Biomedical subjects

Toshihiro Abe

Publications and source records attributed to Toshihiro Abe.

8 recordsLinked to original sources

PubMed2006

CT lymphography-navigated sentinel lymph node biopsy in patients with superficial esophageal cancer.

BACKGROUND: To evaluate experimentally and clinically the feasibility of a newly developed technique of endoscopic computed tomography (CT) lymphography with endoscopic submucosal injection of iopamidol for esophageal sentinel lymph node (SLN) mapping and biopsy examination. METHODS: Nine anesthetized dogs underwent CT after endoscopic submucosal injection of 2 mL iopamidol; 1.25-mm thick CT images were obtained before and at 1, 3, 5, 7, and 10 minutes after contrast injection. Clinically, 12 patients with superficial esophageal cancer (preoperative imaging stage: cT1, cN0) underwent CT lymphography in a similar fashion at 1, 5, and 10 minutes after peritumoral injection, followed by radical esophagectomy and regional lymph node dissection under CT lymphography guidance. RESULTS: CT lymphography visualized the draining lymphatic vessels and SLNs within 5 minutes after contrast injection. All 14 SLNs in dogs (average, 1.5 nodes per animal; range, 1-2) and 28 SLNs in patients (average, 2.3 nodes per patient; range, 1-4) were found intraoperatively at the correct location under CT lymphography guidance. Lymph node metastasis could be detected with excellent sensitivity and accuracy in this small number of patients with no false-negative findings; metastasis was positive only in the preoperatively identified SLNs in 4 patients and in both SLNs and distant nodes in 1 patient, and was negative in all resected nodes in the remaining 7 patients. CONCLUSIONS: Endoscopic CT lymphography appears to allow accurate identification of direction and locations of lymph flow and SLNs, and has the potential clinical applicability for esophageal SLN mapping and biopsy examination, but will require a large study to determine its accuracy and usefulness.

Aged↗

PubMed2006

Esophageal squamous cell carcinomas with distinct invasive depth show different gene expression profiles associated with lymph node metastasis.

We examined the gene expression profiles of esophageal squamous cell carcinomas (ESCCs) with respect to degree of invasive depth and lymph node (LN) involvement in a large cohort. We used high-density oligonucleotide microarrays to examine the expression of 22,115 genes in 54 ESCCs and 11 non-cancerous esophageal tissues. We found that 4,155 genes were biologically significant in both ESCC and non-cancerous esophageal tissue by analysis of Present Call (hybridization quality by Affymetrix) throughout all samples. From these genes, we used a supervised learning method to select genes responsible for the development of ESCC. We found that 999 genes were expressed differentially in pT1/pN0 tumors vs. non-cancerous esophageal tissue. In the same manner, 48, 66 and 30 genes were expressed differentially in pT1/pN0 tumors vs. pT1/pN1 tumors, pT1/pN0 tumors vs. pT2-4/pN0 tumors and pT2-4/pN0 tumors vs. pT2-4/pN1 tumors, respectively. Intriguingly, there were no overlaps between the 48 LN metastasis-related genes of pT1 tumors and the 30 LN metastasis-related genes of pT2-4 tumors, suggesting that ESCCs with distinct invasive depths express different genes linked to LN metastasis. Our present results suggest that the degree of invasive depth must be considered when predicting LN metastasis of ESCC from gene expression profiles.

Aged↗

PubMed2006

Relation between cytokine promoter gene polymorphism and toxicity of 5-fluorouracil plus cisplatin chemotherapy.

Variability in the efficacies and toxicities of anticancer agents is a major problem. We hypothesized that polymorphisms in cytokine gene promoters may underlie genetic susceptibility to chemotherapy-induced toxicities in the Japanese. DNA was extracted from 100 patients undergoing 5-fluorouracil plus cisplatin chemotherapy. We used a case-only design to evaluate the relation between toxicities and cytokine promoter gene polymorphisms. The following polymorphisms were genotyped: tumor necrosis factor (TNF)-alpha-1031T/C, interleukin (IL)-1beta-511C/T, IL-6-634C/G, IL-10-819T/C, IL-18-137G/C, macrophage migration inhibitory factor -173G/C, and 86-basepair variable numbers of tandem repeat in intron 2 of the IL-1 receptor antagonist. The frequency of the IL-6-634 GC and GG genotypes was significantly higher in patients with grades 1-4 leukopenia (P=0.003; Crude-odds ratios (Cr-OR) =4.0), neutropenia (P=0.0051; Cr-OR=3.6), or thrombocytopenia (P<0.0001; Cr-OR=6.1) than in patients without these toxicities. Similarly, the frequency of the IL-1beta-511 TC and TT genotypes and the frequency of the TNF-alpha-1031 TT genotype were significantly higher in patients with grades 1-4 thrombocytopenia (P=0.015; Cr-OR=2.9) and stomatitis (P=0.02; Cr-OR=3.1), respectively. Multivariate analysis of factors such as age, sex, disease type, purpose of the chemotherapy, use of radiotherapy, and cytokine promoter gene polymorphisms showed polymorphisms to be significant predictors of toxicity. Our results suggest that polymorphisms in cytokine gene promoters may be associated with susceptibilities to leukopenia, neutropenia, thrombocytopenia and stomatitis in patients treated with 5-fluorouracil plus cisplatin.

Adult↗

PubMed2003

Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma.

PURPOSE: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. EXPERIMENTAL DESIGN: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). RESULTS: Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. CONCLUSIONS: Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen.

Aged↗

PubMed2003

Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis.

Oncogene amplification in 20 surgically resected esophageal squamous cell carcinomas (ESCC) was examined with DNA microarrays that detected 57 oncogenes and two reference DNA. Alterations in DNA copy numbers detected by microarrays were compared to those obtained by conventional comparative genomic hybridization (CGH). Amplification of eight oncogenes (CCND1, FGF3/FGF4, EMS1, SAS, ERBB2, PDGFRA, MYC, and BCL2) was detected by DNA microarrays in 9 of 20 tumors. Although ERBB2 was 23.2 times higher than the control level in one case, the average magnitude of gene amplification was approximately two to four times that of the control level. EMS1, CCND1, and FGF3/FGF4, which are all located on 11q13, were amplified in 7, 5, and 4 of 20 ESCC, respectively, and they were coamplified in 3 tumors. A comparison of genome DNA microarrays and CGH data revealed that although most amplified oncogenes were included in chromosomal regions for which DNA copy number gains were detected by conventional CGH, not all amplified genes on microarrays showed concomitant DNA copy number gains on CGH. In conclusion, microarrays of oncogenes are useful for the comprehensive identification of amplified oncogenes and for analysis of areas of specific amplification within chromosomal regions with DNA copy number increases detected by CGH analysis.

Aged↗

PubMed2003

[Esophageal diverticula].

Esophageal diverticula are considered to be rare but this has not deterred interest in the condition, either historically or in the present era. Most parabronchial esophageal diverticula are traction diverticula, and resection is thought to be unnecessary. The majority of pharyngoesophageal diverticula and epiphrenic diverticula are pulsion diverticula. It is now well accepted that they correlate with underlying motor disturbance and that surgery is indicated. If there is motor disturbance is preoperative manometry, it is necessary to add myotomy. However, if there is no motor disturbance, the surgical management remains controversial. Recently, minimal access surgery with laparoscopy or thoracoscopy has been successful in the treatment of epiphrenic diverticulum.

Diverticulum, Esophageal↗

PubMed2002

Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells.

To investigate the effect of p33(ING1) on wild-type p53 gene therapy, T.Tn human esophageal carcinoma cells were stably transfected with p33(ING1) cDNA. Infection with Ad-p53 (recombinant adenovirus containing wild-type p53) into p33-transfected cells reduced cell viability, while infection with empty vector had little effect. This reduced viability was shown to be due to apoptotic cell death by the TUNEL (terminal deoxynucleotidyl transferase-mediated nick end-labeling) assay. Following infection with Ad-p53, levels of p53 were similar in p33-expressing cells and in the parental line. However, levels of p21 and Mdm2 were elevated in p33-transfected cells. Nonetheless, this enhanced expression of Mdm2 appeared to be ineffective in downregulating p53. Transient transfection with mutant Mdm2 prior to Ad-p53 infection provided a significant protection as compared with cells transfected with wild-type Mdm2. These results imply a synergistic effect between p33 and p53 in the induction of apoptosis of human esophageal carcinoma cells. A role for Mdm2 in this synergism is suggested.

Adenoviridae↗

PubMed2002

Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma.

Comparative genomic hybridization was applied to 51 primary esophageal squamous cell carcinomas (ESCCs) to clarify the relation between DNA sequence copy number aberrations (DSCNAs) and the clinicopathology of the disease. The average number of DSCNAs was 10.9 DSCNAs/tumor (6.1 gains and 4.9 losses), ranging from 1-30 DSCNAs/tumor. Gain of 3q26-qter and loss of 18q22-qter were detected in >60% of stage I tumors and considered to play an important role in the development of ESCC. Whereas gain of 8q24-qter was observed in 82.6% (19 of 23) of stage III and IV cancers, it was seen in 27.3% (3 of 11) of stage I tumors. It is suggested that gain of 8q24-qter plays an important role in tumor progression. Gains of 8q24-qter and 20q12-qter and loss of 11q22-23 were linked to nodal metastasis (P = 0.0006, 0.002, and 0.02, respectively). Gains of 5p15 and 14q21 were associated with distant organ metastasis after surgery (P = 0.006 and 0.02, respectively). These observations suggest that nodal and distant organ metastases involve different genes. Gains of 5p15, 8q24-qter, and 14q21 were significantly associated with unfavorable prognosis (P = 0.0002, 0.007, and 0.04, respectively). Multivariate analysis revealed the 5p15 gain to be an independent prognostic marker with a higher significance than that of nodal status (risk ratio = 5.95; P = 0.001). The present findings indicate that comparative genomic hybridization analysis may be used to predict the likelihood of a poor or favorable outcome in cases of ESCC.

Aged↗