Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells.

BACKGROUND: Although most non-small-cell lung cancer (NSCLC) patients with the echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene - benefit from ALK tyrosine kinase inhibitors (ALK-TKIs), the efficacy of these drugs varies greatly among individuals. METHODS: The antitumour action of ALK-TKIs in EML4-ALK-positive NSCLC cell lines was evaluated from their effects on cell proliferation, signal transduction, and apoptosis. RESULTS: The ALK-TKI TAE684 inhibited cell proliferation and induced apoptosis, in association with inhibition of STAT3 and ERK phosphorylation, in EML4-ALK-positive H3122 cells. TAE684 inhibited STAT3 phosphorylation, but not ERK phosphorylation, and it showed little effect on cell proliferation or apoptosis, in EML4-ALK-positive H2228 cells. The combination of TAE684 and a MEK inhibitor-induced marked apoptosis accompanied by inhibition of STAT3 and ERK pathways in H2228 cells. Such dual interruption of STAT3 and ERK pathways induced downregulation of the antiapoptotic protein survivin and upregulation of the proapoptotic protein BIM. CONCLUSION: Our results indicate that interruption of both STAT3-survivin and ERK-BIM pathways is required for induction of apoptosis in NSCLC harbouring EML4-ALK, providing a rationale for combination therapy with ALK and MEK inhibitors in EML4-ALK-positive NSCLC patients for whom ALK inhibitors alone are ineffective.

Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer.

BACKGROUND: Although a high level of thymidylate synthase (TS) expression in malignant tumours has been suggested to be related to a reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in non-small cell lung cancer (NSCLC). We have now investigated the effect of TS overexpression on pemetrexed sensitivity in NSCLC cells. METHODS: We established NSCLC cell lines that stably overexpress TS and examined the effects of such overexpression on the cytotoxicity of pemetrexed both in vitro and in xenograft models. We further examined the relation between TS expression in tumour specimens from NSCLC patients and the tumour response to pemetrexed by immunohistochemical analysis. RESULTS: The sensitivity of NSCLC cells overexpressing TS to the antiproliferative effect of pemetrexed was markedly reduced compared with that of control cells. The inhibition of DNA synthesis and induction of apoptosis by pemetrexed were also greatly attenuated by forced expression of TS. Furthermore, tumours formed by TS-overexpressing NSCLC cells in nude mice were resistant to the growth-inhibitory effect of pemetrexed observed with control tumours. Finally, the level of TS expression in tumours of non-responding patients was significantly higher than that in those of responders, suggestive of an inverse correlation between TS expression and tumour response to pemetrexed. CONCLUSION: A high level of TS expression confers a reduced sensitivity to pemetrexed. TS expression is thus a potential predictive marker for response to pemetrexed-based chemotherapy in NSCLC patients.

Marked anti-tumour activity of the combination of YM155, a novel survivin suppressant, and platinum-based drugs.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effects of the combination of YM155, a novel small-molecule inhibitor of survivin expression, and platinum compounds (cisplatin and carboplatin) on human non-small cell lung cancer (NSCLC) cell lines. METHODS: The anti-cancer efficacy of YM155 in combination with platinum compounds was evaluated on the basis of cell death and progression of tumour xenografts. Platinum compound-induced DNA damage was evaluated by immunofluorescence analysis of histone gamma-H2AX. RESULTS: Immunofluorescence analysis of histone gamma-H2AX showed that YM155 delayed the repair of double-strand breaks induced in nuclear DNA by platinum compounds. The combination of YM155 and platinum compounds also induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Finally, combination therapy with YM155 and platinum compounds delayed the growth of NSCLC tumour xenografts in nude mice to an extent greater than that apparent with either treatment modality alone. CONCLUSION: These results suggest that YM155 sensitises tumour cells to platinum compounds both in vitro and in vivo, and that this effect is likely attributable to the inhibition of DNA repair and consequent enhancement of apoptosis.

Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: enzymatic activity, protein processing and structural analysis.

Mucopolysaccharidosis II (Hunter disease), a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), has variable clinical phenotypes. Nearly 300 different mutations have been identified in the IDS gene from patients with Hunter disease, but the correlation between the genotype and phenotype has remained unclear. We studied the characteristics of 11 missense mutations, which were detected in the patients or artificially introduced, using stable expression experiments and structural analysis. The mutants found in the attenuated phenotype showed considerable residual activity (0.2-2.4% of the wild-type IDS activity) and those in the severe phenotype had no activity. In immunoblot analysis, both the 73-75 kDa precursor and processed forms were detected in the expression of 'attenuated' mutants (R48P, A85T and W337R) and the artificial active site mutants (C84S, C84T). The 73-75 kDa initial precursor was detected in the 'severe' mutants (P86L, S333L, S349I, R468Q, R468L). The truncated 68 kDa precursor form was synthesized in the Q531X mutant. The results of immunoblotting indicated rapid degradation and/or insufficiency in processing as a result of structural alteration of the IDS protein. A combination of analyses of genotype and molecular phenotypes, including enzyme activity, protein processing and structural analysis with an engineered reference protein, could provide an avenue to understanding the molecular mechanism of the disease and could give a useful tool for the evaluation of possible therapeutic chemical compounds.

Persistence of systolic coronary flow reversal predicts irreversible dysfunction after reperfused anterior myocardial infarction.

OBJECTIVE: To investigate serial assessments of systolic coronary flow reversal in the infarct related artery for predicting poor left ventricular functional recovery after reperfused acute myocardial infarction. SETTING: Regional hospital. PATIENTS AND METHODS: 49 patients with anterior acute myocardial infarction had transthoracic Doppler echocardiography to record coronary flow velocity in the left anterior descending coronary artery immediately after successful primary coronary angioplasty (day 0), and at 48 hours, one week, and three weeks. MAIN OUTCOME MEASURES: Coronary flow velocity at each time point; regional wall motion score index (RWMSI) at day 0 and at three weeks. Irreversible dysfunction was defined as a decrease in RWMSI to < 0.22. RESULTS: Measurements of coronary flow velocity could be made in 45 patients. Patients were divided into three groups: no systolic flow reversal (group 1, n = 27), systolic flow reversal observed only on day 0 (group 2, n = 8), and systolic flow reversal persisting until 48 hours (group 3, n = 10). Although baseline RWMSI was similar among the three groups, the value at three weeks was significantly higher in group 3 than in the other two groups. In predicting irreversible dysfunction, the persistence of systolic flow reversal up to 48 hours had a higher positive predictive value (100%) than the presence of systolic flow reversal on day 0 (67%, p < 0.04). The negative predictive value of systolic flow reversal at 48 hours (83%) was comparable in accuracy to the presence of systolic flow reversal on day 0 (85%, NS). CONCLUSIONS: In reperfused anterior acute myocardial infarction, serial assessment of coronary flow velocity in the left anterior descending coronary artery is feasible using transthoracic Doppler echocardiography, and the persistence of systolic flow reversal at 48 hours is a more specific marker of irreversible dysfunction than peak creatine kinase or diastolic deceleration time.

Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor in patients with pancreatitis.

PURPOSE: We hypothesized that mutations in the pancreatic secretory trypsin inhibitor (PSTI) gene could promote autodigestion, leading to acute or chronic pancreatitis. Our investigation involved mutation analysis of the PSTI gene in patients with acute or chronic pancreatitis. METHODS: Mutation analysis for the PSTI gene was performed in patients with acute or chronic pancreatitis. Unrelated healthy volunteers and family members of a chronic pancreatitis patient with point mutations in the PSTI gene were also analyzed. RESULTS: Two types of single-point mutation in the PSTI gene were observed in one patient with chronic pancreatitis: 34Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and 67Arg (CGC)-to-Cys (TGC) (199 C > T R67C: R67C) in exon 4. No mutations with amino-acid substitution were found in other patients or in the volunteer group. In the patient with the PSTI gene mutations, no additional mutations were observed in the cationic trypsinogen gene. The family study revealed that the mother and a maternal uncle were homozygotes for the N34S mutation, while the father and brother were compound heterozygotes for the N34S and R67C mutations. The uncle (N34S/N34S) showed clinical manifestations of pancreatitis, but the other family members did not. CONCLUSIONS: The N34S mutation may cause a predisposition to pancreatitis, with incomplete penetrance. However, with the limited information available, it is not known whether the R67C mutation promotes pancreatitis.

[Hemophagocytic syndrome with hemophagocytes in the peripheral blood].

A 79-year-old man developed a high fever, facial erythema, anemia and thrombocytopenia during conservative therapy for ischemic colitis. Peripheral hemophagocytes (PHP) were identified in smear specimens of peripheral blood, and hemophagocytes also showed proliferation in the bone marrow. After treatment with steroid and antibiotics under a diagnosis of bacteria-associated hemophagocytic syndrome, the patient recovered rapidly. Although the prognosis of hemophagocytic syndrome (HPS) depends on the underlying disease, any delay in diagnosis can sometimes result in a poor outcome in cases of infection-associated hemophagocytic syndrome. In the present case, early diagnosis of bacteria-associated hemophagocytic syndrome was made by detection of PHP. The appearance of PHP in virus-associated hemophagocytic syndrome (VAHS) and after administration of macrophage colony stimulating factor has been described. However, the significance and cytological characteristics of PHP have been unknown. In this report, we propose that PHP can be a useful indicator for early diagnosis of HPS, and we report 7 additional cases in which the PHP was detected retrospectively. The cytological characteristics and biological significance of PHP are discussed.

Evolution of the periodicity and the self-similarity in DNA sequence: a Fourier transform analysis.

Fourier transform analysis was applied to elucidate the periodical and self-similar properties in the DNA sequences mainly of beta-globin genes in different species, and the evolutionary change in those properties was then investigated. Map patterns of a two-dimensional DNA walk showed that the stretches of exons are significantly shorter than those of introns, suggesting that the evolution of exons is driven by natural selection, whereas that of introns is generated by unknown internal rules. Using a monomer analysis, we obtained the power spectra of four different bases, A, G, C, and T, in DNA sequences. Periodicities in the short- (2 to 10 base pairs [bp]), medium- (10 to 50 bp) and long-range order (50 to 300 bp) of beta-globin gene sequences could be observed, and power spectral densities of these periodicities were increased with evolution. These results suggest the existence of the internal rules in the occurrence of the synonymous and nonsynonymous substitutions in the sequences, the destabilization of the interaction between DNA and histone protein, and the stabilization of the chromatin structure, respectively. Moreover, 1/f(alpha) analysis of the power spectra (log-log plot) in the far long-range region (160 to 16,000 bp) suggested the increase in the self-similarity (the fractal structure) of DNA sequences with evolution. A general trend of the increase in a 3 bp periodicity with evolution might be functionally related to the CAG trinucleotide repeat diseases such as Huntington chorea, where a marked periodicity of 3 bp could be observed. Fourier transform analysis applied to a DNA sequence offers a great new avenue for extracting information on the evolution of a DNA sequence.

Evaluation of accumulated mucopolysaccharides in the brain of patients with mucopolysaccharidoses by (1)H-magnetic resonance spectroscopy before and after bone marrow transplantation.

In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4 Hunter, 1 Sly), cranial (1)H-magnetic resonance spectroscopy was performed to evaluate the accumulation of mucopolysaccharides and biochemical changes in the CNS in vivo before and after bone marrow transplantation (BMT). In two of seven patients, (1)H-magnetic resonance spectroscopy was performed before and after BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine from patients with mucopolysaccharidoses showed resonance higher than the chemical shift of myoinositol in the brain (3.7 ppm). The resonance was considered to contain signals from mucopolysaccharide molecules. The resonance was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine ratios were consistently higher than control ratios. In white matter without lesions, choline/creatine ratios were higher than control ratios. Patients with higher developmental quotient or intelligence quotient tended to show higher N:-acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia. After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT. In white matter without lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios after BMT, but although the choline/creatine ratios were gradually decreased, they remained higher than the control ratio, 2 y after BMT. These results suggest that evaluation of pMPS, choline, and N:-acetylaspartate by (1)H-magnetic resonance spectroscopy is an important technique that may provide useful biochemical information in vivo on the neurologic process and the efficacy of BMT in patients with mucopolysaccharidoses.

Structural and kinetic characterization of early folding events in beta-lactoglobulin.

We have defined the structural and dynamic properties of an early folding intermediate of beta-lactoglobulin known to contain non-native alpha-helical structure. The folding of beta-lactoglobulin was monitored over the 100 micros--10 s time range using ultrarapid mixing techniques in conjunction with fluorescence detection and hydrogen exchange labeling probed by heteronuclear NMR. An initial increase in Trp fluorescence with a time constant of 140 micros is attributed to formation of a partially helical compact state. Within 2 ms of refolding, well protected amide protons indicative of stable hydrogen bonded structure were found only in a domain comprising beta-strands F, G and H, and the main alpha-helix, which was thus identified as the folding core of beta-lactoglobulin. At the same time, weak protection (up to approximately 10-fold) of amide protons in a segment spanning residues 12--21 is consistent with formation of marginally stable non-native alpha-helices near the N-terminus. Our results indicate that efficient folding, despite some local non-native structural preferences, is insured by the rapid formation of a native-like alpha/beta core domain.

High pressure NMR reveals a variety of fluctuating conformers in beta-lactoglobulin.

High pressure 1H/15N two-dimensional NMR spectroscopy has been used to study conformational fluctuation in bovine beta-lactoglobulin at pH 2.0 and 36 degrees C. Pressure dependencies of 1H and 15N chemical shifts and cross-peak intensities were analyzed at more than 80 independent atom sites between 30 and 2000 bar. Unusually large and non-linear chemical shift pressure dependencies are found for residues centering in the hydrophobic core region, suggesting the existence of low-lying excited native states (N') of the protein. Measurement of 1H/15N cross-peak intensities at individual amide sites as a function of pressure suggests that unfolding events occur independently in two sides of the beta-barrel, i.e. the hydrophobic core side (betaF-H) (producing I2) and the non-core side (betaB-E) (producing I1). At 1 bar the stability is higher for the core region (DeltaG0 = 6.5(+/-2.0) kcal/mol) than for the non-core region (4.6(+/-1.3) kcal/mol), but at high pressure the stability is reversed due to a larger DeltaV value of unfolding for the core region (90.0(+/-35.2) ml/mol) than that for the non-core region (57.4(+/-14.4) ml/mol), possibly due to an uneven distribution of cavities. The DeltaG0 profile along the amino acid sequence obtained from the pressure experiment is found to coincide well with that estimated from hydrogen exchange experiments. Altogether, the high pressure NMR experiment has revealed a variety of fluctuating conformers of beta-lactoglobulin, notably N, N', I1, I2 and the totally unfolded conformer U. Fluctuation of N to I1 and I2 conformers with open barrel structures could be a common design of lipocalin family proteins which bind various hydrophobic compounds in its barrel structure.

[A resected case of lung cancer with an extrapericardial single trunk formed by the left pulmonary veins].

We successfully performed left lower lobectomy in a lung cancer patient with anatomical variation in which left superior and inferior pulmonary veins were connected to the left atrium after foaming an extrapericardial single trunk. When indicating lobectomy, confirming the presence of such anatomical variation is clinically significant to prevent the development of pulmonary edema in the residual lung due to improper division of the single trunk as well as preventing subsequent possibly essential completion pneumonectomy.

[Comparison of pharmacokinetics of 5-FU and alpha-fluoro-beta-alanine, a metabolite of 5-FU, in plasma after administration of UFT, tegafur, 5-FU or doxifluridine to rats].

Toxic effects (neurotoxicity and cardiotoxicity) of 5-FU and its derivatives have been reported by many investigators. These toxicities are considered to be caused by the inhibition of the TCA cycle by alpha-fluoro-beta-alanine (FBAL), a metabolite of 5-FU, and later metabolites. In this study, we focused on FBAL as an index of the above toxicities. We compared the concentrations of 5-FU and FBAL in plasma after administration of UFT, tegafur (FT), 5-FU or doxifluridine (5'-DFUR) to rats (75 mumol/kg) in order to evaluate which compound has the better balance of efficacy and toxicity. UFT exhibited the lowest FBAL concentration in plasma followed by FT, 5'-DFUR and 5-FU. The ratio of FBAL to 5-FU in Cmax and AUC after dosing of UFT was the lowest among these four test compounds. These data indicate that the lowest ratio of FBAL to 5-FU resulted from the inhibitory effect of uracil, a component of UFT, on the metabolism of 5-FU. In conclusion, the present results suggest that UFT has a better balance of efficacy and toxicity than FT, 5-FU and 5'-DFUR.

[SIRS and CARS: discussion based on the pathologic condition of acute pancreatitis].

Relationship between SIRS and CARS in the pathologic condition of acute pancreatitis was discussed. SIRS promotes excessive inflammatory reaction and CARS induces the susceptibility to infection. Both conditions can develop into organ failure in acute pancreatitis. Hence, countermeasures for both conditions are mandatory in the care of patients with acute pancreatitis.

Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm.

Coronary artery spasm is caused primarily by increased contractility of vascular smooth muscle. Excessive Ca2+ entry into vascular smooth muscle cells (VSMCs) may be one of the key mechanisms for the spasm, but no study has ever directly examined the possible alterations of Ca2+ channels in the spastic coronary artery. Here we show that L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery. In a porcine model of coronary spasm with balloon injury, both receptor-mediated stimulation of L-type Ca2+ channels by serotonin and direct stimulation of the channels by Bay K 8644 (a dihydropyridine Ca2+ channel agonist) repeatedly induced coronary spasm in vivo, which was abolished by pretreatment with nifedipine, a dihydropyridine Ca2+ channel antagonist. In a single VSMC freshly dispersed from coronary arteries in vitro, patch-clamp experiments showed that current density of L-type Ca2+ channel current was significantly increased in VSMCs from the spastic site compared with that from the control site even when the channels were maximally stimulated by Bay K 8644. There was no difference in the sensitivity of the channels to Bay K 8644. These results indicate that functionally available L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery in our porcine model, suggesting that increased expression of L-type Ca2+ channels and concomitant increase in Ca2+ entry into VSMCs through the channels may contribute, at least in part, to the pathogenesis of coronary artery spasm.

[Two cases of traumatic diaphragmatic hernia with atypical medical history].

We have recently experienced two cases of traumatic diaphragmatic hernia which has been repaired by surgery. The first case was a 58-year-old man who had suffered left upper abdominal injury with a branch in his childhood. Although he had never symptoms, chest X-ray showed abnormal shadow in the left lower lung field. Radiologic studies indicated that the great omentum was escaped into the thoracic cavity. On patient request, we performed primary repair of the diaphragmatic hernia on thoracotomy. The second case was a 56-year-old woman who had undergone a left nephrectomy for the left renal abscess. Seven months after the operation, she began to feel nausea and vomiting, and the symptom aggravated with time. Chest X-ray showed air bubbles in the left lower lung field. It proved to be a projection of the stomach into the thoracic cavity through the iatrogenic diaphragmatic injury. We successfully performed a repairment of the diaphragm with a mesh.

Is folding of beta-lactoglobulin non-hierarchic? Intermediate with native-like beta-sheet and non-native alpha-helix.

The refolding of beta-lactoglobulin, a beta-barrel protein consisting of beta strands betaA-betaI and one major helix, is unusual because non-native alpha-helices are formed at the beginning of the process. We studied the refolding kinetics of bovine beta-lactoglobulin A at pH 3 using the stopped-flow circular dichroism and manual H/(2)H exchange pulse labeling coupled with heteronuclear NMR. The protection pattern from the H/(2)H exchange of the native state indicated the presence of a stable hydrophobic core consisting of betaF, betaG and betaH strands. The protection pattern of the kinetic intermediate obtained about one second after initiating the reaction was compared with that of the native state. In this relatively late kinetic intermediate, which still contains some non-native helical structure, the disulfide-bonded beta-hairpin made up of betaG and betaH strands was formed, but the rest of the molecule was fluctuating, where the non-native alpha-helices may reside. Subsequently, the core beta-sheet extends, accompanied by a further alpha-helix to beta-sheet transition. Thus, the refolding of beta-lactoglobulin exhibits two elements: the critical role of the core beta-sheet is consistent with the hierarchic mechanism, whereas the alpha-helix to beta-sheet transition suggests the non-hierarchic mechanism.

Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice.

BACKGROUND/AIMS: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony-stimulating factor (M-CSF/CSF-1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M-CSF to lipopolysaccharide (LPS)-induced cytokine expression and neutrophil infiltration in the liver. METHODS: We investigated the effects of LPS administration in M-CSF-deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT-PCR. Neutrophil infiltration in the liver was also examined. RESULTS: After LPS administration, cytokine production and expression of LPS receptors, such as CD14 and scavenger receptor class A (MSR-A), were induced at lower levels in op/op mice than those in littermate mice. Neutrophil infiltration in the liver of op/op mice did not differ significantly from that of littermate mice. Anti-IL-8 receptor homologue and anti-C5a receptor antibody reduced the number of infiltrating neutrophils. CONCLUSIONS: These findings indicate that deficient macrophage activation following LPS injection in op/op mice is associated with decreased expression of CD14 and MSR-A in the liver. Thus, M-CSF plays a critical role in LPS-induced macrophage activation but does not exert a dominant role in neutrophil infiltration in the liver.

Solution structure and dynamics of bovine beta-lactoglobulin A.

Using heteronuclear NMR spectroscopy, we studied the solution structure and dynamics of bovine beta-lactoglobulin A at pH 2.0 and 45 degrees C, where the protein exists as a monomeric native state. The monomeric NMR structure, comprising an eight-stranded continuous antiparallel beta-barrel and one major alpha-helix, is similar to the X-ray dimeric structure obtained at pH 6.2, including betaI-strand that forms the dimer interface and loop EF that serves as a lid of the interior hydrophobic hole. [1H]-15N NOE revealed that betaF, betaG, and betaH strands buried under the major alpha-helix are rigid on a pico- to nanosecond time scale and also emphasized rapid fluctuations of loops and the N- and C-terminal regions.

The characterization of human brain tumor using magnetization transfer technique in magnetic resonance imaging.

The clinical applicability of magnetization transfer (MT) technique in magnetic resonance imaging (MRI) for the estimation of the histological and constitutional feature of brain tumors was investigated. MT effect was evaluated by measuring the MT ratio (MTR). The parameters in 1.5-tesla MRI system were as follows: TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency of off-resonance MT pulse, 1000 Hz. The sequence was performed in 20 normal volunteers and 45 patients with brain tumors which were characterized histologically and surgically. The MTR for brain tumors was significantly lower than that for normal brain tissue (p < 0.05). The MTR for meningioma was higher than that for the other brain tumors (p < 0.05). In the meningiomas, MTR for fibrous type was higher than that for meningothelial type, but there was no statistical significance. Regarding the physical consistency for the brain tumors, as classified by surgery, there was a statistically significant difference in MTR between the soft tumor group (0.22 +/- 0.03, n = 6) and the hard tumor group (0.36 +/- 0.04, n = 10) (p < 0.01). This study suggested that the MT technique for patients with brain tumor may be useful to understand the characteristics of the tumors presurgically, based on the degree of intermolecular interaction of macromolecule such as protein.