Production of Urokinase-Type Plasminogen Activator (u-PA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Human Brain Tumours

Summary We investigated the role of plasminogen activators (PAs) and their inhibitor (plasminogen activator inhibitor-1, PAI-1) in human brain tumours. The amounts of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), and the activity of u-PA and t-PA were determined by enzyme-linked immunosorbent assay (ELISA), and u-PA and PAI-1 were immunolocalized using monoclonal antibodies in human brain tumours and normal brain tissues. The tissues were surgically removed from 64 patients; normal brain tissue (5 cases), low-grade glioma (4 cases), high-grade glioma (17 cases), metastatic tumour (9 cases), meningioma (benign 12 cases, malignant 6 cases), acoustic schwannoma (11 cases). u-PA activity and u-PA and PAI-1 antigen levels were significantly elevated in malignant brain tumours (malignant meningiomas, high-grade gliomas, and metastatic tumours) and acoustic schwannomas but very low in benign meningiomas, low-grade gliomas and normal brain. There was no difference in t-PA antigen levels among normal and malignant tissues, however levels of t-PA activity were markedly decreased in metastastic tumours. All malignant brain tumour tissues showed positive immunostaining for u-PA and PAI-1, however, some tumour cells showed negative intensity while others showed strong intensity for these antibodies. This contrasts to the homogeneous staining pattern found in acoustic schwannoma. These findings indicate that malignancy in human brain tumours is associated with elevated levels of u-PA and PAI-1 and that an imbalance between these proteins in a micro-enviroment contributes (ascribes) to tumour cell invasion.     

111Indium (DTPA-octreotide) scintigraphy in patients with cerebral gliomas

Summary Somatostatin receptors (SR) have been identified in vitro in normal brain tissue, in neuro-endocrine tumours and in cerebral gliomas WHO grade 1 or 2 by autoradiography or using somatostatin-gold conjugates. In vivo, SR detection has become possible by scintigraphy applying the somatostatin analogue octreotide, radio-labelled with¹¹¹Indium. It was supposed that expression of SR in cerebral gliomas corresponds to low grade tumour malignancy and that, in vivo, somatostatin receptor scintigraphy (SRS) could refine and improve the WHO grading system for cerebral gliomas.Nineteen patients with cerebral gliomas (grade 2: n=8, grade 3: n=3, grade4: n=8) were examined with¹¹¹In (DTPA-octreotide) to evaluate, whether SRS could improve the pre-operative estimation of tumour biology and the postoperative management. The results of SRS were related with the histological findings and with the in vitro demonstration of somatostatin-binding sites on cultured tumour cells incubated with a somatostatin-gold conjugate.In vivo, none of the patients with glioma grade 2 showed enhanced tracer uptake in the SRS, whereas in vitro SR were detected in cultured tumour tissue in 5 out of 5 cases. Every patient with glioma grade 3 or 4 demonstrated a high focal uptake of¹¹¹In (DTPA-octreotide), as shown by SRS. Three patients with glioma grade 4, additionally examined with 99mTc-DTPA, showed an increased tracer uptake within the tumour area when compared with results of SRS. In vitro, SR were detected on tumour cell surface in 5 out of 6 tissue samples from patients with gliomas grade 3 or 4. One patient harbouring a cerebral abscess presented with a high focal tracer uptake in the SRS but with absence of somatostatinbinding sites in vitro.We concluded, that in glioma patients enhanced tracer uptake in receptor scintigraphy with¹¹¹In (DTPA-octreotide) does not depend on the presence of SR in tumour tissue but on the dysfunction of the blood-brain barrier. Thus, SRS does not improve the preoperative glioma grading or postoperative management in patients with cerebral tumours of glial origin.The article is dedicated to Prof. H. Leonhardt on the occasion of his 75th birthday.     

Study of correlation between expression of bradykinin B2 receptor and pathological grade in human gliomas

In clinical practice there is a difference in response of the blood-tumour barrier (BTB) permeability induced by bradykinin in brain tumours with the same pathology. The variability in response of tumours to bradykinin is likely to be related to the expression level of bradykinin B(2) receptor. This study used fresh human glioma samples to determine the expression level of bradykinin B(2) receptor on gliomas with different pathological grades. The grade of tumour was classified using the WHO classification. To determine the bradykinin B(2) receptor expression level in gliomas, Immunohistochemistry and Western blot methods were used. In 24 cases of gliomas there were eight cases of WHO I glioma, eight cases of WHO II glioma and eight cases of WHO III glioma. Both Western blot and immunohistochemistry showed bradykinin B(2) receptors localized on tumour cells, whilst brain cells at the edge of the glioma hardly expressed B(2) receptor. There were significant differences of bradykinin B(2) receptor expression level among different pathological grades of glioma. The expression of B(2) receptor in the three grades of glioma was in the order of WHO I < WHO II < WHO III. Determination of bradykinin B(2) receptor expression level in human glioma may be useful in screening glioma patients to predict whether they will be suitable for opening of the blood - tumour barrier with bradykinin or its analogue.     

Association of p53 tumor suppressor gene with paraclinical and clinical modalities of gliomas patients in Malaysia

Summary Background. Alteration of the tumor suppressor gene p53 is considered to be a critical step in the development of human cancer. Changes in this gene have been detected in a wide range of human tumours, including gliomas. In glioma, the presence of p53 gene alterations has been associated with worse prognosis.Methods. Forty-seven Malaysian adult glioma patients of the Malay race were prospectively studied over a period of 3 years where the presence of p53 mutation using cold-SSCP method and their clinical and paraclinical response were correlated.Findings. Among these glioma patients, p53 mutations were detected in 12 tumors, an incidence rate of 25.5%. Mutations were found in 2 patients of grade II, and 5 patients both in grade III and grade IV. The sequencing results revealed the presence of base-substitutions (7) (58.3%) and frameshifts mutations (5) (41.7%). Of the base-substitutions, 57.1% were transversions and 42.9% were transitions.Interpretation. Our analysis shows that 3 factors were associated with p53 mutations i.e. grade, site and consistency of tumour using univariate analysis although multivariate analysis revealed no positive on predictors of mutation. In conclusion, although p53 genetic alterations are involved in glioma patients in Malaysia, it has no impact on prognosis.     

Prognostic value of perfusion-weighted imaging in brain glioma: a prospective study

Summary Object. Biopsy targeting based on MR imaging alone may fail to identify malignant areas in brain gliomas. Considering the differences in relative Cerebral Blood Volume (rCBV) ratios reported among tumour grades, we evaluated whether perfusion-weighted MR imaging (PWI) could usefully implement the routine preoperative imaging by detecting those areas bearing a higher yield for malignancy to guide the stereotactic biopsy or the surgical removal. Clinical material and methods. We studied a series of 55 consecutive patients with newly diagnosed brain glioma using both conventional MR imaging and PWI in the preoperative assessment. The pathological diagnosis was established by stereotactic biopsy in 29 cases and by craniotomy in 24 cases. We evaluated the patient survival to detect undergrading. Discussion. Independent from contrast-enhancement, perfusion-weighted MR imaging improved the target selection in stereotactic biopsy guidance and the removal of malignant areas in tumours amenable to surgery. Particularly sensitive to the perfused part of the tumour as to small regional changes, rCBV maps allowed a better detection of malignant areas. The rCBV ratios correlated significantly to the tumour grade and the final outcome (p < 0.01). Conclusions. We found PWI valuable in the preoperative assessment of brain gliomas, discriminating high from low-grade gliomas. PWI can easily be performed on widely available MR imaging systems as part of the routine imaging of gliomas.     

脑胶质瘤白细胞介素-6自分泌或旁分泌环路的研究

目的　研究白细胞介素 6(IL 6) /IL 6受体 (IL 6R)自分泌或旁分泌环路与脑胶质瘤的关系。方法　采用逆转录 聚合酶链反应 (RT PCR)方法检测IL 6和IL 6R基因在 4株脑胶质瘤细胞株、62例脑胶质瘤组织标本、5例良性脑膜瘤组织和 5例人正常脑胶质细胞中的表达 ;将IL 6单抗 (McAb)或IL 6RMcAb与脑胶质瘤细胞共同孵育 ,四甲基偶氮唑蓝 (MTT)比色法检测对细胞生长的抑制作用。结果　脑胶质瘤细胞株C6、9L、U 2 5 1和SHG44均有IL 6和IL 6R的表达 ,脑胶质瘤组织标本中 47例 (75 .81% )表达IL 6、5 2例 (83 .87% )表达IL 6R、41例 (66.13 % )同时表达IL 6和IL 6R ;良性脑膜瘤组织 4例表达IL 6,人脑正常胶质细胞仅有IL 6弱表达 ,两者均无IL 6R表达。IL 6McAb和IL 6RMcAb能够显著抑制脑胶质瘤细胞的增殖 ,并存在剂量依赖关系(P <0 .0 1)。结论　脑胶质瘤很可能存在IL 6/IL 6R自分泌或旁分泌环路 ,阻断此环路可以明显抑制胶质瘤细胞的恶性增殖     

Expression and immunolocalisation of neutral endopeptidase in prostate cancer

BACKGROUND: Neutral Endopeptidase (NEP) is a cell surface enzyme that cleaves and inactivates neuropeptides. When present on androgen-dependent prostate cancer (PC) cells, NEP inactivates growth stimulatory neuropeptides. After androgen ablation NEP expression decreases and neuropeptides can enhance cell growth, leading to the development of androgen-independent, neuropeptide stimulated PC. Aim of the study was to analyse the expression, localisation and distribution of NEP in benign and malignant prostatic tissues and its relation to the cytoskeleton. METHODS: Immunohistochemistry (IHC) was performed to localise NEP in fixed specimens from normal prostatic tissue, benign prostate hyperplasia (BPH) and PC of Gleason grade 2-5. In situ hybridisation and Western blotting experiments were carried out to confirm NEP gene expression and translation to mature protein in BPH and PC tissue. Confocal laser scanning microscopy was utilised to investigate whether development of high grade prostate tumours was accompanied by changes in intracellular actin/NEP colocalisation patterns. Finally, the proliferative activity in relation to loss of NEP expression was investigated by dual staining of NEP and Ki-67 in prostatic tumours. RESULTS: In situ hybridisation studies revealed preserved expression of NEP mRNA in epithelial cells of PC. NEP was by IHC shown to be located in the apical plasma membrane of normal epithelial cells and BPH tissue. In PC a Gleason grade dependent shift of the NEP distribution pattern towards a heterogeneous, partly cytoplasmic allocation of the protein was found. Compared to BPH tissue, specimens derived from PC showed very low IHC-staining intensity for NEP protein. In high grade PC the typical apical colocalisation of actin and NEP was lost and a strong granular cytoplasmic NEP staining was found. PC areas with a high expression of NEP displayed diminished proliferative activity i.e. low staining intensity for Ki-67. CONCLUSIONS: NEP is differentially expressed in the normal and the pathologically altered prostate with a clear shift from a membrane bound to a cytoplasmic distribution pattern in high-grade tumours and loss of NEP expression in areas of high proliferative activity. The data presented support an active involvement of NEP in the progression of androgen-independent PC. Further studies are needed to unravel the mechanisms underlying the cytoplasmic NEP distribution in PC.     

人脑胶质瘤中连接蛋白基因表达及其临床意义

目的探讨人脑胶质瘤连接蛋白(Cx)43、32基因表达及其临床意义。方法对8例正常脑组织和50例人脑胶质瘤采用Northern印迹和免疫组织化学法检测。结果人脑胶质瘤Cx43mRNA及其蛋白表达阳性率分别为54％、52％，Cx32仅在1例低恶度少枝胶质细胞瘤及1例混合性星形一少枝胶质细胞瘤中表达。Cx43mRNA及其蛋白表达水平随肿瘤恶性程度升高而下降。结论Cx基因在人脑胶质瘤中表达可下降或缺失，与肿瘤的病理类型及恶性程度呈负相关，可作为某些肿瘤的病理诊断参考指标之一。     

三磷酸腺苷结合盒转运体成员2在人脑胶质瘤中的表达及其与神经巢蛋白表达的关系

目的 探讨三磷酸腺苷结合盒转运体成员2(ABCG2)在人脑胶质瘤组织中的表达及其与胶质瘤分级和神经巢蛋白(nestin)表达的关系.方法 实时荧光定量聚合酶链反应(PCR)检测ABCG2在52例不同病理级别胶质瘤中的mRNA表达;免疫组织化学SABC法检测ABCG2和nestin的蛋白表达.结果 ABCG2在脑胶质瘤中的mRNA表达与正常脑组织比较呈过表达(P<0.05),且随着病理级别的升高而增加(P<0.05);免疫组织化学显示ABCG2在52例胶质瘤中的阳性表达率为32.7%(17/52),并与病理级别明显相关(x2=4.62,P<0.05),主要呈亲血管分布;ABCG2的表达与nestin的表达明显相关(x2=7.60,P<0.05).结论 ABCG2在人脑胶质瘤中的表达随着病理级别的升高而逐渐增加,且与nestin的表达呈正相关;脑肿瘤干细胞可能与神经干细胞具有一定的同源性.     

Pyruvate kinase in human brain tumours. Its significance in the treatment of gliomas

Summary Pyruvate kinase isozyme distribution was studied in 101 intracranial tumours of various nature and origin, and in normal human brain (both foetal and adult). In foetal brain, five different forms could be detected by electrophoresis (K₄, K₃M, K₂M₂, KM₃, and M₄). In adult brain, the M₄ type, K₃M hybrid, and K₄ are present; the M type is largely predominant. Alanine inhibition of pyruvate kinase can be used to discriminate between M and K-type pyruvate kinase. The results obtained in an alanine inhibition test are in agreement with the electrophoretic pattern. Pyruvate kinase from foetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. In adult brain a high residual activity of pyruvate kinase is found in the presence of alanine. Well differentiated neuroepithelial tumours,i.e., astrocytomas, oligodendrogliomas, and ependymomas showed also relatively high residual activities, though less than in normal adult brain. On the contrary, in poorly differentiated gliomas low residual activity was found. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumours. There is also a strong correlationship between alanine inhibition of pyruvate kinase and one year survival after total or subtotal resection of gliomas in adults.When in gliomas the residual activity is determined not in the centre of the tumour but more towards the periphery, much higher residual activity is found. It is suggested that brain biopsies in which a residual activity higher than 70% is found probably contain no tumour in the paraffin slides.Poorly differentiated gliomas were characterized by the presence of type K, and the hybrids K₃M. In well differentiated gliomas, besides K₄ and K₃M, M₄ was also present. Alanine inhibition was in agreement with the electrophoretic pattern in all tumours. In children (age 1–11 years) gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading. Of the non-neuro-epithelial tumours studied relatively high residual activities were found for pyruvate kinase in haemangioblastomas, chromophobe adenomas, and craniopharyngiomas. This was also found in an arteriovenous malformation. Other non-neuroepithelial tumours showed much less residual activity. These included benign tumours, meningiomas, neurilemmomas, malignant metastatic tumours, and fibrosarcomas. It was also found in cavernomas. The determination of pyruvate kinase activity in the presence of alanine may be useful for the diagnosis and treatment of intracerebral tumours, in particular gliomas of adults.The alanine inhibition test is a reliable quantitative procedure. It can be performed in 10 minutes, and may well fit in the scope of a surgical procedure.     

Evaluation of brain tumour laser surgery

Summary A surgical carbon dioxide laser unit (laser) has been used since 1977 in twentyfive cases of various brain tumours, including ten meningiomas (four sphenoid ridge, two parasagittal, two falx, one olfactory, one posterior fossa), eleven gliomas (seven glioblastoma, four astrocytoma), two metastatic brain tumours, one haemangioblastoma, and one arteriovenous malformation (AVM).The criteria for laser use, as based on evaluation and location of meningioma, were: grade 1, convenient but adjuvant; grade 2, also necessary; grade 3, indispensable. The laser is obligatory in sphenoid ridge meningioma in order to peel the tumour away from the internal carotid artery, middle cerebral artery, cavernous sinus etc. The grade of necessity for laser use is therefore either 2 or 3. In convexity or parasagittal meningioma, on the other hand, the necessity grade is either 1 or 2.In the glioma group hemorrhage in seven cases of glioblastoma was easily laser-controlled, and the tumours were wasted away in a short time through vaporization, with minimum mechanical effect on adjacent tissue. The laser is therefore very useful in cases of glioma, especially glioblastoma, considering the shortened operating time, decreased blood loss, and extended area of tumour resection.Laser surgery is proposed as being most appropriate, mainly for its vaporizing and coagulating functions, in cases of brain tumour involving the elderly and poor risk cases.     

Radiation-induced gliomas: a comprehensive review and meta-analysis

By conducting a systemic search of the PubMed database, we performed a comprehensive literature review to characterize secondary gliomas following radiotherapy treatment and to determine the most appropriate treatment strategy. Our analysis included 296 cases of radiation-induced gliomas. The primary lesion was characterized as a hematological malignancy in 104 cases (35.1 %), pituitary adenoma in 35 (11.8 %), craniopharyngioma in 19 (6.4 %), medulloblastoma in 38 (12.8 %), germ cell tumor in 13 (4.3 %), low-grade glioma in 28 (9.4 %), cancer/sarcoma in 12 (4.0 %), scalp region disease in 15 (5.0 %), meningioma/schwannoma in 13 (4.3 %), metastatic brain tumor in 5 (1.6 %), and other types (e.g., arteriovenous malformations and angiomas) in 14 (4.7 %). The average age of onset for primary lesions was 16.0?±?15.8 years, and the average radiation dose delivered to the primary lesion was 37.6?±?20.0 Gy. Secondary gliomas could be divided into grade I (1), grade II (32), grade III (88), and grade IV (173) tumors. The median overall survival for all glioma cases was 11 months (95 % confidence interval [CI], 9–12), with a 2-year survival rate of 20.2 %. On multivariate analysis, combined modality treatment and the latency period from the radiotherapy treatment to the glioma diagnosis were variables associated with the overall survival of patients with grade III/IV secondary gliomas. For patients treated with cranial radiotherapy, the risk of secondary glioma incidence warrants a longer follow-up period beyond the standard time frame typically designated for determining the risk of primary tumor relapse. Moreover, combination therapy is a potential treatment option for radiation-induced gliomas.     

Immunohistochemical detection and correlation between MHC antigen and cell-mediated immune system in recurrent glioma by APAAP method.

As part of an on-going clinical trial of immunotherapy for recurrent malignant gliomas, using alkaline phosphatase-anti-alkaline phosphatase method with monoclonal antibodies, we investigated the correlation between expression of the major histocompatibility complex (MHC) and the subpopulation of tumor-infiltrating lymphocytes (TILs) in 38 glioma specimens (20 grade IV, 11 grade III, and 7 grade II) from 33 patients. Thirty specimens (78.9%) were positive to class I MHC antigen and 20 (52.6%) were positive to class II MHC antigen. The correlations between class I MHC antigen expression and the number of infiltrating T8 (p less than 0.01), and also between class II MHC antigen expression and the number of infiltrating T4 (p less than 0.05) were significant. We conclude that TILs are the result of immunoreaction (host-defense mechanism). 31.6% of specimens had perivascular infiltration of T cells. The main infiltrating lymphocyte subset in moderate to marked perivascular cuffing was T4. Our results may indicate that lack of MHC antigen on the glioma cell surface has a share in the poor immunogenicity in glioma-bearing patients. In addition, considering the effector/target ratio, the number of infiltrating lymphocytes against glioma cells was too small, so the immunological intervention seems to be essential in glioma therapy. Previous radiation therapy and chemotherapy, including steroid therapy, did not influence lymphocyte and macrophage infiltration.     

Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma

Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 +/- 0.28 (mean +/- standard deviation), which was significantly higher than the 0.38 +/- 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 +/- 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma.     

脑胶质瘤脑脊液循环肿瘤细胞监测的临床意义

目的探讨脑胶质瘤脑脊液循环肿瘤细胞监测的临床意义。方法选取内蒙古自治区人民医院神经外科2017年1月至2020年1月收治脑胶质瘤患者60例,均行外科手术治疗。采用免疫荧光原位杂交技术(FISH)法检测循环肿瘤细胞(CTC)。比较术前、术后14 d和术后3个月CTC阳性率;不同病理特征CTC阳性率;不同预后CTC阳性率。采用Kaplan-Meier法计算9~45个月患者生存率并绘制生存分析函数曲线。采用Cox回归模型对患者预后因素进行多因素分析,探讨影响脑胶质瘤术后患者生存的因素。结果术后14 d和术后3个月CTC阳性率低于术前(F=3.315,P<0.05),差异有统计学意义;术后3个月CTC阳性率低于术后14 d(χ2=5.714,P<0.05),差异有统计学意义。不同性别、年龄和体重指数CTC阳性率比较差异无统计学意义(χ2=2.000、1.047、0.012,P>0.05);Ⅲ~Ⅳ级CTC阳性率阳性率高于Ⅰ~Ⅱ级(χ2=15.227,P<0.05),差异有统计学意义。纳入60例患者随访9~45个月,随访时间(24.63±6.97)个月,总生存时间(21.87±4.56)个月,随访末预后良好19例、预后不良41例。预后不良组CTC阳性率(85.37%)高于预后良好组(15.79%)(χ2=27.065,P<0.05),差异有统计学意义。经多因素Cox比例风险回归分析显示,病理分级和CTC阳性为影响脑胶质瘤患者预后不良危险因素。结论脑脊液CTC在脑胶质瘤中呈高表达,且与病理分级和预后密切相关,为影响预后危险因素。     

The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours

Summary The monoclonal antibody Ki-67 has been tested as a marker of proliferating cells in 52 stereotactic brain tumour biopsies. The antibody reacts with a nuclear protein expressed in G₁,S, G₂n and Mphases of the cell cycle. Using the immunoperoxidase technique on squash preparations the percentage of Ki-67 positive cells was determined as a fraction of the total number of tumour cells present. This Ki-67 index was in close correlation with the histological grade. Highest values were found in a pineal germinoma (46.3%) and in 3 primary cerebral non-Hodgkin lymphomas (mean 39.5%). Among the gliomas, the highest fraction of proliferating cells was seen in 2 anaplastic paediatric brain stem gliomas (mean 17.4%) and in an anaplastic ependymoma (12.5%). Anaplastic astrocytomas and glioblastomas varied considerably with mean values of 9.5% and 8%, respectively. To some extent this variability may reflect tumour heterogeneity which is more likely to manifest in small stereotactic samples than in large tissue specimens obtained during open surgery. Pilocytic astrocytomas, mixed gliomas and fibrillary astrocytomas had moderate to low percentages.Ki-67 staining of squash preparations can easily be performed on a rountine basis and is, in our experience, superior to frozen sections. This method allows the determination of the growth fraction of an individual tumour and could become an important additional criterion for the decision among alternative and potentially harmful therapeutic regimens.     

Proteomic analysis of gliomas

Primary malignant brain tumours (anaplastic glioma and glioblastoma) display heterogenous histopathology and diverse genetic abnormalities. These tumours remain incurable with no significant improvement in median survival times in the last 20 years, despite significant technological advances in surgery and radiotherapy, and mechanistic insights into their aetiology. Recent clinical trials suggest molecular characterization of tumours is essential in guiding both therapy and predicting prognosis. Genetic insight into tumour biology and increasingly proteomic technology has opened new avenues for novel applied clinical research. Protein expression in human malignant glioma and matched normal brain tissues can now be reliably analysed using quantitative proteomic techniques, the most accessible of which is two-dimensional gel electrophoresis (2DGE) and matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry from which differentially expressed proteins can be identified and characterized. The potential of using differential proteomic profiling in gliomas to identify prognostic markers and to gain insight into tumour biology is currently being investigated. The current status of proteomic technology, its application to gliomas and the utility of such translational studies is reviewed.     

Axial transverse computerized tomography in 73 glioblastomas

Summary Among 2,600 patients, examined by computerized tomography, 404 had brain tumours, which were gliomas in 150 cases. There were 73 glioblastomas. Examination was performed according to Ambrose's method using an intravenous injection of 1 ml 60% contrast medium per kg body weight. Thus 98% of all gliomas could be demonstrated. Glioblastomas are shown in three different forms: an annular type (55%), a nodular type (18%), and a combined type (27%). Perifocal oedema is found in 88% of glioblastomas. The oedema most frequently belongs to grade II or III. Differential diagnosis of gliomas, abscess, metastases and other tumours with central necrosis are discussed.Presented at the Symposium on Glioblastoma, Graz, October 25, 1975.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.