturation of B cells in the germinal center.

Adult↗
PubMed2002

Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers.

The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.

Base Sequence↗
PubMed2002

Telomerase activity in esophageal squamous cell carcinoma: down-regulation by chemotherapeutic agent.

BACKGROUND AND OBJECTIVES: Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors. METHODS: Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase. RESULTS: Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT. CONCLUSIONS: Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity.

Aged↗
PubMed2002

Role of matrix metalloproteinase-9 in in vitro invasion of esophageal carcinoma cells.

BACKGROUND AND OBJECTIVES: Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series). METHODS: Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion. CONCLUSIONS: Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9.

Carcinoma, Squamous Cell↗
PubMed2002

Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53.

BACKGROUND AND OBJECTIVES: Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non-small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. METHODS: We examined 108 resected NSCLCs for the expression of TSG products, p27(KIP1), p16(INK4A), pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. RESULTS: Abnormal expressions of p27(KIP1), p16(INK4A), pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27(KIP1) to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1-T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16(INK4A), pRB, or p53. In the Cox regression analysis, p27(KIP1) expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). CONCLUSIONS: Our results suggest that abnormal p27(KIP1) expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined.

Adenocarcinoma↗
PubMed2002

Ets-1 gene expression in patients with thymoma.

OBJECTIVES: The Ets-1 protooncogene transcription factor is involved in several cellular functions, including the activation of several proteases, and reportedly plays an important role in carcinoma invasion and metastasis. We hypothesize that Ets-1 mRNA expression could be a predictor of thymoma development and invasion. METHODS: Subjects were 37 patients with thymoma whose mRNA expression was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR) using LightCycler, a microvolume multisample fluorimeter. RESULTS: No significant difference was found in Ets-1 mRNA expression for gender, age, or pathological subtype. Ets-1 mRNA expression in tumor tissues from stage II-IV thymoma (25.311 +/- 42.336) was more elevated than in that from stage I thymoma (2.097 +/- 4.492) (p = 0.0374). Ets-1 mRNA expression may thus serve as a marker of higher thymoma stages. CONCLUSIONS: With use of the Light Cycler RT-PCR assay, Ets-1 expression may play an important role in the extension and progression of thymoma as in other cancers. Further study and longer follow-up are, however, needed to confirm the Ets-1 impact on biological tumor behavior.

Adult↗
PubMed2002

High-dose colforsin daropate increases diaphragmatic contractility in dogs.

PURPOSE: To evaluate the effects of colforsin daropate, a water-soluble derivate known to improve contractility in fatigued canine diaphragm, at two different doses (low-dose and high-dose) on contractility of the non-fatigued diaphragm of dogs. METHODS: Twenty-four pentobarbitone-anesthetized dogs were divided into three groups of eight each: Group I received no study drug; Group II received low-dose (0.2 microg x kg-1 x min-1) colforsin daropate; Group III received high-dose (0.5 microg x kg-1 x min-1) colforsin daropate. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). RESULTS: In Group III, with an infusion of high-dose colforsin daropate, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation increased from baseline values (P < 0.05). Compared with Group I, Pdi at both stimuli increased during colforsin daropate administration in Group III (P < 0.05). In Group II, with an infusion of low- dose colforsin daropate, Pdi to each stimulus did not change. CONCLUSION: Colforsin daropate, only when administered at high-dose, increases contractility of non-fatigued diaphragm in dogs.

Animals↗
PubMed2002

Elevated serum pro-MMP2 levels in patients with stage IV thymoma.

PURPOSE: There is increasing evidence that matrix metalloproteinases (MMPs) play important roles in tumor invasion and metastasis. Using a one-step sandwich enzyme immunoassay, we investigated whether serum pro-MMP2 levels could be predictors of the development and extension of thymoma. METHODS: The subjects of this study were 33 patients with thymoma and 26 patients with nonmalignant thoracic disease. RESULTS: Serum pro-MMP2 levels were elevated in patients with stage IV thymoma (938.6+/-80.2ng/ml) compared with those in the controls (P = 0.03). Patients with stage IVb thymoma had significantly higher serum pro-MMP2 levels than patients with other stages, being 1088.7+/-440ng/ml in stage IVb, 686.0+/-74.0ng/ml in stage I (P = 0.01), 685.8+/-48.6ng/ml in stage II (P = 0.01), and 691.7+/-74.0 ng/ml in stage III (P = 0.02). Serum pro-MMP2 levels were elevated in patients with polygonal cell type thymoma compared with those with mixed cell type thymoma, being 823.1+/-55.5ng/ml vs 613.6+/-59.9ng/ml, respectively (P = 0.04). Using the reference limit of 850ng/ml (mean +/- 2SD) set from analyses in the control group, all patients who had pro-MMP2 levels below the cutoff level survived. On the other hand, four of nine patients who had an elevated pro-MMP2 level died from recurrence. CONCLUSION: Serum pro-MMP2 levels may serve as a marker that could be used as an indicator of distant metastases in thymoma. Elevated pro-MMP2 levels may be correlated with poor survival.

Biomarkers, Tumor↗
PubMed2002

The effectiveness of palliative resection for advanced esophageal carcinoma: analysis of 24 consecutive cases.

PURPOSE: In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection. METHODS: Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer. RESULTS: There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days. CONCLUSIONS: With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Adult↗
PubMed2002

Elevated serum pro-mMP2 levels in patients with advanced lung cancer are not suitable as a prognostic marker.

Using the one-step sandwich enzyme immunoassay for pro-MMP2, we investigated whether the serum pro-MMP2 levels could be used as predictors of the development and extension of lung cancer. The study included 52 lung cancer patients and 26 nonmalignant thoracic disease patients. Serum samples were collected before clinical treatment. The serum pro-MMP2 levels were found to be elevated in patients with lung cancer (1006.3+/-37.4 ng/ml) in comparison with nonmalignant controls (767.7+/-41.6 ng/ml) (P = 0.0002). In addition, stage IIIb lung cancer patients (1167.2+/-124.2 ng/ml) had significantly higher pro-MMP2 levels compared with stage I patients (936.0+/-44.8 ng/ml, P = 0.0431). The serum pro-MMP2 levels were similar in the samples between the pathological subtypes. As a result, the serum pro-MMP2 levels may serve as a marker that can be used as a diagnostic indicator of higher stages in lung cancer. There was no difference in the prognosis between the group with normal pro-MMP2 levels (<850 ng/ml) and the group of elevated pro-MMP2 levels (>850 ng/ml), thus indicating that serum analyses of the pro-MMP2 levels were of limited value in the prognosis of lung cancer.

Biomarkers, Tumor↗
PubMed2002

Endobronchial neodymium:yttrium-aluminum garnet laser for noninvasive closure of small proximal bronchopleural fistula after lung resection.

BACKGROUND: Bronchopleural fistula (BPF) is a serious complication of lung resection. The management of persistent BPF is one of the most complex challenges encountered by thoracic surgeons. METHODS: We used neodymium:yttrium-aluminum garnet (Nd:YAG) laser in 8 patients with BPF who were treated at our hospital, between January 1991 and December 1997. Through the flexible fiberoptic bronchoscope, Nd:YAG laser beam was directed to the bronchial mucosa surrounding the BPF. One-half-second energy pulses of 8 to 20 W were used. Close follow-up of successful patients showed complete closure of the BPF without further treatment. RESULTS: The procedure was successful in 4 of 5 patients who had no infection or tumor at the bronchial stump. However, the procedure failed in 3 other patients, who had residual tumor or infection by aspergillus at the stump. CONCLUSIONS: Closure of small BPF by laser seems to be due to edema and to an inflammatory reaction of the bronchial mucosa surrounding the BPF. If the diagnosis of small proximal BPF is made in the absence of tumor or infection, Nd:YAG laser offers an option for endobronchial treatment of small (<2 mm) BPF. If this technique is successful, it avoids the morbidity associated with more invasive surgical procedures.

Adult↗
PubMed2002

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology.

BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.

Adenocarcinoma↗
PubMed2002

Dose-range effects of propofol for reducing emetic symptoms during cesarean delivery.

OBJECTIVE: To evaluate the efficacy and safety of propofol at subhypnotic doses for reducing emetic symptoms in parturients undergoing cesarean delivery under spinal anesthesia. METHODS: In a randomized, double-masked trial, 80 patients received lidocaine intravenously 0.1 mg/kg (for injection pain relief) followed by either placebo or propofol at three different doses (0.5 mg/kg per hour, 1.0 mg/kg per hour, 2.0 mg/kg per hour) (n = 20 in each group) immediately after clamping of the umbilical cord. Emetic episodes and safety assessments were performed during spinal anesthesia for cesarean delivery. To estimate a sufficient sample size, it was calculated that 20 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients experiencing no emetic symptoms in an intraoperative, postdelivery period was 45% with propofol 0.5 mg/kg per hour (P =.5), 80% with propofol 1.0 mg/kg per hour (P =.011), and 80% with propofol 2.0 mg/kg per hour (P =.011), compared with placebo (40%). No clinically serious adverse events caused by the study drugs were observed. CONCLUSION: Propofol 1.0 mg/kg per hour is the minimum effective subhypnotic dose for reducing emetic symptoms during cesarean delivery. Increasing the dose to 2.0 mg/kg per hour provides no further benefit.

Adult↗
PubMed2002

Dexamethasone for the prevention of nausea and vomiting after dilatation and curettage: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of dexamethasone administered intravenously at three different doses (4 mg, 8 mg, 16 mg) for the prevention of nausea and vomiting after dilatation and curettage. METHODS: In a prospective, randomized, double-masked, placebo-controlled trial, 120 women received placebo or dexamethasone intravenously at doses of 4 mg, 8 mg, or 16 mg immediately before induction of anesthesia (n = 30 in each group). Propofol-based general anesthetic was used. Emetic episodes and safety assessments were performed. To estimate a sufficient sample size, it was calculated that 30 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients who were emesis-free (no nausea, retching, or vomiting) 0-24 hours after anesthesia was 57% with dexamethasone 4 mg (P =.796), 87% with dexamethasone 8 mg (P =.005), and 87% with dexamethasone 16 mg (P =.005), compared with placebo (50%). Patients who had received dexamethasone 8 mg or 16 mg were more satisfied than those who had received placebo (P <.05). No clinically important adverse events were observed in any of the groups. CONCLUSION: Dexamethasone 8 mg is an effective antiemetic for preventing postoperative nausea and vomiting 0-24 hours after anesthesia in women undergoing propofol-based general anesthesia for termination of pregnancy. Increasing the dose to 16 mg provided no additional benefit.

Adult↗
PubMed2002

Double-blind, placebo-controlled, dose-ranging study of ramosetron for the prevention of nausea and vomiting after thyroidectomy.

BACKGROUND: Patients receiving general anesthesia during thyroidectomy have a high risk for postoperative nausea and vomiting. OBJECTIVE: This prospective, randomized, double-blind, placebo-controlled, dose-ranging study was undertaken to assess the efficacy and safety of ramosetron, a selective 5-hydroxytryptamine type 3-receptor antagonist, in preventing nausea and vomiting after thyroidectomy. METHODS: Standard general anesthetic technique and postoperative analgesia were employed. Patients undergoing thyroidectomy were randomized to receive IV ramosetron 0.15, 0.3, or 0.6 mg or placebo at completion of the procedure. During the first 48 hours after anesthesia, episodes of emesis and adverse events were assessed by nursing staff who were blinded to patients' treatment assignment. RESULTS: Eighty patients (22 men, 58 women; age range, 28-63 years; weight range, 37-91 kg) were enrolled in the study. There were no differences in demographic characteristics between treatment groups. The numbers of patients who were emesis free (no nausea, retching, or vomiting) 0 to 24 hours after anesthesia were 10 of 20 (50%) with ramosetron 0.15 mg, 17 of 20 (85%) with ramosetron 0.3 mg, 18 of 20 (90%) with ramosetron 0.6 mg, and 8 of 20 (40%) with placebo. The corresponding numbers 24 to 48 hours after anesthesia were 11 of 20 (55%), 18 of 20 (90%), 18 of 20 (90%), and 9 of 20 (45%). At both time points, only the values for ramosetron 0.3 and 0.6 mg were statistically significant versus placebo (P < or = 0.001). No clinically serious adverse events were observed in any group. CONCLUSIONS: In this population of patients receiving general anesthesia while undergoing thyroidectomy, ramosetron 0.3 mg was effective in preventing postoperative nausea and vomiting 0 to 48 hours after anesthesia. Increasing the dose to 0.6 mg provided no demonstrable benefit.

Adult↗