Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages T(a)-T(1)), 65 muscle-invasive TCCs (ITCCs, stages T(2)-T(4)), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.     

Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma

Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n?=?50). We then made correlative analysis of protein overexpression using the Kaplan–Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.     

Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer

Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0. 021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.     

The association of Crk-like adapter protein with poor prognosis in glioma patients

Glioma is the most common of brain tumors that greatly affects patient survival. In our precious study, Crk-like adapter protein (CrkL) was identified as a key regulator in glioblastoma development [1]. Here, we aimed to investigate the correlation of CrkL with patient prognosis as well as pathological indicators. Immunohistochemistry was available to evaluate CrkL expression in 49 gliomas of distinct malignancy grade, and positive stained sites were analyzed. CrkL protein was detected in cell lines by Western blot as well. We observed CrkL protein stained in 59.2 % (29 out of 49) of all glioma tissues, including 41.4 % of low-grade (I + II) gliomas, and 85.0 % of high-grade (III + IV) gliomas. Of four grades, grade IV exhibited the highest CrkL level. CrkL protein was also identified in cell lines NHA, U87, U251, T98G, and A172 by Western blot. On the other hand, CrkL expression was significantly associated with the patient’s age and WHO grade, and patients with high CrkL expression had a significantly shorter median survival time (17 months) than those (median survival time 52 months) with low CrkL expression (p?<?0.001). According to Cox regression, CrkL can be suggested as an independent prognostic factor. In conclusion, CrkL is differently expressed in different grades of gliomas, and correlated to WHO grade. CrkL also independently indicates poor prognosis in old glioma patients, which can further be recommended as an effective prognostic biomarker or therapeutic target.     

ABCG2在胶质瘤组织中的表达及意义

背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member 2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚.本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义.方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况.结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(X2=10.710,P=0.001).在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%.在多种正常组织中亦有不同程度的表达.在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布.结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布.     

Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues: implications for prostate carcinogenesis and progression of prostate cancer

OBJECTIVE: Prostate stem cell antigen (PSCA) is a recently defined homolog of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The objective of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (PCa) and to validate it as a potential molecular target for diagnosis and treatment of PCa. METHODS: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections of 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (PCa) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCA-positive staining cells in the specimens. We then compared the PSCA expression between BPH, PIN and PCa tissues and analyzed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in PCa. RESULTS: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that observed in high grade PIN (HGPIN) and PCa. Moderate to strong PSCA protein and mRNA expression were noted in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) PCa specimens examined by IHC and ISH analyses, and their statistical significance was compared with BPH (20%) and low-grade PIN (22.2%) specimens (P < 0.05). The expression level of PSCA increased with a higher Gleason grade, advanced stage and progression to androgen-independence (P < 0.05). In addition, IHC and ISH staining revealed a high degree of correlation between PSCA protein and mRNA overexpression. CONCLUSIONS: Our data demonstrate that PSCA as a new cell surface marker is overexpressed in a majority of cases of human PCa. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence and speculatively with prostate carcinogenesis. PSCA may possess prognostic utility and may be a promising molecular target for diagnosis and treatment of PCa.     

Expression of the tumor-rejection antigen SART1 in brain tumors

We have reported a tumor-rejection antigen, SART1(259), possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs) in epithelial-cancer patients. This study investigated the expression of SART1(259) antigen in brain tumors, to explore for a potential molecule for use in specific immunotherapy of patients with brain tumors. The SART1(259) antigen was detected in the cytosol fraction of 13 of 18 (72%) glioma cell lines and in 12 of 34 (35%) brain-tumor tissues, with a higher rate of expression among malignant gliomas (5/10, 50%) and schwannomas (3/4). HLA-A24-restricted and SART1-specific CTLs recognized the HLA-A24+ and SART1(259)+ glioma cells, and the levels of recognition correlated both with HLA-A24-antigen expression level and with the concentration of the SART1 peptide antigen. Therefore, the SART1(259) antigen could be a target molecule for specific immunotherapy of patients with brain tumors expressing HLA-class-1 antigens.     

Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration.

PURPOSE: There are a limited number of noninvasive methods available for the monitoring of neoplastic disease in the central nervous system. The goal of our study was to find reliable markers that could be used for disease monitoring as well as to identify new targets for the therapeutic intervention for malignant astrocytoma (WHO grades 3 and 4). EXPERIMENTAL DESIGN: We employed proteomic techniques to identify secreted proteins in the cerebrospinal fluid that were specific to patients with malignant astrocytoma. RESULTS: Among 60 cerebrospinal fluid samples of patients with various central nervous system diseases, attractin was consistently found to be elevated in the samples of patients with malignant astrocytoma. To independently validate these results, we examined attractin expression in a new set of 108 normal and tumoral brain tissue specimens and found elevated expression in 97% of malignant astrocytomas, with the highest levels in grade 4 tumors. Using immunohistochemistry, we further showed that attractin is produced and secreted by the tumor cells. Finally, we showed that cerebrospinal fluid from brain tumor patients induces glioma cell migration and that attractin is largely responsible for this promigratory activity. CONCLUSIONS: Our results find attractin to be a reliable secreted marker for high-grade gliomas. Additionally, our migration studies suggest that it may be an important mediator of tumor invasiveness, and thus, a potential target in future therapies.     

Constitutive activation of c-Jun N-terminal kinase correlates with histologic grade and EGFR expression in diffuse gliomas

The c-Jun NH2–terminal kinase (JNK), which belongs to mitogen-activated protein kinase family, plays a major role in apoptosis in various cell types. JNK activation, however, also contributes to proliferation, survival, and tumorigenesis in some tumors, including gliomas. In this study, we used an immunohistochemical approach to examine the activation status of JNK of 226 gliomas in a high-density tissue microarray comprising all WHO codified WHO diffuse glioma subtypes and grades. The results were correlated with grade and EGFR expression status. Constitutively activated JNK (pJNK) was detected in 90.5%, 62.9% and 17.5% of WHO grade IV, III and II gliomas, respectively (p < 0.001). pJNK expression was not detected in the astrocytes or oligodendrocytes of any of 10 normal cerebral and cerebellar brain tissue samples. Among the 76 diffuse gliomas that exhibited EGFR expression, 63 (82.9%) were positive for pJNK. In contrast, only 50% (36/72) of the gliomas that were negative for EGFR were positive for pJNK (p < 0.0001). Overexpression of EGFR vIII in U87 cells or EGF treatment of U87-EGFR stable cells led to marked increase in JNK activation compared to parental U87 cells. Our data thus provide strong support for the hypothesis that JNK activation plays a role in the tumorigenesis and/or progression of diffuse gliomas, and suggests that EGFR is involved in constitutive JNK activation in diffuse gliomas. The ability to inhibit JNK activation might confer increased sensitivity to therapeutic modalities targeting this pathway. Jian Yi Li and Hua Wang contributed equally to this work.     

Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas

The karyopherin (KPNA) protein family is involved in nucleocytoplasmic trafficking. Increased KPNA levels have been found to predict poor prognosis for a variety of solid tumors, including breast, ovarian, cervical, and prostate cancer, and melanoma. The purpose of this study was to evaluate karyopherin a2 as novel biomarker for astrocytic gliomas of WHO grades II-IV. We semiquantitatively measured nuclear expression of karyopherin a2 and the MIB1 labeling index, by immunohistochemical analysis, for 94 primary (23 astrocytomas WHO grade II, 24 astrocytomas WHO grade III, 47 glioblastomas) and 12 recurrent gliomas. In addition, IDH1 mutation status and Nijmegen breakage syndrome 1 protein expression were assessed, by immunohistochemical analysis, for all 71 malignant (WHO grade III and IV) and all 94 primary gliomas, respectively. Statistical analysis was performed by use of standard techniques. Karyopherin a2 expression correlated significantly with histological grade (p?5?years was seen only in those with KPNA2 expression levels ≤1?% (p?=?0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas.     

胶质瘤miR-29c 表达异常减少及其对肿瘤细胞增殖的影响*

目的:探讨microRNA- 29c（miR-29c）在胶质瘤中的表达及其对细胞分裂周期蛋白42（CDC 42）的调控作用和对细胞增殖的影响。方法:用锁定寡核苷酸原位杂交法和免疫组织化学法检测60例不同级别胶质瘤及10例非肿瘤对照脑组织中miR-29c和CDC 42的表达水平，实时荧光定量RT-PCR、Westernblot及MTS 法分别检测U87MG细胞中miR-29c 瞬时表达、CDC 42mRNA和蛋白表达及其对胶质瘤细胞增殖的影响。结果:各级别胶质瘤的miR-29c 表达水平均明显低于非肿瘤对照脑组织，且随肿瘤级别升高而显著降低，各组间的差异均有统计学意义（P<0.001）。 而CDC 42表达水平则呈相反趋势，其表达水平随胶质瘤良恶性级别增加相应升高，除Ⅰ～Ⅱ级组与非肿瘤对照组之间外，其余各组间的差异均有统计学意义（P<0.001）。 与对照组相比，miR-29c 转染组的CDC 42mRNA（P<0.001）和蛋白表达水平（P<0.01）均明显降低。miR-29c 转染组细胞的增殖能力明显低于U87MG空白对照组和Scr转染组（P<0.05）。 结论:miR-29c 是胶质瘤的抑瘤miRNA，其表达水平可作为评价胶质瘤良恶性级别的重要参考指标。miR-29c 在胶质瘤中表达减少解除了其对靶基因CDC 42转录后水平的抑制作用，并导致肿瘤细胞无限增殖。表明miR-29c 表达异常减少可能是引起胶质瘤发生、发展的关键事件。      

Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors.

PURPOSE: To determine the frequency of abnormalities in human leukocyte antigen (HLA) and antigen processing machinery (APM) component expression in malignant brain tumors. This information may contribute to our understanding of the immune escape mechanisms used by malignant brain tumors because HLA antigens mediate interactions of tumor cells with the host's immune system. EXPERIMENTAL DESIGN: Eighty-eight surgically removed malignant astrocytic tumors, classified according to the WHO criteria, were stained in immunoperoxidase reactions with monoclonal antibody recognizing monomorphic, locus-specific, and allospecific determinants of HLA class I antigens, beta2-microglobulin, APM components (LMP2, LMP7, TAP1, TAP2, calnexin, calreticulin, and tapasin), and HLA class II antigens. RESULTS: HLA class I antigens were lost in approximately 50% of the 47 glioblastoma multiforme (GBM) lesions and in approximately 20% of the 18 grade 2 astrocytoma lesions stained. Selective HLA-A2 antigen loss was observed in approximately 80% of the 24 GBM lesions and in approximately 50% of the 12 grade 2 astrocytoma lesions stained. HLA class I antigen loss was significantly (P < 0.025) correlated with tumor grade. Among the APM components investigated, tapasin expression was down-regulated in approximately 20% of the GBM lesions analyzed; it was associated, although not significantly, with HLA class I antigen down-regulation and tumor grade. HLA class II antigen expression was detected in approximately 30% of the 44 lesions analyzed. CONCLUSION: The presence of HLA antigen defects in malignant brain tumors may provide an explanation for the relatively poor clinical response rates observed in the majority of the T cell-based immunotherapy clinical trials conducted to date in patients with malignant brain tumors.     

周期蛋白依赖性激酶1在胶质瘤组织中的表达及其沉默对胶质瘤细胞恶性表型的影响

目的探讨周期蛋白依赖性激酶1(CDK1)在胶质瘤组织中的表达及其沉默对胶质瘤细胞恶性表型的影响。方法利用自建的人脑胶质瘤体外细胞系SHG44及其移植瘤组织、脑肿瘤干细胞、神经干细胞、不同恶性程度的胶质瘤手术标本构建组织芯片,免疫组化染色检测其CDK1蛋白表达;应用RNA干扰技术使CDK1在SHG44细胞及其移植瘤组织中沉默,观察其随后发生的表型变化。结果CDK1在临床标本中随胶质瘤恶性程度升高表达强度增加,Ⅰ-Ⅳ级的阳性表达率分别为22.2%、40.0%、69.6%和78.6%(P=0.01)。体外培养的人脑胶质瘤SHG44细胞球体和裸小鼠皮下移植瘤CDK1表达强度均较高,而神经干细胞和脑肿瘤干细胞球体表达强度低,在细胞增殖活性高的人胚胎脑组织和裸小鼠骨髓中CDK1亦高表达,但在正常成人脑组织低表达。C1和C3体外转染SHG44细胞后,将细胞周期阻滞在G2/M期,而且诱导了凋亡,细胞凋亡率分别上升至27.8%和36.5%。CDK1沉默的裸鼠皮下移植瘤瘤重明显降低,细胞凋亡率为57.1%,明显高于对照组(8.5%)。结论CDK1的高表达呵促进胶质瘤的发生和发展,CDK1沉默后的肿瘤细胞恶性表型可得到控制,CDK1可作为胶质瘤病因分子行进一步研究。     

MSP58基因表达水平与人脑胶质瘤恶性度的关系

目的:观察MSP58基因表达水平与人脑胶质瘤恶性度的关系.方法:在41例按WHO分类和分级标准为Ⅰ-Ⅳ级的人脑胶质瘤标本、4株人脑胶质瘤细胞系(U251,U87,BT325和SHG44)以及6例正常脑组织标本中,运用半定量RT - PCR及蛋白质印迹法检测MSP58 mRNA和蛋白的表达水平.结果:MSP58 mR-NA和蛋白在人脑胶质瘤组织中存在表达,其表达水平随人脑胶质瘤恶性度的增加而升高.在正常脑组织和恶性脑胶质瘤之间,以及脑胶质瘤Ⅰ-Ⅳ级病理级别间比较均有显著差异.MSP58 mRNA和蛋白在U251、U87、BT325和SHG44细胞中均有高表达.结论:MSP58 mRNA和蛋白在人脑胶质瘤中高表达,其表达水平与脑胶质瘤的恶性度有关,提示MSP58在脑胶质瘤的形成和恶性演进中具有重要作用.     

Elevated expression of chloride intracellular channel 1 is correlated with poor prognosis in human gliomas

Background

Chloride intracellular channel 1 (CLIC1) is expressed ubiquitously in human tissues and is involved in the regulation of cell cycle, cell proliferation and differentiation. Recent studies have shown that CLIC1 is highly expressed in several human malignant tumors. However, its roles in human gliomas are still unclear. The aim of this study was to investigate the clinicopathological significance and prognostic value of CLIC1 expression in human gliomas.

Methods

CLIC1 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay and immunohistochemistry. Its association with clinicopathological factors or prognosis in patients with gliomas was statistically analyzed.

Results

The expression of CLIC1 at both mRNA and protein levels was significantly increased in high-grade (Grade III~IV) glioma tissues compared with that in low-grade (Grade I~II) and nonneoplastic brain tissues, and was up-regulated with ascending tumor World Health Organization (WHO) grades. The elevated expression of CLIC1 protein was also significantly correlated with low Karnofsky performance score (KPS) (P=0.008). Moreover, both univariate and multivariate analysis shown that high CLIC1 expression was significantly associated with poor prognosis in patients with gliomas (P<0.001 and P=0.01, respectively). In particular, the elevated CLIC1 expression also correlated with shorter overall survival in different glioma subgroups stratified according to the WHO grading.

Conclusions

Our data provide the first evidence that CLIC1 expression might play an important role in the regulation of aggressiveness in human gliomas. The elevated expression of CLIC1 might represent a valuable prognostic marker for this disease.     

Gamma-glutamyl transferase expression in higher-grade astrocytic glioma

Increased expression of gamma-glutamyltransferase (GGT) has been detected in a range of human malignancies and is thought to be involved in neoplastic proliferation and treatment resistance. Since GGT expression and its role in malignant glioma biology remain largely unknown, we investigated this phenomenon by immunostaining 26 higher-grade human astrocytic gliomas (WHO grades III and IV) with a monoclonal anti-GGT-antibody (138H11). Further, human pancreatic GGT cDNA was used for liposome-mediated transfection of 9L gliosarcoma cells. GGT-expressing and control 9L cells were cultured in media containing different amounts of essential amino acids and/or cytotoxic agents. Cell viability was evaluated by microplate MTT assay. Immunohistochemical staining of tumor specimens demonstrated that GGT expression is a frequent feature of higher-grade human astrocytic gliomas, but not of normal brain tissue. Human tumors were strongly GGT-positive in 6 of 7 cases of grade III astrocytoma, and in 12 of 19 grade IV astrocytoma (glioblastoma multiforme, GBM) cases. In the cell culture model, 9L-GGT cells had a growth advantage over control cells in cysteine-deficient medium. but not in standard or glutamine-free medium. No significant difference in numbers of viable cells of either clone was found in media containing the alkylating drug BCNU (5-200 microg/ml). In conclusion, GGT is expressed in a high percentage of human WHO grade III astrocytomas and GBM, but not in normal brain tissue. This molecule seems to give neoplastic cells a moderate growth advantage under in vivo conditions.     

Hematopoietic- and Neurologic-Expressed Sequence 1 Expression in the Murine GL261 and High-Grade Human Gliomas

The hematopoietic- and neurologic-expressed sequence 1 (Hn1) gene encodes a highly conserved protein that is expressed in developing and regenerating tissues. In this study, Hn1 expression was evaluated in human and murine malignant gliomas. Hn1 mRNA and protein were detected in the murine GL261 glioma cell line and in GL261 brain tumors in vivo. HN1 is also expressed in human U118MG and U87MG cell lines. Evaluation of human brain tumors using an anti-Hn1 polyclonal antibody detected strong immunoreactivity in high-grade (WHO III and IV) malignant gliomas. The rate of GL261 cell proliferation in vitro was unaltered by Hn1 depletion using an anti-Hn1 siRNA. However, tumors established from Hn1-depleted GL261 cells formed significantly smaller volumes than those established from control-treated cells. These data suggest a role for Hn1 in the biology of malignant brain tumors.     

Vascular Endothelial Growth Factor (VEGF) in Astrocytic Gliomas – A Prognostic Factor?

Survival in astrocytic gliomas is closely related to WHO tumor grade. Within one tumor grade, especially in grade II and III tumors, the clinical course is variable and can hardly be predicted by histological criteria. Neovascularization is a neuropathological hallmark in high grade gliomas and angiogenic factors may play an important role in malignant tumor progression. Therefore, 162 primary astrocytic gliomas (57 astrocytomas WHO grade II, 27 astrocytomas WHO grade III and 78 glioblastomas WHO grade IV) were investigated immunohistochemically for expression of vascular endothelial growth factor (VEGF), which is considered to represent the main angiogenic factor in astrocytic gliomas. Clinical data known to influence prognosis were documented. VEGF expression was found in 21 of 57 astrocytomas WHO grade II (36.8%), in 18 of 27 astrocytomas WHO grade III (66.7%) and in 50 of 78 glioblastomas (64.1%). A strong correlation between VEGF expression and survival was found within the whole study group, however, within one tumor grade no such correlation was obvious. In a multifactorial analysis VEGF expression was not found to be an independent prognostic factor in astrocytic gliomas.