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Biomedical subjects

Keishi Makino

Publications and source records attributed to Keishi Makino.

15 recordsLinked to original sources

A long-term ventricular drainage for patients with germ cell tumors or medulloblastoma.

BACKGROUND: Hydrocephalus associated with intracranial germ cell tumors or disseminated medulloblastoma has been treated with ventriculoperitoneal shunt. However, this procedure has a potential risk of intraperitoneal metastasis of these brain tumors. To prevent this potential risk and to minimize the risk of infection, we developed a percutaneous long-tunneled ventricular drainage (PLTVD). To confirm the effectiveness, we retrospectively analyzed the results of this procedure. METHODS: From 1979 to 2003, we have treated 96 patients with germ cell tumors and medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31; medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal fluid drainage to manage the obstructive hydrocephalus due to persistent tumor or communicating hydrocephalus due to dissemination. We performed PLTVD for these cases using a flow-controlled shunt device and percutaneous long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen and connecting to a closed drainage system. The occurrence of extraneural metastasis and the incidence of infection were evaluated. RESULTS: The average duration of drainage was 74 days (range, 34-115 days). All 13 cases received full-dose chemotherapy and radiotherapy without infectious complications or extraneural metastasis. CONCLUSIONS: Percutaneous long-tunneled ventricular drainage was an effective method to manage long-lasting obstructive or communicating hydrocephalus with germ cell tumors and medulloblastoma.

Adolescent↗

Rising incidence of primary central nervous system lymphoma in Kumamoto, Japan.

BACKGROUND: Primary central nervous system lymphoma is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL is reportedly on the increase in some parts of the world in the last 2 decades. METHODS: We surveyed 4007 patients diagnosed with PIT between 1989 and 2004, with histologic diagnosis being obtained in 70% of the patients. Of these, the PCNSL cases were reviewed. RESULTS: Of 4007, 136 (3.4%) carried a diagnosis of PCNSL. At 0.41 per 100,000 per year, the age-adjusted incidence rate for that period was higher than that for the period from 1989 to 1998 (0.29 per 100,000 per year). Moreover, the number of patients with PCNSL doubled from 45 (1989-1996) to 91 (1997-2004). CONCLUSIONS: Our findings point to an increase in the incidence of PCNSL among immunocompetent individuals in Kumamoto Prefecture.

Age Distribution↗

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Adolescent↗

Third ventricular ependymal cyst presenting with acute hydrocephalus.

Ependymal cysts are generally located in the cerebral parenchyma but rarely found in the third ventricle. A 4-year-old boy presented with headache, vomiting, and upward gaze palsy. His consciousness gradually deteriorated in the course of 6 h. A magnetic resonance imaging study disclosed dilation of the lateral ventricle and a cystic mass in the third ventricle. We performed an endoscopic resection of the cyst wall. The cyst originated on the lateral wall of the third ventricle and obstructed the aqueduct. Histological examination confirmed a diagnosis of ependymal cyst. The patient recovered quickly and his headache and nausea disappeared. Third ventricular ependymal cysts are a rare cause of acute hydrocephalus but an important differential diagnosis. Their neuroendoscopic resection can resolve disturbances in cerebrospinal fluid circulation, is useful for cyst wall removal, and appears to be superior to shunt placement.

Acute Disease↗

C-kit expression in germinoma: an immunohistochemistry-based study.

In our immunohistochemical study of 25 human primary intracranial germinomas and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the same sections for c-kit and placental alkaline phosphatase (PLAP). Immunohistochemical expression was graded using a semi-quantitative scoring system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3 cases negative for PLAP-staining were strongly positive and all embryonal carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in cerebral spinal fluid of patients with germinomas and germinomas with STGC. C-kit and s-kit may be powerful tumor markers for germinomas with or without STGC.

Adolescent↗

Comparative clinical study of the anti-emetic effects of oral ramosetron and injected granisetron in patients with malignant glioma undergoing ACNU chemotherapy.

The effectiveness of ramosetron tablets and granisetron injection was compared for reducing the frequency of nausea, vomiting, and anorexia in patients with malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to be treated with ACNU chemotherapy were randomly assigned to receive oral ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU injection. Gastrointestinal toxicity within 48 hours of ACNU injection was compared to that in patients who had received ACNU chemotherapy with dopamine D2 receptor-blocker as a historical control group. Within 24 hours of the administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of the latter regained their normal appetite. There was no significant difference in the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6 hours of the injection of ACNU, five were nausea-free within 24 hours, and two retained their normal appetite within 24 hours. Oral ramosetron has the same anti-anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets are less expensive and are easy to take, so should be on the list of first-choice anti-emetic drugs for patients treated with ACNU chemotherapy.

Adult↗

Effect of oral colestimide on the elimination of high-dose methotrexate in patients with primary central nervous system lymphoma--case report.

Delayed methotrexate (MTX) elimination occurred in two patients with primary central nervous system lymphoma undergoing high-dose MTX treatment. Oral administration of the anion exchange resin colestimide, which binds MTX effectively in vitro, effectively accelerated MTX elimination. Colestimide probably interrupts the enterohepatic circulation, and is a potential oral antidote to MTX toxicity.

Administration, Oral↗

Upregulation of IKKalpha/IKKbeta by integrin-linked kinase is required for HER2/neu-induced NF-kappaB antiapoptotic pathway.

Constitutively active HER2/neu activates nuclear factor kappa-B (NF-kappaB) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor-alpha (TNF-alpha). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediated activation of NF-kappaB. Expression of HER2/neu increases ILK activity. Blocking ILK activity with a kinase-deficient mutant ILK (ILK-KD) inhibits NF-kappaB activation and sensitizes HER2/neu-transformed cells to TNF-alpha-induced apoptosis. Stable expression of ILK-KD in HER2/neu-transformed cells suppressed Akt phosphorylation and the expression of IkappaB kinase alpha and beta (IKKalpha and beta) at both the protein and mRNA levels, preventing IkappaB-alpha degradation and NF-kappaB activation. Furthermore, HER2/neu stimulated the transcriptional activity of the putative IKKbeta promoter through ILK and Akt. Our results demonstrate that upregulation of IKKalpha and IKKbeta by the ILK/Akt pathway is required for the HER2/neu-mediated NF-kappaB antiapoptotic pathway.

Animals↗

The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme.

OBJECT: Glioblastoma multiforme (GBM) remains incurable by conventional treatments, although some patients experience long-term survival. A younger age, a higher Karnofsky Performance Scale (KPS) score, more aggressive treatment, and long progression-free intervals have been reported to be positively associated with long-term postoperative patient survival. The aim of this retrospective study was the identification of additional favorable prognostic factors affecting long-term survival in surgically treated adult patients with supratentorial GBM. METHODS: Of 113 adult patients newly diagnosed with histologically verified supratentorial GBM who were enrolled in Phase III trials during the period between 1987 and 1998, six (5.3%) who survived for longer than 5 years were defined as long-term survivors, whereas the remaining 107 patients served as controls. All six were women and were compared with the controls; they were younger (mean age 44.2 years, range 31-60 years), and their preoperative KPS scores were higher (mean 85, range 60-100). Four of the six patients underwent gross-total resection. In five patients (83.3%) the progression-free interval was longer than 5 years and in three a histopathological diagnosis of giant cell GBM was made. This diagnosis was not made in the other 107 patients. CONCLUSIONS: Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

Adolescent↗

Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.

Adolescent↗

The adenoviral E1A induces p21WAF1/CIP1 expression in cancer cells.

The adenovirus-5 E1A gene encodes two main proteins of 289 and 243 amino acid residues from 13S and 12S mRNA, respectively. The E1A gene products function as transcriptional regulators and have anti-tumor activities. Despite the fact that E1A gene therapy has been tested in clinical trials, the molecular mechanism by which it suppresses tumor cell growth is still not completely understood. Here, we show that E1A increases the expression of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1), which inhibits cell growth. We further show that 13S E1A, but not 12S E1A, can transactivate the p21 promoter through Sp1 sites. Interestingly, the E1A-induced transactivation occurs only in cancer cells, not in normal cells. This study provides new insight into the links between E1A and the CDK inhibitor and may have important clinical implications.

Adenovirus E1A Proteins↗

Influence of p53 mutations on prognosis of patients with glioblastoma.

BACKGROUND: The influence of p53 mutations on the biology of astrocytic tumors is controversial. p53 is thought to be inactivated in the early stage of gliomagenesis; however, what role its inactivation plays in the malignancy of gliomas remains unknown. To understand the significance of p53 inactivation, the authors identified the locus of p53 gene mutation in glioma samples at different stages of progression and studied the correlation between the mutation and clinical behavior. METHODS: Samples from newly diagnosed gliomas, including pure and mixed astrocytomas, were analyzed for p53 mutations using a yeast functional assay. To determine the locus of the gene mutations, DNA sequencing was performed. RESULTS: The incidence of p53 mutations was higher in anaplastic astrocytomas (AA, 48%) than glioblastomas (GBM, 31%). There was no significant difference in the average ages of GBM patients with and without p53 mutations (54.9 years +/- 2.3 and 53.2 years +/- 4.6, respectively). In GBM patients, the mutation did not affect progression free survival or overall survival. Astrocytomas and GBM differed in the distribution of p53 mutation loci. CONCLUSIONS: The p53 gene mutation does not markedly affect the survival of GBM patients. The difference in the location of p53 mutations between AA and GBM suggests that in gliomas, the p53 mutation may contribute not only to tumorigenesis (as an early event) but also to progression to malignancy (as a late event).

Adolescent↗

[A case of juvenile cerebral infarction caused by bilateral anterior cerebral artery dissection].

A 38-year-old man was admitted to our hospital with headache, dysarthria and paraparesis. Brain CT and diffusion MRI disclosed cerebral infarction at bilateral anterior cerebral artery (ACA) territories. His symptoms and signs deteriorated in several days despite intensive antithrombotic therapy, resulting in right hemiparesis, akinetic mutism, memory disturbance, change of personality, urinary incontinence, forced grasping, and starting delay of speech and motion. Cerebral angiography demonstrated occlusion with contrast pooling at the right ACA A2 portion. Stenosis and dilatation were found at left ACA A2 portion. An intimal flap was also demonstrated on serial angiography. This case was diagnosed as cerebral infarction caused by dissection of bilateral ACA. Although no definite primary arteriopathy was demonstrated, bilateral dissection could be occurred simultaneously.

Adult↗

Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence.

BACKGROUND AND PURPOSE: Differentiation between tumor recurrence and treatment-related brain injury is often difficult with conventional MRI. We hypothesized that the diffusion-weighted imaging (DWI) could help differentiate these 2 conditions, because water diffusion may be greater for necrotic tissues in the treatment-related brain injury than for tumor tissues in recurrence. Our aim was to analyze whether DWI findings of recurrent tumor are distinct from those of radiation necrosis. METHODS: Seventeen patients were examined prospectively. Two readers assessed the images by consensus for homogeneity and signal intensity of the lesions. Five regions of interest were drawn within the lesions on trace DWI images and apparent diffusion coefficient (ADC) maps. The minimal, maximal, and mean values of each lesion were compared between the 2 groups. Findings in 12 of 17 patients were verified histologically by surgery or biopsy; the diagnoses in the remaining 5 patients were made on the basis of follow-up MRI findings and clinical follow-up. RESULTS: There were a total of 20 lesions; 12 lesions were due to radiation necrosis and 8 lesions to tumor recurrence. In the radiation necrosis group, 8 lesions had marked hypointensity. In the recurrence group, however, no marked hypointensity was seen. The maximal ADC values within each lesion were significantly smaller for the recurrence group than for the necrosis group (P = .039). CONCLUSION: Radiation necrosis usually showed heterogeneity on DWI images and often included spotty, marked hypointensity. Significant difference was found in the maximal ADC values between radiation necrosis and tumor recurrence. DWI was useful in differentiating recurrent neoplasm from radiation necrosis.

Adult↗