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Biomedical subjects

M Kochi

Publications and source records attributed to M Kochi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region.

The loss of chromosome 10 is the most frequent genetic alteration found in malignant astrocytomas. In particular, the long arm of chromosome 10 was previously reported to have two or more common deletion regions where tumor suppressor genes may be located. In this study, we performed deletion mapping of 44 malignant astrocytomas using 12 microsatellite markers on chromosome 10q and demonstrated that the minimal common region of loss of heterozygosity (LOH) was present between D10S192 and D10S566 localized at 10q25.1. Subsequently, we have identified a novel gene, termed h-neu, within the region frequently deleted and found that h-neu encodes a protein with strong homology to the Drosophila neuralized (D-neu) protein. Northern blot and RT-PCR analyses revealed that h-neu mRNA was expressed at very low levels in human malignant astrocytoma tissues and the majority of glioma cell lines examined, while normal brains expressed h-neu transcript. Furthermore, DNA sequencing analysis of the h-neu transcript revealed one of the glioma cell lines, U251MG, had a single nucleotide substitution which resulted in an amino acid change from glycine (GGC) to serine (AGC) at codon 253. The D-neu gene is known to serve a critical function in neurogenesis in Drosophila, and loss-of-function mutations produce hyperplasia of primitive neuronal cells. These observations led us to hypothesize that h-neu gene plays a role in determination of cell fate in the human central nervous system and may act as a tumor suppressor whose inactivation could be associated with malignant progression of astrocytic tumors.

Amino Acid Sequence↗
PubMed1998

Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas.

OBJECTIVE: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas. SUBJECTS AND METHODS: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established. RESULTS: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively). CONCLUSION: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities.

Adolescent↗
PubMed1998

Loss of merlin-p85 protein complex in NF2-related tumors.

The NF2 tumor suppressor gene product, designated merlin, belongs to the family of molecules that links membranous protein with the cytoskeleton. We have previously shown that merlin was co-immunoprecipitated with a cellular protein, p85, in cultured cell. To analyze the alteration of merlin and associated proteins in surgical specimens, we developed a new method for biotin-labeling of whole cellular proteins. Screening of tumor tissues using our method showed that none of malignant gliomas and half of the NF2-related tumors had altered p85 and merlin. Our detection method seems useful for the screening of merlin alterations in NF2-related tumors.

Avian Proteins↗
PubMed1996

Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study.

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), one of the chloroethyl nitrosoureas, is effective against malignant glioma. To develop its use in intrathecal chemotherapy, we encapsulated BCNU in hybrid liposomes composed of dimyristoylphosphatidylcholine and micellar surfactants (Tween 20) and dissolved it in artificial cerebrospinal fluid (lipo-BCNU). We then studied the toxicity of hybrid liposomes and cellular proliferation inhibition of lipo-BCNU in vitro. We found that 3 mM hybrid liposomes did not affect the viability of human endothelial cells and that lipo-BCNU inhibited the proliferation of human glioma cell lines U-105MG, U-251MG, and U-373MG, and rat glioma cell lines C6 and 9L in a concentration-dependent fashion. Wistar rats that were administered lipo-BCNU intracisternally showed no weight loss, neurological symptoms, or histological changes of the brain and spinal cord. A Wistar rat model of meningeal gliomatosis was established by intracisternal inoculation of 0.1 ml cell suspension containing 1 x 10(6) or 5 x 10(6) viable C6 glioma cells. Two days after inoculation, lipo-BCNU (BCNU, 2.5 mg/kg) was administered intracisternally. When 1 x 10(6) glioma cells were inoculated (experiments 1 and 2), the median survival times were 24.5 and 26 days in the control groups and 32 and 45 days in the lipo-BCNU-treated groups. respectively. When 5 x 10(6) glioma cells were inoculated (experiments 3-6), the median survival times were 17-29.5 days in the control groups and 23-44 days in the treated groups, respectively. Significantly prolonged survival was obtained in three of six experimental groups. After the administration of 1 ml lipo-BCNU (BCNU, 4.67 mM) or 1 ml BCNU solubilized with 5% dextrose/water (BCNU, 4.67 mM) into the cisterna magna of dogs, the cisterna magna cerebrospinal fluid was sampled, and the BCNU concentrations were assayed by high-performance liquid chromatography. The half-life of the lipo-BCNU was longer than that of BCNU solubilized with 5% dextrose/water. These results suggest that the intrathecal administration of lipo-BCNU may be possible for the treatment of meningeal gliomatosis.

Animals↗
PubMed1996

[Prognostic factors in malignant gliomas].

The most important prognostic factor in malignant gliomas is histopathological diagnosis of the tumor. The survival of patients with anaplastic astrocytoma is much longer than that of patients with glioblastoma. The median survival of the former has been improved up to almost 4 years by the recent progress of multidisciplinary treatment, whereas that of the latter has still remained in less than 1.5 years. Other important factors proved to be associated with survival of patients with malignant gliomas are the age of patients, Karnofsky performance status on admission, surgery, radiotherapy and chemotherapy. There is substantial evidence suggesting an association between younger patient age and longer survival in adults with supratentorial anaplastic astrocytoma as well as glioblastoma. It is also consistent with evidence that the patients with better performance status on admission live longer after treatment. Gross total resection of supratentorial anaplastic astrocytoma is directly associated with longer and better survival when compared to subtotal or partial resection. For glioblastoma, however, gross total resection has not been proved to have a significant survival advantage over subtotal or partial removal. Radiotherapy has been proved to be associated with longer survival of patients with supratentorial anaplastic astrocytoma and glioblastoma. Chemotherapy has not proved effective in prolonging the survival of patients with glioblastoma. Multidrug chemotherapy with CCNU, procarbazine and vincristine has proved to have significant survival advantage over BCNU alone, suggesting chemotherapy is also a prognostic factor in patients with anaplastic astrocytoma.

Adolescent↗
PubMed1996

[A case of lung metastasis from breast cancer successfully treated by FLEP (5-FU leucovorin, etoposide CDDP) combined arterial infusion chemotherapy].

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Adult↗
PubMed1995

Treatment of intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein.

We treated 10 patients with intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein between 1969 and 1992. Two patients were treated with radiotherapy (RT) only (RT group), and three were treated with RT and cisplatin plus vinblastine plus bleomycin therapy with or without surgery (cisplatin plus vinblastine plus bleomycin group). The most recently treated five patients received cisplatin plus etoposide (PE) therapy with or without RT and/or surgery (PE group). The level of alpha-fetoprotein in serum was elevated in all 10 patients. In the PE group, PE therapy consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given two or three times at 4-week intervals and then once every 4 months; the patients received three to six courses (mean, 4.2 courses). In the RT group (n = 2), one patient died 3 months after diagnosis and the other died at 12 months. In the cisplatin plus vinblastine plus bleomycin group (n = 3), complete remission was obtained in one patient, but the other two patients died 12 and 24 months after diagnosis. In contrast, in the PE group (n = 5), complete remission was obtained in all patients who are all currently alive without recurrence, at 35 to 71 months (average, 53.6 mo) after diagnosis. The results indicate that multidisciplinary treatment including combination chemotherapy with cisplatin and etoposide with or without surgery and/or RT is highly effective in the treatment of patients with alpha-fetoprotein-producing intracranial nongerminomatous malignant germ cell tumor.

Adolescent↗
PubMed1995

[Pharmacokinetic study of intraperitoneal cisplatin chemotherapy for gastric cancer as an adjuvant setting].

The pharmacokinetic studies of intraperitoneal cisplatin (CDDP) for gastric cancer were discussed elsewhere, but those studies were investigated in patients with ascites. The purpose of this study is to compare the difference in pharmacokinetics between patients with malignant ascites and those curatively resected without ascites. One hundred mg of CDDP and 300 ml of saline were administered intraperitoneally for 9 curatively resected patients by catheter just after operation, and the same doses of CDDP were administered for 3 advanced or recurrent patients with ascites just after removal of whole fluid. Blood samples were corrected at 6 points after administration. Results were as follows: The 0-t area under the curve (AUC) and the Cmax of both total and free CDDP in the patients without ascites was higher than in the patients with ascites. The 0-infinity AUC and MRT of the ascites patients were higher than in the patients without ascites. These data suggest that intraperitoneal CDDP chemotherapy for gastric cancer as an adjuvant setting is more effective than chemotherapy for advanced malignant ascites patients.

Ascitic Fluid↗
PubMed1994

Sodium benzylideneascorbate induces apoptosis in HIV-replicating U1 cells.

U1 cells, a subclone of U937 cells chronically infected with human immunodeficiency virus type 1 (HIV-1), produced HIV-1 only in the presence of inducers such as 12-O-tetradecanoxylphorbol 13-acetate (TPA) or tumor necrosis factor (TNF)-alpha. The expression of HIV-antigen on U1 cells induced by TPA or TNF-alpha was found to be prevented by sodium 5,6-benzylidene-L-ascorbate (SBA) in a concentration-dependent manner. Treatment of U1 cells with SBA in the presence of inducers resulted in cell death with cell shrinkage, chromatin condensation and DNA fragmentation into nucleosomal oligomers, characteristics of apoptosis. In contrast, SBA had scarcely any apoptotic effect on U1 cells in the absence of inducers. SBA did not also induce apoptosis in parental U937 cells in the presence or absence of inducers. These results suggest that HIV-replicating U1 cells selectively undergo apoptosis on treatment with SBA.

Antiviral Agents↗
PubMed1994

Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs.

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.

Animals↗
PubMed1994

Expression of PDGF, PDGF-receptor, EGF-receptor and sex hormone receptors on meningioma.

The expression of platelet derived growth factors (PDGF), the PDGF-Receptor (R) (alpha and beta types), epidermal growth factor (EGF)-Receptor (R) and sex hormone (oestrogen and progesterone) receptors was studied in 22 meningiomas. All tumours were PDGF-R beta type positive and 21 (95%) were PDGF positive. Only 2 (9%) were PDGF-R alpha type positive, 13 (59%) were EGF-R positive. The expression of these proteins was not related to the histological type or the malignancy of the meningiomas although the expression of PDGF and PDGF-R beta tended to be stronger in malignant meningiomas. Oestrogen and progesterone receptor protein were examined in 19 patients (10 females and 9 males). None of the meningioma cells revealed oestrogen receptor protein while 17 (89%) of the 19 meningiomas were positive for progesterone receptor protein. The expression of progesterone receptor was not related to histological type or malignancy. Our studies suggest that the autocrine system, through PDGF and PDGF-R type beta, may play an important role in the tumourigenicity of meningiomas. EGF-R was present in almost half and progesterone receptor in most of the meningiomas. There was no correlation between the expression of either PDGF, PDGF-R or EGF-R and the expression of progesterone receptor protein.

Adult↗
PubMed1994

[The optimal period for orally administered fluoropyrimidines as an adjuvant chemotherapy for gastric cancer--a pilot study using 5-FU tablets compared with surgical operation alone].

Long-term oral administration of fluoropyrimidines such as 5-fluorouracil (5-FU) or tegafur is commonly used as an adjuvant chemotherapy for gastric cancer, but the optimal period or optimal total doses of fluoropyrimidines have not been studied. Two hundred cases of macroscopical Stage II and III curatively resected gastric cancer patients were entered in this study, and divided into three groups (6 months group: mitomycin C was given i.v. at day 0 and day 1 and 5-FU tablets were orally administered at a dose of 200 mg/day for 6 months. 12 months group: MMC was given the same as for the 6 months group and 5-FU tablets were administered for 12 months. Surgery alone group: No chemotherapy, operation only). As the result, 185 cases were eligible. There was no significant difference between the 6 months group and the 12 months group among Stage II patients. Although there was also no significant difference between the 2 groups in Stage III patients, the survival curve of 12 months group was always higher than in the 6 months group. When comparing with surgery alone group, 5-year survival of the 12 months group was always higher than in the surgery alone group of Stage III patients; however, the survival rate in the 6 months group was worse than in the surgery alone group at Stage II and III. These results suggest that MMC i.v. and 12 months or over administration of 5-FU tablets is useful for Stage III gastric cancer patients, and that cooperative study is required comparing with surgery alone in Stage II patients.

Administration, Oral↗
PubMed1994

[Neurocutaneous melanosis--a case report].

Neurocutaneous melanosis is a rare congenital phacomatosis characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigmented cell tumors of the leptomeninges. A 14-month-old boy was admitted with a recent history of vomiting and drowsiness. He was found to have multiple congenital melanocytic nevi. Gd-enhanced MRI showed ventriculomegaly and leptomeningeal enhancement in the ambient cistern. CSF cytology revealed abnormal cells with pigmented granules. A diagnosis of hydrocephalus with malignant neurocutaneous melanosis was made. The patient was treated with combination chemotherapy (DAV therapy, ACNU intrathecal perfusion therapy, interferon beta therapy) while controlling intracranial pressure by CSF drainage, but in spite of treatment he died due to rapid progression of leptomeningeal infiltration. Postmortem examination revealed meningeal malignant melanomas predominantly at the base of the brain and benign meningeal melanosis over the cerebral cortex. Newborn infants or infants with large or multiple congenital melanocytic nevi should be carefully followed, especially for the first two years. When hydrocephalus or convulsions occur in patients with skin lesions, Cd-enhanced-MRI and careful CSF cytology studies should be performed to detect meningeal abnormalities.

Humans↗
PubMed1993

Benzylideneascorbate induces apoptosis in L929 tumor cells.

Sodium 5,6-benzylideneascorbate (SBA), which is known to be an antitumor substance, was found to induce apoptotic cell death of L929 tumor cells directly in a concentration- and time-dependent manner. The dying cells exhibited cell shrinkage, disappearance of cell surface microvilli, chromatin condensation and DNA fragmentation into nucleosomal oligomers characteristic of apoptosis. These results indicate a possible mechanism by which SBA induces tumor regression in vivo.

Animals↗
PubMed1993

Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosou rea hydrochloride.

We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid dissemination of primary central nervous system tumors. Fifteen patients received ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar perfusion of ACNU alone, and the others underwent concomitant systemic chemotherapy; three of these patients received irradiation as well. ACNU was administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment. During ACNU administration, the lumbar CSF was drained at approximately the same rate as that of the infusion. Twelve patients received from 3 to 42 courses (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg (average, 82.9 mg). One patient had a convulsion; two patients experienced transient headache, nausea, and vomiting; two others reported transient headache, nausea, vomiting, and fecal incontinence; and one experienced transient nausea, vomiting, and fecal incontinence. No side effects were noted in the other nine patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF, was administered for 37 to 52 min, the maximum concentration of ACNU in the lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effect of radiation therapy against intracranial hemangiopericytoma.

Seven cases of intracranial hemangiopericytoma were studied retrospectively to investigate the efficacy of radiation therapy. Tumor response evaluated by computed tomography and magnetic resonance imaging was obvious after 20-30 Gy irradiation. The total reduction rate was 80-90% and continued as long as 5-7 months after treatment. In five patients receiving radiation therapy before radical removal, the tumors were easily removed without massive hemorrhage. Histological inspection of specimens after irradiation showed a significant disappearance of tumor cells. Pyknosis frequently occurred in endothelial cells, and proliferating vessels with hyalinoid degeneration were also seen. Reticulin fibers between tumor cells were fewer, split, or absent. Preoperative radiation therapy is useful in the treatment of hemangiopericytoma involving considerable surgical risk. Postoperative radiation therapy should be given even if removal is complete.

Adolescent↗