Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA,CCKB and CCKC) in human tumors of the central and peripheral nervous system

Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.     

Quantitative analysis of copper,zinc and copper/zinc ratio in selected human brain tumors

Summary Serum copper and zinc concentrations and copper/zinc ratios have been shown to be increased in several types of human malignancies, including human brain tumors. In this study, copper and zinc levels and copper/zinc ratios were determined by atomic absorption analysis in tissue and serum from 29 primary and metastatic brain tumor patients. Metastatic carcinomas and malignant gliomas revealed significantly higher tissue copper concentrations than control tissues and meningiomas. Malignant gliomas demonstrated significantly higher tissue copper/zinc ratios. Both serum copper and copper/zinc ratio were significantly higher in the metastatic carcinoma group than control; however, serum copper levels in malignant glioma patients were not significantly different from control tissues. There were no differences both in the serum and the tissue concentrations of these trace elements in meningiomas and controls. These data suggested that copper, an important angiogenic factors, is accumulated within the malignant tissues of metastatic carcinoma and malignant glioma, but not meningiomas. These findings may have implications regarding angiogenesis in these tumors.     

Reproductive factors and the risk of brain tumors: A population-based study in Sweden

Possible associations between childbearing and the risk of brain cancer were explored in a case-control study “nested” within a large nationwide cohort defined by the Swedish Fertility Registry. Among women born between 1925–1975, 1,088 patients with meningiomas and 1,657 patients with gliomas were identified in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age-matched controls were selected among those in the Fertility Registry. Relative risks were estimated by odds ratios from conditional logistic regression. Ever-parous women were at a reduced risk of glioma compared to nulliparous women, while parity was unrelated to meningioma risk. Age at first birth was unrelated to both meningioma and glioma risk. The gradient in risk between ever-parous and nulliparous women for gliomas, but not meningiomas, is difficult to explain biologically. A possible explanation is that pregnancy-induced alterations in androgen levels reduce the risk of glioma in parous women. Alternatively, childlessness may represent a marker of an occult glioma, negatively affecting fecundity. Overall, our present results do not support the notion that hormonal changes, or other physiological changes induced by childbearing, play an important role in the development of brain tumors. Int. J. Cancer 72:389–393, 1997. © 1997 Wiley-Liss, Inc.     

Low-molecular weight caldesmon as a potential serum marker for glioma.

PURPOSE: Testing the feasibility of using the serum low-molecular weight caldesmon (l-CaD) level as a serum marker for the presence of glioma. EXPERIMENTAL DESIGN: Within a total of 230 serum samples, the l-CaD level was measured in healthy volunteers (30), patients with gliomas (57), nonglial intracranial tumors (107), and nontumor neurologic diseases (36) by ELISA. The specificity of the assay was monitored by combination of immunoprecipitation and immunoblotting. RESULTS: The serum level of l-CaD is significantly higher in the group of glioma patients as compared with any of the other groups (P < 0.001). The cutoff value of 45 yields optimal sensitivity and specificity of the assay (91% and 84%, respectively; area under the curve score = 0.91). The specificity of ELISA was confirmed by the immunoprecipitation/immunoblotting control experiments. There were no significant differences in serum l-CaD levels between patients with low- or high-grade gliomas. CONCLUSIONS: The serum l-CaD level as determined by ELISA is a good discriminator between glioma patients versus patients with other intracranial tumors, other neurologic diseases, and healthy people. Prospective studies are required to test the contribution of the assay in making the diagnosis of glioma, or its feasibility for monitoring the tumor during treatment.     

Elevated Serum IL-17A but not IL-6 in Glioma Versus Meningioma and Schwannoma

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours.We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patientsas well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercialELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in theirsera (0.29±0.54, 0.03±0.15 and 0.16±0.68 vs. 0.00±0.00pg/ml; p=0.01, p=0.01 and p=0.001, respectively). Therewas also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls (2.34±4.35 vs.4.67±4.32pg/ml; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients(p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared tothe young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 wasobserved in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Ourdata suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarkerand/or immunotherapeutic target in glioma cases.     

Immunohistochemical demonstration of alpha-1-proteinase inhibitor in brain tumors

Using light microscopy and immunoperoxidase methods (PAP), the presence of alpha-1-proteinase inhibitor (API) was studied in seventeen brain tumors and four normal brain samples. The brain tumors included four glioblastomas, five low-grade gliomas, two metastatic lung carcinomas, two acoustic schwannomas, and four meningiomas. Normal brain displayed a finely granular intracytoplasmic staining confined to neuronal cells. Glial cells were negative for API. Fifteen of the 17 brain tumors were positive for API. Only two of five low-grade gliomas were negative for API. Glioblastoma and metastatic tumors exhibited the strongest positivity followed by acoustic neuroma, meningioma, and low-grade glioma. All positive samples exhibited finely granular intracytoplasmic API, and 50% exhibited extracellular API positivity. Metastatic and glioblastoma tumors demonstrated prominent extracellular API staining. Our results support the concept of a local production of API by brain tumors.     

Cohort studies of association between self-reported allergic conditions,immune-related diagnoses and glioma and meningioma risk

An inverse association between self-reported allergies and glioma and meningioma risk, has been previously observed in case-control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = -0.94; 95% CI = -1.00 to -0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self-report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre-brain tumor immune-related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19-1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11-1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86-7.81) gliomas in Cohort II. In Cohort III, immune-related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14-1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.     

Dendritic cell based vaccination strategy: an evolving paradigm

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p?<?0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p?=?0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r?=?0.418 and p?=?0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.     

弥散张量成像在脑肿瘤中的应用

目的 探讨脑肿瘤弥散张量成像(DTI)的特点及其在脑肿瘤中的诊断和鉴别诊断价值.方法 对39例经病理证实的脑肿瘤患者(脑膜瘤10例,胶质瘤17例,转移瘤12例),采用PhilipsAchieva 1.5 T磁共振行常规MRI和DTI,在工作站上重建部分各向异性(FA)图、表观弥散系数(ADC)图和三维白质纤维束图,选择...     

Th1/Th2 cytokine imbalance in meningioma, anaplastic astrocytoma and glioblastoma multiforme patients

The balance between Th1 and Th2 cytokines is thought to be an important factor in terms of tumour prognosis. Serum samples from 61 newly diagnosed patients with brain tumours and 50 age- and sex-matched non-tumour controls were analysed by ELISA for circulating levels of interleukin-12 (IL-12p70 and p40) and interleukin-10 (IL-10); pivotal Th1 and Th2 cytokines, respectively. Patients were divided into various groups depending on their histological diagnosis: meningioma (n=11), anaplastic astrocytoma (n=4) and glioblastoma multiforme (GBM; n=46). Significant reduction in serum IL-12 was seen in all groups as compared with the controls: meningioma, p=0.03; anaplastic astrocytoma, p<0.001; and GBM, p<0.001. Conversely, serum IL-10 was significantly increased in anaplastic astrocytoma, p=0.02, and GBM, p=0.03. The changes in the serum cytokines were not caused by the effects of steroids, as sequential analysis of patients pre- and post-steroid treatment commencement showed no difference. This study shows that patients with advanced primary intracranial malignancies have decreased circulating IL-12 and increased circulating IL-10, demonstrating that brain tumours have a major systemic effect on the immune system.     

Use of mobile phones in Norway and risk of intracranial tumours.

To test the hypothesis that exposure to radio-frequency electromagnetic fields from mobile phones increases the incidence of gliomas, meningiomas and acoustic neuromas in adults. The incident cases were of patients aged 19-69 years who were diagnosed during 2001-2002 in Southern Norway. Population controls were selected and frequency-matched for age, sex, and residential area. Detailed information about mobile phone use was collected from 289 glioma (response rate 77%), 207 meningioma patients (71%), and 45 acoustic neuroma patients (68%) and from 358 (69%) controls. For regular mobile phone use, defined as use on average at least once a week or more for at least 6 months, the odds ratio was 0.6 (95% confidence interval 0.4-0.9) for gliomas, 0.8 (95% confidence interval 0.5-1.1) for meningiomas and 0.5 (95% confidence interval 0.2-1.0) for acoustic neuromas. Similar results were found with mobile phone use for 6 years or more for gliomas and acoustic neuromas. An exception was meningiomas, where the odds ratio was 1.2 (95% confidence interval 0.6-2.2). Furthermore, no increasing trend was observed for gliomas or acoustic neuromas by increasing duration of regular use, the time since first regular use or cumulative use of mobile phones. The results from the present study indicate that use of mobile phones is not associated with an increased risk of gliomas, meningiomas or acoustic neuromas.     

Place des méningiomes dans les tumeurs du système nerveux central au centre hospitalier universitaire Yalgado Ouédraogo (CHU-YO) de Ouagadougou : approche histopathologique

Background

Worldwide there are varying reports on the prevalence of meningiomas among central nervous system neoplasms. Different reports state meningiomas, gliomas, or metastatic tumors as the most common tumors among central nervous system neoplasms. The aim of our study was to determine the relative frequency of meningiomas among central nervous system neoplasms in our environment.

Method

Consecutive patients (86) seen at Neurosurgery Office of Yalgado Ouédraogo Teaching Hospital of Ouagadougou, with histologically proven central nervous system tumor over a 7 years period (2005–2011), were retrospectively analyzed.

Results

The commonest histological types were meningiomas, gliomas, metastasis, and pituitary tumors. Thirty-one patients (36.04%) had histologically confirmed meningioma during the study period, 25 (29.07%) had glioma, 6 (7.33%) had metastasis, and 5 (5.81%) had pituitary adenoma. The mean age of the 86 patients was 37.05 years, with 55.61% of male. The mean age of the meningiomas cases was 45.32, with 61.3% of female. 90.31% had grade I meningioma.

Conclusion

The study showed that meningioma is the most common tumor among central nervous system neoplasms in our environment, with a predominance of grade I meningothelial sub-type.     

基质金属蛋白酶及其抑制剂在边缘系统胶质瘤侵袭中的作用

 目的 探讨基质金属蛋白酶(MMP-2、MMP-9)及其组织抑制因子(TIMP-2)在边缘系统胶质瘤侵袭中的作用。方法 利用免疫组织化学技术SP法检测MMP-2、MMP-9及TIMP-2在35例高、低级别胶质瘤和20例脑良性肿瘤(脑膜瘤)中的表达。结果 ①Ⅲ～Ⅳ级胶质瘤MMP-2、MMP-9蛋白的表达明显高于Ⅰ～Ⅱ级，Ⅰ～Ⅱ级胶质瘤MMP-2、MMP-9蛋白的表达明显高于脑膜瘤，其两两之间比较具有显著性差异。②高级别胶质瘤组TIMP-2蛋白表达明显低于低级别组，低级别组TIMP-2蛋白表达明显低于脑膜瘤组，其两两之间比较具有显著性差异。③35例胶质瘤和20例脑膜瘤中MMP-2与MMP-9呈正相关(y=0．86，P<0．01)，MMP-2与TIMP-2呈负相关(γ=-0．65，P<0．01)，MMP-9与TIMP-2呈负相关(γ=-0．58，P<0．01)。结论 ①MMP-2、MMP-9蛋白的表达与胶质瘤的恶性程度有关，可能成为胶质瘤恶性程度、侵袭能力和预后的判断指标。②TIMP-2是MMP-2的抑制因子，两者之间失衡是促进胶质瘤侵袭的重要因素之一。     

Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors.

Arachidonic acid is stored in the cell membrane and released when the cell is activated by appropriate stimuli. It is the substrate for prostaglandins. Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). Some experiments suggest that these compounds increase tumor growth through their actions on host immunocytes. In this study, 22 patients with various brain tumors and 12 control brain tissues were studied. PGE2 levels in tissue samples were measured by ELISA. Arachidonic acid levels in the plasma membrane of tissue samples were analyzed by capillary gas chromatography. The levels of PGE2 were significantly higher in gliomas (n = 10) and meningiomas (n = 7) compared with control tissues (P = 0.000 and P = 0.000, respectively). Also, PGE2 levels in meningiomas were significantly higher than in gliomas (P = 0.000). Arachidonic acid levels in the plasma membrane of gliomas (n = 9) and meningiomas (n = 6) were significantly higher than in the control tissues (P = 0.000 and P = 0.000, respectively). These results suggest that the increased production of PGE2 may suppress the immune system and play an important role in tumor growth.     

Evaluation of VEGF,FGF and PDGF and Serum Levels of Inflammatory Cytokines in Patients with Glioma and Meningioma in Southern Iran

Background: Meningioma and glioma are common central nervous system tumors. Hypoxic tumor cells secrete angiogenic cytokines, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) that stimulate neovascular formation and inflammatory cytokine, such as TNF-α and IL-1β. We measured these serum levels in patients with glial cell tumors and meningioma. Materials and Methods: This was a case-control study in 2014-2015 on patients diagnosed with meningioma/glioma. All demographic and clinical data were registered. The tumor volume and intraoperative bleeding were recorded. Serum levels of VEGF, PDGF, FGF, TNF-α and IL-1β were measured by ELISA methods. Results: Ninety-six patients were enrolled in this study, 32 in each group. Patients VEGF level with cranial tumor, glioma/meningioma had increased. VEGF level was highest among grade IV tumors, larger tumors, and in glioblastoma multiform. There was an upsurge in VEGF serum level as glioma grade increased. The highest VEGF levels were seen in parasagittal meningioma. In contrast to VEGF, PDGF was slightly elevated in glial cell tumors, which was significantly elevated in meningioma. Higher PDGF correlated with increased intraoperative bleeding, especially in meningioma cases. Oligodendroglial tumors expressed higher PDGF levels in contrast to other glial tumors. FGF level was not statistically significant. TNF-α and IL-1β expressions were significantly higher in the meningioma and glioma group in comparison to control group. Conclusion: We found increased VEGF and PDGF serum levels in CNS patient’s tumor. A different role for PDGF was found in the pathogenesis of neovascularization of meningioma, as well as oligodendroglioma. No significant result was found for FGF. TNF-α and IL-1β can serve as key prognostic biomarker in high-grade glioma and meningioma patients.     

Simultaneous Increase in Serum Levels of IL-37 and IL-18 Binding Protein In Low-Grade and High-Grade Brain Tumors

Background: IL-18binding protein (IL-18BP) might play a role in tumor escape from immune surveillance through interacting with IL-37. Such interactions modulate the antitumor activity of IL-18 and affect regulatory T cell (Treg) function. However, the biological roles of IL-37 and IL-18BP have not yet been explored in brain tumors. This study aimed to investigate serum levels of IL-37 and IL-18BP in high-grade and low-grade brain tumors and determine their associations with pathological characteristics of the patients. Subjects and methods: This case-control study consisted of 60 patients with brain tumors (40 low-grade and 20 high-grade) and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the levels of IL-37 and IL-18BP in serum. Results: Our results indicated that serum levels of IL-37 and IL-18BP were significantly higher in patients with brain tumors (109.02, 426.37 pg/mL), high-grade (104.44, 428.87 pg/mL), and low-grade (113.88, 426.37 pg/mL) tumors in compared to healthy controls (35.03, 362.00 pg/mL), (P<0.05). Interestingly, our results revealed a significant positive correlation between IL-37 and IL-18BP serum levels in brain tumors (n=60, R=0.42, P=0.001). Our study also showed that serum levels of IL-37 and IL-18BP in glioblastoma grade IV were approximately similar to those in astrocytoma grade II, meningioma type I, and pituitary adenoma. Furthermore, no significant differences were found in serum levels of IL-37 and IL-18BP between patients with low-grade and high-grade tumors (P=0.24 and P=0.61, respectively). Conclusion: The simultaneous increase in IL-37 and IL-18BP serum levels and their positive correlation may facilitate disease progression in low-grade and high-grade brain tumors by inhibiting antitumor immune responses.     

Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population

Background: The association of primary brain tumors with Single Nucleotide polymorphisms (SNPs) in genes offolate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied theassociation of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indianpopulation. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study populationfrom North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerasechain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase)and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment LengthPolymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756Gof the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B12 and folate levels were evaluated in controls/patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results:The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype(odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk ofglioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype ofMTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6μmol/L, p=0.048) and CC genotype (11.2μmol/L, p=0.039) respectively. Conclusion: Our findings provide an insightinto the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients.Further studies are needed to evaluate their clinical implications.     

Molecular imaging correlates of tryptophan metabolism via the kynurenine pathway in human meningiomas

BackgroundIncreased tryptophan metabolism via the kynurenine pathway (KP) is a key mechanism of tumoral immune suppression in gliomas. However, details of tryptophan metabolism in meningiomas have not been elucidated. In this study, we evaluated in vivo tryptophan metabolism in meningiomas and compared it with gliomas using α-[¹¹C]-methyl-L-tryptophan (AMT)-PET. We also explored expression patterns of KP enzymes in resected meningiomas.MethodsForty-seven patients with MRI-detected meningioma (n = 16) and glioma (n = 31) underwent presurgical AMT-PET scanning. Tumoral AMT uptake and tracer kinetic parameters (including K and k₃′ evaluating unidirectional uptake and trapping, respectively) were measured, correlated with meningioma grade, and compared between meningiomas and gliomas. Patterns of KP enzyme expression were assessed by immunohistochemistry in all meningiomas.ResultsMeningioma grade showed a positive correlation with AMT k₃′ tumor/cortex ratio (r = 0.75, P = .003), and this PET parameter distinguished grade I from grade II/III meningiomas with 92% accuracy. Kinetic AMT parameters could differentiate meningiomas from both low-grade gliomas (97% accuracy by k₃′ ratios) and high-grade gliomas (83% accuracy by K ratios). Among 3 initial KP enzymes (indoleamine 2,3-dioxygenase 1/2, and tryptophan 2,3-dioxygenase 2 [TDO2]), TDO2 showed the strongest immunostaining, particularly in grade I meningiomas. TDO2 also showed a strong negative correlation with AMT k₃′ ratios (P = .001).ConclusionsPET imaging of tryptophan metabolism can provide quantitative imaging markers for differentiating grade I from grade II/III meningiomas. TDO2 may be an important driver of in vivo tryptophan metabolism in these tumors. These results can have implications for pharmacological targeting of the KP in meningiomas.     

Cancer incidence in families with multiple glioma patients

Twenty-four Finnish families with 2 or more glioma patients were identified through questionnaires sent to 369 consecutive glioma patients receiving surgery at Tampere University Hospital during 1983-94. To explore whether unusual cancer susceptibility is involved, the cancer risk of 2,664 family members was estimated using population-based data from the Finnish Cancer Registry. Among the total cohort of relatives, 88 cancers were observed during 1953-97. The overall cancer risk among 12 families with juvenile onset gliomas was significantly decreased (standardized incidence ratio [SIR] 0.6, 95% confidence interval [CI]: 0.4-0.9). Among 12 families with adult onset gliomas, the overall cancer risk was equal to that of the reference population (SIR 1.1, 95% CI: 0.8-1.4) whereas the risk of skin melanoma (SIR 4.0, 95% CI: 1.5-8.8) and meningioma (SIR 5.5, 95% CI: 1.1-16) were significantly increased. Several other tumors, including those associated with neurofibromatosis 1 and 2, tuberous sclerosis and Li-Fraumeni and Turcot syndromes were surveyed, but no elevated risks were observed. In conclusion, the presence of meningiomas and skin melanomas in glioma families may indicate a novel association as a cancer susceptibility trait.