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T Nagashima

Publications and source records attributed to T Nagashima.

At least 253 records · Page 14Linked to original sources

Pediatric central nervous system tumors: a cell kinetic study with bromodeoxyuridine.

Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.

Adolescent↗

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling.

Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.

Adolescent↗

The proliferative potential of human pituitary tumors in situ.

At the start of transsphenoidal microsurgery for removal of various types of pituitary adenomas, 21 patients received a 1-hour intravenous infusion of 5-bromodeoxyuridine (BUdR, 200 mg/sq m) to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). Excised tumor specimens were fixed in 70% ethanol and stained by the indirect peroxidase method using anti-BUdR monoclonal antibody as the first antibody. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated for each specimen. The S-phase fraction was less than 0.1% in nine cases, 0.1% to 0.5% in seven, and greater than 0.5% in five. Except in two cases of Nelson's syndrome, in which it was greater than 1%, the S-phase fraction did not correlate with any other variable, including patient age, tumor size, or the duration of signs and symptoms. The small S-phase fraction of most of the pituitary adenomas correlates well with the clinical behavior of these tumors, which grow much more slowly than other kinds of brain tumors such as gliomas. However, the S-phase fractions varied by as much as one order of magnitude. The higher S-phase fractions may reflect aggressive and invasive growth. These results indicate that immunohistochemical studies of cell kinetics using BUdR and anti-BUdR monoclonal antibodies may provide information about the biological characteristics of pituitary adenomas which could lead to the design of appropriate treatment regimens (including surgery, radiation therapy, and chemotherapy) for individual patients.

Adenoma↗

Cell kinetics analysis in a case of teratoma of the thoracic spine.

The authors report cell kinetics studies in an infant who had multiple operations for removal of a rare benign thoracic spinal teratoma with retroperitoneal extension. Before the final surgical procedure for recurrent tumor, bromodeoxyuridine (BUdR), 200 mg/sq m, was administered intravenously to label tumor cells in the S (deoxyribonucleic acid (DNA) synthesis) phase of the cell cycle. Histologically, the tumor was a mature teratoma consisting of components derived from all three germ-cell layers. Cells labeled with BUdR were found in the basal layer of stratified squamous epithelia, in respiratory epithelia, in the cartilage and surrounding perichondrial mesenchyme, and in loose mesenchymal tissue throughout the teratoma. In contrast to neuroectodermal tumors, which show widespread BUdR uptake throughout the tissue and which have different average labeling indices according to their histological type (range less than 1% to 15.2%), the teratoma showed BUdR labeling only in certain areas, indicating fairly organized growth patterns; the labeling indices in these areas ranged from 0.39% to 1.9%.

Bromodeoxyuridine↗

Prediction of tumor doubling time in recurrent meningiomas. Cell kinetics studies with bromodeoxyuridine labeling.

Eight patients with recurrent meningiomas (four malignant, two hemangiopericytic, and two nonmalignant) were given intravenous bromodeoxyuridine (BUdR), 200 mg/sq m, at the time of surgery to label cells in the deoxyribonucleic acid (DNA) synthesis phase; labeled cells were detected in excised tumor specimens by immunoperoxidase staining using anti-BUdR monoclonal antibody. These tumors showed a wide range of BUdR labeling indices (LI's), calculated as the percentage of BUdR-labeled cells divided by the total number of cells scored, from 0.3% to 5.4%. The tumor doubling times (Td's), estimated from serial computerized tomography scans, ranged from 8 to 440 days and showed a close inverse correlation with the BUdR LI's. A semilogarithmic linear regression analysis of these values yielded a correlation coefficient of 0.99. Tumor doubling time (Td) can be estimated using the formula: Td = 500 X Exp (-0.73 X LI), where Exp signifies the natural log base. By predicting the growth rate of meningiomas, the BUdR LI may supplement histopathological diagnosis and improve both the determination of prognosis and the design of treatment modalities in individual patients.

Adult↗

[Flow cytometric analysis of the effect of cAMP on the cell cycle of the 9 L rat glioma in vitro].

Perturbed cell kinetics in 9 L rat brain tumor treated with dibutyryl cyclic AMP (DBcAMP) and theophylline were studied. The methods include a procedure for simultaneous flow cytometric measurements of cellular DNA and amount of bromodeoxyuridine (BrdU) incorporated into cellular DNA and a procedure for flow cytometric measurements of cellular DNA and RNA. Propidium iodide and monoclonal antibody against BrdU were used as a fluorescent probe for total cellular DNA and for BrdU incorporated into cellular DNA, respectively. For analysis of cellular DNA and RNA, acridine orange staining was also applied. The results were as following; cells in S and G2 phase at the time of drug administration (1 mM, each) can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration were arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrest in the G1 phase. These results have been inferred from the study by autographic method with 3H-thymidine. However, using these new methods, these were clearly demonstrated and furthermore, flow cytometric analysis with acridine orange revealed that DBcAMP induced 9 L cells into resting position (G0 cells).

Animals↗

[Application of NMR-CT in the staging of cancer of the digestive organs].

To assess the potential of NMR-CT for demonstrating cancer of the digestive organs, we examined a total of 232 patients (89 with esophageal cancer, 52 with liver cancer, 40 with colorectal cancer, 9 with pancreatic cancer, 9 with gastric cancer, and 33 with other diseases). NMR-CT has many features, but we use especially those features which it is possible to select not only in the transverse plane but also in the coronal and sagittal planes, and it has excellent soft tissue contrast resolution. Our machine is a Picker International NMR-CT using a superconducting magnet of 0.256 tesla. Diagnosis of lymph node involvement of esophageal cancer. Using only the coronal plane, each patient was scanned by the spin echo technique (TE = 40, TR = 400) from the plane of the descending aorta to the plane of the trachea 1 cm in thickness, at 1 cm intervals, continuously. All the vessels were clearly differentiated as no-signal regions, especially in coronal images, from areas of carcinomatous involvement. Lymph nodes were identified as intense grey masses in fat tissue of high intensity. Twenty cases were proved by surgery or autopsy, and it was possible to assess 160 lymph-node groups. A total of 25 patients were imaged as having positive lymph nodes, but 17 of them had metastasis-positive nodes. In other 135 nodes imaged as negative lymph nodes, only two had metastasis and 133 were negative for metastasis. Overall accuracy was 93.8%. Diagnosis of liver cancer. Intrahepatic vessels were clearly imaged without using contrast enhancement in NMR-CT, so it was easy to diagnose the segment containing the tumor and to detect tumor emboli in the portal vein. The capsule was imaged in 84% (16/19) using IR techniques, although only 37% (7/19) could be imaged by X-CT. Diagnosis of colorectal cancer. Using the sagittal plane, the sacrum, urinary bladder and other organs were imaged better parallel to their axis, so that the relationship between rectal cancer and surrounding organs could be clearly visualised with NMR-CT. With regard to lymphatic metastasis, coronal imaging was useful for picturing mesenteric and pelvic vessels, so that lymph nodes were imaged as low-intensity masses along the vessels. Lymph metastasis almost 1 cm size can be detected using coronal NMR-CT.

Digestive System Neoplasms↗

[Tissue CEA as a prognostic factor in advanced and recurrent breast cancers].

We stained tissue CEA in specimens of 25 advanced and reccurrenced breast cancers using the PAP method. We concluded the following: Tissue CEA positivity was 56.0% (14 out of 25 cases). Tissue CEA positivity was not correlated with age, clinical stage or histological type of primary breast cancer. Tissue CEA-positive breast cancers tended to have multiple distant metastases and very poor prognoses as opposed to negative ones.

Adult↗

[Focal cerebral infarction in the rat: II. Neuropathological study and local cerebral blood flow pattern].

We have recently reported that middle cerebral artery (MCA) occlusion in the rat produces a uniform pattern of cerebral ischemia in an acute phase. This study was done to determine if this model is also useful for quantitative evaluation of infarction size in a chronic phase. [Methods] Sprague-Dawley rats were anesthetized with halothane and left MCA was occluded via transretro-orbital approach. The following studies were done. Neuropathological study was done one week after MCA occlusion. After perfusion fixation, the brain was cut into 6 coronal slices and stained sections were examined. Local cerebral blood flow patterns were observed by 14C-iodoantipyrine autoradiographic technique 1, 2, and 5 days after the occlusion. [Results] Neuropathological studies invariably showed infarct in the cortex and the lateral part of the basal ganlia. The ratio of the infarct to the total areas of both hemispheres in 6 coronal sections was 14.05 +/- 2.66% (Mean +/- SD) in MCA occluded animals (N = 14) and 0.59 +/- 0.46% in sham operated animals (N = 12). Relative to the contralateral hemisphere, marked reduction in CBF was seen in the territory of the MCA and moderate reductions were also seen in the surrounding areas. The same pattern of increased CBF as previously reported was also seen in the ipsilateral substantia nigra and globus pallidus 1, 2, and 5 days after the occlusion. These results indicate the usefulness of this chronic focal cerebral infarction model in the evaluation of infarction.

Animals↗

[Combination therapy of local administration of OK-432 and radiation on a murine fibrosarcoma (NFSa)--combination effect and histological examination].

The combined effect of radiation with local administration of OK-432 was studied using natural fibrosarcoma (NFSa) of C3H mice that are less immunogenic and resistant to radiation (TCD 50, 83, 15 Gy). When 2KE of OK-432 was administered together with 1 X 10(6) tumor cells, tumor survival was inhibited in 7/8 (87.5%) of mice. Single local administration of OK-432 (2KE, 4KE, 8KE) showed hardly any effect on tumor survival. Combined treatment of 2KE of OK-432 and 4-Gy radiation, however, not only controlled tumor growth but also eradicated 1/5 (20%) of them, compared with single application of 45-Gy radiation. OK-432 worked most effectively when administered just before or after the application of X-rays. The optimum dose of OK-432 was studied by administering 2KE, 4KE and 8KE of the agent together with the application of 55-Gy radiation. 8KE groups showed the best eradication rate but 4KE groups showed the best cure rate. Therefore, the optimum dose was considered to be between 4KE and 8KE. With regard to histological effects, both the single radiation treatment and its combined treatment with OK-432 were most effective on the 6th day. The degree of degeneration and necrosis of tumor cells together with lymphocyte exudation were much higher in the combined treatment than in single radiation application.

Animals↗

[A clinicopathological study of five cases of adenosquamous carcinoma of the stomach].

Five cases of adenosquamous carcinoma with resected stomach were subjected to this study, and the clinicopathological characteristics of this condition were described. The five patients represented 0.8% of 589 cases of resected stomach. There were two men and three women ranging in age from 40 to 70 (average, 62.8). Macroscopically, the adenosquamous carcinomas were all advanced gastric cancer situated in the lower body along the lesser curvature of the stomach, averaging 7.6 cm in size. The characteristic finding was the histologically differentiated type, invading to the serosa. Lymph node metastasis was most prominent.

Adenocarcinoma↗

Cell kinetic studies of in situ human brain tumors with bromodeoxyuridine.

At the time of surgery, 18 patients with various brain tumors were given a 1-h i.v. infusion of bromodeoxyuridine (BrdUrd), 150-200 mg/m2. At an infusion rate of 200 mg/m2/h, serum BrdUrd levels of 8 microM were achieved. After the infusion, tumor tissue was obtained and divided into two portions. One portion was fixed in 70% ethanol, embedded in paraffin, and sectioned; the sections were deparaffinized, denatured with 2 N HCl, and reacted with monoclonal antibodies against BrdUrd (anti-BrdUrd MAb). BrdUrd-labeled nuclei were demonstrated satisfactorily by an indirect peroxidase method. The other portion was dissociated into single cells with a DNase enzyme cocktail and reacted with FITC-conjugated anti-BrdUrd MAb to determine the percentage of BrdUrd-labeled cells or with chromomycin A3 for DNA analysis. The single-cell suspensions were analyzed by flow cytometry. The fraction of S-phase cells in the tissue sections was similar to both the percentage of BrdUrd-labeled nuclei and the S-phase fraction determined by flow cytometric analysis. The results obtained with BrdUrd-labeled nuclei were similar to those obtained from previous autoradiographic studies of various brain tumors exposed to a pulse of 3H-thymidine. Since BrdUrd is not radioactive and is nontoxic at the dosage used, these techniques, together with the histopathological diagnosis, may help to predict the biological malignancy of individual tumors.

Antibodies, Monoclonal↗

Immunocytochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in human brain tumor tissues.

Five patients with various brain tumors received bromodeoxyuridine (BrdU), 150-200 mg/m2 i.v., at the time of craniotomy. Biopsied materials were fixed in 70% ethanol, sectioned, denatured with hydrochloric acid, and reacted with monoclonal antibodies against BrdU. Immunofluorescence and immunocytochemical methods were used to visualize BrdU-labeled nuclei. Our results showed that both methods demonstrated BrdU-labeled nuclei satisfactorily in tissue sections. Thus, BrdU can be used to measure the proliferative potential of human tumors in situ.

Aged↗