[Gonadotropin-secreting pituitary adenoma].
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Adenoma↗
Biomedical subjects
Akira Teramoto
Publications and source records attributed to Akira Teramoto.
[5-ALA fluorescence guided tumor resection].
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Aminolevulinic Acid↗
Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.
Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.
Biomarkers, Tumor↗
Hypoxia inducible factor 1-alpha regulates of platelet derived growth factor-B in human glioblastoma cells.
Hypoxia inducible factors (HIF) are transcription factors regulating expression of several genes related to oxygen homeostasis in response to hypoxic stress. Although HIF1-alpha and platelet derived growth factor-B (PDGF-B) are expressed in glioma tissue and closely related to tumor angiogenesis mediating vascular endothelial growth factor (VEGF) activity, their direct relationship has not yet been clarified. The aim of this study is to investigate whether HIF1-alpha regulates PDGF-B expression. The human glioblastoma cell lines, U87MG, U251MG, and A172, were exposed to 1-21% oxygen for 24 h. PDGF-B mRNA expression were quantitatively analyzed by real time RT-PCR, their intracellular protein levels were determined by computerized image analysis supported by flow cytometry to detect intracellular PDGF-B, and the concentration of secreted PDGF-B protein was assayed by ELIA. We also assayed following transfection of the cells with short interference RNA (siRNA) targeting HIF1-alpha mRNA. Relative PDGF-B mRNA and secretion of PDGF-B protein were significantly elevated at 1% oxygen. Following transfection of HIF1-alpha siRNA at 1% oxygen, PDGF-B expression was significantly suppressed at mRNA level. Our findings indicated that HIF1-alpha up-regulated expression of PDGF-B in human glioblastoma cells and showed the feasibility of siRNA technology in glioblastoma cell lines.
Brain Neoplasms↗
Long-term outcome and reconsideration of intracystic chemotherapy with bleomycin for craniopharyngioma in children.
OBJECT: We first reported postoperative intratumoral chemotherapy with bleomycin for craniopharyngiomas in 1985. However, this local bleomycin chemotherapy has not yet been used very frequently. It seems to be necessary for us to report long-term outcome and reconsideration of this treatment. METHODS AND RESULTS: Local bleomycin chemotherapy was performed on 7 children (to 1985) and 11 children (from 1988 to 2004). A total of 11 pediatric patients with recurrent cystic craniopharyngioma was treated by intracystic injection of bleomycin after 1988 and followed up from 3 to 16 years. After 1985, 1 of 7 children whose clinical outcome was fair underwent intracystic injection of bleomycin again. This patient has never had recurrent tumor until now. The children whose clinical outcomes were excellent have no recurrence during follow-up from 21 to 26 years. After 1988, the results showed that cystic recurrences of 7 children have almost disappeared and the children have achieved a good school life, and 3 children are also achieving a good life after additional stereotactic radiosurgery. CONCLUSION: Our results indicate that local bleomycin chemotherapy is effective and that recurrence does not occur after follow-up, which ranged in duration from 3 to 16 years.
Adolescent↗
Inhibition of cell invasion by indomethacin on glioma cell lines: in vitro study.
Malignant glioma invasion into the surrounding brain tissue is still a major problem for any therapeutical methods. Matrix metalloproteinases (MMPs) have been implicated as important factors in this pathological process. In this study, one of the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin was employed to investigate the effect of inhibition of cell invasion mediated by MMP-2 and MMP-9 in human malignant glioma cell lines, A172, U87MG, U251MG, and U373MG in vitro. MTT assay was firstly examined to determine non-cytotoxic dose range, then gelatin zymography, matrigel invasion assay, migration assay and MMP-2 activity assay for 24 h exposure in indomethacin were employed to assess the inhibitory effect of indomethacin. MTT assay revealed that dose with 0, 50, and 500 microM/ml were non-cytotoxic. Zymography demonstrated: (a) expression of MMP-2 and MMP-9 activity was downregulated along with elevated dose of indomethacin. (b) MMP-2 activity that changed from pro-MMP-2 to active form of MMP-2 in supernatants of cell lines could not be inhibited by indomethacin. Invasion assay disclosed that the number of invading cells through the matrigel were significantly decreased in a dose dependent manner. Migration assay indicated indomethacin did not affect cells migration. MMP-2 activity assay showed the total and active MMP-2 secretion was suppressed by 500 microM/ml of indomethacin. Our present study is the first report on inhibitive effect of indomethacin mediated by MMP-2 and MMP-9 in invasion assay of glioma cell lines. The current study suggested that non-cytotoxic level of indomethacin was able to reduce the cell invasion of malignant gliomas mediated by MMP-2 and MMP-9, but it did not affected on cell motility. It also lowered down the activity of MMP-2 and MMP-9, and could reduce of MMP-2 secretion of cell lines. Thus, high concentration of indomethacin within non-cytotoxic dose might offer a new therapeutic strategy to impair cell invasion of gliomas.
Anti-Inflammatory Agents, Non-Steroidal↗
Double-platinum chemotherapy combined with etoposide in metastatic brain tumor from small cell lung carcinoma.
The platinum-based chemotherapeutic agents, such as cisplatin (CDDP) and carboplatin (CBDCA), are effective for small cell lung carcinoma (SCLC). However, high dose treatment of these agents required for advanced-stage SCLC is often associated with severe toxicity. The authors used combination of lower doses of both cisplatin and carboplatin combined with etoposide (VP-16) to minimize side effects of these agents. This goal was accomplished by utilizing the facts that each agent has its own toxicity that can be controlled individually. Two patients (60- and 71-year old men) with multiple metastatic brain tumors from SCLC were treated by our chemotherapeutic regimen. After fourth chemotherapy, remarkable shrinking of brain masses was associated with significant decrease the size of original lung lesions in both cases. The two patients were discharged without any side effects of the treatment, and neurological deficits subsided in both cases. Each course provided the following schedules: carboplatin 200 mg/m2 x 1 day, cisplatin 25 mg/m2 x 2 days (intravenous administration), and etoposide 25 mg oral x 14 days. After second chemotherapy, the patient of Case 1 was irradiated to both brain and chest lesions, and only to brain in Case 2. The authors concluded from our two cases that the combination of these agents extremely effective to treat this malignancy with less toxicity. We named this double platinum chemotherapy as 'PEC', abbreviated from cisplatin, etoposide, and carboplatin. m
Antineoplastic Agents↗
Prognostic significance of the immunohistochemical index of survivin in glioma: a comparative study with the MIB-1 index.
OBJECTIVE: Survivin has been identified as a protein expressed in cancer cells and a member of the inhibitor-of-apoptosis protein family. Recent studies suggest that the expression of survivin increases during the G2/M phase of the cell cycle, and may be used in clinical prognosis. We examined whether survivin expression in human gliomas would be a correlative of prognosis. METHODS: We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4. RESULTS: On staining with the anti-survivin antiserum, all specimens contained positive cells, but the survivin index was heterogeneous among grades. The mean percentage of immunoreactive cells in each specimen was 70.0 (SD 18.2) in grade II, 81.3 (16.5) in grade III, and 85.0 (13.6) in grade IV. Then we compared the survivin index to the MIB-1 index and found that in low-grade gliomas (grade II and III), the difference in survival times between the high and low survivin indexes was significant (P=0.007), whereas that between the high and low MIB-1 indexes was not significant (P=0.092). ONCLUSION: Survivin is more sensitive marker than MIB-1 for the evaluation of low-grade gliomas in that it helps to predict patient survival. Much larger glioma patient series are needed to validate the findings of our limited study.
Adult↗
Expression of cathepsin B and microvascular density increases with higher grade of astrocytomas.
Samples were taken from supratentorial gliomas border and normal brain autopsy which were divided into four groups, these including eight cases normal brain tissues, 30 cases of astrocytomas, 25 cases of anaplastic astrocytomas and 22 cases of glioblastomas. Cathepin B (CB) expression and microvessel density (MVD) were determined with immunohistochemical studies. Staining results of CB was scored according to the percentage of positive cells, graded as negative (-), weak (+), moderate (++), and strong (+ + +). MVD was analyzed by Weidner's revised technique. CB positive staining was negative in eight cases of normal brain tissue. Only 9 out of 30 cases of astrocytomas showed a low percentage of positive cells that were stained in a light, diffuse cytoplasmic pattern (score +). Twenty-two out of 35 cases of anaplastic astrocytomas showed positive light, granular staining pattern, it including five samples (score +), and 17 samples (score + +). In contrast, all 22 cases of glioblastomas were stained all, and it was present in a course, granular staining pattern with an intensity of score (+ +) of two sample, and score (+ + +) of 20 samples. Positive staining tumor cells were found in extracellular matrix (ECM), basement membrane (BM), and the endothelial cells of blood vessels were also positive stained. Along with elevating glioma grade, CB expression and MVD value were both increased. Therefore, it showed MVD value was positive correlated with expression of CB. It highly suggested that CB and angiogenesis plays an important role in glioma progression.
Adolescent↗
The response of normal human osteoblasts to anionic polysaccharide polyelectrolyte complexes.
Polyelectrolyte complexes (PEC) were prepared from chitosan as the polycation and several synthesized functional anion polysaccharides, and their effects on cell attachment, morphology, proliferation and differentiation were estimated using normal human osteoblasts (NHOst). After a 1-week incubation, PEC made from polysaccharides having carboxyl groups as polyanions showed low viability of NHOst on it although the NHOst on it showed an enhancement in their differentiation level. On the other hand, NHOst on PEC made from sulfated or phosphated polysaccharides showed similar attachment and morphology to those on the collagen-coated dish. When the number of NHOst was estimated after 1 week, the number on the PEC was ranged from 70% to 130% of those on the collagen-coated dish, indicating few effects of these PEC on cell proliferation. In addition, NHOst on PEC films made from sulfated polysaccharides differentiated to a level very similar to that observed on the collagen-coated dish, indicating that these PEC films maintain the normal potential of NHOst to both proliferate and differentiate. Measurement of gap junctional intercellular communication of NHOst on PEC revealed that PEC did not inhibit communication, suggesting that PEC films have few effects on cell homeostasis. Thus, PEC made from the sulfated polysaccharide may be a useful material as a new scaffold for bone regeneration.
Alkaline Phosphatase↗
Method for measuring sinus and vein pressure during surgery: technical note.
BACKGROUND: Measurement of dural sinus or drainage vein pressure is useful for determining the appropriate treatment for some patients. We report a novel measurement procedure that reduces bleeding from the needle puncture site as well as further tearing of the wall. METHODS: The vessel is punctured through the patch by gelatin sponge with fibrin sealant and a siliconized elastic needle is introduced. After obtaining the desired measurements, the needle is withdrawn through the fibrin sealant-bearing patch whose presence facilitates sealing of the puncture site. To further decrease the incidence of complications due to incomplete hemostasis, an additional identically prepared path is placed over the site. RESULTS: We have used this method in several operations and have encountered no complications. Our method also makes it possible to safely approach the drainers of pial arteriovenous malformations. CONCLUSIONS: Our method is easy and convenient and prevents the leakage of blood from the puncture site and further tearing of the venous wall.
Cerebral Veins↗
The long-term effects of transluminal balloon angioplasty for vasospasms after subarachnoid hemorrhage: analyses of cerebral blood flow and reactivity.
BACKGROUND: Transluminal balloon angioplasty (TBA) has come into wide use for management of symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). The long-term effects of TBA in this clinical context on cerebral blood flow (CBF) and the functional properties of the arterial wall after aneurysmal SAH remain controversial. We therefore studied these effects. METHODS: All patients underwent unilateral TBA. Xenon-enhanced computed tomography was performed for an average of 18 days after TBA to measure CBF and cerebrovascular reactivity (CVR). Cerebral blood flow and CVR were compared between the side of TBA and the contralateral side. RESULTS: Nineteen vascular territories were treated successfully with TBA in 12 patients. Angiographic improvement of vasospasm was demonstrated in all 12 patients, and 9 (75%) patients showed neurological improvement. After balloon angioplasty, global CBF was 35.1 +/- 8.2 mL/100 g per minute, with CBF on the side with TBA (37.8 +/- 10.3 mL/100 g per minute) being essentially the same as that on the other side (P = .0671, paired Student t test). Likewise, reactivity to acetazolamide did not differ significantly between sides (P = .0817). CONCLUSION: Transluminal balloon angioplasty increased proximal vessel diameters but showed no significant influence on CBF or vascular reactivity 3 weeks later. Benefits presumably were short term, but the procedure was clinically safe.
Adult↗
Anomalous internal carotid anastomosis to contralateral anterior cerebral artery.
BACKGROUND: Many anomalies and variants in vascular anatomy have been reported in relation to the anterior cerebral artery (ACA). PATIENTS AND METHODS: We encountered an apparently novel anomaly in a 30-year-old man admitted for disturbance of consciousness following a traffic accident. Computed tomography revealed an acute subdural hematoma and subarachnoid hemorrhage. RESULTS AND CONCLUSIONS: No vascular abnormalities related to the hemorrhage were detected by conventional angiography, so we concluded that the bleeding was of traumatic origin. Anomalous origin of the ACA was disclosed incidentally, with both A1 segments arising from the right internal carotid artery; no normal A1 segment of the left ACA was visualized. We discuss possible bases for this anomalous origin.
Accidents, Traffic↗
Management of pituitary incidentalomas: according to a survey of pituitary incidentalomas in Japan.
The development of computed tomography (CT) and magnetic resonance imaging (MRI) has resulted in the discovery of unsuspected endocrinologically silent pituitary masses (pituitary incidentalomas). The aim of this study was to clarify the natural history of pituitary incidentalomas in order to establish an appropriate approach to them. Five hundred fifty patients with pituitary incidentalomas were analyzed in this study; 261 patients (47.4%) underwent surgery (surgical group; SG), whereas 289 patients (52.6%) were followed up conservatively (nonsurgical group; NSG) for a mean period of 27.3 months (range, 6-173 months). Clinical and biochemical assessment, CT or MRI of the pituitary, and visual field testing were assessed at baseline and at 6 months and yearly thereafter. A total of 261 tumors in the SG group consisted of 211 (80.8%) nonfunctioning pituitary adenomas and 42 (16.1%) Rathke's cysts. During a follow-up period, of 289 tumors in the NSG group, 209 (72.3%) tumors stayed the same size as before, 35 tumors (12.1 %) increased in size, and 41 tumors (14.2%) decreased in size. The estimated diagnoses of the tumors that increased consist of 28 nonfunctioning pituitary adenomas, 5 Rathke's cyst, and 2 others. The decreased tumors consist of 11 nonfunctioning adenomas, 21 Rathke's cysts, and 3 others. Pituitary incidentalomas usually follow a benign course. We recommend transsphenoidal adenomectomy for a solid mass attached to the optic chiasma estimated to be a pituitary adenoma by MRI. Other patients should be followed up by MRI and biochemical assessment. Especially asymptomatic cystic masses (including Rathke's cleft cysts) could be followed up without surgical intervention because they tend to stay the same size or sometimes be cured spontaneously.
Adenoma↗
Growth hormone enhances natural killer cell activity against glioma.
Although it is now known that pituitary hormones activate the immune system, there are still numerous questions to be answered with regard to the mechanisms involved. In this study, which focuses on growth hormone (GH) and natural killer (NK) cells, the latter's antitumor effects on glioma were investigated. Using fluorescein isothiocyanate-labeled rat 9L glioma and NK-receptive YAC-1 cells as target cells and rat splenocytes as effector cells, a cytotoxicity assay was carried out with the fluorescence-activated cell sorter method, which stains dead cells with propidium iodide. The effector cells were pretreated 48 hours in advance with various concentrations of GH. A similar experiment was also carried out in the presence of anti-asialo-GM1 antibodies. When the GH concentration of 9L was 10 to 40 microg/ml, cytotoxicity was confirmed to have been enhanced 17% to 39%. This enhancement disappeared in the presence of anti-asialo-GM1 antibodies. A similar increase in cytotoxic activity was also confirmed in YAC-1 cells. In this experiment we observed GH enhancement of natural killer activity against glioma.
Animals↗
Recent progress in studies of pituitary tumor pathogenesis.
The mechanisms of tumorigenesis of the human pituitary have been elucidated to a limited extent. Classically, pituitary tumor formation was shown to be induced by thyroidectomy and estrogen administration. Molecular biological and immunohistochemical studies have revealed several aspects of pituitary tumorigenesis. Translineage cell differentiation has been shown to be induced by the aberrant expression of transcription factors and co-factors, such as Pit-1, Prop-1, and estrogen receptor. Defects or overexpression of cell cycle regulators, such as CDK inhibitors, PTTG, and GADD45gamma, result in the abnormal proliferation of pituitary cells. Recently, epigenetic regulation has been suggested to be related to pituitary tumor formation. This article presents a review and update of recent progress in studies of the development and differentiation of pituitary tumors.
Adenoma↗
Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in pituitary adenomas.
Hypoxia-inducible factor (HIF)-1alpha is a transcription factor in hypoxia adaptation mechanisms. In malignant tumors, HIF-1alpha upregulates vascular endothelial growth factor (VEGF) expression to induce tumor angiogenesis. Although VEGF and HIF-1alpha are expressed in pituitary adenomas, the relationships of these factors remain unclear. Therefore, we examined the expression of HIF-1alpha and VEGF using real-time RT-PCR and immunohistochemistry to clarify the relationship of these factors in pituitary adenomas. HIF-1alpha mRNA and VEGF mRNA levels in pituitary adenoma tissues from 25 operated patients were quantified using real-time RT-PCR. Some tissues were also studied by double fluorescent immunohistochemical methods. HIF-1alpha mRNA and protein were expressed in all pituitary adenomas examined. Their expression tended to be higher in GH-producing and lower in ACTH-producing tumors. VEGF mRNA and protein were also expressed in all pituitary adenomas. There was no significant correlation in the expression levels of HIF-1alpha and VEGF mRNA. The mutual expression of HIF-1alpha and VEGF was of no significance; in only a few cells were HIF-1alpha and VEGF co-localized. Our results suggest that in pituitary adenomas VEGF expression may not depend strongly on HIF-1alpha expression.
Adenoma↗
Expression of hypoxia-inducible factor 1alpha and cathepsin D in pituitary adenomas.
Hypoxia-inducible factor (HIF)-1alpha is a crucial transcription factor involved in the adaptive response to hypoxia, whereas cathepsin D, which regulates angiostatin in several cancer cell lines, has been reported to be upregulated by HIF-1alpha. In order to determine the involvement of angiogenesis in pituitary adenomas, we studied the expression of both HIF-1alpha and cathepsin D in tissues from 58 patients (39 women, 19 men, ranging in age from 20 to 78 yr), sorted by histological group, and assayed by double immunohistochemistry. HIF-1alpha immunoreactivity, confined to the nucleoplasm, was present in both tumor and vascular endothelial cells. There was no difference in microvascular density (p = 0.7761) by histotype. ACTH-producing adenomas showed the lowest level of HIF-1alpha, whereas prolactin (PRL)-producing adenomas and HIF-1alpha-positive microvessels showed the highest (p < 0.001). In contrast, the lowest expression of cathepsin D was observed in PRL-producing adenomas, whereas the highest expression was detected in ACTH-producing adenomas (p < 0.0001). Imaging analysis with fluorescence double immunohistochemistry showed that HIF-1alpha-negative tumor cells did not express significantly higher levels of cathepsin D. In these poorly vascularized tumors, the hypoxic marker HIF-1alpha may not downregulate cathepsin D. The mechanisms of tumor angiogenesis and cell invasion in pituitary adenomas may differ from those in other tumor cells.
Adenoma↗