Katsuzo Kunishio

Matrix metalloproteinase-2 and -9 expression in astrocytic tumors.

In this study, we investigated whether the expression of matrix metalloproteinase (MMP)-2 and MMP-9 correlated with invasiveness, proliferative potential, or prognosis in astrocytic tumors. Thirty-seven astrocytic tumors (8 diffuse astrocytomas, 15 anaplastic astrocytomas, and 14 glioblastomas) and three gliomatosis cerebri were investigated immunohistochemically. The invasive glioma group included three cases of gliomatosis cerebri and two of glioblastoma associated with cerebrospinal fluid dissemination. The expression of MMP-2 and MMP-9 was evaluated by assigning an immunohistochemical (IHC) score defined as the sum of expression frequency and intensity. mRNA expression patterns for the MMPs were also evaluated in a reverse transcription-polymerase chain reaction assay. Neither the MMP-2 nor MMP-9 IHC score was related to histological malignancy. The MMP-2 IHC score of the invasive glioma group was significantly higher than those of other kinds of astrocytic tumors. However, the MMP-9 IHC score did not correlate with dissemination among astrocytic tumors. An inverse correlation was observed between the MIB-1 labeling index and the IHC scores of MMP-2, but it was not significant. A Kaplan-Meyer survival analysis revealed no significant relationship between the survival rate and MMP-2 or MMP-9 expression. Our study showed that MMP-2 expression, but not MMP-9 expression, may be associated with invasion in astrocytic tumors.

Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expressions Correlate with the Recurrence of Intracranial Meningiomas

AbstractBackground: We studied whether or not the expressions of MMP-2 and MMP-9 were correlated with the proliferative potential or recurrence of intracranial meningiomas. Methods: The expressions of MMP-2 and MMP-9 of 56 meningioma tissues were examined and scored by immunohistochemistry (IHC). Expressions of the mRNA of each MMP were also examined by reverse transcriptase polymerase chain reaction (RT-PCR) assay in 15 cases. The relationships between IHC score and each of age, sex, tumor location, histology, MIB-1 labeling index (LI), and recurrence or regrowth rate were studied. Results: Nine of 56 cases showed recurrence or regrowth. IHC revealed that MMP-2 was highly expressed in 13 of 56 cases, whereas MMP-9 was highly expressed in 22 of 56 cases. Among the 15 cases analyzed by RT-PCR assay, MMP-2 and MMP-9 were expressed in 9 and 13 cases, respectively. Based on the Kaplan–Meier curve, the high expressions of MMPs were related to recurrence/regrowth (MMP-2: p < 0.001; MMP-9: p < 0.05). No significant relationship was observed between the expressions of MMPs and either age, sex, tumor location, or MIB-1 LI. Conclusions: Our study indicated that MMP-2 and MMP-9 expressions are prognostic factors predicting the recurrence of meningioma, independent of proliferative potential.

Agenesis of the left internal carotid artery, common carotid artery, and main trunk of the external carotid artery associated with multiple cerebral aneurysms

A case of agenesis of the left internal carotid artery, common carotid artery, and the main trunk of the external carotid artery with multiple cerebral aneurysms is presented. This case was diagnosed by angiography and computed tomography scanning and confirmed by operation. Correlation between the anomaly of the circle of Willis based on the absence of the internal carotid artery and the development of cerebral aneurysm is discussed on the basis of the reported cases.

Histopathologic investigation of a case of meningioangiomatosis not associated with von Recklinghausen's disease

A case of meningioangiomatosis not associated with von Recklinghausens disease is reported. Microscopically, irregularly branched blood vessels extending into the gray matter from the meningeal surface are surrounded by a concentric arrangement of proliferating spindle-formed cells. Ultrastructurally these proliferating cells are composed of elongated heterochromatin-rich nuclei and slender cytoplasm-containing microfilaments, occasionally associated with desmosomal junctions and basal laminalike structures. Judging from these findings, together with a negative immune reaction for S-100 protein, the histogenesis of these proliferating cells is most probably meningothelial in origin.

Matrix metalloproteinase-2 expression correlates with cavernous sinus invasion in pituitary adenomas

UNLABELLED The aim of this study was to evaluate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and cavernous sinus invasion in pituitary adenoma. METHOD Tissue samples from 54 pituitary adenomas were examined for expression of MMP-2 protein by immunohistochemistry. In sixteen tumors, the expression of MMP-2 mRNA was also examined by RT-PCR. Immunostaining was semiquantatively scored based on intensity (0-3) and distribution (0-3). RESULTS There were 34 women and 20 men, with a mean age of 49.9 years (range 18-76). There were 12 tumors with cavernous sinus invasion, and 42 noninvasive cases. The MMP-2 score of pituitary adenomas with cavernous sinus invasion (3.9 +/- 0.5) was significantly higher than those without invasion (2.3 +/- 0.2; P < 0.01). There was no difference in MMP-2 score between macroadenomas (3.0 +/- 0.3) and microadenomas (2.1 +/- 0.4; P > 0.05), and also, no difference between the functioning adenomas (2.8 +/- 0.3) and non-functioning adenomas (2.8 +/- 0.3; P > 0.05). We found no correlation between the MMP-2 score and the Ki-67 labeling index (r2 = -0.05; P = 0.72). MMP-2 mRNA expression was also intense in invasive pituitary adenomas and was significantly higher in invasive pituitary adenomas than those without invasion (68.2 +/- 15.3; 21.8 +/- 8.2; P < 0.05). CONCLUSION This study suggests that MMP-2 may be associated with aggressiveness and invasion in pituitary adenoma but is not related to tumor size or secretory function. MMP-2 may be a useful tool for assessing the invasive potential.

The efficacy and safety of transvenous embolisation in the treatment of intracranial dural arteriovenuous fistulas

Abstract To evaluate the role of transvenous embolisation including its efficacy and safety in the treatment of intracranial dural arteriovenous fistulas (DAVFs), we retrospectively analysed seven cases of intracranial DAVFs treated with transvenous embolisation in combination with arterial embolisation. Four DAVFs were in the cavernous sinus, two in the transverse-sigmoid sinus, and one in the inferior petrosal sinus. The transarterial and transvenous embolic agents included fibred platinum coils (FPC) and int erlocking detachable coils (IDC). In all patients, the transaterial embolisation alone had failed to cure the DAVFs. After the combined transvenous embolisation, the anatomical cure was proven in five patients, and all patients were clinically cured. The re were no complications in any patient. In conclusion, the transvenous embolisation is a useful and safe approach in the management of intracranial DAVFs.

Craniopharyngioma in the third ventricle: necropsy findings and histogenesis.

A case of craniopharyngioma confined within the third ventricle with necropsy is reported. A stalk-like structure in this tumour was present in the wall of the third ventricle at its base. It is suggested that this tumour might have arisen from the remnants of Rathkes pouch persisting in the tuber cinereum.

Technetium-99m Sestamibi Single Photon Emission Computed Tomography Findings Correlated With P-glycoprotein Expression, Encoded by the Multidrug Resistance Gene-1 Messenger Ribonucleic Acid, in Intracranial Meningiomas

The present study evaluated whether technetium-99m sestamibi (99mTc-MIBI) single photon emission computed tomography (SPECT) characteristics of intracranial meningioma are correlated with the histological malignancy, proliferative potential, and P-glycoprotein (Pgp) expression, encoded by the multidrug resistance gene-1 (MDR-1) messenger ribonucleic acid (mRNA). Twenty-one patients with intracranial meningiomas, including 17 benign and four nonbenign meningiomas, underwent 99mTc-MIBI SPECT imaging at 15 minutes (early) and 3 hours (delayed) after injection. The tumor-to-normal pituitary gland ratio was calculated on both early (ER) and delayed (DR) images. Retention index (RI) was calculated using the following formula: (DR - ER)/ER x 100%. Meningioma specimens were examined by immunohistochemistry using anti-Pgp and MIB-1 monoclonal antibody. MDR-1 mRNA expression was also investigated using reverse transcription-polymerase chain reaction assay. 99mTc-MIBI was highly accumulated and retained in the tumors. 99mTc-MIBI SPECT findings were not related to MIB-1 labeling index. 99mTc-MIBI SPECT RI of the Pgp-positive group (-9.12 +/- 22.27%) was significantly lower than that of the Pgp-negative group (28.79 +/- 22.80%) (p = 0.0016). No significant difference was seen in ER and DR between the positive and negative groups. These results show that 99mTc-MIBI may not be useful for determining proliferative potential and histological malignancy, but could predict anticancer drug resistance related to the expression of MDR-1 mRNA and its gene product Pgp in patients with intracranial meningiomas.

Incidence of Mutation and Deletion in Topoisomerase IIα mRNA of Etoposide and mAMSA–resistant Cell Lines

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to VP–16 (etoposide) or mAMSA (m–amsacrine). Subsequently, a population of cells from each subline was exposed to three–fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Finally, 66 sublines were picked up. The frequency and nature of mutations in the topoisomerase II gene in the drug–selected cell lines were evaluated. In order to screen a large number of cell lines, an RNAse protection assay was developed and mismatches were observed in 13.6% of resistant cell lines (12% of resistant cell lines exposed to lower drug concentrations and 18.8% of resistant cell lines exposed to higher drug concentrations). Some of these mutations are located in vital regions of topoisomerase II (phosphorylation sites in the C–terminal or N–terminal, and nuclear localizing signal of topoisomerase II). Our findings suggest that mutations of topoisomerase II gene are an important and frequent mechanism of resistance to topoisomerase II inhibitors.

Expression of Drug Resistance Genes in VP-16 and mAMSA-selected Human Carcinoma Cells

The cell lines described in the present study were isolated as part of an effort to understand resistance to topoisomerase (topo) II inhibitors. To that end, 50 sublines were isolated from four human breast cancer cell lines, i.e., MCF‐7, T47D, MDA‐MB‐231, and ZR‐75B. As an initial step, a concentration that would be lethal to the majority of cells (IC99) was selected for both VP‐16 and mAMSA, for each cell line. The identification of an increasing number of putative drug resistance‐related proteins provided the opportunity to examine expression of the corresponding genes in the selected cell lines. Northern blot analysis revealed different responses to the selecting agents in the different cell lines. Previous studies examining expression of multidrug resistance (MDR)‐l in resistant cell lines had found undetectable levels in all cells. In the ZR‐75B sublines, increased expression of MDR‐associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) was observed, and when the relative levels of overexpression were compared, a high correlation was found. In contrast, increased expression of MRP was observed in some of the MDA‐MB‐231 sublines, without a concomitant increase in cMOAT expression. Finally, in both T47D and MCF‐7 sublines, increased expression of cMOAT or MRP was observed infrequently, and where it occurred, was of a much smaller magnitude. In the analysis of expression of MRP, the highest levels were found in the ZR‐75B and MDA‐MB‐231 sublines, with lower levels in the MCF‐7 and T47D clones. Similarly, differences in the expression of topo IIα were observed among the sublines. Although the differences in expression appear to depend on the parental cell line from which the resistant sublines were derived, a strong correlation was observed between the expression of MRP and the levels of topo IIα. Cell lines with low levels of MRP had lower levels of topo IIα, while those with high levels of MRP maintained higher levels of topo IIα. While a reduced topo IIα level was common, there did not appear to be a compensating increase in the expression of topo IIβ or topo I or casein kinase (CK) IIα in any of the cell lines. While the possibility that such compensation could occur has been discussed and even reported in some cell lines, such an adaptation was not observed in the present study, suggesting that it is not common.