Biomedical subjects

S Shibui

Publications and source records attributed to S Shibui.

At least 37 records · Page 2Linked to original sources

PubMed1995

Investigation of chemoresistance-related genes mRNA expression for selecting anticancer agents in successful adjuvant chemotherapy for a case of recurrent glioblastoma.

BACKGROUND: Glioblastoma multiforme represents one of the most malignant forms of primary intracranial tumors, often intractable to multimodality of treatment including chemotherapy. The unsatisfactory results of chemotherapy are chiefly attributed to chemoresistance. Since various molecules that could confer drug resistance have been elucidated, screening of the amount of such molecules in the tumor cells could provide possibilities for predicting their chemoresistance beforehand and help select more effective drugs. METHODS: We present a 45-year-old woman with recurrent glioblastoma multiforme in the cerebellum and invading the brain stem, treated successfully by postoperative chemotherapy. In this patient, anticancer drugs were determined by measurements of mRNA expression of chemoresistance-related genes, such as O6-methylguanine-DNA methyltransferase (MGMT), mdr1, glutathione S-transferase (GST)-pi, and metallothionein (MT) in the resected tumor. RESULTS: Northern blot analysis demonstrated the moderate mRNA level of MGMT, a major molecule causing ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride) resistance. On the other hand, expression levels of mdr1 which codes the P-glycoprotein responsible for multidrug resistance, and GST-pi, a detoxification enzyme, were low. Transcript of MT, another thiol containing molecule for cellular detoxification possibly associated with cisdiamminedichloroplatinum(II) (CDDP) resistance, was only faintly detectable. Postoperatively, the patient was treated initially with intravenous administration of ACNU and etoposide (VP16), resulting in a minor response of tumor regression. For maintenance therapy, we changed ACNU to CDDP according to the findings of the Northern blot analysis. Consequently, the residual tumor showed a marked response and almost disappeared after two courses of systemic chemotherapy with CDDP and VP16. CONCLUSIONS: The successful tumor regression in this case suggests that Northern blot analysis on expression of these chemoresistance-related genes in tumor tissues could provide beneficial information for determination of optimal anticancer agents to improve the efficacy of chemotherapy.

Antineoplastic Agents↗

PubMed1994

Ossified and calcified epidural hematoma incidentally found 40 years after head injury: case report.

The authors report a 57-year-old man with an ossified and calcified epidural hematoma found incidentally 40 years after incurring a severe head injury. Since the introduction of computed tomography (CT) scan, few such cases have been described in the literature. A characteristic intracranial "double-outlined" contour on plain skull x-ray films and CT scans represented bone formation and calcification of the hematoma capsule adjacent to the dura.

Calcinosis↗

PubMed1993

Linac-based small-field radiotherapy for brain tumors.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 mm. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8-14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Brain Neoplasms↗

PubMed1993

[Recurrence with tumor bleeding in a patient with malignant astrocytoma during the treatment with intracranial injection of lymphokine-activated killer cells--a case report].

A 22-year-old woman harboring recurrent malignant astrocytoma presented with intracranial hypertension by tumor hemorrhage during repeated administration of lymphokine-activated killer (LAK) cells via Ommaya's reservoir. She first suffered from the tumor located at the right occipital lobe at the age of 13. The tumor regressed completely by subtotal removal of the tumor, followed by external irradiation. Nine years later, however, the occipital tumor recurred and was subtotally resected. Pathological diagnosis was astrocytoma grade 3. Postoperatively, LAK cells induced from her peripheral blood lymphocytes incubated with interleukin-2 and anti-CD3 antibody were injected into the tumor cavity via Ommaya's reservoir for eight times. At the end of the LAK therapy, the tumor regrew with massive hemorrhage in the tumor cavity causing intracranial hypertension. At the reoperation, thick granulation tissue covered the surface of the recurrent tumor and dense deposits of clot were noted around the tip of the Ommaya's tube. Histologically the superficial layer of the tumor was infiltrated with macrophages and lymphocytes, mostly CD3-positive T cells, accompanied with capillary hyperplasia. Viable astrocytoma cells were abundant beneath the granulation layer. It should be considered that in local LAK therapy granulation tissue formation with hypervascularization at the surface of the tumor cavity may lead to tumor bleeding as well as resistance to the treatment.

Adult↗

PubMed1992

Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy.

CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a well-known DNA topoisomerase I inhibitor. SN-38 is a metabolite of this compound. Both emit fluorescence when activated by a laser beam. With a confocal laser scanning microscope (CLSM), we determined the intracellular distribution of CPT-11 and SN-38 and the chronological changes in drug-treated PC-7, a cell line of human non-small cell lung cancer, and its CPT-11 resistant variant, PC-7/CPT cells. There were many more granules in the cytoplasm in PC-7/CPT than in the parent cell line (PC-7). The granule formation of the resistant cell could indicate a different drug metabolism in the cytoplasm from that of the parent cell. This technique would provide a new way of investigating the mechanism of resistance of cancer cells to anticancer drugs.

Antineoplastic Agents, Phytogenic↗

PubMed1992

[Chemo-sensitivity test for malignant brain tumors by DNA histogram, in vitro].

Application of flow cytometric DNA analysis was tried to determine the sensitivity of ACNU, one of nitrosourea derivatives which had been used very commonly for malignant brain tumors, to tumor cells. To evaluate the degree of chemo-sensitivity of ACNU, factor B was introduced, indicating the accumulated cells in SG2M phases after ACNU treatment as the percentage of cells that was previously in the SG2M phases and it revealed that ACNU sensitive cell clones gave much larger values of Factor B than ACNU resistant ones at the concentration of 10 micrograms/ml ACNU treatments. Twenty clinical materials obtained by operation were examined by measuring the degree of values of this Factor B, and the findings indicated that this method would be applicable as a clinical test for chemo-sensitivity of malignant brain tumors, after some improvement of the method.

Animals↗

PubMed1992

Expression of O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea resistance of human brain tumors.

Northern blot analysis with O6-methylguanine-DNA methyltransferase (MGMT) cDNA as a probe was used to analyze the MGMT activity regulating drug resistance of human cells to chloroethylnitrosoureas (CENUs). By this method, the expression levels of MGMT mRNA in six human glioma cell lines and 12 human brain tumor tissues from surgical specimens were determined. These MGMT mRNA levels were compared with the SD10 values of the tumor cells, estimated by cell survival assay, which indicated their resistance to the anticancer drug, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Human brain tumors that were highly resistant to ACNU, such as glioblastoma Gbl1 and metastatic brain tumor Col1 with SD10 values (microM) of above 100, expressed markedly increased amounts of 0.95 kb MGMT mRNA. In contrast, tumor cells such as U-87MG, U-251MG, U-343MG, U-373MG and SF-126 with SD10 values of under 14 indicating low resistance to ACNU scarcely synthesized any MGMT mRNA. These results indicated that the level of expression of MGMT mRNA in human brain tumors determined by Northern blot analysis truly reflects their cellular resistance to ACNU. Thus the Northern method with MGMT cDNA probe reported here is a practical and reliable method for estimation of cellular resistance to CENUs such as ACNU and for screening the chemotherapeutic response to CENUs of human brain tumors.

Blotting, Northern↗

PubMed1992

Skull base malignant lymphoma: a case report and review of the literature.

A case of primary malignant lymphoma of the skull base is reported. A 62-year-old man was admitted with headache and diplopia. Computed tomography and magnetic resonance imaging showed an abnormal mass in the right parasellar region. The final diagnosis after surgery was primary malignant lymphoma of the skull base. Primary malignant lymphomas sometimes occur in the central nervous system but those in the skull base are exceptional. The present paper presents just such a rare case of malignant lymphoma of the skull base. Diagnosis and combined therapy consisting of surgery, radiotherapy and chemotherapy for the disease are discussed, and the literature on recent clinical problems of central nervous system lymphomas is reviewed.

Brain Neoplasms↗

PubMed1990

Cell kinetics of rat 9L brain tumors determined by double labeling with iodo- and bromodeoxyuridine.

Rats with 9L brain tumors received intraperitoneal injections of iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) to estimate the duration of the deoxyribonucleic acid (DNA) synthesis phase (Ts) and the potential doubling time (Tp) of individual tumors. Different sequences and intervals (2 or 3 hours) of IUdR and BUdR administration were evaluated. After denaturation, tumor sections were reacted with Br-3, a monoclonal antibody that identifies only BUdR, and then were stained immunohistochemically by the avidinbiotin complex method. An antibody that recognizes both IUdR and BUdR, IU-4, was applied to the sections and identified by the alkaline phosphatase-antialkaline phosphatase method. Nuclei labeled only with IUdR stained blue, while those labeled with BUdR or with BUdR and IUdR stained brown. The fraction of cells that either left or entered the S-phase during the time between administration of IUdR and BUdR was measured to calculate Ts and Tp, assuming that the labeled cohort completed the DNA synthesis at a constant rate. The Ts was 8.8 hours (coefficient of variation (cv) = 0.05) and the Tp was 64.2 hours (cv = 0.08). The sequence and interval of administration of IUdR and BUdR had a minimal effect on Ts and Tp. In studies of 9L cells in monolayer culture, the Ts was 9.6 hours (cv = 0.08) and the TP was 30.6 hours (cv = 0.06). Double labeling with BUdR and IUdR allows the duration of the S-phase and potential doubling time of individual brain tumors to be estimated in situ from a single biopsy specimen.

Animals↗

PubMed1990

[Treatment of metastatic brain tumor from renal cell carcinoma].

Twenty-eight patients with metastatic brain tumor from renal cell carcinoma were treated at the National Cancer Hospital, Tokyo, between 1962 and March 1989. In 13 patients, the median time interval between the initial diagnosis and pulmonary metastasis was 18 months, and the interval between pulmonary metastasis and brain metastasis was 13 months. In 10 patients, whose initial diagnosis was pulmonary metastasis, the median interval between pulmonary metastasis and brain metastasis was also 13 months. There were 2 patients who presented brain metastasis initially. The median survival time from the diagnosis of brain metastasis was 17 months for the patients whose brain tumors were surgically resected, but only 4 months for the patients who didn't receive surgery. The median survival time of the patients who received postoperative radiation was 20 months, while it was 10.5 months for the patients who received radiation therapy alone. Repeated serial CT scans of 7 patients with measurable brain metastases revealed partial response (PR) to radiotherapy in 2 patients (28.6%), no change (NC) in 4 patients (57.2%), and progressive disease (PD) in one patient (14.3%). BrdU labeling indices of resected brain metastases were about 2%, and the doubling time calculated on repeated serial CT scans was about 20 days. As these lesions are rather resistant to radiotherapy and grow relatively slowly they should be resected as much as possible.

Adult↗

PubMed1989

Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4).

A method of identifying thymidylate synthase (TS) at the cellular level was developed using anti-TS monoclonal antibody (M-TS-4), a monoclonal antibody created against purified TS from a HeLa cell line. In HeLa cells and four human glioma cell lines (U-251, U-87, 343-MGA, and SF-188), TS was identified primarily in the cytoplasm. Autoradiographic and flow cytometric studies showed that TS appeared mainly in the G1 phase and subsided early in the S phase; thus, the G1 phase can be divided into TS-positive and -negative fractions. Nuclear TS was not demonstrated unequivocally with M-TS-4, and the relationship between nuclear TS and DNA synthesis could not be determined. Although the percentage of TS-positive cells was larger than the S-phase fraction measured by autoradiography after a pulse of tritiated thymidine or by the immunoperoxidase method using BUdR, the ratios were within a similar range (1.2-1.4) in all cell lines studied. Therefore, the S-phase fraction can be estimated indirectly from the percentage of TS-positive cells measured by M-TS-4. Because the emergence of TS detected by our method is cell cycle dependent, M-TS-4 may be useful for biochemical studies of TS and for cytokinetic analysis.

Antibodies, Monoclonal↗

PubMed1989

Double labeling with iodo- and bromodeoxyuridine for cell kinetics studies.

The rate of progression through the cell cycle was determined in five human glioma cell lines by a new sequential immunohistochemical staining technique. The cells were labeled first with iododeoxyuridine (IdUrd) for 1-3 hr and then with bromodeoxyuridine (BrdUrd) for 30 min. Labeled cells were identified with Br-3, a monoclonal antibody that recognizes only BrdUrd, and with IU-4, an antibody that recognizes both IdUrd and BrdUrd. Each slide was stained sequentially, first with the immunoperoxidase method for Br-3 and then with the alkaline phosphatase-anti-alkaline phosphatase method for IU-4. Cells that were positive only for IU-4 represented the fraction of S-phase cells that passed into the G2 phase during the period of incubation with IdUrd. The rates of progression measured by this method were constant in each cell line and resulted in smaller standard errors than were obtained by measurements from specimens stained singly for IdUrd and BrdUrd in different slides. The duration of the S-phase calculated from this fraction in the five cell lines ranged from 8-13 hr; the estimated potential doubling times were 25-32 hr and were very similar to the actual doubling times.

Bromodeoxyuridine↗

PubMed1988

[Cell kinetic studies using monoclonal antibody to thymidylate synthase].

Thymidylate synthase was identified at the cellular level using anti-thymidylate synthase monoclonal antibody (M-TS-4) developed against HeLa cell line. HeLa cells, 9L rat gliosarcoma cells, and some of human brain tumor cells (medulloblastoma, metastatic brain tumors from lung cancer and osteosarcoma) were cultured in complete medium for 72 hr and fixed with 10% buffered formalin. These were covered with 1:20 dilution of M-TS-4 in Burridge buffer and 1% bovine serum albumin for 4 or 24 hr. After rinsing twice with phosphate-buffered saline solution (PBS), the cell staining was made with avidin-biotin peroxidase complex (ABC). In addition, HeLa cells were exposed to 2 microCi/ml of tritiated thymidine for 30 min, cultured again for 0 to 5 hr, and subjected to autoradiography after M-TS-4 staining with ABC. All cells were stained satisfactorily with ABC except 9L rat gliosarcoma cells. Autoradiography revealed that 38% of the cells were stained with ABC, 28% were labeled with tritiated thymidine, while only 8% of the cells were stained simultaneously at 0 hr specimen. However, the cells labeled with both agents subsided when the cells were incubated in complete medium for 1 or 2 hr before fixation. Therefore, thymidylate synthase appears to exist mainly in G1-phase and to subside in early S-phase. Although the number of thymidylate synthase positive cells was greater than that of the cells labeled with tritiated thymidine, the ratio was constant (r = 0.99). The fraction of S-phase can be estimated from that of thymidylate synthase positive cells. Thymidylate synthase positive cell fraction may become another important segment for cell cycle analysis.

Antibodies, Monoclonal↗

PubMed1988

[The effects of surgery and radiation therapy of metastatic brain tumors from lung cancer].

Metastatic brain tumor patients (193 cases: Small cell carcinoma; 44, large cell carcinoma; 19 adenocarcinoma; 110, squamous cell carcinoma; 14 and mixed carcinoma; 6) from lung cancer in 1978-1986 were studied to determine what treatments would be best for the local control of cancer. Treatment with radiation alone (29 cases received more than 30 Gy to the brain lesion) revealed CR(complete response) of 37.9% and PR(partial response) of 37.9%. On the other hand, radiation after operation with or without chemotherapy (33 cases) showed CR of 87.9%. Modes of response after radiation in relation to tumor size indicated CR of 34.8% and PR of 34.8% for the tumors (total of 23 cases), 2 cm or less in diameter and CR of 20% and PR of 25% for the tumors (total of 25 cases), more than 2 cm in diameter. Median period to tumor recurrence for the cases attained CR showed 10.5 (range 7-34) months and 4.0 (range 1-7) months, respectively. These data suggest that radiation after surgery could attain the highest percentage of CR and will promise the further improvement of survival time for the patients with metastatic brain tumors.

Adenocarcinoma↗

PubMed1987

[Application of flow cytometry to the chemosensitivity test by the BrdU labeling method; a preliminary report].

In the present paper we discussed whether a new method of chemosensitivity test could be developed using FCM (flow cytometry) and applied to malignant brain tumor cells labelled with BrdU monoclonal antibody. For this purpose, a basic study was performed with an ACNU-resistant C6 cell line and a sensitive one to see if this method was able to detect the difference of sensitivity between these cell lines. After 8 hours treatment with ACNU (concentration: 10 micrograms/ml), ACNU-sensitive cells revealed on LI (labeling index) of 46%, which was very high in comparison with controls, whereas the figure for ACNU-resistant cells was 34%, which was almost the same LI value as non-treated control cells. This means that change in the BrdU labeling index after chemotherapy in vitro can be used to determine the chemosensitivity of malignant brain tumors when FCM is employed. Furthermore, this method can detect the chemosensitivity of each clone in polyclonal human tumors which is impossible for the HCSA method, since the latter can reveal only the chemosensitivity as a whole in such tumors.

Antibodies, Monoclonal↗

PubMed1987

[Two cases of the middle fossa tumor following radiotherapy against retinoblastoma].

Two cases of brain tumors which developed after radiotherapy against retinoblastomas are reported. A 17-year-old girl was admitted with a chief complaint of swelling in her forehead after head injury in July, 1981. At 7 months old her left eye had been enucleated and she had received radiation therapy of 40 Gy to the right eye because of her bilateral retinoblastoma. On admission a CT scan revealed a high density mass with a partial low density area in her right middle fossa. A right frontotemporal craniotomy was performed and the tumor was removed subtotally, which was diagnosed as a malignant fibrous histiocytoma. The second case was a 14-year-old boy, who had received radiotherapy of 39.6 Gy against retinoblastoma of the right eye after enucleation at 2 months old. He had been well for 14 years after the therapy and was admitted to the hospital with complaints of headache, nausea, vomiting and unsteady gait in January 1985. A CT scan demonstrated a large contrast enhancing mass in the righ middle fossa, which was removed subtotally on January 14, 1985. A histological diagnosis of fibroblastic meningioma was made. Each patient developed a secondary brain tumor after radiotherapy against retinoblastoma. Those tumors appear to be radiation induced, although 10 to 15% of the patients who survived retinoblastoma without radiotherapy had been reported to develop secondary nonocular tumors. The patients with retinoblastoma should be followed up carefully after the initial treatment.

Adolescent↗

PubMed1987

[Primary intracranial epidermoid carcinoma accompanied with epidermoid cyst in the cerebellopontine angle--a case report].

A case of epidermoid carcinoma arising in an epidermoid cyst in the cerebellopontine angle is presented. Clinical features and CT appearance are discussed in comparison with those of benign epidermoid cyst. A 43-year-old man was admitted to the Department of Neurosurgery, University of Tokyo Hospital on April 14, 1983, with complaints of right facial numbness and weakness of six months' history. On neurological examination, sensation of the right half of the face was decreased in all modalities. Marked atrophy of the ipsilateral temporal muscle was also noted. Right facial paresis of peripheral type was evident. Gag reflex was decreased on the same side. Except for a slightly increased left deep tendon reflexes, there were no pyramidal tract signs. A CT without contrast material failed to show any abnormalities. A postcontrast CT demonstrated an irregular enhancement in the right cerebellopontine angle. The finding of asymmetry of the ambient cistern indicated minimum mass effect on the metrizamide CT cisternography. Suboccipital exploration of the right cerebellopontine angle was carried out on April 28, 1983. Leaving a part of the capsule indenting the pons between the roots of the fifth and the seventh nerve, we removed a white pearly tumor. Histological diagnosis was typical epidermoid cyst. He left the hospital one month later with signs of the right seventh and the eighth nerve. His postoperative course, however, was beyond our expectation. Over a few months following his discharge, left hemiparesis as well as horizontal and vertical nystagmus gradually developed. He was readmitted on November 10, 1983. A postcontrast CT revealed enlargement of the enhanced lesion filling the right ambient cistern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

[Surgery of metastatic brain tumors with new surgical instruments].

The risk of damages of neurological function by the operation of metastatic brain tumors was reduced considerably after introduction of neurosurgical apparatuses, such as ultrasonograph, ultrasonic surgical aspirator and laser scalpel. Of these, ultrasonograph is useful to indicate the exact location of brain tumor at real time during the operation. Ultrasonic surgical aspirator reduced the risk of damage on important brain structures due to the selectivity of fragmentation and the safety of the dissection in the vicinity of important vessels and nerve tissues. Laser scalpel is also useful to extirpate the hemorrhagic tumor with hard consistency. Cases introduced in this paper were: case 1, brain metastasis from lung cancer located just under the left motor area in brain; case 2, metastasis with abundant neovascularization from renal cancer to orbital cavity which showed invasion to orbital roof and frontal bone; case 3, radiation induced sarcoma after the treatment of retinoblastoma; case 4, a large cerebellar metastatic tumor; case 5, neurogenic sarcoma which were successfully removed by using one of or combination of ultrasonograph, ultrasonic aspirator and laser scalpel. Advantage of these new instruments for the surgery on metastatic brain tumor was mentioned here. However, it is necessarily to get a custom before we use these apparatuses at operation efficiently.

Adult↗