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Biomedical subjects

Yoshitaka Fujii

Publications and source records attributed to Yoshitaka Fujii.

At least 37 records · Page 2Linked to original sources

Age-related differences in metoclopramide requirement for pain on injection of propofol.

OBJECTIVE: Pain on injection is still a major problem with propofol; metoclopramide effectively decreases this pain. The purpose of this study was to evaluate the influence of aging on metoclopramide requirement for propofol-induced pain. METHODS: In a randomised, double-blind manner, 120 patients, 60 younger (aged 20-40 years) and 60 older (aged 60-80 years) adults, received placebo (saline) or metoclopramide intravenously at two different doses (2.5mg and 5 mg) [younger group n = 20 each, older group n = 20 each], with venous occlusion for 1 minute, followed by administration of propofol 0.5 mg/kg into a dorsal hand vein. A blinded researcher asked the patient to assess the pain according to a pain score (0 = none, 1 = mild, 2 = moderate, 3 = severe) during injection of propofol. RESULTS: For younger patients, the incidence of propofol-induced pain was 30% in patients receiving metoclopramide 5mg (both p < 0.05), 70% in those receiving metoclopramide 2.5mg and 80% in those receiving placebo. The median pain score was lower in patients receiving metoclopramide 5mg (0) than in those receiving placebo (1.5) [p < 0.05]. For older patients, 15 patients (75%) complained of pain in the placebo group, compared with six (30%) in the metoclopramide 5mg group (p < 0.01) and seven (35%) in the metoclopramide 2.5mg group (p < 0.05). The median pain score was lower in patients receiving metoclopramide 5mg (0) [p < 0.01] or metoclopramide 2.5mg (0) [p < 0.05] than in those receiving placebo (1). CONCLUSION: This study showed that older patients require less metoclopramide, with venous occlusion for 1 minute, to reduce pain on injection of propofol than do younger patients.

Adult↗

Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer.

BACKGROUND: The importance of establishing hormone receptor status of tumors for the treatment of women with hormone receptor-positive breast cancer has been emphasized, however, there is no general agreement as to how immunohistochemical assays should be evaluated. It is critical to evaluate hormone receptor status when considering response to endocrine therapy. METHODS: Estrogen receptor (ER) and progesterone receptor (PgR) expression was examined by immunohistochemistry using Allred's score for primary breast tumors from 75 metastatic breast cancer patients who received first-line treatment with endocrine therapy (56 patients received tamoxifen, 11 patients received aromatase inhibitors, and 8 patients received LH-RH agonist or other endocrine reagents) on relapse. Correlation between hormone receptor status and response to endocrine therapy as well as post-relapse survival was analyzed. RESULTS: The most significant correlation between positive ER expression and response to any endocrine therapy (p = 0.011) or tamoxifen only (p = 0.030) occurred when the cutoff score was set at 10%. When the evaluation was based on Allred's score (TS), a cutoff point of TS>or=4 showed a more significant association between positive ER expression and response to all kinds of endocrine therapy (p = 0.020) or tamoxifen only (p = 0.047). When evaluated at a cutoff point of 1% positive cells, there were fifteen patients with both ER- and PgR-negative tumors, and three patients (20.0%) responded to the therapy. Patients with 1% or more ER or PgR positive cells had better survival after relapse (p = 0.0005 and p = 0.0008, respectively). CONCLUSIONS: The proportion score alone might be enough to predict hormone responsiveness and post-relapse survival in metastatic breast cancer. The cutoff might be set low, for example 1%, especially for metastatic disease.

Antineoplastic Agents, Hormonal↗

Decreased fragile histidine triad gene messenger RNA expression in lung cancer.

BACKGROUND: The fragile histidine triad (FHIT) gene is located at 3p14.2, a region frequently lost in various tumor types. Lack of FHIT expression has been found to occur frequently in multiple tumor types including lung cancer. We have investigated FHIT messenger RNA (mRNA) levels and other clinicopathologic data, including FHIT and p21 expression in lung cancer. PATIENTS AND METHODS: The study included 97 lung cancer cases. The FHIT mRNA levels were quantified by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using LightCycler. RESULTS: The FHIT/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were decreased in tumor tissues from lung cancer (13.844 +/- 33.047) compared with adjacent nonmalignant lung tissues (195.763 +/- 678.469; P < 0.0001). No significant difference in FHIT/GAPDH mRNA levels was found among age, T status, or lymph node metastasis. The FHIT/GAPDH mRNA level was less in squamous cell carcinoma (0.144 +/- 0.246), a smoking-related cancer, than in adenocarcinoma (0.72 +/- 1.321; P = 0.0355). FHIT/GAPDH mRNA levels were correlated with FHIT protein (P = 0.0139) and p21 protein (P = 0.0484) expression by immunohistochemistry. The prognosis for patients with lung cancer with low FHIT/GAPDH levels (< 0.26; n = 57) was significantly worse than in the patients with high FHIT/GAPDH levels (> 0.26; n = 40; log-rank test, P = 0.0404). CONCLUSION: Using the LightCycler RT-PCR assay, decreased FHIT gene expression might occur early and play an important role in lung tumorigenesis and also correlate with the prognosis of lung cancer. However, further studies are needed to confirm the impact of FHIT in the biologic behavior of the tumor.

Acid Anhydride Hydrolases↗

Decreased kallikrein 11 messenger RNA expression in lung cancer.

BACKGROUND: Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. A recently developed method for measuring hK11 suggested that the hK11 level was an indicator of favorable prognosis in patients with ovarian cancer. We have investigated hK11 messenger RNA (mRNA) levels in lung cancer. PATIENTS AND METHODS: This study included 64 lung cancer cases. The hK11 mRNA levels were quantified by real-time reverse-transcriptase polymerase chain reaction using LightCycler. RESULTS: The hK11 mRNA levels were lower in tumor tissues from lung cancer (1.88 +/- 6.314) compared with adjacent nonmalignant lung tissues (8.271 +/- 9.002; n = 45; P = 0.0001). No significant difference was found among sex, age, clinical stages, tumor status, and lymph node metastasis. The hK11 mRNA levels were lower in moderately or poorly differentiated adenocarcinoma lung cancer (0.452 +/- 1.614) compared with well-differentiated adenocarcinoma lung cancer (1.728 +/- 2.829; P = 0.0281). The group with low hK11/gylceraldehyde 3-phosphate dehydrogenase levels (< 0.6) had a significantly worse prognosis compared with the group with high hK11/gylceraldehyde 3-phosphate dehydrogenase levels (> 0.6; log-rank test, P = 0.0131; Breslow-Gehan-Wilcoxon test, P = 0.0172). CONCLUSION: Cox proportional hazard regression model (multivariate analysis) indicated that pathologic stages (P = 0.0443) and low hK11 expression levels (P = 0.0469) were the prognostic factors of lung cancers. However, additional studies and a longer follow-up are needed to confirm the impact of hK11 on the biologic behavior of the tumor.

Adenocarcinoma↗

Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with tumor progression and postoperative survival.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.

Aged↗

Expression of ACP6 is an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.

ACP6 (acid phosphatase 6, lysophosphatidic) is a lysophosphatidic acid (LPA)-specific phosphatase that hydrolyzes LPA to monoacylglycerol and is involved in lipid metabolism in the mitochondria. Its role in oncogenesis and cancer progression has not been studied. In this study, we examined the expression of ACP6 mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). Expression of ACP6 mRNA was quantified by real-time reverse transcription polymerase chain reaction using the LightCycler in 70 esophageal ESCC specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. ACP6 mRNA expression in esophageal cancer tissue was significantly lower than that in corresponding normal esophageal mucosa (P=0.0301). Among the esophageal cancer tissues, ACP6 mRNA expression significantly correlated with local tumor invasion (T factor, P=0.0461) and lymph node metastasis (P=0.0128). Furthermore, low ACP6 mRNA expression was associated with a significantly shorter survival time compared with high expression (log-rank test, P=0.0358). In multivariate analysis, ACP6 mRNA expression emerged as a significant independent factor (P=0.0148). Impaired ACP6 expression may lead to more aggressive invasion of ESCC, and ACP6 mRNA expression level could be an independent prognostic factor for patients with ESCC.

Aged↗

Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy.

Several studies have suggested that epidermal growth factor receptor (EGFR) gene mutation, EGFR gene amplification, and some other biomarkers may be predictors of gefitinib sensitivity. We analyzed EGFR mutation and EGFR copy number in 22 gefitinib-treated non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied 143 gefitinib-naïve Japanese NSCLC cases. The erbB2 copy number was also studied in 59 gefitinib-naïve NSCLC cases. In gefitinib-treated patients, the presence of EGFR mutation was associated with a higher response rate to gefitinib and a longer overall survival, but the increased EGFR gene copy number was not. In gefitinib-naïve cases, EGFR mutation but not EGFR gene copy number was significantly correlated with gender, pathological subtypes, and smoking status. The erbB2 copy number was not significantly correlated with the EGFR mutation or EGFR copy number in 59 cases. In conclusion, EGFR mutation was a better predictor of clinical outcome in gefitinib-treated patients than the EGFR gene copy number.

Adenocarcinoma↗

[Thymoma--clinical aspects and its biological function].

Thymoma is a neoplasm of thymic epithelial cells. The tumor grows relatively slowly, and the prognosis is very good after surgical resection. However, therapy for advanced thymoma has not been established, and the effect of modern chemotherapy is being evaluated. Thymoma is unique in that 25-30% of the patients have associated myasthenia gravis with autoantibodies to acetycholine receptor. The malignant epithelial cells maintain the function of cortical epithelial cells and harbor non-neoplastic immature T cells of CD 3(low) CD 4(+)CD 8(+) phenotype. This function has a causative relationship with the associated myasthenia gravis. Also, the presence of CD 3(low) CD 4(+)CD 8(+) T cells is diagnostic of thymoma and can be utilized for rapid diagnosis using needle biopsy specimen.

Autoantibodies↗

[Results of surgical treatment for pimary germcell tumors of the mediastinum].

Primary germ cell tumors of the mediastinum are relatively rare with complicated backgrounds including various pathology with mixed types and characteristics. The primary treatment for mature teratoma is surgical resection. It is sometimes difficult because of the giant tumor size and severe adhesion. Pneumonectomy is sometimes necessary to resect a tumor completely. In elderly patients, mature teratomas possibly involve epithelial malignant transformation. Cisplatin-based chemotherapy plays an important role in the treatment of both seminoma and nonseminoma. In our institution, 10-year survival rates are 91.7% for seminoma and 53.0% for nonseminoma. In terms of survival, nonseminoma has a worse prognosis compared with seminoma. Cases with pleural dissemination or metastasis also have a worse prognosis, with a median survival time of 5 months. The reasons for the poor prognosis in nonseminoma are the inclusion of patients in whom chemotherapy is not effective and those with advanced disease with metastasis. It would be possible to improve the prognosis with the establishment of a standard treatment regimen, development of new agents for the treatment of tumors resistant to current chemotherapy regimens, and detection of more tumors in the early stage.

Adolescent↗

Uncommon V599E BRAF mutations in Japanese patients with lung cancer.

BACKGROUND: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene and Braf gene were found in patients with lung cancer. These mutations might be correlated with a clinical response to molecular target therapy. Although a few Caucasian lung cancer patients harbored BRAF mutations, there have been no reports about the BRAF mutation in Japanese patients with lung cancer. MATERIALS AND METHODS: We investigated BRAF mutations in Japanese lung cancer patients. The study included 129 surgically removed lung cancer cases from Nagoya City University Hospital. Braf, EGFR, and erbB2 mutations also were analyzed by reverse transcript polymerase chain reaction (RT-PCR) and direct sequencing. RESULTS: In exon 15, one BRAF mutation (1796 thymine to adenine; V599E) was found in nonsmoking woman with well-differentiated adenocarcinoma. We detected the 43 EGFR mutations, including 19 at exon 19 and 20 at exon 21 from the 129 patients analyzed (33.3%). We also detected one erbB2 mutation from 76 patients analyzed. All these mutations existed exclusively. CONCLUSIONS: V599E BRAF mutation was uncommon in Japanese lung cancer. All three genes mutations were predominantly found in female nonsmoking subjects with adenocarcinomas. However, completely exclusive mutation status would help us to choose custom-made molecular target therapy for the lung cancer.

Adenocarcinoma↗

Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.

Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.

Adolescent↗

Phosphorylation of estrogen receptor alpha serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer.

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone-receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and crosstalk between ER and other growth factor signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. METHODS: Using immunohistochemical techniques, we focused on the expression and phosphorylation of hormone receptors themselves and examined the phosphorylation of ER-alpha Ser118 and ER-alpha Ser167 and the expression of ER-alpha, ER-beta1, ER-betacx/beta2, progesterone receptor (PR), PRA, and PRB in the primary breast carcinomas of 75 patients with metastatic breast cancer who received first-line treatment with endocrine therapy after relapse. RESULTS: Phosphorylation of ER-alpha Ser118, but not Ser167, was positively associated with overexpression of HER2, and HER2-positive tumors showed resistance to endocrine therapy. The present study has shown for the first time that phosphorylation of ER-alpha Ser167, but not Ser118, and expression of PRA and PRB, as well as ER-alpha and PR in primary breast tumors are predictive of response to endocrine therapy, whereas expression of ER-beta1 and ER-betacx/beta2 did not affect response to the therapy. In addition, patients with either high phosphorylation of ER-alpha Ser167, or high expression of ER-alpha, PR, PRA, or PRB had a significantly longer survival after relapse. CONCLUSION: These data suggest that phosphorylation of ER-alpha Ser167 is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in metastatic breast cancer.

Amino Acid Sequence↗

EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler.

PURPOSE: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in approximately 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. EXPERIMENTAL DESIGN: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. RESULTS: In exon 21, EGFR mutations (CTG --> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 < or = versus 600, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. CONCLUSIONS: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

Adenocarcinoma↗

A randomized clinical trial of a single dose of ramosetron for the prevention of vomiting after strabismus surgery in children: a dose-ranging study.

BACKGROUND: Postoperative vomiting (POV) after pediatric strabismus surgery remains a major problem. OBJECTIVE: To evaluate the efficacy and safety of a single dose of ramosetron, a new serotonin antagonist, for preventing POV in children undergoing strabismus surgery. METHOD: In a prospective, randomized, double-masked, placebo-controlled study, 80 children (38 boys and 42 girls), aged 4 to 10 years, scheduled for strabismus surgery, received intravenously either placebo or ramosetron at 1 of 3 different doses (3 microg/kg, 6 microg/kg, or 12 microg/kg) (n = 20 each) at the end of the surgical procedure. A standard general anesthetic technique was used. MAIN OUTCOME MEASURES: Emetic episodes were recorded and safety assessments performed during the first and second 24-hour periods (ie, 0-24 and 24-48 hours) after receiving anesthesia. RESULTS: The rate of patients who were emesis-free (defined as no retching and no vomiting), during the 0- to 24-hour period after anesthesia was 35% with 3 microg/kg of ramosetron (P = .37), 90% with 6 microg/kg of ramosetron (P = .001), and 90% with 12 microg/kg of ramosetron (P = .001) compared with placebo (25%). The corresponding rate during the 24- to 48-hour period after anesthesia was 40% (P = .371), 90% (P = .001), and 90% (P = .001), respectively, compared with placebo (30%). No clinically important adverse events were observed in any group. CONCLUSIONS: A 6-microg/kg dose of ramosetron is sufficient, but a 3-microg/kg dose is insufficient for preventing POV during the 0- to 48-hour period after anesthesia in children undergoing strabismus surgery. Increasing the dose to 12 microg/kg of ramosetron provides no demonstrable additional benefit.

Antiemetics↗

A lidocaine/metoclopramide combination decreases pain on injection of propofol.

PURPOSE: Injection pain is a well-known adverse effect of propofol which distresses patients. Lidocaine pretreatment is the most popular method for reducing this pain but this drug cannot entirely eliminate the problem. The purpose of this study was to examine the analgesic effect of lidocaine/metoclopramide combination, compared with lidocaine alone, during propofol injection. METHODS: In a randomized, double-blind, placebo-controlled trial, 90 patients, 40 males and 50 females, scheduled for elective plastic surgery received either lidocaine 20 mg plus metoclopramide 10 mg iv, lidocaine 20 mg iv, or placebo (saline); (n = 30 in each), with venous occlusion for one minute, followed by administration of propofol 0.5 mg.kg(-1) into a dorsal hand vein. Pain was assessed on a four-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) during propofol injection. RESULTS: 25 patients (83%) complained of pain in the placebo group, compared with 12 (40%) in the lidocaine group (P < 0.05) and three (10%) in the combination group (P < 0.05). Pain score (median) was less in the lidocaine (0) and combination (0) groups than in the placebo group (2); (P < 0.05). The difference in the incidence of pain between the combination and lidocaine groups was significant (P < 0.05). CONCLUSION: A lidocaine/metoclopramide combination is more effective than lidocaine alone for reducing pain on injection of propofol in a peripheral vein.

Adult↗