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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 415 records · Page 23Linked to original sources

Skull base tumors: evaluation with contrast-enhanced MP-RAGE sequence.

The purpose of this study is to assess the value of contrast-enhanced MP-RAGE sequence for evaluation of skull base tumors. A total of 36 patients were prospectively evaluated. MP-RAGE showed relatively higher CNRs than other sequences, and there was a significant difference of CNR between the MP-RAGE and contrast T1-weighted SE images when fat tissue was chosen as the background. MP-RAGE was significantly superior to other sequences in the diagnosis of the extent of tumors. Contrast-enhanced MP-RAGE sequence is useful in evaluation of skull base tumors because of its higher contrast, higher spatial resolution, multiplanar capability, and suppression of the fat signal.

Adolescent↗

An artificial esophagus consisting of cultured human esophageal epithelial cells, polyglycolic acid mesh, and collagen.

Previously, the authors successfully grafted collagen sheets covered with cultured human esophageal epithelial cells onto latissimus dorsi muscles of athymic mice. To make a tubular artificial esophagus they developed a polyglycolic acid mesh-collagen complex tube whose inner side was epithelialized in vitro by cultured human esophageal epithelial cells. Human esophageal epithelial cells were isolated from normal mucosa resected from specimens of esophageal cancer patients and cultured on the surface of the collagen gel in which polyglycolic acid mesh was embedded. After the culture reached confluence, polyglycolic acid mesh was sutured to create a tubular form lined with cultured cell layers (restructured mucosal tube). Such tubes were wrapped in the latissimus dorsi muscle flaps of athymic rats using a fibrin glue. The animals were killed 4, 8, 20, and 28 days after grafting and the grafted tubes were studied histologically. Up to 28 days after grafting, the luminal structure was maintained without structure. Eight days after grafting, rat fibroblasts infiltrated from the muscle and neovascularization appeared in the collagen layer. The grafted epithelium remained healthy and grew to 15 cell layers by 20 days, much like normal human esophageal epithelium. Staining by anti-laminin monoclonal antibody confirmed a basement membrane.

Animals↗

An artificial esophagus constructed of cultured human esophageal epithelial cells, fibroblasts, polyglycolic acid mesh, and collagen.

We have been developing an artificial esophagus constructed of autologous esophageal component cells by cell culture. Because human esophageal epithelial cells are stratified in 20 layers, we attempted to construct an artificial esophageal epithelium 20 twenty layers thick. In in vitro experiments, we investigated how keratinocyte growth factor produced by fibroblasts accelerates the proliferation and differentiation of epithelial cells. Esophageal epithelial cells were cultured on collagen sheets in which dermal fibroblasts (0, 1, 4, 8 x 10(5) cells/ml of collagen) were embedded. In cultured epithelial cells on collagen gels without fibroblasts, 2.1 layer stratification was observed on the 21st day. With 1 x 10(5) fibroblasts/ml of collagen, 3.0 layer stratification was observed, 5.0 layers with 4 x 10(5) fibroblasts, and 18.1 layers with 8 x 10(5) fibroblasts. The degree of epithelial cell stratification was thus correlated with the number of embedded fibroblasts. Tubes constructed of a polyglycolic acid mesh frame, a collagen layer with esophageal fibroblasts, and an inner layer of esophageal epithelial cells were transplanted into muscle flaps of athymic rats. The luminal structures were observed to be patent without stenosis for 14 days. Histology of the epithelium revealed 20 layers of stratification. We thus succeeded in constructing epithelium similar to human esophageal epithelium. In the future we will attempt to use the tubular structures as a substitute for the esophagus after esophagectomy.

Animals↗

Intratumoural thymidylate synthase and dihydropyrimidine dehydrogenase activities are good predictors of 5-fluorouracil sensitivity in colorectal cancer.

To identify factors that influence the clinical response to 5-fluorouracil (5-FU), we studied the correlation between in vitro sensitivity to 5-FU and the expression of seven biological markers. The markers, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), pyrimidine nucleoside phosphorylase, p53 (wild/mutant), p21, cyclo-oxygenase-2, and inducible nitric oxide synthase were measured in tumour tissues from 32 colorectal cancer patients. The activities of TS and DPD were significantly lower in the tumours sensitive to 5-FU compared with those that were not sensitive to 5-FU. In tumours with TS < 3.7 pmol/min per mg protein and DPD < 98 pmol/min per mg protein, the percentage of cases sensitive to 5-FU (67%) and the mean percentage inhibition of tumour cells by 5-FU (42.8%) were significantly higher than in the other tumours (0% and 13.1%, respectively). The other biological markers did not correlate with in vitro sensitivity to 5-FU. Tumour sensitivity to 5-FU can be more precisely predicted by taking the activities of both TS and DPD into consideration than by using either alone.

Antimetabolites, Antineoplastic↗

Technique for iliac artery reconstruction in abdominal aortic aneurysm repair.

The aim of this retrospective study was to evaluate the technique for iliac artery reconstruction in abdominal aortic aneurysm repair, when external and internal iliac arteries were required to reconstruct individually. Among 203 elective infrarenal abdominal aortic aneurysm repairs, 22 patients (10.8%) required individual reconstruction of bilateral or unilateral iliac arteries, including 56 external or internal iliac arteries. Mainly, three types of procedures were performed: (1) the external iliac artery was anastomosed to the end of the bifurcated graft limb in an end-to-end manner, and the internal iliac artery was attached to the side of the external iliac artery, (2) the external iliac artery was anastomosed to the end of the bifurcated graft limb in an end-to-end manner and the internal iliac artery was bypassed with the use of a straight prosthetic graft extending from the limb of the bifurcated graft, and (3) the internal iliac artery was anastomosed to the end of the bifurcated graft limb in an end-to-end fashion, and the external iliac artery was sewn to the side of the graft limb. In these three types of procedures, the third technique was the easiest and simplest anatomically.

Aged↗

Interferon gamma increases the antitumor activity of mitomycin C against human colon cancer cells in vitro and in vivo.

A combined antitumor activity of mitomycin C (MMC) and interferon gamma-1a (IFN-gamma) was evaluated to be synergistic by the 3-(4, 5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide assay and human tumor xenografts/severe combined immunodeficient (SCID) mouse system using colon cancer cell lines. The experimental metastasis of WiDr cells in SCID mouse was inhibited by MMC and IFN-gamma with their synergism. Intracellular uptake of MMC in WiDr cells in vitro was significantly increased by IFN-gamma, suggesting the mode of synergism of these agents. This model may also partly explain the antitumor activity of combined MMC, 5-fluorouracil and interleukin-2 treatment on hepatic metastasis of colon cancer.

Animals↗

Further evidence that altered p16/CDKN2 gene expression is associated with lymph node metastasis in squamous cell carcinoma of the esophagus.

Esophageal squamous cell carcinoma (ESCC) has high malignant potential with a poor outcome. Lymph node metastasis is the most useful indicator for predicting the outcome of ESCC. The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate CDK4-mediated phosphorylation of RB protein in the cell cycle. We immunohistochemically detected p16, cyclin D1, and RB expressions in both primary lesions and metastatic lymph nodes in ESCC. Among the 50 ESCC primary lesions, 24 (48%) were positive for p16, while 26 (52%) were negative for p16. Sixteen (32%) were p16-positive, 34 (68%) were p16-negative among the 50 ESCC metastatic lymph nodes. Eight cases (16%) were p16-positive in primary lesion and p16-negative in lymph node, however, no cases that was p16-negative in the primary tumor exhibited p16-positivity in metastatic lymph nodes (p < 0.0001). Seventeen (34%) of the 50 ESCC primary lesions were cyclin D1-positive, while 33 (66%) were cyclin D1-negative. Twenty-four (48%) were cyclin D1-positive, 26 (52%) were cyclin D1-negative among the 50 metastatic lymph nodes. Five cases (10%) were cyclin D1-positive in primary lesion and cyclin D1-negative in lymph node, and 12 cases (24%) were cyclin D1-negative in primary lesion and cyclin D1-positive in lymph nodes. Nine cases (18%) were RB-negative in 50 primary lesions, and the rate of loss of RB expression in metastatic lymph nodes was not markedly higher than in primary lesions. Thirty-nine (78%) of 50 primary lesions and 46 (92%) of 50 metastatic lymph nodes had altered expression of at least one of the three G1 control genes. Tumor cell with disruption of these cell cycle regulators can get a growth advantage and metastatic potential during tumor progression, especially p16/CDKN2 alterations may be associated with lymph node metastasis in ESCC. These results also suggest that tumor cells in metastatic lymph nodes may have more aggressive proliferation and higher malignant potential than tumor cells in primary lesions.

Adult↗

Correlation between EGF receptor expression and peplomycin cytotoxicity in squamous cell carcinoma cell lines.

The relationship between sensitivity to anti-cancer agents and EGF receptor expression on squamous cell carcinoma (SCC) cells was investigated. The cytotoxicity of peplomycin (PEP) was correlated with the number of the EGF receptors expressed on the cancer cells, but no correlations were found between the cytotoxicity of adriamycin and cisplatin and EGF receptors. Addition of TNFalpha increased the number of EGF receptors in the SCC cell lines 1.5- to 2-fold. The cytotoxic effect of combined administration of PEP and TNFalpha was correlated with the number of EGF receptors, and produced a 2- to 5-fold increase in IC50 compared with administration of PEP alone. These observations suggest that EGF receptor expression is closely associated with the cytotoxic effect of PEP on SCC cells.

Antibiotics, Antineoplastic↗

Combined antitumour activity of mitomycin C, 5-fluorouracil and interleukin-2 against human colon cancer cells.

Combined treatment of interleukin-2 (IL-2), 5-fluorouracil (5-FU) and mitomycin C (MMC) is reported to be effective against hepatic metastasis of colon carcinoma. To clarify this modality, we investigated lymphokine activated killer (LAK) activity of human peripheral lymphocytes on colon cancer cell lines by 51Cr release assay. LAK activity against Colo 205 cells by untreated lymphocytes was 12%, which increased to 25% upon the addition of 5-FU, but remained unchanged upon the addition of MMC. The combined antitumour activity of MMC or 5-FU with or without LAK-supernatant was evaluated by MTT assay; antitumour activity of MMC was increased by the addition of LAK-supernatant. The concentration of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) was increased in LAK-supernatant, and the antitumour activity of combined IFN-gamma and MMC was synergistic. The mechanism of this therapy seemed to be associated with both increased LAK activity by 5-FU and increased antitumour activity of MMC with IFN-gamma.

Antineoplastic Combined Chemotherapy Protocols↗

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

Adult↗

Three-dimensional helical CT for treatment planning of breast cancer.

PURPOSE: The role of three-dimensional (3D) helical CT in the treatment planning of breast cancer was evaluated. METHODS: Of 36 patients examined, 30 had invasive ductal carcinoma, three had invasive lobular carcinoma, one had DCIS, one had DCIS with minimal invasion, and 1 had Paget's disease. Patients were examined in the supine position. The whole breast was scanned under about 25 seconds of breath-holding using helical CT (Proceed, Yokogawa Medical Systems, or High-speed Advantage, GE Medical Systems). 3D imaging was obtained with computer assistance (Advantage Windows, GE Medical Systems). RESULTS: Linear and/or spotty enhancement on helical CT was considered to suggest DCIS or intraductal spread in the area surrounding the invasive cancer. Of 36 patients, 24 showed linear and/or spotty enhancement on helical CT, and 22 of those 24 patients had DCIS or intraductal spread. In contrast, 12 of 36 patients were considered to have little or no intraductal spread on helical CT, and eight of the 12 patients had little or no intraductal spread on pathological examination. The sensitivity, specificity, and accuracy rates for detecting intraductal spread on MRI were 85%, 80%, and 83%, respectively. CONCLUSIONS: 3D helical CT was considered useful in detecting intraductal spread and planning surgery, however, a larger study using a precise correlation with pathology is necessary.

Breast Neoplasms↗

Hyperintensities of the optic radiation on T2-weighted MR images of elderly subjects.

BACKGROUND AND PURPOSE: Although abnormal hyperintensities are frequently observed at or around the optic radiation in elderly subjects, no previous reports have mentioned the clinical significance and pathologic changes of these hyperintensities. We evaluated the hyperintensity patterns of the optic radiation and its surrounding structures on T2-weighted MR images and compared these findings with pathologic observations and visual field measurements. METHODS: High-resolution coronal T2-weighted MR images of 102 consecutive patients (51-84 years old) were evaluated retrospectively for the presence and morphology of hyperintensities of the optic radiation (204 sides) and its surrounding structures. Pathologic specimens were obtained from 25 other patients (60-91 years old) who had died of nonneurologic causes. The histopathologic changes of the optic radiation and its surrounding structures were evaluated and correlated with the MR findings. Finally, MR findings and visual field measurements were correlated in 46 elderly volunteers (70-91 years old). RESULTS: Hyperintensities of the optic radiation or its surrounding structures or both were observed on 125 sides (93%) of 67 patients (61%), and linear/laminar hyperintensity of the optic radiation and the tapetum was the characteristic finding. Eleven (44%) of 25 pathologic specimens exhibited pallor of three anatomic layers (the external sagittal stratum or the optic radiation, the internal sagittal stratum, and the tapetum). No subjects with hyperintensity of the optic radiation had visual field abnormalities. CONCLUSION: Linear/laminar hyperintensity of the optic radiation and tapetum on T2-weighted images is common in elderly subjects, and may reflect differences in the internal structures and in the water content of three anatomic structures. Hyperintensities of this region did not cause visual field abnormalities in a group of elderly volunteers.

Aged↗