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Biomedical subjects

Kaoru Ishida

Publications and source records attributed to Kaoru Ishida.

12 recordsLinked to original sources

Study of alkyl organic monolayers with different molecular chain lengths directly attached to silicon.

Alkyl organic monolayers with different alkyl molecular chain lengths directly attached to silicon were prepared at 160 degrees C from 1-decene (C10), 1-dodecene (C12), 1-tetradecene (C14), 1-hexadecene (C16), and 1-octadecene (C18). These monolayers were characterized on the basis of water contact angle measurement, ellipsometry, X-ray reflectivity (XR), X-ray photoelectron spectroscopy (XPS), and grazing incidence X-ray diffraction (GIXD) to elucidate the effect of the molecular chain length on the molecular arrangement and packing density of the monolayers. Water contact angle and XPS measurements showed that C12, C14, and C16 monolayers have a comparably higher quality, while the quality of C10 and C18 monolayers is worse. GIXD revealed that the alkyl monolayers directly attached to the Si were all amorphously structured regardless of their alkyl chain length. The amorphous structure of the alkyl monolayers could be attributed to the rigid Si-C bonding, low quality of hydrogen-terminated silicon substrate, and/or low mobility of physisorbed molecules.

Journal Article↗

Coexistence of esophageal superficial carcinoma and multiple leiomyomas: A case report.

Leiomyomas are the most common benign tumors of the esophagus. They usually occur as a single lesion or as two or three nodules. Only two cases of esophageal multiple leiomyomas comprising more than 10 nodules have been reported previously. Moreover, there have been few reports of esophageal squamous cell carcinoma overlying submucosal tumors. We describe a 71-year-old man who was diagnosed as having a superficial esophageal cancer coexisting with two or three leiomyoma nodules. During surgery, 10 or more nodules that had not been evident preoperatively were palpable in the submucosal and muscular layers throughout the esophagus. As intramural metastasis of the esophageal cancer was suspected, we considered additional lymphadenectomy, but had to rule out this option because of the patient's severe anoxemia. Microscopic examination revealed that all the nodules were leiomyomas (20 lesions, up to 3 cm in diameter), and that invasion of the carcinoma cells was limited to the submucosal layer overlying a relatively large leiomyoma. This is the first report of superficial esophageal cancer coexisting with numerous solitary leiomyomas. Multiple minute leiomyomas are often misdiagnosed as intramural metastasis, and a leiomyoma at the base of a carcinoma lesion can also be misdiagnosed as tumor invasion. The present case shows that accurate diagnosis is required for the management of patients with coexisting superficial esophageal cancer and multiple leiomyomas.

Aged↗

Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.

Envoplakin (EVPL) is a member of the desmosomal plaque proteins attached to desmosomal cadherin and keratin filaments. The EVPL gene has been mapped to the tylosis oesophageal cancer (TOC) locus on chromosome 17q25, where it has been demonstrated to be frequently deleted in both familial and sporadic forms of oesophageal squamous cell carcinoma (OSC). In this study, we examined EVPL gene mutations in 10 OSC cell lines and 20 sporadic OSCs using reverse transcription-polymerase chain reaction single-strand conformational analysis (RT-PCR SSCP) followed by direct sequencing. We observed one somatic mutation (GCG to ACG at codon 1104, Ala to Thr: 1/20, 5%) in the central rod domain and 5 intragenic polymorphic sites, where frequent loss of heterozygosity (LOH) (63%) was detected. No mutations were detected in the OSC cell lines. The rate of EVPL gene mutation was quite low in contrast to the frequency of LOH on the TOC locus in sporadic OSCs, and the high incidence of oesophageal cancer development in tylosis families. Our results suggest that EVPL might not be the target gene responsible for OSC, despite its strong candidacy in terms of character and localization.

Alleles↗

Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516).

BACKGROUND: In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer. METHODS: Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. RESULTS: The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients. CONCLUSION: Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.

Aged↗

Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma.

PinX1 was isolated as a Pin2/TRF1 binding protein that also binds to the telomerase catalytic subunit hTERT. The gene is a potent telomerase inhibitor and a putative tumor suppressor since it inhibits telomerase activity and affects tumorigenicity in nude mice. This study investigated aberrations of PinX1 gene in gastrointestinal tract carcinomas (GITCs). We examined mutations, mRNA expression and promoter methylation of PinX1 gene in 15 GITC cell lines, and 20 patients with primary GITC. We found a missense mutation at codon 254 (AGC/TGC) in a colon and an esophageal carcinoma cell line, and in cancerous and matching normal tissues of 2 patients with primary GITC (10%). It might be a benign polymorphism. No hyper-methylation was found in the promoter region and the treatment by 5-Aza-2'-deoxycytidine did not affect PinX1 mRNA expression level in any of the cell lines. It was concluded that the human PinX1 does not affect tumorigenesis of human GITC.

Azacitidine↗

[Perioperative nutrition for gastrointestinal surgery].

In elective gastrointestinal (GI) surgery, the patients' nutritional status should be assessed and if protein-energy malnutrition exists, preoperative nutritional support should be scheduled 7 to 14 days before surgery. In malnourished patients in particular, preoperative nutrition with total parenteral nutrition (TPN) reduces postoperative complication rates of infection. Preoperative enteral nutrition (EN) is considered to be as effective as TPN in improving postoperative surgical outcome. Many prospective randomized trials or meta-analyses comparing postoperative EN and TPN have revealed that postoperative EN improves surgical outcomes and lowers postoperative complication rates of infection to a degree similar to TPN. Although two recent prospective multicenter randomized trials in malnourished patients undergoing elective GI cancer surgery are controversial, no evidence that EN was less effective than TPN was recognized. Thus postoperative EN, prior to TPN, is recommended in patients with malnutrition or insufficient oral intake for 7 days or more after surgery. When TPN is administered, hyperglycemia due to overfeeding should be carefully controlled. Patients who undergo distal gastrectomy or colectomy can start oral intake 3 to 4 days after surgery, with pertinent peripheral infusion. Immunonutrition containing immune-enhancing nutrients such as arginine, n-3 polyunsaturated fatty acid, glutamine, etc., especially administered preoperatively, is a promising nutritional therapy for reducing postoperative infectious complications.

Adjuvants, Immunologic↗

Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204.

PURPOSE: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND METHODS: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. RESULTS: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Adult↗

A rapid biosensor chip assay for measuring of telomerase activity using surface plasmon resonance.

Considerable interest has been focused on telomerase because of its potential use in assays for cancer diagnosis, and for anti-telomerase drugs as a strategy for cancer chemotherapy. A number of assays based on the polymerase chain reaction (PCR) have been developed for evaluation of telomerase activity. To overcome the disadvantages of the conventional telomerase assay [telomeric repeat amplification protocol (TRAP)] related to PCR artifacts and troublesome post-PCR procedures, we have developed a telomeric repeat elongation (TRE) assay which directly measures telomerase activity as the telomeric elongation rate by biosensor technology using surface plasmon resonance (SPR). 5'-Biotinylated oligomers containing telomeric repeats were immobilized on streptavidin-pretreated dextran sensor surfaces in situ using the BIACORE apparatus. Subsequently, the oligomers associated with the telomerase extracts were elongated in the BIACORE apparatus. The rate of TRE was calculated by measuring the SPR signals. We examined elongation rates by the TRE assay in 18 cancer and three normal human fibroblast cell lines, and 12 human primary carcinomas and matching normal tissues. The elongation rates increased in a concentration- and time-dependent manner. Those of cancer cells were two to 10 times higher than fibroblast cell lines and normal tissues. Telomerase activities and its inhibitory effects of anti-telomerase agents as measured by both the TRE and TRAP assays showed a good correlation. Our assay allows precise quantitative comparison of a wide range of human cells from somatic cells to carcinoma cells. TRE assay is suitable for practical use in the assessment of telomerase activity in preclinical and clinical trials of telomerase-based therapies, because of its reproducibility, rapidity and simplicity.

Cell Line↗

Esophageal extraskeletal Ewing's sarcoma.

Extraskeletal Ewing's sarcoma is a rare tumor. The most common sites of occurrence are on the trunk, extremities, and retroperitoneum. This type of tumor is well characterized by recurrent chromosomal translocation such as t (11;22) (q24;q12) (EWSR1/FLI1) or t (21;22) (q22;q12) (EWSR1/ERG) and overexpression of MIC2/CD99 on tumor cell membrane. We describe the first reported case of an esophageal extraskeletal Ewing's sarcoma with confirmation from immunohistochemical and molecular diagnoses. A 56-year-old man developed a polypoid tumor located in the lower part of the esophagus. The tumor was composed of small-sized round cells showing prominent fibrillar cytoplasmic processes. Intracytoplasmic glycogen was detected in all the tumor cells. Immunoreactivity for MIC2/CD99 was positive on the membrane of all tumor cells. A reverse transcriptase-polymerase chain reaction followed by sequencing revealed an EWSR1/ERG chimeric transcript, which combined EWSR1 exon 10 with ERG exon 6. The present report added a new entity of esophageal small round cell tumor.

12E7 Antigen↗

Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer.

OBJECTIVE: To investigate whether preoperative corticosteroid administration plays a role in attenuating postoperative morbidity. SUMMARY BACKGROUND DATA: There is as yet no consensus on the beneficial effects of steroids in alleviating surgical stress. METHODS: A total of 66 patients undergoing surgery for thoracic esophageal cancer were randomly categorized preoperatively into two groups of 33 patients each. One group was administered an intravenous infusion of methylprednisolone (10 mg/kg body weight) 30 minutes before the surgery (MP group), while the other group received a placebo infusion (control group). The primary endpoint was organ system failure during the first 7 days after surgery. Comparisons of surgery-related complications, cytokine responses, and blood counts were also made between the two groups. RESULTS: The percentage of patients in the MP group who had one or more organ system failures was 33%, significantly lower than the corresponding percentage of 61% in the control group. The surgery-related complication rate and long-term survival rate were similar in the two groups. The peak plasma levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8 were significantly lower in the MP group than in the control group. Changes in the plasma levels of IL-10 were significantly larger in the MP group. No significant differences in the circulating lymphocyte and neutrophil counts were observed between the groups. CONCLUSIONS: The results suggest that prophylactic administration of corticosteroids is associated with a decrease in postoperative morbidity in patients undergoing invasive surgery. The laboratory data suggest that corticosteroids may attenuate surgical stress-induced inflammatory responses both directly by suppressing the release of proinflammatory cytokines and via inducing IL-10 synthesis.

Aged↗

Gastrointestinal stromal tumour of the oesophagus: significance of immunohistochemical and genetic analyses of the c-kit gene.

Oesophageal gastrointestinal stromal tumours (GISTs) are rare in comparison to those of the stomach and intestines. Recently, it has been clarified that mutations of the c-kit gene resulting in gain of function might be associated with histogenesis of this type of tumour arising in the stomach and intestines. We describe an oesophageal GIST on immunohistochemical and genetic analyses of the gene. A 71-year-old man had an intramural tumour of the middle third of the oesophagus. Tumour cells were composed predominantly of spindle-shaped and partially epithelioid cells. They were diffusely positive for CD117. Six base deletion resulting in in-frame mutation of the c-kit gene was confirmed at codon 556-558 (cag tgg aag to cag) of exon 11. Patients with mutations of the c-kit gene revealed worse prognoses in GISTs arising from other locations. A long-term follow-up observation is needed for the case.

Aged↗

Failure in presumption of residual disease by quantification of FDG uptake in esophageal squamous cell carcinoma immediately after radiotherapy.

To assess whether differentiation is possible between residual disease and complete response, 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography was performed in 17 cases of primary squamous cell carcinoma of the thoracic esophagus before (five control cases) or immediately after full-dose irradiation (12 treated cases). The FDG counts in the esophageal tumors were corrected by the dose of injected isotope and the weight of the patient, to produce a standardized uptake value (SUV). Endoscopy for post-treatment evaluation showed almost complete clearance of the tumor in seven treated cases (good-responders) and apparent residual tumor in the other five cases (poor-responders). There was a significant difference in the average median SUV between the controls and the treated (8.1 +/- 1.6 vs. 3.3 +/- 1.1), and between the poor-responders and good-responders (4.1 +/- 0.8 vs. 2.7 +/- 0.9). Three of the good-responders showed locoregional recurrence after four, six, and 18 months. Among the good-responders, the SUV of the cases of local recurrence was not inevitably higher than that of the others. The rate of FDG uptake in irradiated esophageal cancer approximately represents tumor response to radiotherapy, but it seemed impossible to differentiate residual disease from complete response.

Aged↗