Koji Adachi

Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor α

SummaryRecombinant tumor necrosis factor α (rTNFα; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF-α was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNFα may be protein-synthesis-dependent. The dose of rTNFα that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells.125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNFα, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNFα effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials,125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with125I-labeled mAb 425 and rTNFα.

Experimental model of human melanoma metastases

Models for spontaneous metastasis of human melanoma have recently been developed in nude mice [1, 2, 3, 4, 5, 6, 7]. These models have helped to define the three major steps within the metastatic cascade: cell attachment to basement membranes, membrane degradation, and cell locomotion [8]. Cells selected in these animal models have a relatively stable metastatic phenotype. Cultured cells from metastatic melanoma lesions, on the other hand, show instability of their metastatic phenotype. They are noninvasive when injected into nude mice [7] and have antigenic and genetic similarities with primary melanoma cells [9]. Instability of the metastatic properties of cells from metastatic lesions occurs either during in-vitro growth or as a result of variant selection during rapid proliferation in the human host [10].

3.0-T diffusion images after clipping of middle cerebral artery aneurysm.

AIM Replacement of aneurysm clips or temporary parent artery occlusion during aneurysm clipping (AC) carries the risk of inducing postoperative neurologic deficits. When studying the risk of surgical complications associated with cerebral aneurysms, patients with similar conditions should be compared to eliminate the influence of rupture and location of aneurysm. MATERIAL AND METHODS We used 3.0-Tesla (3.0T) magnetic resonance diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) to analyze surgical complications after AC. A total of 42 AC procedures for 40 unruptured and 2 delayed-phase ruptured MCA aneurysms were evaluated. RESULTS In six patients, temporary parent artery occlusion was performed. Asymptomatic hyperintensities were observed on DWI of three patients. In one patient, an asymptomatic lesion was most likely caused by a small contusion that occurred during dissection of an aneurysm attached to the brain surface. In two patients, asymptomatic cortical lesions were caused by brain surface contusions due to lacerations of the open dura. No symptomatic hyperintensities on DWI were observed after surgery. No fixed ischaemic neurologic deficits resulted from AC. CONCLUSION Although some postoperative abnormalities were observed with 3.0T DWI, we found clipping of MCA aneurysms to be a safe procedure with a low risk of ischaemic complications.

Gliomaにおけるcytokineのepidermal growth factor receptor (EGF-R) 発現に関する増強効果について

Recombinant tumor necrosis factor alpha (TNF-alpha) significantly enhanced epidermal growth factor receptor (EGF-R) expression in U373-MG glioma cell line as determined by binding of anti-EGF-R monoclonal antibody (MAb) 425. The optimal dose of TNF-alpha was 1000 U/ml of media. When TNF-alpha was combined with recombinant interferon gamma (IFN-gamma), further upregulation of EGF-R was observed. However, IFN-gamma itself did not show any EGF-R enhancement in this cell line. Scatchard analysis of receptor binding revealed that this enhancement of EGF-R expression was due to an increase in the EGF-R density. TNF-alpha did not affect expression of other brain tumor-associated antigens defined by MAb ASHE2, ASHG4 and ASAY1. Cultured fibroblasts showed no upregulation of EGF-R by TNF-alpha, suggesting a differential effect of TNF-alpha on EGF-R expression on glioma cells and normal cells. We investigated whether TNF-alpha treatment of glioma cells increased the tumoricidal effects of radiolabeled MAb 425 which correlate with MAb density on tumor cell surfaces. Growth inhibition of glioma cells in culture by 125I-labeled MAb 425 was significantly enhanced after treatment of the cells with TNF-alpha. In previous clinical trials, 125I-labeled MAb 425 has shown immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled MAb 425 and cytokines.

An intraoperative motor tract positioning method in brain tumor surgery: technical note

Intraoperative 3D recognition of the motor tract is indispensable to avoiding neural fiber injury in brain tumor surgery. However, precise localization of the tracts is sometimes difficult with conventional mapping methods. Thus, the authors developed a novel brain mapping method that enables the 3D recognition of the motor tract for intrinsic brain tumor surgeries. This technique was performed in 40 consecutive patients with gliomas adjacent to motor tracts that have a risk of intraoperative pyramidal tract damage. Motor tracts were electrically stimulated and identified by a handheld brain-mapping probe, the NY Tract Finder (NYTF). Sixteen-gauge plastic tubes were mounted onto the NYTF and inserted in the estimated direction of the motor tract with reference to navigational information. Only the NYTF was removed, leaving the plastic tubes in their places, immediately after muscle motor evoked potentials were recorded at the minimum stimulation current. Motor tracts were electrically identified in all cases. Three-dimensional information on the position of motor tracts was given by plastic tubes that were neurophysiologically placed. Tips of tubes showed the resection limit during tumor removal. Safe tumor resection with an arbitrary safety margin can be performed by adjusting the length of the plastic tubes. The motor tract positioning method enabled the 3D recognition of the motor tract by surgeons and provided for safe resection of tumors. Tumor resections were performed safely before damaging motor tracts, without any postoperative neurological deterioration.

A non-functional pituitary adenoma in a 13-year-old boy of short stature

of the right frontal, temporal, and parietal lobes. He develdifference between our patient and reported patients with oped a GTC 1 month after this MRI procedure. typical hemimegalencephaly. Conclusion: Neuronal migration disorders can be recognized distinctly on MRI. MRI revealed that the ectopic gray matter exhibits a wide spectrum, from the double cortex syndrome (case 3) to a nodular heterotopia (case 1). The accumulation of patient records will help to clarify the clinical status more precisely.