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Shota Tamagawa, Takatoshi Okuda, Hidetoshi Nojiri, Tatsuya Sato, Rei Momomura, Yukoh Ohara, Takeshi Hara, and Muneaki Ishijima

OBJECTIVE

Previous reports have focused on the complications of L5 nerve root injury caused by anterolateral misplacement of the S1 pedicle screws. Anatomical knowledge of the L5 nerve root in the pelvis is essential for safe and effective placement of the sacral screw. This cadaveric study aimed to investigate the course of the L5 nerve root in the pelvis and to clarify a safe zone for inserting the sacral screw.

METHODS

Fifty-four L5 nerve roots located bilaterally in 27 formalin-fixed cadavers were studied. The ventral rami of the L5 nerve roots were dissected along their courses from the intervertebral foramina to the lesser pelvis. The running angles of the L5 nerve roots from the centerline were measured in the coronal plane. In addition, the distances from the ala of the sacrum to the L5 nerve roots were measured in the sagittal plane.

RESULTS

The authors found that the running angles of the L5 nerve roots changed at the most anterior surface of the ala of the sacrum. The angles of the bilateral L5 nerve roots from the right and left L5 intervertebral foramina to their inflection points were 13.77° ± 5.01° and 14.65° ± 4.71°, respectively. The angles of the bilateral L5 nerve roots from the right and left inflection points to the lesser pelvis were 19.66° ± 6.40° and 20.58° ± 5.78°, respectively. There were no significant differences between the angles measured in the right and left nerve roots. The majority of the L5 nerves coursed outward after changing their angles at the inflection point. The distances from the ala of the sacrum to the L5 nerve roots in the sagittal plane were less than 1 mm in all cases, which indicated that the L5 nerve roots were positioned close to the ala of the sacrum and had poor mobility.

CONCLUSIONS

All of the L5 nerve roots coursed outward after exiting the intervertebral foramina and never inward. To prevent iatrogenic L5 nerve root injury, surgeons should insert the S1 pedicle screw medially with an angle > 0° toward the inside of the S1 anterior foramina and the sacral alar screw laterally with an angle > 30°.

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Takashi Shingu, Kazuo Yamada, Nobumasa Hara, Kouzo Moritake, Harumi Osago, Masaharu Terashima, Takeshi Uemura, Toshiki Yamasaki, and Mikako Tsuchiya

Object. The phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a tumor suppressor by negatively regulating the growth/survival signals of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. The PI3-K/Akt pathway in PTEN-deficient tumors may be one of the key targets for anticancer therapy. The authors examined the effects of the PI3-K inhibitor 2-(4-morpholinyl)-8-phenylchromone (LY294002) on human malignant glioma cells, and compared these effects on PTEN-deficient cells with those on PTEN—wild-type (PTEN-wt) cells.

Methods. Using human malignant glioma cell lines, including the PTEN-deficient cells A172 and U87MG and the PTEN-wt cells LN18 and LN229, the effects of LY294002 on cell growth, apoptosis, and chemotherapeutic agent—induced cytotoxicity were evaluated. The LY294002 inhibited the growth of U87MG cells associated with reduced phosphatidylinositol 3,4,5,-trisphosphate and phosphorylated Akt, and also induced growth inhibition in three other cell lines. Although LY294002 caused apoptosis in all four cell lines, apoptosis seemed to contribute to only a small portion of growth inhibition induced by LY294002. There was no link between the status of PTEN and the median inhibitory concentration values for LY294002 or between the gene status and the extent of LY294002-induced apoptosis. The LY294002 significantly augmented the cytotoxicity induced by etoposide in PTEN-deficient cells, but not in PTEN-wt cells. Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea— and cisplatin-induced cytotoxicity by LY294002 was not linked to the status of PTEN. No marked difference in the amounts of phosphorylated Akt was found between PTEN-deficient and PTEN-wt cells.

Conclusions. The findings show that PI3-K is a possible target for therapy in patients with gliomas, and PI3-K inhibitors in combination with chemotherapeutic agents could be potent therapeutic modalities for patients with malignant gliomas.

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Takeshi Miyazaki, Kouzo Moritake, Kazuo Yamada, Nobumasa Hara, Harumi Osago, Tomoko Shibata, Yasuhiko Akiyama, and Mikako Tsuchiya

Object

Indoleamine 2,3-dioxygenase (IDO), a kynurenine pathway (KP) enzyme catalyzing oxidation of the essential amino acid tryptophan (Trp), is thought to be involved in the immune resistance of malignant tumors through T-cell inactivation caused by Trp depletion and metabolite accumulation. Human malignant gliomas may use this strategy to escape immune attack. The object of this study was to investigate the possibility of IDO-dependent Trp depletion by malignant gliomas and the practicability of using an IDO inhibitor together with anticancer drugs to reserve Trp without decreasing the cytotoxicity of the drugs.

Methods

The authors studied expression of IDO and other KP enzymes and the effects of an IDO inhibitor, 1-methyl L-tryptophan (1MT), on Trp metabolism and cytotoxicity of anticancer drugs, together with direct measurement of KP metabolites, in cultured human malignant glioma cells.

Results

Upon interferon-γ (IFN-γ) stimulation, the glioma cells greatly increased their IDO mRNA expression concomitant with depletion of Trp. The IDO inhibitor 1MT successfully prevented Trp consumption by the stimulated glioma cells. Combining 1MT with anticancer drugs (temozolomide, bischloroethylnitrosourea [BCNU], etoposide and cisplatin) did not interfere with the drugs' suppression of growth of LN229 glioma cells but rather increased their inhibitory effects on IDO activity.

Conclusions

These findings suggest that the robust IDO expression with rapid consumption of Trp in human glioma cells induced by IFN-γ could lead to immune resistance in glioma cells. Indoleamine 2,3-dioxygenase inhibitors that prevent Trp depletion could be used with anticancer drugs to improve therapeutic effects.