Biomedical subjects

Yasuto Uchikado

Publications and source records attributed to Yasuto Uchikado.

8 recordsLinked to original sources

PubMed2006

Carcinoembryonic antigen messenger RNA expression in blood predicts recurrence in esophageal cancer.

PURPOSE: The clinical significance of isolated tumor cells (ITC) in blood has not been clearly established, particularly during follow-up in cancer patients. We conducted a longitudinal analysis of the relationship between ITC in blood during follow-up and clinicopathologic findings in patients with esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: Blood samples obtained from 106 patients were examined by real-time RT-PCR assay targeting carcinoembryonic antigen (CEA) mRNA. Follow-up examination every 3 months after surgery included testing for CEA mRNA and tumor markers, as well as imaging. RESULTS: Thirty-nine (36.8%) patients were positive for CEA mRNA expression. CEA mRNA positivity significantly correlated with tumor depth, lymph node metastasis, stage, and venous invasion. Recurrent disease was found in 34 of 106 (32.1%) cases. CEA mRNA was found in 28 (76.5%) patients experiencing relapse. Of these 28 patients, the number positive of CEA mRNA before detection by imaging, at the same time of detection by imaging, and after detection by imaging was 18 (52.9%), 8 (23.5%), and 2 (5.9%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for CEA mRNA were higher than those for serum CEA or squamous cell carcinoma. Patients positive for CEA mRNA experienced significantly shorter disease-free interval than those with negative CEA mRNA (P < 0.001). According to multivariate analysis, CEA mRNA positivity was an independent factor for disease-free interval. CONCLUSIONS: Examination of CEA mRNA in peripheral blood during follow-up is useful for early detection of occult recurrence. We believe that CEA mRNA in blood will be a new marker for recurrence in esophageal squamous cell carcinoma.

Adult↗

PubMed2006

Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. RESULTS: The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. CONCLUSIONS: We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma.

Analysis of Variance↗

PubMed2006

[A case of successful treatment by low-dose 5-fluorouracil and cisplatin for liver metastases of esophageal adenosquamous carcinoma].

Adenosquamous carcinoma of the esophagus is an uncommon type of esophageal tumor. In the present case, a 54-year-old man without symptoms was diagnosed with esophageal squamous cell carcinoma, based on endoscopic examination of a biopsy specimen. Endoscopy and barium roentgenography revealed a superficial plateau-type lesion, 2 cm in length, in the lower esophagus. Esophagectomy with lymphadenectomy was performed via a right thoraco-abdominal approach. The histological diagnosis was adenosquamous carcinoma with no lymph node metastasis. Three years after the surgery, multiple liver metastases were detected by computed tomography. The patient was treated with a combination of low-dose 5-fluorouracil(350 mg/body/day) and low-dose cisplatin (7 mg/body/day). Because the first course of chemotherapy was very effective and the number of liver metastases was reduced,a further 6 courses were administered. After 6 courses of chemotherapy, no liver metastases were detected. Based on the present findings, we recommend low-dose 5-fluorouracil/cisplatin therapy for liver metastasis from esophageal adenosquamous carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma.

We applied oligomicroarray analysis of 17086 genes to identify the genes related to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The samples of cancer and non-cancerous paired tissue were taken from 16 patients with ESCC who underwent esophagectomy with lymph node dissection. Total ribonucleic acid was extracted from the cancer cells obtained by using laser microdissection and was amplified by T7 based-amplification for the application to the oligomicroarray. The oligomicroarray demonstrated 43 overexpressed genes, such as cell-cycle regulators, cell adhesion related genes, anti-apoptosis related genes, and 138 suppressed genes such as cell differentiation related and apoptosis related genes in ESCC cells with lymph node metastasis. Among them, 5 overexpressed genes (SPP-1, CKS2, CCT5, STMN1, NDUFB9) and one suppressed expression gene (GJB2) were selected in the gene profiles, and then the expressions of those genes were confirmed by real-time semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) method for confirmation of the result not only in study cases but also in additional 21 cases. The gene expression by real-time semi-quantitative RT-PCR was in accordance with the microarray data. Although we were able to extract some genes related to nodal metastasis in ESCC, further examination is necessary in other genes as well as the interaction of stromal tissues.

Aged↗

PubMed2005

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer.

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

Adult↗

PubMed2005

Predictive value of p53 and 14-3-3sigma for the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The p53 family regulates cell-cycle arrest, triggers apoptosis, repairs DNA damage caused by various genotoxic stresses, and protects cells from death upon irradiation. The purpose of the present study was to examine the expressions of p53 and one of the p53 family proteins, 14-3-3sigma, in biopsy specimens and to predict the clinical and histological responses to chemoradiation therapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We investigated with the relationship between p53 and 14-3-3sigma expressions in biopsy specimens obtained from 62 patients with ESCC and analyzed these patients' clinical and histological responses to CRT. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. RESULTS: Following CRT, 71.0% of patients showed a positive clinical response and 52.8% showed a positive histological response. The rate of positive expression was 43.5% for p53 and 58.1% for 14-3-3sigma. Statistically significant correlations were found between p53 expression and clinical response to CRT (P = 0.001) and histological response to CRT (P = 0.041), and between 14-3-3sigma expression and histological response to CRT (P = 0.01). Furthermore, in p53-positive tumors, CRT was more effective in tumors with 14-3-3sigma-positive expressions than those with 14-3-3sigma-negative expressions (P = 0.037). The survival rate of the patients with 14-3-3sigma-positive tumors was better than those with 14-3-3sigma-negative tumors in patients with p53-positive tumors (P = 0.047). CONCLUSIONS: We demonstrated that p53-negative or 14-3-3sigma-positive expressions were closely related to the response to CRT. It is clinically useful to examine the expression of these genes in biopsy specimens for predicting the CRT outcomes in patients with ESCC.

14-3-3 Proteins↗

PubMed2005

Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: The expression of E-cadherin correlates with the development, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). Slug, a member of the snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in ESCC. EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 203 patients with ESCC. The relationships between expression of these proteins and clinicopathologic factors, including prognosis, were analyzed. RESULTS: Positive expression of E-cadherin and Slug was observed in 43% and 48% of cases, respectively. The tumors with reduced E-cadherin expression or positive Slug expression invaded deeper, had more lymph node metastasis, and had more lymphatic invasion than the tumors with preserved E-cadherin expression or negative Slug expression. Slug expression significantly correlated with reduced E-cadherin expression. Sixty-seven of the 98 (68.4%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0011). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.035). Multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. CONCLUSIONS: Evaluation of not only the expression of E-cadherin but also the co-expression of E-cadherin and Slug in preserved E-cadherin group is useful for predicting malignant properties of ESCC.

Aged↗

PubMedDate not supplied

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer.

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P < 0.05, P < 0.0001, and P < 0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P < 0.005 and P < 0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P < 0.0001 and P < 0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM.

Adult↗