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Sample records for human malignant meningioma

  1. In vitro culture of various typed meningiomas and characterization of a human malignant meningioma cell line (HKBMM).

    PubMed

    Ishiwata, Isamu; Ishiwata, Chieko; Ishiwata, Emiko; Sato, Yoshiro; Kiguchi, Kazushige; Tachibana, Toshiaki; Ishikawa, Hiroshi

    2004-12-01

    We placed on culture the 13 cases of meningiomas, succeeded in making a primary culture of 10 cases and maintained 5 cases in vitro over considerable period of time (over three month), and one cell line derived from a malignant meningioma were established. In the early period of the primary culture, meningioma cells were spindle- or round-shaped cells. In the case of psammomatous type, the cultured cells were characterized as forming psammoma bodies. A cell line designated "HKBMM" was established from a human malignant meningioma occurred from frontal lobe. This line grew well without interruption for 5 years and was subcultivated over 120 times. The cells were spindle and fibrous in shape, and neoplastic and pleomorphic features, and multilayering without contact inhibition. The cells proliferated rapidly, and the population doubling time was about 29 hours. The chromosome number showed a wide distribution of aneuploidy. The mode was in the diploid range. The culture cells were easily transplanted into the subcutis of nude mice and produced the tumor resembling the original tumor.

  2. Meningioma after radiotherapy for malignancy.

    PubMed

    Morgenstern, Peter F; Shah, Kalee; Dunkel, Ira J; Reiner, Anne S; Khakoo, Yasmin; Rosenblum, Marc K; Gutin, Philip

    2016-08-01

    Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04-33years). The mean radiation dose was 34Gy (range 16-60Gy) and latency time to meningioma was 26years (range 8-51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy.

  3. Meningioma after radiotherapy for malignancy

    PubMed Central

    Morgenstern, Peter F.; Shah, Kalee; Dunkel, Ira J.; Reiner, Anne S.; Khakoo, Yasmin; Rosenblum, Marc K.; Gutin, Philip

    2017-01-01

    Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1 years (range 0.04–33 years). The mean radiation dose was 34 Gy (range 16–60 Gy) and latency time to meningioma was 26 years (range 8–51 years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8 years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy. PMID:27068012

  4. Case Report: Pulmonary metastases of malignant meningioma

    PubMed Central

    Basunaid, Suhail; Franssen, Frits M.E.; Accord, Ryan; Hamid, Myrurgia Abdul; Mahesh, Shekar; Baumert, Brigitta G.; Schijns, Olaf E.M.G.

    2014-01-01

    Meningioma accounts for approximately one-third of primary central nervous system tumors. Most meningiomas are benign, although up to one third are classified as atypical or malignant. We describe a 63-year Caucasian male presenting with pleural metastases from an intracranial meningioma. Distant metastases from meningiomas are infrequently found in clinical practice and mostly are associated with atypical or malignant meningiomas. There is no standard treatment; however surgical resection of both the primary and metastatic lesions is the safest therapy. The overall prognosis of atypical meningiomas is poor. Our patient died one week after discharge from our hospital. PMID:25254095

  5. Intraspinal meningioma with malignant transformation and distant metastasis.

    PubMed

    Ito, Kenyu; Imagama, Shiro; Ando, Kei; Kobayashi, Kazuyoshi; Shido, Yoji; Go, Yoshida; Arima, Hideyuki; Kanbara, Shunsuke; Hirose, Takanori; Matsuyama, Yukihiro; Nishida, Yoshihiro; Ishiguro, Naoki

    2017-02-01

    Meningioma is typically considered to be a benign tumor. Malignant transformation and metastasis of meningiomas are rare. Moreover, most meningiomas are intracranial, and there are few reports on intraspinal meningiomas. This report aimed to describe the clinical features and pathological findings of a case of malignant transformation and distant metastasis of intraspinal meningioma, with a review of the literature. A 44-year-old man with a bilateral lower limb paresis was diagnosed with an intradural extramedullary tumor of the thoracic spine. Primary tumor resection was performed, and the histological findings revealed atypical meningioma. The meningioma recurred 2 years after the primary surgery, and a second resection was performed, but only partial resection was possible because of decreased motor evoked potential. At age 48, the patient's lower limb weakness returned, and a third resection was performed, and the histological finding remained atypical meningioma. At age 54, the tumor increased and stereotactic irradiation was performed. At age 60, the patient was diagnosed with metastatic tumors of the rib, lumbar vertebra, cervical spine, and sacrum. Biopsy of the rib metastatic tumor was performed, and the histological findings revealed anaplastic meningioma. This case is the first report of an intraspinal meningioma that transformed from atypical to anaplastic meningioma with distant hematogenous metastasis.

  6. Intraspinal meningioma with malignant transformation and distant metastasis

    PubMed Central

    Ito, Kenyu; Imagama, Shiro; Ando, Kei; Kobayashi, Kazuyoshi; Shido, Yoji; Go, Yoshida; Arima, Hideyuki; Kanbara, Shunsuke; Hirose, Takanori; Matsuyama, Yukihiro; Nishida, Yoshihiro; Ishiguro, Naoki

    2017-01-01

    ABSTRACT Meningioma is typically considered to be a benign tumor. Malignant transformation and metastasis of meningiomas are rare. Moreover, most meningiomas are intracranial, and there are few reports on intraspinal meningiomas. This report aimed to describe the clinical features and pathological findings of a case of malignant transformation and distant metastasis of intraspinal meningioma, with a review of the literature. A 44-year-old man with a bilateral lower limb paresis was diagnosed with an intradural extramedullary tumor of the thoracic spine. Primary tumor resection was performed, and the histological findings revealed atypical meningioma. The meningioma recurred 2 years after the primary surgery, and a second resection was performed, but only partial resection was possible because of decreased motor evoked potential. At age 48, the patient’s lower limb weakness returned, and a third resection was performed, and the histological finding remained atypical meningioma. At age 54, the tumor increased and stereotactic irradiation was performed. At age 60, the patient was diagnosed with metastatic tumors of the rib, lumbar vertebra, cervical spine, and sacrum. Biopsy of the rib metastatic tumor was performed, and the histological findings revealed anaplastic meningioma. This case is the first report of an intraspinal meningioma that transformed from atypical to anaplastic meningioma with distant hematogenous metastasis. PMID:28303067

  7. SU11657 Enhances Radiosensitivity of Human Meningioma Cells

    SciTech Connect

    Milker-Zabel, Stefanie Bois, Angelika Zabel-du; Ranai, Gholamreza; Trinh, Thuy; Unterberg, Andreas; Debus, Juergen; Lipson, Kenneth E.; Abdollahi, Amir; Huber, Peter E.

    2008-03-15

    Purpose: To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells. Methods and Materials: Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects. Results: Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells. Conclusion: Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

  8. Malignant progression to anaplastic meningioma: Neuropathology, molecular pathology, and experimental models.

    PubMed

    Cimino, Patrick J

    2015-10-01

    Meningioma is a common adult intracranial tumor, and while several cases are considered benign, a subset is malignant with biologically aggressive behavior and is refractory to current treatment strategies of combined surgery and radiotherapy. Anaplastic meningiomas are quite aggressive and correspond to a World Health Organization (WHO) Grade III tumor. This highly aggressive phenotype mandates the need for more efficacious therapies. Designing rational therapies for treatment will have its foundation in the biologic understanding of involved genes and molecular pathways in these types of tumors. Anaplastic meningiomas (WHO Grade III) can arise from malignant transformation of lower grade (WHO Grade I/II) tumors, however there is an incomplete understanding of specific genetic drivers of malignant transformation in these tumors. Here, the current understanding of anaplastic meningiomas is reviewed in the context of human neuropathologic specimens and small animal models.

  9. Malignant intraventricular meningioma with craniospinal dissemination and concurrent pulmonary metastasis

    PubMed Central

    2014-01-01

    Background Malignant intraventricular meningiomas are quite rare and may spread along the craniospinal axis or extraneurally. However, simultaneous cerebrospinal dissemination and distal extraneural metastasis has seldom been reported. Case presentation A 51-year-old woman presented with recurrent anaplastic meningioma in the trigone of right lateral ventricle over a 1.5-year period. Suggested radiotherapy was refused after each operation. The patient showed a local relapse and dissemination around the previous tumoral cavity and along the spinal canal during the last recurrence. Left pulmonary metastasis was also found. She died despite multiple lesion resections. Conclusions Malignant intraventricular meningiomas are an uncommon subset of intracranial meningiomas, and have a great potential for intraneural and extraneural metastasis. Systemic investigation for metastasis is required after surgery, especially for those without adjuvant therapies. PMID:25073808

  10. Malignant meningioma of the cerebellopontine angle in a 2-year-old girl: a case report and literature review.

    PubMed

    Fan, Ming-Chao; Zhang, Xin; Wang, Qiao-Ling; Cheng, Lei; Dai, Cai-Yun; Yu, Dan; Sun, Peng

    2013-07-01

    Meningioma is a common intracranial tumor in adults. Pediatric cases account for approximately 1.5% of all intracranial meningiomas, and very few cases show malignant histological features. Primary pediatric malignant meningioma in the cerebellopontine angle is extremely uncommon. Herein, we report a 2-year-old girl with malignant meningioma in the cerebellopontine angle. The clinical features, diagnosis, and treatment protocol are discussed.

  11. Adoptive transfer of genetically modified Wilms' tumor 1–specific T cells in a novel malignant skull base meningioma model

    PubMed Central

    Iwami, Kenichiro; Natsume, Atsushi; Ohno, Masasuke; Ikeda, Hiroaki; Mineno, Junichi; Nukaya, Ikuei; Okamoto, Sachiko; Fujiwara, Hiroshi; Yasukawa, Masaki; Shiku, Hiroshi; Wakabayashi, Toshihiko

    2013-01-01

    Background Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat meningiomas. The goal of this study was to investigate the potential of build-in short interfering RNA-based Wilms' tumor protein (WT1)–targeted adoptive immunotherapy in a reproducible mouse model of malignant skull base meningioma that we recently established. Methods We compared WT1 mRNA expression in human meningioma tissues and gliomas by quantitative real-time reverse-transcription polymerase chain reaction. Human malignant meningioma cells (IOMM-Lee cells) were labeled with green fluorescent protein (GFP) and implanted at the skull base of immunodeficient mice by using the postglenoid foramen injection (PGFi) technique. The animals were sacrificed at specific time points for analysis of tumor formation. Two groups of animals received adoptive immunotherapy with control peripheral blood mononuclear cells (PBMCs) or WT1-targeted PBMCs. Results High levels of WT1 mRNA expression were observed in many meningioma tissues and all meningioma cell lines. IOMM-Lee-GFP cells were successfully implanted using the PGFi technique, and malignant skull base meningiomas were induced in all mice. The systemically delivered WT1-targeted PBMCs infiltrated skull base meningiomas and significantly delayed tumor growth and increased survival time. Conclusions We have established a reproducible mouse model of malignant skull base meningioma. WT1-targeted adoptive immunotherapy appears to be a promising approach for the treatment of difficult-to-treat meningiomas. PMID:23460320

  12. Malignant spinal meningioma in a CD-1 mouse.

    PubMed

    Balme, Emmanuelle; Roth, Daniel Robert; Perentes, Elias

    2008-08-01

    Spontaneous meningiomas are extremely rare tumors in small laboratory animals, except in some strains of rats and in the B6C3F1 mouse. We report the case of a male CD-1 mouse in poor health condition, with severe apathy and partial paresis of hindlegs. No macroscopic lesion was noticed at necropsy. Microscopic examination revealed the presence of a malignant meningioma (approximately 3mm in diameter) at the distal lumbar level of the spinal cord, invading the vertebral canal, and bilaterally the ventral and dorsal nerve roots and the dorsal root ganglia. The tumor displayed highly cellular sheets of polygonal cells with a well-delineated, abundant, eosinophilic cytoplasm and scarce fibrovascular stroma; epithelioid and sarcomatous areas were also present. The mitotic activity was moderate. Tumor cells expressed vimentin immunoreactivity and were negative for periodic acid-Schiff (PAS), silver impregnation for reticulin, chromogranin A, glial fibrillary acidic protein (GFAP), cytokeratin (CK) and S-100 protein. The diagnosis of malignant spinal meningioma was based on the morphologic features of the neoplasm, the evidence of local invasion and the immunohistochemical results.

  13. Malignant meningioma of the cerebellopontine angle in a 2-year-old girl: a case report and literature review

    PubMed Central

    Fan, Ming-Chao; Zhang, Xin; Wang, Qiao-Ling; Cheng, Lei; Dai, Cai-Yun; Yu, Dan; Sun, Peng

    2013-01-01

    Meningioma is a common intracranial tumor in adults. Pediatric cases account for approximately 1.5% of all intracranial meningiomas, and very few cases show malignant histological features. Primary pediatric malignant meningioma in the cerebellopontine angle is extremely uncommon. Herein, we report a 2-year-old girl with malignant meningioma in the cerebellopontine angle. The clinical features, diagnosis, and treatment protocol are discussed. PMID:23470145

  14. High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression.

    PubMed

    Goutagny, Stéphane; Nault, Jean C; Mallet, Maxime; Henin, Dominique; Rossi, Jessica Z; Kalamarides, Michel

    2014-03-01

    Meningiomas are common central nervous system tumors. The World Health Organization (WHO) defines three grades, predictive of the risk of recurrence. These tumors can relapse frequently and sometimes undergo malignant transformation. Maintenance of telomere length is a key process in malignant progression, and mutations in TERT promoter have recently been identified in various types of cancer. We sequenced the TERT promoter in 85 meningiomas from 73 patients. We found a high incidence of TERT promoter mutations in patients with meningiomas undergoing malignant histological progression (28%, n = 5/18 patients). In this subset of patients with histological progression, TERT promoter mutations were found in both the lowest and the highest grade tumors, and in both NF2-mutated and nonmutated samples. In contrast, one mutation was identified in 35 meningiomas without recurrence or progression, belonging to various histological grades. This sample was an aggressive meningioma in a patient who died shortly after surgery. Interestingly, tumors showing relapse without histological progression were not mutated for TERT promoter (n = 20). Finally, TERT promoter mutations were associated with a marked increase in TERT expression. Thus, TERT promoter mutations are pivotal genetic alterations involved in malignant progression of meningiomas and could be used as a biomarker to identify meningiomas at risk of malignant transformation. © 2013 International Society of Neuropathology.

  15. Expression and clinical value of EGFR in human meningiomas

    PubMed Central

    Backer-Grøndahl, Thomas; Ytterhus, Borgny; Granli, Unn S.; Lydersen, Stian; Gulati, Sasha; Torp, Sverre H.

    2017-01-01

    Background Meningiomas are common intracranial tumors in humans that frequently recur despite having a predominantly benign nature. Even though these tumors have been shown to commonly express EGFR/c-erbB1 (epidermal growth factor receptor), results from previous studies are uncertain regarding the expression of either intracellular or extracellular domains, cellular localization, activation state, relations to malignancy grade, and prognosis. Aims This study was designed to investigate the expression of the intracellular and extracellular domains of EGFR and of the activated receptor as well as its ligands EGF and TGFα in a large series of meningiomas with long follow-up data, and investigate if there exists an association between antibody expression and clinical and histological data. Methods A series of 186 meningiomas consecutively operated within a 10-year period was included. Tissue microarrays were constructed and immunohistochemically analyzed with antibodies targeting intracellular and extracellular domains of EGFR, phosphorylated receptor, and EGF and TGFα. Expression levels were recorded as a staining index (SI). Results Positive immunoreactivity was observed for all antibodies in most cases. There was in general high SIs for the intracellular domain of EGFR, phosphorylated EGFR, EGF, and TGFα but lower for the extracellular domain. Normal meninges were negative for all antibodies. Higher SIs for the phosphorylated EGFR were observed in grade II tumors compared with grade I (p = 0.018). Survival or recurrence was significantly decreased in the time to recurrence analysis (TTR) with high SI-scores of the extracellular domain in a univariable survival analysis (HR 1.152, CI (1.036–1.280, p = 0.009)). This was not significant in a multivariable analysis. Expression of the other antigens did not affect survival. Conclusion EGFR is overexpressed and in an activated state in human meningiomas. High levels of ligands also support this growth factor

  16. A role for matrix remodelling proteins in invasive and malignant meningiomas.

    PubMed

    Jalali, Shahrzad; Singh, Sanjay; Agnihotri, Sameer; Wataya, Takafumi; Salehi, Fatemeh; Alkins, R; Burrell, Kelly; Navab, Roya; Croul, Sidney; Aldape, Kenneth; Zadeh, Gelareh

    2015-02-01

    Meningiomas are one of the most common brain tumours in adults. Invasive and malignant meningiomas present a significant therapeutic challenge due to high recurrence rates and invasion into surrounding bone, brain, neural and soft tissues. Understanding the molecular mechanism of invasion could help in designing novel therapeutic approaches in order to prevent the need for repeat surgery, decrease morbidity and improve patient survival. The aim of this study was to identify the key factors and underlying mechanisms which govern invasive properties of meningiomas. Formalin-fixed paraffin-embedded (FFPE) as well as frozen tumour tissues from bone-invasive, non-invasive and malignant meningiomas were used for RNA microarray, quantitative real-time PCR or Western blot analyses. Malignant meningioma cell lines (F5) were subject to MMP16 downregulation or overexpression and used for in vitro and in vivo functional assays. Subdural xenograft meningioma tumours were generated to study the invasion of tumour cells into brain parenchyma using cell lines with altered MMP16 expression. We establish that the expression level of MMP16 was significantly elevated in both bone-invasive and brain invasive meningiomas. Gain- and loss-of-function experiments indicated a role for MMP16 in meningioma cell movement, invasion and tumour cell growth. Furthermore, MMP16 was shown to positively regulate MMP2, suggesting this mechanism may modulate meningioma invasion in invasive meningiomas. Overall, the results support a role for MMP16 in promoting invasive properties of the meningioma tumours. Further studies to explore the potential value for clinical use of matrix metalloproteinases inhibitors are warranted. © 2014 British Neuropathological Society.

  17. Meningioma

    MedlinePlus

    ... brain tissue, nerves or vessels may cause serious disability. Meningiomas occur most commonly in women, and are often discovered at older ages, but ... meningioma. Female hormones. Meningiomas are more common in women, ... tumors. Obesity. A high BMI (body mass index) is an established risk ...

  18. "Malignancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications.

    PubMed

    Perry, A; Scheithauer, B W; Stafford, S L; Lohse, C M; Wollan, P C

    1999-05-01

    Due to the rarity of malignancy in meningiomas, prior studies have been limited to small series. Controversies regarding the definition of malignant meningioma have complicated matters further. Although histologic anaplasia and extracranial metastasis are established criteria, the former is difficult to define and the latter represents a clinical finding. Traditionally, brain invasion has also been accepted, although this has recently been debated. In a prior series, the authors were unable to prove that 23 meningiomas that had invaded the brain were more aggressive than atypical meningiomas. The authors expanded their analysis to include 116 patients diagnosed with "malignant meningioma" due to brain invasion, frank anaplasia (20 mitoses per 10 high-power fields or histology resembling carcinoma, sarcoma, or melanoma), and/or extracranial metastasis. Patients were followed until death or for a median of 3.7 years. Survival time was highly variable, ranging from 10 days to 24 years. In multivariate analysis, histologic anaplasia (P=0.0035), subtotal resection (P=0.0038), 20 mitoses per 10 high-power fields (P=0.0071), and nuclear atypia (P=0.0068) were associated with poor survival. Of the 89 cases of meningioma that had invaded the brain, 23% were otherwise benign, 61% were otherwise atypical, and 17% were frankly anaplastic. Those without anaplasia behaved similarly to atypical meningiomas from the authors' prior study. In contrast, anaplastic meningiomas were usually fatal, associated with a median survival of 1.5 years. Based on these findings, the authors suggest that brain invasion constitutes an additional criterion for the diagnosis of atypical meningioma (World Health Organization [WHO] Grade II), whereas frank anaplasia indicates high grade (WHO Grade III-IV) malignancy.

  19. Extent of resection and overall survival for patients with atypical and malignant meningioma.

    PubMed

    Aizer, Ayal A; Bi, Wenya Linda; Kandola, Manjinder S; Lee, Eudocia Q; Nayak, Lakshmi; Rinne, Mikael L; Norden, Andrew D; Beroukhim, Rameen; Reardon, David A; Wen, Patrick Y; Al-Mefty, Ossama; Arvold, Nils D; Dunn, Ian F; Alexander, Brian M

    2015-12-15

    The prognosis for patients with atypical and malignant meningioma is guarded; whether the extent of resection is associated with survival-based outcomes in this population remains poorly defined. This study investigated the association between gross total resection (GTR) and all-cause mortality in patients with atypical and malignant meningioma. The Surveillance, Epidemiology, and End Results program was used to identify 575 and 64 patients betweens the ages of 18 and 70 years who were diagnosed with atypical and malignant meningioma, respectively, between 2004 and 2009. Multivariate Cox proportional hazards regression was used to assess the adjusted impact of GTR versus subtotal resection on all-cause mortality. Baseline patient characteristics were similar for patients who did undergo GTR and patients who did not undergo GTR. The 5-year overall survival rates were 91.3% (95% confidence interval [CI], 86.2%-94.5%) and 78.2% (95% CI, 70.0%-84.3%) for patients with atypical meningioma who did and did not undergo GTR, respectively, and 64.5% (95% CI, 45.9%-78.1%) and 41.1% (95% CI, 17.9%-63.1%) for patients with malignant meningioma who did and did not undergo GTR, respectively. After adjustments for available, pertinent confounding variables, GTR was associated with lower all-cause mortality in patients with atypical (hazard ratio, 0.39; 95% CI, 0.23-0.67; P < .001) and malignant meningioma (hazard ratio, 0.35; 95% CI, 0.15-0.81; P = .01). The extent of resection is a powerful predictor of outcome for patients with atypical and malignant meningioma. These data highlight the hazard associated with the presence of gross tumor bulk after surgery and suggest a value for more extensive resections that should be balanced against the additional potential morbidity. © 2015 American Cancer Society.

  20. Atypical and malignant meningiomas: Considerations for treatment and efficacy of radiotherapy.

    PubMed

    Cain, Sarah A; Smoll, Nicolas R; Van Heerden, J; Tsui, Alpha; Drummond, Katharine J

    2015-11-01

    The purpose of this study was to add to the current body of literature which is aimed at establishing the role of postoperative adjuvant radiotherapy (RT) in the treatment of atypical and malignant meningiomas. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The majority of meningiomas are benign, with atypical and malignant tumours accounting for only 6-18%. Utilising a prospective multi-institutional database, we retrospectively reviewed 67 patients with documented World Health Organisation (WHO) Grade II/III meningiomas, diagnosed between 1989 and 2012 and resected at two major Australian hospitals. Nine patients were excluded and the remaining 58 were analysed. The patient demographics, tumour characteristics, surgical details and adjuvant therapy were retrieved. Kaplan-Meier curves were used to compare the survival of patients treated with RT versus surgery alone. The 3 year progression free survival (PFS) and overall survival (OS) were 44 and 76% for the entire cohort, respectively. Of the patients who had gross total resections, 42% had 3 years PFS and 77% had 3 years OS, which was not significantly different from those with subtotal resection. The overall median survival was 11.0 years, 12.2 for atypical and 1.6 for malignant meningiomas. The patients with malignant meningiomas were 14 times as likely to receive RT as the patients with atypical meningiomas. The patients who received RT had a 3 year PFS of 63% compared to 40% in those who did not receive radiation. The 3 year OS was 31% higher for females than males. Histopathological progression was noted in 17% of our cohort. This study reinforces a number of important factors that should be considered when treating patients presenting with WHO Grade II and III meningiomas, including sex, potential for grade progression, and the lack of evidence for adjuvant RT and the timing thereof. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. MENINGIOMAS

    PubMed Central

    Rogers, Leland; Barani, Igor; Chamberlain, Marc; Kaley, Thomas; McDermott, Michael; Raizer, Jeffrey; Schiff, David; Weber, Damien C.; Wen, Patrick Y.; Vogelbaum, Michael A.

    2016-01-01

    Evolving interest in meningioma, the most common primary brain tumor, has refined contemporary management of these tumors. Problematic, however, is the paucity of prospective clinical trials that provide an evidence-based algorithm for managing meningioma. The current review summarizes the published literature regarding the treatment of newly diagnosed and recurrent meningioma, with an emphasis on outcomes stratified by World Health Organization (WHO) tumor grade. In particular this review focuses on patient outcomes following treatment (either adjuvant or at recurrence) with surgery or radiation therapy inclusive of radiosurgery and fractionated irradiation. Phase II trials for patients with meningioma have recently completed accrual within the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) consortia, and phase III studies are being developed. However, at present, there are no completed prospective, randomized trials assessing the role of either surgery or radiotherapy. Successful completion of future studies will require a multidisciplinary effort, dissemination of the current knowledge base, improved implementation of WHO grading criteria, standardization of response criteria and other outcome endpoints, and concerted efforts to address weaknesses in present treatment paradigms, particularly for patients with progressive or recurrent low grade meningioma, or with high-grade meningioma. In parallel efforts, Response Assessment in Neuro-Oncology (RANO) subcommittees are developing a manuscript on systemic therapies for meningioma, and a separate article proposing standardized endpoint and response criteria for meningioma. PMID:25343186

  2. Long Term Surgical Outcome and Prognostic Factors of Atypical and Malignant Meningiomas

    PubMed Central

    Wang, Yu-Chi; Chuang, Chi-Cheng; Wei, Kuo-Chen; Chang, Cheng-Nen; Lee, Shih-Tseng; Wu, Chieh-Tsai; Hsu, Yung-Hsin; Lin, Tzu-Kan; Hsu, Peng-Wei; Huang, Yin-Cheng; Tseng, Chen-Kan; Wang, Chun-Chieh; Chen, Yao-Liang; Chen, Pin-Yuan

    2016-01-01

    Atypical and malignant meningiomas are rare. Our aim was to examine the treatment outcomes following surgical resection, and analyze associations between clinical characteristics and overall survival (OS) or relapse free survival (RFS). 102 patients with atypical or malignant meningiomas underwent microsurgical resection between June 2001 and November 2009 were analyzed retrospectively. We compared demographics, clinical characteristics, treatment, and complications. The five-year and ten-year overall survival rates were 93.5% and 83.4%, respectively. Three factors significantly reduced OS: Malignant meningiomas (p < 0.001), which also decreased RFS (p < 0.001); female patients (p = 0.049), and patients with Karnofsky Performance Status (KPS) < 70 at diagnosis (p = 0.009). Fifty two patients (51%) experienced tumor relapse. Total resection of tumors significantly impacted RFS (p = 0.013). Tumors located at parasagittal and posterior fossa area lead to higher relapse rate (p = 0.004). Subtotal resection without adjuvant radiotherapy lead to the worst local control of tumor (p = 0.030). An MIB-1 index <8% improved OS and RFS (p = 0.003). Total resection of atypical and malignant meningiomas provided better outcome and local control. Adjuvant radiation therapy is indicated for patients with malignant meningiomas, with incompletely excised tumors; or with tumors in the parasagittal or posterior fossa area. The MIB-1 index of the tumor is an independent prognostic factor of clinical outcome. PMID:27760993

  3. Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

    PubMed Central

    Huang, Yin-Cheng; Wei, Kuo-Chen; Chang, Chen-Nen; Chen, Pin-Yuan; Hsu, Peng-Wei; Chen, Carl P.; Lu, Chin-Song; Wang, Hung-Li; Gutmann, David H.; Yeh, Tu-Hsueh

    2014-01-01

    Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth. PMID:25247996

  4. Benign spinal meningioma without dural attachment presenting delayed CSF dissemination and malignant transformation.

    PubMed

    Tsuda, Kyoji; Akutsu, Hiroyoshi; Yamamoto, Tetsuya; Ishikawa, Eiichi; Saito, Atsushi; Nakai, Kei; Takano, Shingo; Matsumura, Akira

    2013-07-01

    Benign spinal meningiomas have good prognoses, with low rates of recurrence and no cerebrospinal fluid (CSF) dissemination. However, we experienced an extremely rare case of initially benign non-dura-based spinal meningioma that showed multiple CSF disseminated lesions, which progressed for 14 years. A 29-year-old woman without neurofibromatosis presented with progressing dysesthesia in her lower limbs, low back pain, and intermittent claudication. Magnetic resonance imaging (MRI) showed an intradural extramedullary mass lesion at the Th10/11 level. The patient underwent a tumor resection. Intraoperative findings indicated that the tumor had no dural attachment. Histopathological diagnosis after gross total removal was microcystic meningioma (grade I, WHO 2007). Seven years after the first operation, other lesions appeared at the levels of Th11/12, L1, and L2/3 in MRI. These tumors were slow growing and became symptomatic; thus, a second surgery was performed 14 years after the first operation. The histopathological diagnosis was atypical meningioma (grade II, WHO 2007). Benign spinal meningiomas show CSF dissemination extremely rarely, although some authors have reported non-dura-based intraspinal clear-cell meningiomas showing CSF dissemination. However, even in cases of WHO grade I, neurosurgeons should pay attention to late CSF dissemination and malignant transformation after surgical removal of non-dura-based intraspinal meningiomas.

  5. [Malignant meningioma with adenocarcinoma-like metaplasia: a rare entity to be not misdiagnosed].

    PubMed

    Marguet, Florent; Proust, François; Crahes, Marie; Basset, Carole; Joly-Helas, Géraldine; Chambon, Pascal; Laquerrière, Annie

    2014-06-01

    We report on a 51-year-old woman who presented with a cervical spinal cord tumor clinically suspected to be a metastasis. Histological examination revealed an anaplastic meningioma containing epithelial nests arranged in a gland-like pattern suggestive of adenocarcinoma. This component strongly expressed cytokeratins whereas the meningothelial component was vimentin--epithelial membrane antigen--and progesterone receptor-immunoreactive, suggesting either anaplastic meningioma with adenocarcinoma-like metaplasia, or adenocarcinoma metastasis in a meningioma, but the search for a primitive neoplasia including thoracic-abdominal-pelvic computed tomography and mammography was negative. Anaplastic meningiomas with adenocarcinoma-like metaplasia are uncommon lesions, 4 cases having been reported in the literature so far. Their immunohistochemical and chromosomal characteristics are similar to those observed in secretory meningiomas. When available, fluorescence in situ hybridization detects the same chromosomal alterations in the two components, confirming a common clonal origin. This observation demonstrates the necessity to perform the correct diagnosis of malignant meningioma with adenocarcinomatous metaplasia, whose prognosis and treatment radically differ from those of metastatic adenocarcinoma located in a meningioma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Meningioma

    MedlinePlus

    ... based dye is used to augment the picture. Magnetic resonance imaging (MRI). With this imaging study, a magnetic field ... Accessed Dec. 2, 2013. Pinto PS, et al. Magnetic resonance imaging features of meningioma in children and young adults: ...

  7. Differentially Expressed MicroRNAs in Meningiomas Grades I and II Suggest Shared Biomarkers with Malignant Tumors

    PubMed Central

    El-Gewely, Mohamed Raafat; Andreassen, Morten; Walquist, Mari; Ursvik, Anita; Knutsen, Erik; Nystad, Mona; Coucheron, Dag H.; Myrmel, Kristin Smistad; Hennig, Rune; Johansen, Steinar D.

    2016-01-01

    Meningiomas represent the most common primary tumors of the central nervous system, but few microRNA (miRNA) profiling studies have been reported so far. Deep sequencing of small RNA libraries generated from two human meningioma biopsies WHO grades I (benign) and II (atypical) were compared to excess dura controls. Nineteen differentially expressed miRNAs were validated by RT-qPCR using tumor RNA from 15 patients and 5 meninges controls. Tumor suppressor miR-218 and miR-34a were upregulated relative to normal controls, however, miR-143, miR-193b, miR-451 and oncogenic miR-21 were all downregulated. From 10 selected putative mRNA targets tested by RT-qPCR only four were differentially expressed relative to normal controls. PTEN and E-cadherin (CDH1) were upregulated, but RUNX1T1 was downregulated. Proliferation biomarker p63 was upregulated with nuclear localization, but not detected in most normal arachnoid tissues. Immunoreactivity of E-cadherin was detected in the outermost layer of normal arachnoids, but was expressed throughout the tumors. Nuclear Cyclin D1 expression was positive in all studied meningiomas, while its expression in arachnoid was limited to a few trabecular cells. Meningiomas of grades I and II appear to share biomarkers with malignant tumors, but with some additional tumor suppressor biomarkers expression. Validation in more patients is of importance. PMID:26950155

  8. MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

    SciTech Connect

    Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

    2015-05-01

    MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

  9. [Malignant meningioma in nasal cavity and paranasal sinuses: a case report].

    PubMed

    Huang, Jie; Zhou, Zhaoxia; Jin, Xiaxiang

    2015-05-01

    Female patients, 50 years old, have a recurrent unilateral aggravating headache for 5 years. Without runny nose, sneezing, nasal hemorrhage, smell or vision loss. Prefessional examination: there is a visible hoar neoplasm in the right middle nasal meatus With smooth surface and rich in vascular. The nasopharyngeal MRI shows that there is a occupancy lesion in the right nasal cavity and sinuses, well-demarcated, about 21. 5 mm x 25.5 mm x 37.0 mm. Angiofibroma is the most likely diagnosis. Postoperative pathological section shows that tumor are hypercellular, which contains big nucleus. Cells are spindle or short fusiform shape, there are stripes and nuclear division in some cells. There are vortex structures in partial region. Immunohistochemical examination shows: CD34(++), Ki-67 (< 5%), CD68(-), Des (-), NSE(+), S-100(++), SMA(-), EMA (+). Histopathologic diagnosis: atypical meningioma, some were differentiated to rhabdoid meningioma. The final diagnosis is malignant meningioma in nasal cavity and paranasal sinuses.

  10. Intracranial malignant meningioma with multiple spinal metastases--a case report and literature review: case report.

    PubMed

    Chuang, Hao-Che; Lee, Han-Chung; Cho, Der-Yang

    2006-12-15

    Case report. To report a case and review the literature on intracranial malignant meningioma with metastasis to the spine. Because so few cases have been recognized and reported, the radiologic and pathologic assessment, pathway of metastasis, and the concepts of surgical resection and other palliative management of this disease are still controversial. A big lobulated mass in the left frontal lobe containing calcifications and tumor bleeding was resected. Pathologic findings indicated malignant meningioma due to bone destruction and dura invasion grossly, and tumor cellular atypism with mitotic activity and massive tumor necrosis microscopically. Radiotherapy followed, and brain computed tomography revealed no definite evidence of recurrence. Three months later, spinal magnetic resonance imaging revealed multiple bone metastasis in lower T-L-S1, and pathologic fracture of L1 with compression of the dural sac and spinal cord. Surgical resection was done for decompression, fixation, and pathologic proof. Both pathologic and immunohistochemical survey found evidence consistent with malignant meningioma with spinal metastasis. Advanced treatment was refused, and the patient died. Spinal magnetic resonance imaging should be performed because of the high spinal metastatic rate, especially when spinal symptoms and signs are present. Immunohistochemical study has an important role in the differential diagnosis of primary or metastatic intracranial neoplasms.

  11. Targeting different types of human meningioma and glioma cells using a novel adenoviral vector expressing GFP-TRAIL fusion protein from hTERT promoter

    PubMed Central

    2011-01-01

    Objective The objective of this study was to evaluate the anti-tumor effects of Ad/gTRAIL (an adenoviral vector in which expression of GFP and TRAIL is driven by a human telomerase reverse transcriptase promoter, hTERT) on malignant meningiomas and gliomas. Background Gliomas and meningiomas are the two most common types of human brain tumors. Currently there is no effective cure for recurrent malignant meningiomas or for gliomas. Ad/gTRAIL has been shown to be effective in killing selected lung, colon and breast cancer cells, but there have been no studies reporting its antitumor effects on malignant meningiomas. Therefore, we tested the antitumor effect of Ad/gTRAIL for the first time in human malignant meningioma and glioma cell lines, and in intracranial M6 and U87 xenografts. Methods Materials and Methods: Human malignant meningioma and glioma cells were infected with adenoviruses, Ad/gTRAIL and Ad/CMV-GFP. Cell viability was determined by proliferation assay. FACS analysis and quantification of TRAIL were used to measure apoptosis in these cells. We injected Ad/gTRAIL viruses in intracranial M6 and U87 xenografts, and measured the brain tumor volume, quantified apoptosis by TUNEL assay in the brain tumor tissue. Results Our studies demonstrate that in vitro/in vivo treatment with Ad/gTRAIL virus resulted in significant increase of TRAIL activity, and elicited a greater tumor cell apoptosis in malignant brain tumor cells as compared to treatment with the control, Ad/CMV-GFP virus without TRAIL activity. Conclusions We showed for the first time that adenovirus Ad/gTRAIL had significant antitumor effects against high grade malignant meningiomas as well as gliomas. Although more work needs to be done, our data suggests that Ad/gTRAIL has the potential to be useful as a tool against malignant brain tumors. PMID:22035360

  12. Atypical primary meningioma in the nasal septum with malignant transformation and distant metastasis

    PubMed Central

    2012-01-01

    Background Primary extracranial meningiomas (PEMs) originating from the nasal septum are extremely rare, as are extracranial metastases of meningiomas. Case presentation A 44-year-old male presented with a 2-month history of left-side nasal obstruction and frequent episodes of epistaxis. A friable mass originating from the nasal septum was resected completely via an endoscopic endonasal approach. According to WHO criteria, the tumor was diagnosed as an atypical meningioma radiologically and histopathologically. Two years later, a tumor recurred at the primary site with the same histopathological findings, and the patient was given local external radiotherapy (6840 cGy in 38 fractions). Two months after this local recurrence, a left anterior chest wall mass and a left parietal area scalp mass were observed. The subcutaneous mass was resected and showed histological evidence of malignant transformation. Several months after the last operation, the patient died. Conclusions We describe the clinical, radiological, and bio-pathological features of this unique case and review the literature on atypical PEMs originating in the nasal septum. To our knowledge, this is the first reported case of an atypical PEM originating from the nasal septum that recurred with malignant transformation and extracranial metastasis. PMID:22759338

  13. Telomerase activity in human brain tumors: astrocytoma and meningioma.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mohammadi-asl, Javad; Mehdipour, Parvin

    2013-05-01

    Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the standard protocols. In the brain tissues, telomerase activity was positive in 39 (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

  14. Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

    ClinicalTrials.gov

    2014-07-09

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

  15. APOBEC3B expression in human leptomeninges and meningiomas

    PubMed Central

    Johnson, Mahlon D.; Reeder, Jay E.; O'Connell, Mary

    2016-01-01

    Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas. PMID:28101245

  16. Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study

    PubMed Central

    Telugu, Ramesh Babu; Chowhan, Amit Kumar; Rukmangadha, Nandyala; Patnayak, Rashmi; Phaneendra, Bobbidi Venkata; Prasad, Bodapati Chandra Mowliswara; Reddy, Mandyam Kumaraswamy

    2016-01-01

    Background: Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. Aim: To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade. Materials and Methods: It was 3½ years prospective (March 2010–October 2011) and retrospective (May 2008–February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance. Results: A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity. Conclusion: HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas. PMID:27695231

  17. Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study.

    PubMed

    Telugu, Ramesh Babu; Chowhan, Amit Kumar; Rukmangadha, Nandyala; Patnayak, Rashmi; Phaneendra, Bobbidi Venkata; Prasad, Bodapati Chandra Mowliswara; Reddy, Mandyam Kumaraswamy

    2016-01-01

    Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade. It was 3½ years prospective (March 2010-October 2011) and retrospective (May 2008-February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance. A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity. HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

  18. Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma.

    PubMed

    Ando, Hitoshi; Natsume, Atsushi; Senga, Takeshi; Watanabe, Reiko; Ito, Ichiro; Ohno, Masasuke; Iwami, Kenichiro; Ohka, Fumiharu; Motomura, Kazuya; Kinjo, Sayano; Ito, Maki; Saito, Kiyoshi; Morgan, Richard; Wakabayashi, Toshishiko

    2014-01-01

    Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX. We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers. We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors. There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.

  19. Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature

    PubMed Central

    Vaubel, Rachael A.; Chen, Selby G.; Raleigh, David R.; Link, Michael J.; Chicoine, Michael R.; Barani, Igor; Jenkins, Sarah M.; Aleff, Patrice Abell; Rodriguez, Fausto J.; Burger, Peter C.; Dahiya, Sonika; Perry, Arie

    2016-01-01

    The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10–79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17–14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I–II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended. PMID:26705409

  20. Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature.

    PubMed

    Vaubel, Rachael A; Chen, Selby G; Raleigh, David R; Link, Michael J; Chicoine, Michael R; Barani, Igor; Jenkins, Sarah M; Aleff, Patrice Abell; Rodriguez, Fausto J; Burger, Peter C; Dahiya, Sonika; Perry, Arie; Giannini, Caterina

    2016-01-01

    The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10-79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17-14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I-II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended.

  1. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  2. "Inverse signaling" of the transmembrane chemokine CXCL16 contributes to proliferative and anti-apoptotic effects in cultured human meningioma cells.

    PubMed

    Hattermann, Kirsten; Bartsch, Kareen; Gebhardt, Henrike H; Mehdorn, H Maximilian; Synowitz, Michael; Schmitt, Anne Dorothée; Mentlein, Rolf; Held-Feindt, Janka

    2016-10-27

    Chemokines and their receptors play a decisive role in tumor progression and metastasis. We recently found a new signaling mechanism in malignant glioma cells mediated by transmembrane chemokines that we termed "inverse signaling". According to this hypothesis, soluble (s)-CXCL16 binds to the surface-expressed transmembrane (tm) -CXCL16, and induces signaling and different biological effects in the stimulated cells, so that the transmembrane ligand itself acts as a receptor for its soluble counterpart. Now, we hypothesized that "inverse signaling" via tm-CXCL16 might also take place in meningiomas, a completely different, benign tumor entity. We used quantitative reverse-transcription polymerase chain reaction, immunocytochemistry and western blot to detect CXCL16 and CXCR6 in human meningioma cells isolated from 28 human meningiomas. Subsequently, we stimulated cultured human tm-CXCL16-positive, CXCR6-negative meningioma cells with recombinant s-CXCL16 and analyzed binding, signaling and biological effects using RNAi silencing to verify specificity. In fact, cultured human meningioma cells considerably express CXCL16, but substantially lack CXCR6, the only known CXCL16 receptor. These receptor-negative cells could bind s-CXCL16, and responded to s-CXCL16 application with activation of the intracellular kinases ERK1/2 und Akt. As a consequence, we observed increased proliferation and rescue of apoptosis of cultured meningioma cells. Since binding and signaling were abolished by siRNA silencing, we concluded that tm-CXCL16 specifically acts as a receptor for s-CXCL16 also in human meningioma cells. These findings underline our recent report on the mechanism of inverse signaling as a broad biological process also observable in more benign tumor cells and contributing to tumor progression.

  3. A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/β-catenin signaling pathway.

    PubMed

    Das, Arabinda; Miller, Rickey; Lee, Philip; Holden, Chrysanthe Alyssa; Lindhorst, Scott M; Jaboin, Jerry; Vandergrift, William A; Banik, Naren L; Giglio, Pierre; Varma, Abhay K; Raizer, Jeffery J; Patel, Sunil J

    2015-09-01

    Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, and interferon-α) are only of marginal benefit. There is an urgent need for more effective treatments for meningioma patients who have failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that have anti-tumorgenic properties and cause cell death in meningioma cells in vitro. Due to its ease of administration, long-term tolerability, and low incidence of long-term side effects, we explored its potential as a therapeutic agent against meningiomas by examining their efficacy in vitro against meningioma cells. Treatment effects were assessed using MTT assay, Western blot analysis, caspases assay, and DNA fragmentation assay. Results indicated that treatments of IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 β (GSK3β) via inhibition of the Wnt5/β-catenin pathway. These drugs did not induce apoptosis in normal human neurons. Other events in apoptosis included downregulation of tetraspanin protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression apoptotic factors (Bax and caspase-3). These results provide preliminary strong evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol, Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade meningiomas as a therapeutic agent, and suggests that further in vivo studies are necessary to explore its potential as a therapeutic agent against malignant meningiomas.

  4. The role of MAPK signaling pathway in the Her-2-positive meningiomas

    PubMed Central

    Wang, Zhaoyin; Wang, Weijia; Xu, Shan; Wang, Shanshan; Tu, Yi; Xiong, Yifeng; Mei, Jinhong; Wang, Chunliang

    2016-01-01

    Meningiomas are common types of adult nerve system tumors. Although most cases are considered benign, due to its high rate of recurrence and easy malignant progression to anaplastic meningioma they present a puzzle for the current treatment. The HER-2 oncogene has important value for meningioma cells development and progression. So far, little is known about the effect on the exact underlying signal pathway and molecular mechanisms of HER-2-positive meningioma cells. The goal of the present study was to determine the effects of HER-2 gene and possible involvement of MAPK signal pathway in human malignant meningioma. We applied q-PCR analysis, immunofluorescence (IF) staining, western blot analysis, animal model, MAPK inhibition, MTT assay and cell invasion analysis for the investigation. The results demonstrated that the downregulation of the expression of HER-2 significantly inhibited cell motility and proliferation of human meningioma cells in vivo. Accordingly, in the HER-2-overexpression meningioma cells with the inhibition of ERK1/2, ERK5, JNK, in the cells with the ERK1/2, ERK5 inhibition, protein expression was markedly suppressed as well as the cell proliferation resistance. No difference was observed in the HER-2-overexpression meningioma cells with the inhibition of JNK. These findings suggest that HER-2 gene can affect the proliferation ability of human meningioma cells in vivo and MAPK signal pathway may contribute to the carcinogenesis and development of human meningiomas combinating with HER-2. PMID:27279438

  5. Taurine concentration in human gliomas and meningiomas: tumoral, peritumoral, and extratumoral tissue.

    PubMed

    Cubillos, Suzana; Obregón, Francisco; Vargas, María Fernanda; Salazar, Luis Antonio; Lima, Lucimey

    2006-01-01

    Taurine concentrations were determined in gliomas from 16 patients and in meningiomas from 15 patients. After imaging analysis and clinical evaluation to consider the level of functional deterioration by the scale of Karnosky, tissue was obtained by surgery. Tumoral, peritumoral and extratumoral samples were taken and analyzed by HPLC with fluorescence detector. The concentration of taurine (nmol/mg protein) was higher in tumoral and peritumoral tissues than in the extratumoral samples for gliomas. In the case of meningiomas, the taurine concentration was higher in tumoral than in peritumoral and extratumoral samples. These modifications might be due to specific functions of this amino acid, being either protective or involved in the proliferation of cells. The differential distribution in the two types of tumors could be related to the malignancy of them, which is higher in gliomas than in meningiomas.

  6. Fatty acid synthase as a novel target for meningioma therapy

    PubMed Central

    Haase, Daniela; Schmidl, Stefan; Ewald, Christian; Kalff, Rolf; Huebner, Christian; Firsching, Raimund; Keilhoff, Gerburg; Evert, Matthias; Paulus, Werner; Gutmann, David H.; Lal, Anita; Mawrin, Christian

    2010-01-01

    High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma. PMID:20511185

  7. Analysis of Several PLA2 mRNA in Human Meningiomas

    PubMed Central

    Denizot, Yves; De Armas, Rafael; Durand, Karine; Robert, Sandrine; Moreau, Jean-Jacques; Caire, François; Weinbreck, Nicolas; Labrousse, François

    2009-01-01

    In view of the important oncogenic action of phospholipase A2(PLA2) we investigated PLA2 transcripts in human meningiomas. Real-time PCR was used to investigate PLA2 transcripts in 26 human meningioma tumors. Results indicated that three Ca2+-dependent high molecular weight PLA2 (PLA2-IVA, PLA2-IVB, PLA2-IVC), one Ca2+-independent high molecular weight PLA2 (PLA2-VI) and five low molecular weight secreted forms of PLA2 (PLA2-IB, PLA2-IIA, PLA2-III, PLA2-V, and PLA2-XII) are expressed with PLA2-IVA, PLA2-IVB, PLA2-VI, and PLA2-XIIA as the major expressed forms. PLA2-IIE, PLA2-IIF, PLA2-IVD, and PLA2-XIIB are not detected. Plasma (PLA2-VIIA) and intracellular (PLA2-VIIB) platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA2 transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA2 are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks. PMID:20339511

  8. P06.13OUTCOME AND PROGNOSTIC FACTORS IN ATYPICAL AND MALIGNANT MENINGIOMA: UNIVERSITY OF FLORENCE EXPERIENCE

    PubMed Central

    Detti, B.; Scoccianti, S.; Greto, D.; Cassani, S.; Cappelli, S.; Giacomelli, I.; Bordi, L.; Di cataldo, V.; Monteleone, E.; Livi, L.

    2014-01-01

    AIM: This study aim to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. MATERIAL AND METHODS: Data of 68 patients affected by meningioma between january 1993 and december 2011 were retrospective analyzed. In 80 % of the patients surgical resection was macroscopical; in 51 patients histology resulted atypical and in 17 malignant. All patients performed radiation treatment, of them 56% after surgical resection, 26% at the first relapse and 18% at the secon relapse, mean dose delivered was 54.6 Gy. RESULTS: Median follow-up was 6.7 years, (range 1.5-19.9 years). The actuarial overall survival rates at 5- and 10-year were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years and radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis only radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). The 5- and 10-year disease-free survival rates were 76.5 and 69.5 % respectively, on univariate analysis they were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003), both still remained significant prognostic factors at multivariate analysis (p = 0.044 and p = 0.0006, respectively). Treatment related toxicities were limited: 16 % of the patients experienced grade ≤ 2 acute side effects, no ≥ grade 3 acute toxicity was exeperienced. CONCLUSIONS: In study, age and radiotherapy dose were associated with a longer overall survival, while disease free survival was influenced by preoperative size and grading of the tumor . Although there were some advantages in terms of overall survival for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

  9. CD133-Positive Cells Might Be Responsible for Efficient Proliferation of Human Meningioma Cells

    PubMed Central

    Tang, Hailiang; Gong, Ye; Mao, Ying; Xie, Qing; Zheng, Mingzhe; Wang, Daijun; Zhu, Hongda; Wang, Xuanchun; Chen, Hong; Chen, Xiancheng; Zhou, Liangfu

    2012-01-01

    Owing to lack of appropriate model systems, investigations of meningioma biology have come to a stop. In this study, we developed a comprehensive digestion method and defined a culture system. Using this method and system, primary meningioma cells in conditioned suspension medium and a hypoxic environment could be amplified in spheres and were passaged for more than ten generations. Meningioma sphere cells were positive for meningioma cell markers and negative for markers of neural cell types. Importantly, we found the cells expressed the stem cell marker, CD133, but not nestin. All of the tumor sphere cell populations showed a slower degree of cell proliferation than that of human glioma cells and fetal neural stem cells (NSCs). Further studies showed that the proliferative rate was positively correlated with CD133 expression. The higher the CD133 expression, the faster the cell proliferation. With the increase in cell generations, the cell proliferation rate gradually slowed down, and CD133 expression also decreased. Single CD133+ cells rather than CD133− cells could form spheres. Thus, the results above indicated that those cells expressing CD133 in spheres might be stem-like cells, which may be responsible for efficient amplification of human meningioma cells. Decreased expression of CD133 may lead to the failure of long-term passaging. PMID:22754374

  10. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    SciTech Connect

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-08-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

  11. A rare case of a large spinal meningioma with mediastinal extension and malignant behavior classified histologically as benign.

    PubMed

    Dahdal, S; Andres, R H; Hewer, E; Reubi, J C; Klaeser, B; Raabe, A; Cihoric, N; Schmid, R; Tänzler, K; Krause, T; Aebersold, D M; Schmuecking, M

    2013-01-01

    To report a rare case of a spinal WHO grade I meningioma extending through intervertebral foramina C7 to D4 with an extensive mediastinal mass and infiltration of the vertebrae, and to discuss the malignant behavior of a tumor classified as benign. (Clinical Presentation, Histology, and Imaging): A 54-year-old man suffered from increasing lower back pain with gait difficulties, weakness and numbness of the lower extremities, as well as urge incontinence. CT scan of the thorax and MRI scan of the spine revealed a large prevertebral tumor, which extended to the spinal canal and caused compression of the spinal cord at the levels of C7 to D4 leading to myelopathy with hyperintense signal alteration on T2-weighted MRI images. The signal constellation (T1 with and without contrast, T2, TIR) was highly suspicious for infiltration of vertebrae C7 to D5. Somatostatin receptor SPECT/CT with (111)In-DTPA-D: -Phe-1-octreotide detected a somatostatin receptor-positive mediastinal tumor with infiltration of multiple vertebrae, dura, and intervertebral foramina C7-D4, partially with Krenning score >2. Percutaneous biopsies of the mediastinal mass led to histopathological findings of WHO grade I meningioma of meningothelial subtype. (Therapy): C7 to D4 laminoplasty was performed, and the intraspinal, extradural part of the tumor was microsurgically removed. Postoperative stereotactic radiation therapy was done using the volumetric modulated arc therapy (VMAT) technique (RapidArc). No PRRNT with (90)Y-DOTA-TOC was done. Due to the rare incidence and complex presentation of this disease not amenable to complete surgical resection, an individualized treatment approach should be worked out interdisciplinarily. The treatment approach should be based not only on histology but also on clinical and imaging findings. Close clinical and radiological follow-up may be mandatory even for benign tumors.

  12. Calcification in the human choroid plexus, meningiomas and pineal gland.

    PubMed

    Alcolado, J C; Moore, I E; Weller, R O

    1986-01-01

    Calcification in the stroma of adult telencephalic choroid plexus was studied of 20 postmortem brains and one biopsy by light microscopy, transmission and scanning electron microscopy and compared with calcification in psammoma bodies in normal arachnoid, five spinal meningiomas and in calcospherites of six pineal glands. Fifteen fetal and newborn choroid plexuses were also examined by light microscopy. Calcium deposition was observed in the subepithelial regions of the adult choroid plexus, in the walls of blood vessels but was mostly seen in spherical psammoma bodies. Collagen whorls 20-60 microns in diameter and surrounded by arachnoid cells, were observed in the stroma of the choroid plexus; calcium, phosphorous and iron were deposited in the collagen whorls to form psammoma bodies. Matrix vesicles and spicules resembling hydroxyapatite were associated with the arachnoid cells surrounding the collagen whorls and with the collagen fibres within the whorls. The dense amorphous calcified core of each psammoma body was surrounded by an outer coating of entwined collagen fibres readily visible by scanning electron microscopy. Similar psammoma bodies were occasionally observed in normal arachnoid. Psammoma bodies in meningiomas resembled those in the choroid plexus stroma. Calcospherites in the pineal differed from psammoma bodies; they were lobulated, more irregular in shape and did not have a collagen base. The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres. The presence of iron in the choroid plexus psammoma bodies may be a result of haemorrhage into the stroma. The mechanism of calcification in pineal remains unclear.

  13. Proteome analysis of human cerebrospinal fluid as a diagnostic biomarker in patients with meningioma

    PubMed Central

    Kim, Jae Ho; Lee, Sang Kwang; Yoo, Yong Cheol; Park, Nam Hyun; Park, Dan Bi; Yoo, Jong Shin; An, Hyun Joo; Park, Young Mok; Cho, Kyung Gi

    2012-01-01

    Summary Background To identify meningioma-specific proteins, cerebrospinal fluid (CSF) from 4 patients with a meningioma and 4 patients with a non-brain tumorous lesion were analyzed. Material/Methods Two-dimensional electrophoresis and electrospray quadrupole time-of-flight tandem mass spectrometry analyses revealed 10 unique spots, containing 11 independent proteins (spot #2 and #4 each contained 2 proteins and spot #3 was not identified) were evident in CSF associated with human meningioma: serum albumin precursor (3 different isoforms), Apolipoprotein E (Apo E), Apolipoprotein J precursor (Apo J), Transthyretin precursor (TTR), Prostaglandin D2 synthase 21kDa (PTGDS), proapolipoprotein, Chain D hemoglobin Ypsilanti, alpha-1-antitrypsin (AAT), and beta-2-microglobulin precursor (β2M). Results The contents of Apo E, Apo J and AAT were increased, while PTGDS, TTR and β2M were decreased. Conclusions The results observed by 2-dimensional electrophoresis were verified by Western blot analysis. The unique proteins may represent possible candidate biomarkers of meningioma. PMID:23111736

  14. Atypical and Malignant Meningioma: Outcome and Prognostic Factors in 119 Irradiated Patients. A Multicenter, Retrospective Study of the Rare Cancer Network

    SciTech Connect

    Pasquier, David Bijmolt, Stefan; Veninga, Theo; Rezvoy, Nicolas; Villa, Salvador; Krengli, Marco; Weber, Damien C.; Baumert, Brigitta G.; Canyilmaz, Emine; Yalman, Deniz; Szutowicz, Ewa; Tzuk-Shina, Tzahala; Mirimanoff, Rene O.

    2008-08-01

    Purpose: To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. Methods and Materials: Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean ({+-}SD) age was 57.6 {+-} 12 years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 {+-} 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. Results: The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. Conclusions: In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.

  15. [A case of malignant extrameningeal meningioma of the spinal canal with multiple metastases in a 17-year-old patient. Clinical and morphologic studies].

    PubMed

    Sobaniec, W; Czerwińska-Ciechan, K; Zimnoch, L; Sobaniec-Lotowska, M; Lewko, J

    1988-01-01

    A clinical description and pathological findings are reported in a case of extrameningeal, angiogenic malignant meningioma of the vertebral canal (Th7-Th11) in a patient aged 17 years. Clinical picture was that of transverse myelitis at the Th9 level, with spastic paraparesis, funicular loss of all sensory functions and sphincter disturbances. The authors suppose that the used combined treatment (chemotherapy and radiotherapy, surgery) improved greatly the health state inhibiting the spread of metastases and prolonged survival to 3 years. Autopsy demonstrated recurrence of he tumour in the vertebral canal and numerous metastases to the brain, lungs, liver, bones and pancreas.

  16. PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss.

    PubMed

    Peyre, Matthieu; Salaud, Céline; Clermont-Taranchon, Estelle; Niwa-Kawakita, Michiko; Goutagny, Stephane; Mawrin, Christian; Giovannini, Marco; Kalamarides, Michel

    2015-10-20

    The role of PDGF-B and its receptor in meningeal tumorigenesis is not clear. We investigated the role of PDGF-B in mouse meningioma development by generating autocrine stimulation of the arachnoid through the platelet-derived growth factor receptor (PDGFR) using the RCAStv-a system. To specifically target arachnoid cells, the cells of origin of meningioma, we generated the PGDStv-a mouse (Prostaglandin D synthase). Forced expression of PDGF-B in arachnoid cells in vivo induced the formation of Grade I meningiomas in 27% of mice by 8 months of age. In vitro, PDGF-B overexpression in PGDS-positive arachnoid cells lead to increased proliferation.We found a correlation of PDGFR-B expression and NF2 inactivation in a cohort of human meningiomas, and we showed that, in mice, Nf2 loss and PDGF over-expression in arachnoid cells induced meningioma malignant transformation, with 40% of Grade II meningiomas. In these mice, additional loss of Cdkn2ab resulted in a higher incidence of malignant meningiomas with 60% of Grade II and 30% of Grade III meningiomas. These data suggest that chronic autocrine PDGF signaling can promote proliferation of arachnoid cells and is potentially sufficient to induce meningiomagenesis. Loss of Nf2 and Cdkn2ab have synergistic effects with PDGF-B overexpression promoting meningioma malignant transformation.

  17. PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss

    PubMed Central

    Peyre, Matthieu; Salaud, Céline; Clermont-Taranchon, Estelle; Niwa-Kawakita, Michiko; Goutagny, Stephane; Mawrin, Christian; Giovannini, Marco; Kalamarides, Michel

    2015-01-01

    The role of PDGF-B and its receptor in meningeal tumorigenesis is not clear. We investigated the role of PDGF-B in mouse meningioma development by generating autocrine stimulation of the arachnoid through the platelet-derived growth factor receptor (PDGFR) using the RCAStv-a system. To specifically target arachnoid cells, the cells of origin of meningioma, we generated the PGDStv-a mouse (Prostaglandin D synthase). Forced expression of PDGF-B in arachnoid cells in vivo induced the formation of Grade I meningiomas in 27% of mice by 8 months of age. In vitro, PDGF-B overexpression in PGDS-positive arachnoid cells lead to increased proliferation. We found a correlation of PDGFR-B expression and NF2 inactivation in a cohort of human meningiomas, and we showed that, in mice, Nf2 loss and PDGF over-expression in arachnoid cells induced meningioma malignant transformation, with 40% of Grade II meningiomas. In these mice, additional loss of Cdkn2ab resulted in a higher incidence of malignant meningiomas with 60% of Grade II and 30% of Grade III meningiomas. These data suggest that chronic autocrine PDGF signaling can promote proliferation of arachnoid cells and is potentially sufficient to induce meningiomagenesis. Loss of Nf2 and Cdkn2ab have synergistic effects with PDGF-B overexpression promoting meningioma malignant transformation. PMID:26418719

  18. [Extradural spinal meningioma: case report].

    PubMed

    Dagain, A; Dulou, R; Lahutte, M; Dutertre, G; Pouit, B; Delmas, J-M; Camparo, P; Pernot, P

    2009-12-01

    We report a case of purely extradural spinal meningioma and discuss the potential pitfalls in differential diagnosis. Spinal meningiomas account for 20-30% of all spinal neoplasms. Epidural meningiomas are infrequent intraspinal tumors that can be easily confused with malignant neoplasms or spinal schwannomas. A 62-year-old man with a previous history of malignant disease presented with back pain and weakness of the lower limbs. Magnetic resonance imaging revealed a well-enhanced T4 intraspinal lesion. The intraoperative histological examination showed a meningioma (confirmed by postoperative examination). Opening the dura mater confirmed the purely epidural location of the lesion. The postoperative course was uneventful with no recurrence 12 months after surgery. Purely extradural spinal meningiomas can mimic metastatic tumors or schwannomas. Intraoperative histology is mandatory for optimal surgical decision making.

  19. Posttraumatic meningioma.

    PubMed

    Schiffer, J; Avidan, D; Rapp, A

    1985-07-01

    This report concerns three patients with intracranial meningioma developing at the site of an old head injury with skull fracture. These cases, along with literature reports, suggest a causal relationship between head trauma and the subsequent development of meningioma.

  20. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    PubMed Central

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  1. NDRG4 is a novel oncogenic protein and p53 associated regulator of apoptosis in malignant meningioma cells

    PubMed Central

    Kotipatruni, Rama P.; Ren, Xuan; Thotala, Dinesh; Jaboin, Jerry J.

    2015-01-01

    Aggressive meningiomas exhibit high levels of recurrence, morbidity and mortality. When surgical and radiation options are exhausted, there is need for novel molecularly-targeted therapies. We have recently identified NDRG4 overexpression in aggressive meningiomas. NDRG4 is a member of the N-Myc Downstream Regulated Gene (NDRG) family of the alpha/beta hydrolase superfamily. We have demonstrated that NDRG4 downregulation results in decreased cell proliferation, migration and invasion. In follow up to our prior studies; here we demonstrate that the predominant form of cell death following NDRG4 silencing is apoptosis, utilizing Annexin-V flow cytometry assay. We show that apoptosis caused by p53 upregulation, phosphorylation at Ser15, BAX activation, Bcl-2 and BcL-xL downregulation, mitochondrial cytochrome c release and execution of caspases following NDRG4 depletion. Sub-cellular distribution of BAX and cytochrome c indicated mitochondrial-mediated apoptosis. In addition, we carried out the fluorescence cytochemical analysis to confirm mitochondrial-mediated apoptosis by changes in mitochondrial membrane potential (Ψm), using JC-1 dye. Immunoprecipitation and immunofluorescence confirmed binding of NDRG4 to p53. In addition, we demonstrate that apoptosis is mitochondrial and p53 dependent. The proapoptotic effect of p53 was verified by the results in which a small molecule compound PFT-α, an inhibitor of p53 phosphorylation, is greatly protected against targeting NDRG4 induced apoptosis. These findings bring novel insight to the roles of NDRG4 in meningioma progression. A better understanding of this pathway and its role in meningioma carcinogenesis and cell biology is promising for the development of novel therapeutic targets for the management of aggressive meningiomas. PMID:26053091

  2. Spatio-temporal anomalous diffusion imaging: results in controlled phantoms and in excised human meningiomas.

    PubMed

    Capuani, Silvia; Palombo, Marco; Gabrielli, Andrea; Orlandi, Augusto; Maraviglia, Bruno; Pastore, Francesco S

    2013-04-01

    Recently, we measured two anomalous diffusion (AD) parameters: the spatial and the temporal AD indices, called γ and α, respectively, by using spectroscopic pulse gradient field methods. We showed that γ quantifies pseudo-superdiffusion processes, while α quantifies subdiffusion processes. Here, we propose γ and α maps obtained in a controlled heterogeneous phantom, comprised of packed micro-beads in water and in excised human meningiomas. In few words, α maps represent the multi-scale spatial distribution of the disorder degree in the system, while γ maps are influenced by local internal gradients, thus highlighting the interface between compartments characterized by different magnetic susceptibility. γ maps were already obtained by means of AD stretched exponential imaging and α-type maps have been recently achieved for fixed rat brain with the aim of highlighting the fractal dimension of specific brain regions. However, to our knowledge, the maps representative of the spatial distribution of α and γ obtained on the same controlled sample and in the same excised tissue have never been compared. Moreover, we show here, for the first time, that α maps are representative of the spatial distribution of the disorder degree of the system. In a first phase, γ and α maps of controlled phantom characterized by an ordered and a disordered rearrangement of packed micro-beads of different sizes in water and by different magnetic susceptibility (Δχ) between beads and water were obtained. In a second phase, we investigated excised human meningiomas of different consistency. Results reported here, obtained at 9.4T, show that α and γ maps are characterized by a different image contrast. Indeed, unlike γ maps, α maps are insensible to (Δχ) and they are sensible to the disorder degree of the microstructural rearrangement. These observations strongly suggest that AD indices α and γ reflect some additional microstructural information which cannot be obtained

  3. Rhabdoid Meningioma Arising Concurrent in Pulmonary and Intracranial with a Rare Malignant Clinical Progression: Case Report and Literature Review.

    PubMed

    Zhao, Peng; Li, Ning; Cao, Jinfeng; Lin, Xiangtao; Liang, Changhu

    2017-08-07

    Rhabdoid meningioma (RM) is an unusual variant of meningioma, classified as World Health Organization grade III. Although its recurrence is common, extracranial metastasis is rare and usually misdiagnosed. The transfer mechanism and pathway are ambiguous; once the metastasis occurs, the prognosis is poor, and there is no effective management. The present case is the first report of concurrent intracranial and pulmonary RM with rapid and widespread metastasis. We hope this report can serve as a helpful reference for clinicians and radiologists. A 39-year-old woman presented to our hospital complaining of headache and memory disturbances. Magnetic resonance imaging (MRI) of the brain revealed a well-defined, inhomogeneous signal tumor with intense enhancement and severe peritumoral edema. Postoperatively, RM (grade III) was confirmed by histopathology. A chest CT performed 2 weeks later revealed an isolated lung mass, which was confirmed as RM on subsequent surgery. Three months after the first radiotherapy, the cancer had progressed uncommonly rapidly with widespread metastasis to the cerebellum, lung, kidney, and thigh. Gamma knife radiosurgery, chemotherapy, and molecular-targeted therapy were performed; however, the patient's condition continued to worsen, and she died 1 year after the initial operation. Intracranial RM is a relatively rare tumor with the potential for wide intracranial and extracranial transfer. Cystic components and necrosis can be seen in this type of meningioma. Metastatic meningioma should be kept in mind when dealing with isolated lung lesions. This case report may serve as a helpful reference for clinicians and radiologists. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold

    PubMed Central

    Negah, Sajad Sahab; Aligholi, Hadi; Khaksar, Zabihollah; Kazemi, Hadi; Mousavi, Sayed Mostafa Modarres; Safahani, Maryam; Dowom, Parastoo Barati; Gorji, Ali

    2016-01-01

    Objective(s): In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs). Materials and Methods: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods. In addition, we designed a new method for measurement of migration distance in 3D cultivation of hMgSCs in PuraMatrix. Results: Our results revealed that hMgSCs have the ability to form spheres in stem cell culture condition. These meningioma cells expressed GFAP, CD133, vimentin, and nestin. Using the injection method, a higher proliferation rate of the hMgSCs was observed after seven days of culture. Furthermore, the novel migration assay was able to measure the migration of a single cell alone in 3D environment. Conclusion: The results indicate the injection method as an efficient technique for culturing hMgSCs in PuraMatrix. Furthermore, the novel migration assay enables us to evaluate the migration of hMgSCs. PMID:28096958

  5. Expression of Cellular Oncogenes in Human Malignancies

    NASA Astrophysics Data System (ADS)

    Slamon, Dennis J.; Dekernion, Jean B.; Verma, Inder M.; Cline, Martin J.

    1984-04-01

    Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

  6. The integrin inhibitor cilengitide affects meningioma cell motility and invasion.

    PubMed

    Wilisch-Neumann, Annette; Kliese, Nadine; Pachow, Doreen; Schneider, Thomas; Warnke, Jan-Peter; Braunsdorf, Werner Ek; Böhmer, Frank-Dietmar; Hass, Peter; Pasemann, Diana; Helbing, Cornelia; Kirches, Elmar; Mawrin, Christian

    2013-10-01

    Meningiomas are frequent intracranial or spinal neoplasms, which recur frequently and can show aggressive clinical behaviour. We elucidated the impact of the integrin inhibitor cilengitide on migration, proliferation, and radiosensitization of meningioma cells. We analyzed integrin expression in tissue microarrays of human meningiomas and the antimeningioma properties of cilengitide in cell cultures, subcutaneous and intracranial nude mouse models by measuring tumor volumes and survival times. αvβ5 was the predominantly expressed integrin heterodimer in meningiomas, whereas αvβ3 was mainly detected in tumor blood vessels. Application of up to 100 μg/mL cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. Effects on cell survival could be enhanced by irradiation. One μg/mL cilengitide was sufficient to significantly inhibit meningioma cell migration and invasion in vitro. A daily dosage of 75 mg/kg did neither affect tumor volumes nor overall survival (P = 0.813, log-rank test), but suppressed brain invasion in a significant fraction of treated animals. A combination of 75 mg/kg cilengitide daily and irradiation (2 × 5 Gy) led to a 67% reduction of MRI-estimated tumor volumes in the intracranial model (P < 0.01), whereas the corresponding reduction reached by irradiation alone was only 55% (P < 0.05). These data show that a monotherapy with cilengitide is not likely to achieve major responses in rapidly growing malignant meningiomas, although brain invasion may be reduced because of the strong antimigratory properties of the drug. The combination with radiotherapy warrants further attention. ©2013 AACR.

  7. Meningioma mimics: five key imaging features to differentiate them from meningiomas.

    PubMed

    Starr, C J; Cha, S

    2017-09-01

    There are a wide variety of intracranial mass lesions, both benign and malignant, which can closely mimic meningioma on imaging. We present five characteristic imaging features that can alert the radiologist to consider other differential diagnoses. Of the five imaging characteristics that were rarely seen in meningiomas, but common and specific for meningioma mimics, absence of dural tail is the most common (83.7%). Homogeneous T2 hyperintensity or T2 hypointensity are seen in nearly half of meningioma mimics and osseous destruction and leptomeningeal extension are present in 40.5% and 21.6% of meningioma mimics, respectively. The distinction between meningioma and its mimics is important because a large portion of the meningioma mimics requires substantially different clinical and surgical management. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. Long-Term Outcome After Radiotherapy in Patients With Atypical and Malignant Meningiomas-Clinical Results in 85 Patients Treated in a Single Institution Leading to Optimized Guidelines for Early Radiation Therapy

    SciTech Connect

    Adeberg, Sebastian; Hartmann, Christian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Deimling, Andreas von; Debus, Juergen; Combs, Stephanie E.

    2012-07-01

    Purpose: Previously, we could show that the new World Health Organization (WHO) classification of meningiomas significantly correlated with outcome in patients with atypical and anaplastic histology. In the present work, we analyzed our long-term experience in radiotherapy for atypical and malignant meningioma diagnosed according to the most recent WHO categorization system. Patients and Methods: Sixty-two patients with atypical and 23 patients with malignant meningioma have been treated with radiotherapy. Sixty percent of all patients received radiotherapy (RT) after surgical resection, 19% at disease progression and 8.3% as a primary treatment. Radiation was applied using different techniques including fractionated stereotactic RT (FSRT), intensity-modulated RT, and combination treatment with carbon ions. The median PTV was 156.0 mL. An average dose of 57.6 Gy (range, 30-68.4 Gy) in 1.8-3 Gy fractions was applied. All patients were followed regularly including clinical-neurological follow-up as well as computed tomographies or magnetic resonance imaging. Results: Overall survival was impacted significantly by histological grade, with 81% and 53% at 5 years for atypical or anaplastic meningiomas, respectively. This difference was significant at p = 0.022. Eighteen patients died of tumor progression during follow-up. Progression-free survival was 95% and 50% for atypical, and 63% and 13% for anaplastic histology at 2 and 5 years. This difference was significant at p = 0.017. Despite histology, we could not observe any prognostic factors including age, resection status, or Karnofsky performance score. However, preexisting clinical symptoms observed in 63 patients improved in 29.3% of these patients. Conclusion: RT resulted in improvement of preexisting clinical symptoms; outcome is comparable to other series reported in the literature. RT should be offered after surgical resection after initial diagnosis to increase progression-free survival as well as overall

  9. [Multiple meningiomas].

    PubMed

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs.

  10. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

    PubMed Central

    El-Khatib, Mustafa; Tepe, Carolin; Senger, Brigitte; Dibué-Adjei, Maxine; Riemenschneider, Markus Johannes; Stummer, Walter; Steiger, Hans Jakob; Cornelius, Jan Frédérick

    2015-01-01

    Objective: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2). The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001). Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the potential

  11. Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

    PubMed

    Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

    2011-11-01

    The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas.

  12. Regulation of vascular endothelial growth factor secretion in human meningioma cells.

    PubMed

    Tsai, J C; Hsiao, Y Y; Teng, L J; Shun, C T; Chen, C T; Goldman, C K; Kao, M C

    1999-02-01

    Previously, we induced vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) secretion in glioma cell lines by using physiologic concentrations of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet-derived growth factor-BB (PDGF-BB). We hypothesized that VEGF/VPF might enhance the blood supply required for the unregulated growth of tumors, and that it acts as the central mediator of tumor angiogenesis. The objective of this study was to determine whether the expression of VEGF/VPF by meningiomas is regulated by growth factors or sex hormones. By means of an enzyme-linked immunosorbent assay of CH-157MN meningioma cell supernatants, we demonstrated that EGF and bFGF similarly induce VEGF secretion by CH-157MN meningioma cells. At the maximum concentrations of EGF (50 ng/mL) and bFGF (50 ng/mL) used in this study, VEGF secretion was induced to 140% to 160% above baseline constitutive secretion. PDGF-BB homodimer did not enhance VEGF secretion significantly. Estradiol (up to 10(-7) mol/L), progesterone (up to 10(-5) mol/L), or testosterone (up to 10(-5) mol/L) did not stimulate or inhibit VEGF secretion in CH-157MN meningioma cells (p > 0.05). Furthermore, we demonstrated that dexamethasone decreased VEGF secretion to 32% of baseline constitutive secretion. This might explain the effect of corticosteroids in alleviating peritumoral brain edema in meningiomas. These results suggest that VEGF secretion in CH-157MN meningioma cells is mainly regulated by growth factors and corticosteroids, but not by sex hormones. Understanding the regulation of VEGF/VPF secretion in meningiomas might contribute to the development of a new therapeutic strategy.

  13. Grading Meningioma

    PubMed Central

    Okuchi, Sachi; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Fushimi, Yasutaka; Okada, Tsutomu; Yamauchi, Moritaka; Kataoka, Masako; Arakawa, Yoshiki; Takahashi, Jun C.; Minamiguchi, Sachiko; Miyamoto, Susumu; Togashi, Kaori

    2015-01-01

    Abstract The purpose was to compare capability of fluorine-18 fluorodeoxyglucose (FDG)-PET and thallium-201 (Tl)-SPECT for grading meningioma. This retrospective study was conducted as a case-control study under approval by the institutional review board. In the hospital information system, 67 patients (22 men and 45 women) who had both FDG-PET and Tl-SPECT preoperative examinations were found with histopathologic diagnosis of meningioma. The maximum FDG uptake values of the tumors were measured, and they were standardized to the whole body (SUVmax) and normalized as gray matter ratio (SUVRmax). Mean and maximum Tl uptake ratios (TURmean and TURmax, respectively) of the tumors were measured and normalized as ratios to those of the contralateral normal brain. Receiver-operating characteristic curve analyses of the 4 indexes were conducted for differentiation between low- and high-grade meningiomas, and areas under the curves (AUCs) were compared. Correlation coefficients were calculated between these indexes and Ki-67. Fifty-six meningiomas were classified as grade I (low grade), and 11 were grade II or III (high grade). In all 4 indexes, a significant difference was observed between low- and high-grade meningiomas (P < 0.05). AUCs were 0.817 (SUVmax), 0.781 (SUVRmax), 0.810 (TURmean), and 0.831 (TURmax), and no significant difference was observed among the indexes. Their sensitivity and specificity were 72.7% to 90.9% and 71.4% to 87.5%, respectively. Correlation of the 4 indexes to Ki-67 was statistically significant, but coefficients were relatively low (0.273–0.355). Tl-SPECT, which can be used at hospitals without a cyclotron or an FDG distribution network, has high diagnostic capability of meningioma grades comparable to FDG-PET. PMID:25674763

  14. Sclerosing Meningioma : Radiological and Clinical Characteristics of 21 Cases

    PubMed Central

    Kang, Ho; Se, Young-Bem; Dho, Yun-Sik; Choi, Seung Hong; Park, Sung-Hye

    2016-01-01

    Objective A rare subtype of meningioma, sclerosing meningioma is not included in the current World Health Organization classification of meningiomas and is classified into the category of other morphological variation subtypes. Sclerosing meningioma is often misdiagnosed to other non-benign meningioma or malignant neoplasm, so it is important to diagnose sclerosing type correctly. We analyzed the radiological and clinical characteristics of a series of sclerosing meningiomas. Methods Twenty-one patients who underwent surgery in one institute with a histopathologically proven sclerosing meningioma were included from 2006 to 2014. Eighteen tumors were diagnosed as a pure sclerosing-type meningioma, and 3 as mixed type. Magnetic resonance image was taken for all patients including contrast enhancement image. Computed tomography (CT) scan was taken for 16 patients. One neuroradiologist and 1 neurosurgeon reviewed all images retrospectively. Results In the all 16 patients with preoperative CT images, higher attenuation was observed in the meningioma than in the brain parenchyma, and calcification was observed in 11 (69%). In 15 of the 21 patients (71%), a distinctive very low signal intensity appeared as a dark color in T2-weighted images. Nine of these 15 tumors (60%) exhibited heterogeneous enhancement, and 6 (40%) exhibited homogeneous enhancement that was unlike the homogeneous enhancing pattern shown by conventional meningiomas. Ten patients had a clear tumor margin without peritumoral edema. Conclusion Although these peculiar radiological characteristics are not unique to sclerosing meningioma, we believe that they are distinctive features that may be helpful for distinguishing sclerosing meningioma from other subtypes. PMID:27847571

  15. A hypoxia-inducible factor (HIF)-3α splicing variant, HIF-3α4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3α4

    SciTech Connect

    Ando, Hitoshi; Natsume, Atsushi; Iwami, Kenichiro; Ohka, Fumiharu; Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae; Ito, Kengo; Saito, Kiyoshi; Sugita, Sachi; Hoshino, Tsuneyoshi; Wakabayashi, Toshihiko

    2013-03-29

    Highlights: ► HIF-3α4 is silenced by DNA methylation in meningiomas. ► Induction of HIF-3α4 impaired angiogenesis in meningiomas. ► Induction of HIF-3α4 impaired proliferation and oxygen-dependent metabolism. -- Abstract: Hypoxia inducible factor is a dominant regulator of adaptive cellular responses to hypoxia and controls the expression of a large number of genes regulating angiogenesis as well as metabolism, cell survival, apoptosis, and other cellular functions in an oxygen level-dependent manner. When a neoplasm is able to induce angiogenesis, tumor progression occurs more rapidly because of the nutrients provided by the neovasculature. Meningioma is one of the most hypervascular brain tumors, making anti-angiogenic therapy an attractive novel therapy for these tumors. HIF-3α has been conventionally regarded as a dominant-negative regulator of HIF-1α, and although alternative HIF-3α splicing variants are extensively reported, their specific functions have not yet been determined. In this study, we found that the transcription of HIF-3α4 was silenced by the promoter DNA methylation in meningiomas, and inducible HIF-3α4 impaired angiogenesis, proliferation, and metabolism/oxidation in hypervascular meningiomas. Thus, HIF-3α4 could be a potential molecular target in meningiomas.

  16. GLO1 Overexpression in Human Malignant Melanoma

    PubMed Central

    Bair, Warner B; Cabello, Christopher M; Uchida, Koji; Bause, Alexandra S; Wondrak, Georg T

    2010-01-01

    Glyoxalase I [lactoylglutathione lyase (EC 4.4.1.5) encoded by GLO1] is a ubiquitous cellular defense enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis. Accumulative evidence suggests an important role of GLO1 expression in protection against methylglyoxal-dependent protein adduction and cellular damage associated with diabetes, cancer, and chronological aging. Based on the hypothesis that GLO1 upregulation may play a functional role in glycolytic adaptations of cancer cells, we examined GLO1 expression status in human melanoma tissue. Quantitative RT-PCR analysis of a cDNA tissue array containing 40 human melanoma tissues (stages III and IV) and 13 healthy controls revealed pronounced upregulation of GLO1 expression at the mRNA level. Immunohistochemical analysis of a melanoma tissue microarray confirmed upregulation of glyoxalase 1 protein levels in malignant melanoma tissue versus healthy human skin. Consistent with an essential role of GLO1 in melanoma cell defense against methylglyoxal cytotoxicity, siRNA interference targeting GLO1-expression (siGLO1) sensitized A375 and G361 human metastatic melanoma cells towards the antiproliferative, apoptogenic, and oxidative stress-inducing activity of exogenous methylglyoxal. Protein adduction by methylglyoxal was increased in siGLO1-transfected cells as revealed by immunodetection using a monoclonal antibody directed against the major methylglyoxal-derived epitope argpyrimidine that detected a single band of methylglyoxal-adducted protein in human LOX, G361, and A375 total cell lysates. Using 2D-proteomics followed by mass spectrometry the methylglyoxal-adducted protein was identified as heat shock protein 27 (Hsp27; HSPB1). Taken together, our data suggest a function of GLO1 in the regulation of detoxification and target-adduction by the glycolytic byproduct methylglyoxal in malignant melanoma. PMID:20093988

  17. Pathology and Molecular Genetics of Meningioma: Recent Advances

    PubMed Central

    SHIBUYA, Makoto

    2015-01-01

    Meningiomas are the most common intracranial primary neoplasm in adults. Although the spectrum of clinical and molecular genetic issues regarding meningiomas remains undefined, novel genetic alterations that are associated with tumor morphology, malignancy, or location have recently been discovered. This review focuses on recent advances in understanding of the heterogenous pathology of meningiomas, particularly on associations between the clinical, histological, etiological, epidemiological, and molecular genetical aspects of the neoplasm. PMID:25744347

  18. Physical mapping of the NF2/meningioma region on human chromosome 22q12

    SciTech Connect

    Ruttledge, M.H.; Xie, Y.G.; Han, F.Y.; Janson, M.; Fransson, I.; Werelius, B. ); Giovannini, M.; Evans, G. ); Delattre, O.; Thomas, G. )

    1994-01-01

    Loss of genetic information from chromosome 22 has been implicated in the development of neurofibromatosis type 2, meningioma, and several other neoplasia. Molecular studies indicate that genes within chromosomal band 22q12 may be involved in tumorigenesis. The authors have mapped 29 loci into 16 groups in this region, using pulsed-field gel electrophoresis, fluorescence in situ suppression hybridization, and somatic cell hybrid mapping. The region spans more than 5 Mb of genomic DNA and contains the genes for neurofibromatosis type 2 and meningioma. The order of loci presented here provides the framework for the fine mapping of this region using cosmids and yeast artificial chromosomes, and it facilitates the speedy cloning of novel genes from 22q12. 51 refs., 4 figs.

  19. Primary Intraosseous Meningioma.

    PubMed

    Chen, Thomas C

    2016-04-01

    Primary intraosseous meningiomas are a subtype of primary extradural meningiomas. They represent approximately two-thirds of extradural meningiomas and fewer than 2% of meningiomas overall. These tumors originate within the bones of the skull and can have a clinical presentation and radiographic differential diagnosis different from those for intradural meningiomas. Primary intraosseous meningiomas are classified based on location and histopathologic characteristics. Treatment is primarily surgical resection with wide margins if possible. Sparse literature exists regarding the use of adjuvant therapies. The literature regarding primary intraosseous meningiomas consists primarily of clinical case reports and case series. This literature is reviewed and summarized in this article.

  20. Cholesteryl esters in human malignant neoplasms.

    PubMed

    Tosi, M R; Bottura, G; Lucchi, P; Reggiani, A; Trinchero, A; Tugnoli, V

    2003-01-01

    Cholesteryl esters (CholE) were detected in human malignant neoplasms by means of in vitro nuclear magnetic resonance spectroscopy. Spectroscopic analysis of the total lipid extracts obtained from cerebral tumors revealed appreciable amount of esterified cholesterol in high grade gliomas such as glioblastomas and anaplastic oligodendrogliomas, characterized by prominent neovascularity. The finding that no CholE were detected in the healthy brain and in low grade and benign tumors supports a possible correlation between this class of lipids and histological vascular proliferation. Compared with high grade gliomas, renal cell carcinomas show higher levels of CholE, absent in the healthy renal parenchyma and in benign oncocytomas. In nefro-carcinomas, cytoplasmic lipid inclusions and prominent vascularization contribute to the increased levels of CholE present mainly as oleate. CholE are discussed as potential biochemical markers of cancer and as a target for new therapeutic strategies.

  1. Human malignant melanoma heterotransplanted to nude mice.

    PubMed

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

  2. Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications

    PubMed Central

    Bi, Wenya Linda; Zhang, Michael; Wu, Winona W.; Mei, Yu; Dunn, Ian F.

    2016-01-01

    There has been a recent revolution in our understanding of the genetic factors that drive meningioma, punctuating an equilibrium that has existed since Cushing’s germinal studies nearly a century ago. A growing appreciation that meningiomas share similar biologic features with other malignancies has allowed extrapolation of management strategies and lessons from intra-axial central nervous system neoplasms and systemic cancers to meningiomas. These features include a natural proclivity for invasion, frequent intratumoral heterogeneity, and correlation between biologic profile and clinical behavior. Next-generation sequencing has characterized recurrent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA, which are collectively present in ~80% of sporadic meningiomas. Genomic features of meningioma further associate with tumor location, histologic subtype, and possibly clinical behavior. Such genomic decryption, along with advances in targeted pharmacotherapy, provides a maturing integrated view of meningiomas. We review recent advances in meningioma genomics and probe their potential applications in diagnostic, therapeutic, and prognostic frontiers. PMID:27458586

  3. [Primary osteolytic intraosseous meningioma of the occipital bone].

    PubMed

    Bernal-García, Luis Miguel; Cabezudo-Artero, José Manuel; Marcelo-Zamorano, María Bella; Fernández-Alarcón, Luis; Gilete-Tejero, Ignacio

    2015-01-01

    Primary intraosseous meningiomas are considered extradural meningiomas when no dural attachment is present. Most of them arise from the cranial bones and can present either as an osteoblastic or an osteolytic lesion. Osteolytic intraosseous meningiomas are the rarest and very few cases have been reported. Given that many of these may develop signs of malignancy, early histological confirmation is important in order to ensure appropriate treatment. The recommended therapy is surgery, with complete resection whenever possible. We present the case of a large primary intraosseous osteolytic meningioma within the occipital bone, which was completely excised five years ago, currently presenting no signs of recurrence.

  4. Cucurbitacin I blocks cerebrospinal fluid and platelet derived growth factor-BB stimulation of leptomeningeal and meningioma DNA synthesis

    PubMed Central

    2013-01-01

    Background Currently, there are no consistently effective chemotherapies for recurrent and inoperable meningiomas. Recently, cucurbitacin I (JSI-124), a naturally occurring tetracyclic triterpenoid compound used as folk medicines has been found to have cytoxic and anti-proliferative properties in several malignancies thru inhibition of activator of transcription (STAT3) activation. Previously, we have found STAT3 to be activated in meningiomas, particularly higher grade tumors. Methods Primary leptomeningeal cultures were established from 17, 20 and 22 week human fetuses and meningioma cell cultures were established from 6 World Health Organization (WHO) grade I or II meningiomas. Cells were treated with cerebrospinal fluid from patients without neurologic disease. The effects of cucurbitacin I on cerebrospinal fluid stimulation of meningioma cell DNA synthesis phosphorylation/activation of JAK1, STAT3, pMEK1/2, p44/42MAPK, Akt, mTOR, Rb and caspase 3 activation were analyzed in human leptomeningeal and meningioma cells. Results Cerebrospinal fluid significantly stimulated DNA synthesis in leptomeningeal cells. Co-administration of cucurbitacin I (250 nM) produces a significant blockade of this effect. Cucurbitacin I alone also produced a significant reduction in basal DNA synthesis. In grade I and II meningiomas, cerebrospinal fluid also significantly stimulated DNA synthesis. Co-administration of cucurbitacin I (250 nM) blocked this effect. In the leptomeningeal cultures, cerebrospinal fluid stimulated STAT3 phosphorylation but not p44/42MAPK, Akt or mTOR. Cucurbitacin I had no effect on basal STAT3 phosphorylation but co-administration with cerebrospinal fluid blocked cerebrospinal fluid stimulation of STAT3 phosphorylation in each. In the grade I meningiomas, cerebrospinal fluid stimulated phosphorylation of STAT3 and decreased MEK1/2 and cucurbitacin I had no effect on basal STAT3, p44/42MAPK, Akt, JAK1, mTOR, or Rb phosphorylation. In the grade II

  5. Immunoprevention of human papillomavirus-associated malignancies

    PubMed Central

    Wang1, Joshua W.; Hung, Chein-fu; Huh, Warner K.; Trimble, Cornelia L.; Roden, Richard B.S.

    2014-01-01

    Persistent infection by one of fifteen high risk human papillomavirus (hrHPV) types is a necessary but not sufficient cause of 5% of all human cancers. This provides a remarkable opportunity for cancer prevention via immunization. Since Harald zur Hausen’s pioneering identification of hrHPV types 16 and 18, found in ~50% and ~20% of cervical cancers respectively, two prophylactic HPV vaccines containing virus-like particles (VLP) of each genotype have been widely licensed. These vaccines are beginning to impact infection and HPV-associated neoplasia rates after immunization campaigns in adolescents. Here we review recent progress and opportunities to better prevent HPV-associated cancers, including: broadening immune-protection to cover all hrHPV types, reducing the cost of HPV vaccines especially for developing countries that have the highest rates of cervical cancer, and immune-based treatment of established HPV infections. Screening based upon George Papanicolaou’s cervical cytology testing, and more recently detection of hrHPV DNA/RNA, followed by ablative treatment of high grade cervical intraepithelial neoplasia (CIN2/3) have substantially reduced cervical cancer rates, and we examine their interplay with immune-based modalities for the prevention and eventual elimination of cervical cancer and other HPV-related malignancies. PMID:25488410

  6. Analysis of Gene Expression Profiling in Meningioma: Deregulated Signaling Pathways Associated with Meningioma and EGFL6 Overexpression in Benign Meningioma Tissue and Serum

    PubMed Central

    Wang, Xuanchun; Gong, Ye; Wang, Daijun; Xie, Qing; Zheng, Mingzhe; Zhou, Yu; Li, Qin; Yang, Zhen; Tang, Hailiang; Li, Yiming; Hu, Renming; Chen, Xiancheng; Mao, Ying

    2012-01-01

    Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFβ signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum. PMID:23285163

  7. Analysis of gene expression profiling in meningioma: deregulated signaling pathways associated with meningioma and EGFL6 overexpression in benign meningioma tissue and serum.

    PubMed

    Wang, Xuanchun; Gong, Ye; Wang, Daijun; Xie, Qing; Zheng, Mingzhe; Zhou, Yu; Li, Qin; Yang, Zhen; Tang, Hailiang; Li, Yiming; Hu, Renming; Chen, Xiancheng; Mao, Ying

    2012-01-01

    Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFβ signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum.

  8. Meningioma recurrence

    PubMed Central

    Bencze, János; Varkoly, Gréta; Kouhsari, Mahan C; Klekner, Álmos

    2016-01-01

    Abstract Meningioma accounts for more than 30% of all intracranial tumours. It affects mainly the elderly above the age of 60, at a female:male ratio of 3:2. The prognosis is variable: it is usually favourable with no progression in tumour grade and no recurrence in WHO grade 1 tumours. However, a minority of tumours represent atypical (grade 2) or anaplastic (grade 3) meningiomas; this heterogeneity is also reflected in histopathological appearances. Irrespective of the grade, the size of the tumour and the localisation may have severe, sometimes lethal consequences. Following neurosurgical interventions to remove the tumour, recurrence and progression in WHO grade may occur. Our knowledge on predisposing histomorphological and molecular factors of recurrence is rather limited. These can be classified as I) demographic II) environmental, III) genetic and epigenetic IV) imaging, V) neuropathological, and VI) neurosurgical. In view of the complex background of tumour recurrence, the recognition of often subtle signs of increased risk of recurrence requires close collaboration of experts from several medical specialties. This multidisciplinary approach results in better therapy and fewer complications related to tumour recurrence. PMID:28352788

  9. Neurotensin high affinity binding sites and endopeptidase 24. 11 are present respectively in the meningothelial and in the fibroblastic components of human meningiomas

    SciTech Connect

    Mailleux, P.; Przedborski, S.; Beaumont, A.; Verslijpe, M.; Depierreux, M.; Levivier, M.; Kitabgi, P.; Roques, B.P.; Vanderhaeghen, J.J. )

    1990-11-01

    The presence of neurotensin receptors and endopeptidase 24.11 (E-24.11) in 16 human meningioma specimens, obtained at surgery, was assessed by measuring the binding of {sup 125}I-(tyrosyl3)neurotensin(1-13) ({sup 125}I-NT) and the inhibitor {sup 3}H-N(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-(oxopropyl)glycine ({sup 3}H-HACBO-Gly), for the receptor and enzyme, respectively. E-24.11 activity was also measured. Autoradiography, on the 16 meningiomas, showed that specific {sup 125}I-NT labeling (nonspecific labeling was assessed in the presence of excess NT) was exclusively located in the meningothelial regions. In contrast, specific {sup 3}H-HACBO-Gly labeling (nonspecific labeling was assessed in the presence of an excess of the E-24.11 inhibitor thiorphan) was exclusively found in fibroblastic regions. No specific labeling of either ligand was found on collagen or blood vessels. In vitro binding assays were performed on membranes of 10 of the 16 meningiomas. In the 4 meningiomas rich in meningothelial cells, {sup 125}I-NT specifically bound to one population of sites with Bmax ranging from 57 to 405 fmol/mg protein and Kd around 0.3 nM. These sites share common properties with the brain NT receptor, since the carboxy terminal acetyl NT(8-13) fragment bound to the same sites but with a higher affinity. The carboxy terminal analogue of NT, neuromedin N, also bound to the same sites with a 10-fold lower affinity and the sites were bradykinin and levocabastine insensitive. In the 4 meningiomas rich in fibroblastic cells, {sup 3}H-HACBO-Gly specifically bound to one population of sites with Bmax ranging from 251 to 739 fmol/mg protein and Kd around 2.8 nM.

  10. Human herpesvirus 6 in hematological malignancies.

    PubMed

    Ogata, Masao

    2009-11-01

    Pathogenetic roles of human herpesvirus (HHV)-6 in lymphoproliferative diseases have been of continued interest. Many molecular studies have tried to establish a pathogenic role for HHV-6 in lymphoid malignancies. However, whether HHV-6 plays a role in these pathologies remains unclear, as positive polymerase chain reaction results for HHV-6 in those studies may reflect latent infection or reactivation rather than presence of HHV-6 in neoplastic cells. A small number of studies have investigated HHV-6 antigen expression in pathologic specimens. As a result, the lack of HHV-6 antigen expression on neoplastic cells argues against any major pathogenic role of HHV-6. The role of HHV-6 in childhood acute lymphoblastic leukemia (ALL) has also been of interest but remains controversial, with 2 studies documenting higher levels of HHV-6 antibody in ALL patients, and another 2 large-scale studies finding no significant differences in HHV-6 seroprevalences between ALL patients and controls. Alternatively, HHV-6 is increasingly recognized as an important opportunistic pathogen. HHV-6 reactivation is common among recipients of allogeneic stem cell transplantation (SCT), and is linked to various clinical manifestations. In particular, HHV-6 encephalitis appears to be significant, life-threatening complication. Most HHV-6 encephalitis develops in patients receiving transplant from an unrelated donor, particularly cord blood, typically around the time of engraftment. Symptoms are characterized by short-term memory loss and seizures. Magnetic resonance imaging typically shows limbic encephalitis. Prognosis for HHV-6 encephalitis is poor, but appropriate prophylactic measures have not been established. Establishment of preventive strategies against HHV-6 encephalitis represents an important challenge for physicians involved with SCT.

  11. The WHO Grade I Collagen-forming Meningioma Produces Angiogenic Substances. A New Meningioma Entity.

    PubMed

    Haybaeck, Johannes; Smolle, Elisabeth; Schökler, Bernadette; Kleinert, Reinhold

    2016-03-01

    Meningiomas arise from arachnoid cap cells, the so-called meningiothelial cells. They account for 20-36% of all primary intracranial tumours, and arise with an annual incidence of 1.8-13 per 100,000 individuals/year. According to their histopathological features meningiomas are classified either as grade I (meningiothelial, fibrous/fibroblastic, transitional/mixed, psammomatous, angiomatous, microcystic, secretory and the lympholasmacyterich sub-type), grade II (atypical and clear-cell sub-type) or grade III (malignant or anaplastic phenotype). A 62-year-old female patient presented to the hospital because of progressive obliviousness and concentration difficulties. In the magnetic resonance imaging (MRI) of the brain, an occipital convexity-meningioma was found in the left hemisphere, which was subsequently resected. Within the tumour tissue there were multiple spheroid precipitates, i.e. secretion products that turned out to consist of collagen. Part of the tumour cells displayed positive reactions for vasogenic substances, namely for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Correspondingly, the diagnosis "WHO Grade I collagen-forming meningioma" seems to be most appropriate. The "WHO Grade I collagen-forming meningioma" reported herein produces collagen and angiogenic substances. To the best of our knowledge, no such entity has been reported on in previous literature. We propose this collagen-producing meningioma as a novel WHO grade I meningioma sub-type. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Intercellular crosstalk in human malignant melanoma.

    PubMed

    Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel

    2017-05-01

    Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

  13. Extradural en-plaque spinal meningioma with intraneural invasion.

    PubMed

    Tuli, Jayshree; Drzymalski, Dan Michael; Lidov, Hart; Tuli, Sagun

    2012-01-01

    Extradural spinal meningiomas are rare. Our understanding of purely extradural spinal meningiomas is incomplete because most reports rarely differentiate purely extradural meningiomas from extradural meningiomas with an intradural component. Occasionally, reports have described involvement of the adjacent nerve root, but there has never been a description of an extradural meningioma that actually infiltrates the nerve root. A 42-year-old woman presented with progressive lower extremity weakness and numbness below T3 during the span of 4 months with imaging evidence of an extradural lesion compressing the cord from T4 through T6. Surgical resection revealed an extradural mass extending through the foramen at T5-6 and encompassing the cord and T5 root on the left. Pathologically, the lesion was a World Health Organization grade I meningioma with nerve root invasion and a concerning elevated mindbomb homolog 1 (MIB-1) of 9.4%. Purely extradural meningiomas are rare, and our case is one of the first to describe a patient with an extradural meningioma that actually infiltrates the nerve root. Extradural spinal meningiomas are usually not adherent to the dura, but only appear to be adherent or invade (as in our patient) the adjacent nerve root. They are easily mistaken preoperatively and grossly intraoperatively for malignant metastatic tumors and can change the proposed surgical treatment. The long-term prognosis remains uncertain, but our patient's last follow-up suggests a favorable prognosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma.

    PubMed

    Qu, Min; Qiu, B O; Xiong, Wende; Chen, Dong; Wu, Anhua

    2015-05-01

    The aim of the present study was to determine the expression of a-disintegrin and metalloproteinase 10 (ADAM10) in human glioma tissues from surgical specimens and discuss its possible significance in glioma biology. A total of 43 glioma specimens obtained from patients between 2007 and 2010 were collected and a series of assays were performed. Of these, 22 cases were low-grade gliomas, while 21 cases were high-grade gliomas. In addition, 20 cases of meningioma were used as the control group. Reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry were used to determine the mRNA and protein expression levels of ADAM10. Besides the quantitative analysis, histological observations were also performed to localize ADAM10 expression in glioma cells. The RT-PCR and western blot analysis results demonstrated increased ADAM10 expression in the low-grade glioma samples compared with the control (P<0.05), while ADAM10 expression was further increased in the high-grade glioma samples (P<0.01 vs. control; P<0.05 vs. low-grade glioma), indicating that the mRNA and protein expression levels of ADAM10 were malignancy-dependent. The immunohistochemical analysis revealed that the ADAM10 protein was located on both the tumor cell membrane and blood vessel walls within tumor tissues. In conclusion, these results indicated that ADAM10 expression correlates with the grade of malignancy in human glioma from surgical specimens. In addition, the fact that ADAM10 protein was expressed on cell membranes and blood vessel walls within tumor tissues, indicates that its expression may be associated with invasive tumor growth and peritumoral edema formation.

  15. Hypomethylation of DNA from Benign and Malignant Human Colon Neoplasms

    NASA Astrophysics Data System (ADS)

    Goelz, Susan E.; Vogelstein, Bert; Hamilton, Stanley R.; Feinberg, Andrew P.

    1985-04-01

    The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, γ -globin, α -chorionic gonadotropin, and γ -crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

  16. Pulmonary metastasis of a meningioma presenting as a solitary pulmonary nodule: 2 case reports.

    PubMed

    Leemans, J; Van Calenbergh, F; Sciot, R; Debiec-Rychter, M; Decaluwe, H; Nackaerts, K

    2016-04-01

    Distant metastases of meningioma are rare, especially in grade 1 meningiomas. In a recent literature review, only 115 cases were found. In almost all published cases, the meningioma was treated several years before the metastasis was diagnosed. The lungs are the most frequent site of metastasis. We describe two patients treated for meningioma (one case grade 1, the other grade 3) who were referred to the Respiratory Oncology Unit because of the incidental finding of a pulmonary nodule on routine chest radiography. Both had undergone several neurosurgical procedures but the last operation was more than 7 years before in both cases. Positron emission tomography scan was suggestive of a malignant lung tumour. The lesions were surgically removed. Pathology confirmed meningioma in both cases with the same WHO grade, immunohistochemical and genetic profiles as the original meningioma. Both patients recovered well from thoracic surgery. The patient with grade 3 meningioma died three years later from intracranial recurrence. When a patient previously treated for meningioma develops a nodular lung lesion, metastasis of the meningioma should be in the differential diagnosis list. Because of the occurrence of distant metastasis even in grade I meningiomas, we suggest that the grading system should take into account genetic changes in the meningioma. Chromosome 1p and 14q losses possibly explain the aggressive behaviour of the grade 1 meningioma.

  17. Glioblastoma induction after radiosurgery for meningioma.

    PubMed

    Yu, J S; Yong, W H; Wilson, D; Black, K L

    2000-11-04

    A 70-year-old woman developed a glioblastoma in the irradiated field 7 years after stereotactic radiosurgery for meningioma. Glioma induction has been previously reported after external beam radiation for leukaemia, pituitary adenoma, tinea capitus, and meningioma. This radiosurgery-induced malignancy may portend further reports of tumour induction. The theoretical risk of tumour induction by low doses of radiation to normal neural tissue after radiosurgery is now confirmed. Reports of additional cases of radiosurgery-induced tumours might temper the use of this increasingly used technique for benign surgically accessible lesions.

  18. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  19. Anaplastic and meningothelial meningiomas in a single tumor: A "dedifferentiated meningioma"?

    PubMed

    Shintaku, Masayuki; Adachi, Yasushi; Arai, Atsushi; Koyama, Junji

    2016-12-01

    The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein. © 2016 Japanese Society of Neuropathology.

  20. Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

    PubMed Central

    Ma, Jie; Frank, Markus H.

    2010-01-01

    Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

  1. Tumor initiation in human malignant melanoma and potential cancer therapies.

    PubMed

    Ma, Jie; Frank, Markus H

    2010-02-01

    Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

  2. A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues.

    PubMed

    Suetani, Rachel J; Ho, Kristen; Jindal, Shalini; Manavis, Jim; Neilsen, Paul M; Pishas, Kathleen I; Rippy, Elisabeth; Bochner, Melissa; Kollias, James; Gill, P Grantley; Morris, Howard A; Callen, David F

    2012-10-15

    Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)(2)D(3) (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.

  3. Benzene and lymphohematopoietic malignancies in humans.

    PubMed

    Hayes, R B; Songnian, Y; Dosemeci, M; Linet, M

    2001-08-01

    Quantitative evaluations of benzene-associated risk for cancer have relied primarily on findings from a cohort study of highly exposed U.S. rubber workers. An epidemiologic investigation in China (NCI/CAPM study) extended quantitative evaluations of cancer risk to a broader range of benzene exposures, particularly at lower levels. We review the evidence implicating benzene in the etiology of hematopoietic disorders, clarify methodologic aspects of the NCI/CAPM study, and examine the study in the context of the broader literature on health effects associated with occupational benzene exposure. Quantitative relationships for cancer risk from China and the U.S. show a relatively smooth increase in risk for acute myeloid leukemia and related conditions over a broad dose range of benzene exposure (below 200 ppm-years mostly from the China study and above 200 ppm-years mostly from the U.S. study). Risks of acute myeloid leukemia and other malignant and nonmalignant hematopoietic disorders associated with benzene exposure in China are consistent with other information about benzene exposure, hematotoxicity, and cancer risk, extending evidence for hematopoietic cancer risks to levels substantially lower than had previously been established. Published 2001 Wiley-Liss, Inc.

  4. Genetic landscape of meningioma.

    PubMed

    Yuzawa, Sayaka; Nishihara, Hiroshi; Tanaka, Shinya

    2016-10-01

    Meningioma is the most common intracranial tumor, arising from arachnoid cells of the meninges. Monosomy 22 and inactivating mutations of NF2 are well-known genetic alterations of meningiomas. More recently, mutations in TRAF7, AKT1, KLF4, SMO, and PIK3CA were identified by next-generation sequencing. We here reviewed 553 meningiomas for the mutational patterns of the six genes. NF2 aberration was observed in 55 % of meningiomas. Mutations of TRAF7, AKT1, KLF4, PIK3CA, and SMO were identified in 20, 9, 9, 4.5, and 3 % of cases, respectively. Altogether, 80 % of cases harbored at least one of the genetic alterations in these genes. NF2 alterations and mutations of the other genes were mutually exclusive with a few exceptions. Clinicopathologically, tumors with mutations in TRAF7/AKT1 and SMO shared specific features: they were located in the anterior fossa, median middle fossa, or anterior calvarium, and most of them were meningothelial or transitional meningiomas. TRAF7/KLF4 type meningiomas showed different characteristics in that they occurred in the lateral middle fossa and median posterior fossa as well as anterior fossa and median middle fossa, and contained a secretory meningioma component. We also discuss the mutational hotspots of these genes and other genetic/cytogenetic alterations contributing to tumorigenesis or progression of meningiomas.

  5. Temporal bone meningiomas.

    PubMed

    Hooper, R; Siu, K; Cousins, V

    1990-10-01

    Meningiomas should be considered in the differential diagnosis of space-occupying lesions of the temporal bone. Five cases of meningiomas of the temporal bone are described and the literature reviewed. These tumours may stimulate Schwannomas and glomus tumours in their presentation and radiological findings. The tumours were managed by combining standard neurosurgical approaches with temporal bone and skull base techniques.

  6. Relevance of lipids to heterotransplantation of human malignancies.

    PubMed

    Perez, R L; Mitchell, J R; Lozzio, B B

    1982-01-01

    Although the transplantation of human neoplasms in immunodeficient mice is now a well-established procedure, the majority of primary malignancies cannot be successfully maintained for long periods of time in adult athymic (nude) and asplenic-athymic (lasat) mice. Various lipids such as cholesterol, cholesterol oleate, stearic and palmitic acid esters markedly depress the RES phagocytic activity and immunocompetence of mammals. In view of the immunosuppressive properties of certain lipids and in order to graft and grow as many tumors as possible, further studies into the effects of lipids on the growth of heterotransplanted human tumors is warranted. Lipids may enhance local growth and facilitate the development of metastases rarely seen in nude and lasat mice bearing xenogeneic cancer cells. Lipids may accelerate human malignant cell proliferation in mice by both depressing further the defense of host and modifying the cancer cell membrane. The relationship of lipids to the onset and progression of 'spontaneous' tumors in humans is not known.

  7. DNA content and chromosomal composition of malignant human gliomas.

    PubMed

    Bigner, S H; Bjerkvig, R; Laerum, O D

    1985-11-01

    A short review is given on DNA aberrations and chromosomal composition of malignant human gliomas. By flow cytometric DNA analysis, a wide range of different ploidies has been reported in biopsied gliomas, from diploid to strongly aneuploid nuclear DNA. However, with the preparation and analysis methods used so far, no clear relationship between the type of ploidy and histology or prognosis has been established. A high proportion of glioblastomas is near-diploid, indicating a high degree of biologic malignancy is not necessarily connected to aberration of the nuclear DNA content. It is possible that improved methods giving a higher degree of resolution will allow separation of the near-diploid populations of malignant human gliomas from normal diploid cells and permit the detection of subpopulations with small differences from the dominant DNA mode. Chromosomal studies of malignant gliomas have confirmed that the majority of them have near-diploid stemlines. These populations are seldom normal diploid, however, as both numerical and structural abnormalities are usually present. In addition, chromosomal analyses have shown that when gliomas are bimodal, the polyploid populations are usually doubled versions of the near-diploid ones. In contrast to the near-diploid populations that characterize biopsied malignant gliomas, both FCM studies and karyotyping have demonstrated that permanent cultured cell lines derived from malignant gliomas are usually near-triploid or near-tetraploid. Sequential karyotypic studies of these tumors from biopsy through establishment in vitro have shown an evolutionary pattern consisting of doubling of the original stemline, followed by gains or losses of individual chromosomes with new marker formation in late culture. Evaluation of biopsied malignant gliomas by karyotyping has also demonstrated that subgroups of them are characterized by specific numerical and structural deviations. These groupings may prove useful in predicting prognosis

  8. Unusual presentations of intracranial meningiomas: Report of two cases and review of the literature.

    PubMed

    Dhingra, Shruti; Gandhi, Jatin Sundersham; Gupta, Divya

    2015-01-01

    Meningiomas at extracranial sites are uncommon clinical presentations. They may present in the form of benign, slow.growing masses or may exhibit aggressive malignant behavior. We report two cases of intracranial meningiomas presenting at extracranial sites that are, at the sinonasal tract/external auditory canal and as a neck mass. The clinical presentations, histopathological features and appropriate management are discussed.

  9. Papillary meningioma: clinical and histopathological observations

    PubMed Central

    Wang, Dai-Jun; Zheng, Ming-Zhe; Gong, Ye; Xie, Qing; Wang, Yin; Cheng, Hai-Xia; Mao, Ying; Zhong, Ping; Che, Xiao-Ming; Jiang, Cheng-Chuan; Huang, Feng-Ping; Zheng, Kang; Li, Shi-Qi; Gu, Yu-Xiang; Bao, Wei-Min; Yang, Bo-Jie; Wu, Jing-Song; Xie, Li-Qian; Tang, Hai-Liang; Zhu, Hong-Da; Chen, Xian-Cheng; Zhou, Liang-Fu

    2013-01-01

    Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality. PMID:23638219

  10. HCG variants, the growth factors which drive human malignancies

    PubMed Central

    Cole, Laurence A

    2012-01-01

    The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules, each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. The 5 molecules are each produced by separate cells and each having separate biological functions. hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies. hCGβ and hyperglycosylated hCGβ are autocrines produce by most advanced malignancies. These molecules, particularly the malignancy promoters are presented in this review on hCG and cancer. hCGβ and hyperglycosylated hCGβ are critical to the growth and invasion, or malignancy of most advanced cancers. In many ways, while hCG may appear like a nothing, a hormone associated with pregnancy, it is not, and may be at the center of cancer research. PMID:22206043

  11. Parasite Infection, Carcinogenesis and Human Malignancy.

    PubMed

    van Tong, Hoang; Brindley, Paul J; Meyer, Christian G; Velavan, Thirumalaisamy P

    2017-02-01

    Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. WHO grade related expression of TRAIL-receptors and apoptosis regulators in meningioma.

    PubMed

    Koschny, Ronald; Krupp, Wolfgang; Xu, Li-Xin; Mueller, Wolf C; Bauer, Manfred; Sinn, Peter; Keller, Marius; Koschny, Thomas; Walczak, Henning; Bruckner, Thomas; Ganten, Tom M; Holland, Heidrun

    2015-02-01

    The expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors and key regulators of the extrinsic apoptosis pathway correlate with clinical features and the WHO grade of malignancy in some tumor entities. Expression of pro-apoptotic TRAIL receptors and executioners of apoptosis are a prerequisite for TRAIL-based therapies as a promising future targeted therapy. Human meningioma tissues (n=24 WHO grade I, n=7 WHO grade II, n=6 WHO grade III) were immunohistochemically analyzed for the expression of TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4, caspase-8, cFLIP, Bcl-2, Bcl-XL, Mcl-1, Bax, and Bak. Staining intensities were quantified by an automated software-based algorithm. While TRAIL-R1 and TRAIL-R3 were nearly absent in meningiomas, TRAIL-R2 and TRAIL-R4 were abundantly expressed. However, only TRAIL-R4 expression correlated with the WHO grade of malignancy. Bcl-2 showed a non-significant upregulation in WHO grade III meningiomas. Bcl-XL and Mcl-1 expression was significantly higher in WHO grade II compared to grade I. Bcl-XL and TRAIL-R4 expression correlated with the mitotic activity (Ki67) of the tumor. Furthermore, TRAIL-R2 expression correlated with TRAIL-R4. Bak expression correlated with both, Bcl-XL and Mcl-1 expression. The expression patterns did neither correlate with the progression-free nor with the overall survival of the meningioma patients. Apoptosis-inducing TRAIL-R2 and all key executioners of the extrinsic apoptosis pathway are abundantly expressed in meningioma. For some regulators of apoptosis with opposite functions, the expression of the pro-apoptotic protein significantly correlated with the expression level of the respective anti-apoptotic binding partner, possibly resulting in a steady-state of apoptosis. TRAIL-R2 might serve as a novel therapeutic target in meningioma. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Cystic meningioma: unusual imaging appearance of a common intracranial tumor

    PubMed Central

    Layton, Kennith F.; Finn, S. Sam; Snipes, George J.; Opatowsky, Michael J.

    2010-01-01

    Meningiomas are common tumors of the central nervous system that account for approximately 15% of all intracranial tumors and are the most common extra-axial neoplasm. Most meningiomas are benign, although atypical and malignant meningiomas also exist. Typical imaging characteristics include a well-circumscribed, homogeneously enhancing, extra-axial mass on both computed tomography and magnetic resonance imaging. The presence of an associated cyst is an uncommon imaging feature that may make it difficult to distinguish the tumor from a primary intra-axial glial neoplasm. The presence of peritumoral edema can also be a misleading finding. We present a case of a woman who presented with a history of multiple recent falls, decreased energy, and increased somnolence and was found to have a “cystic meningioma.” Typical imaging characteristics, histologic subtypes, treatment, and prognosis are also discussed. PMID:21240328

  14. Quantitative Proteomic Analysis of Meningiomas for the Identification of Surrogate Protein Markers

    PubMed Central

    Sharma, Samridhi; Ray, Sandipan; Moiyadi, Aliasgar; Sridhar, Epari; Srivastava, Sanjeeva

    2014-01-01

    Meningiomas are the most common non-glial tumors of the brain and spine. Pathophysiology and definite histological grading of meningiomas are frequently found to be deceptive due to their unusual morphological features and locations. Here for the first time we report a comprehensive serum proteomic analysis of different grades of meningiomas by using multiple quantitative proteomic and immunoassay-based approaches to obtain mechanistic insights about disease pathogenesis and identify grade specific protein signatures. In silico functional analysis revealed modulation of different vital physiological pathways including complement and coagulation cascades, metabolism of lipids and lipoproteins, immune signaling, cell growth and apoptosis and integrin signaling in meningiomas. ROC curve analysis demonstrated apolipoprotein E and A-I and hemopexin as efficient predictors for meningiomas. Identified proteins like vimentin, alpha-2-macroglobulin, apolipoprotein B and A-I and antithrombin-III, which exhibited a sequential increase in different malignancy grades of meningiomas, could serve as potential predictive markers. PMID:25413266

  15. Breast adenocarcinoma metastatic to epidural cervical spine meningioma: case report and review of the literature.

    PubMed

    Aghi, Manish; Kiehl, Tim-Rasmus; Brisman, Jonathan L

    2005-11-01

    While several cases of cancer metastatic to cranial meningiomas have been reported, metastasis to spinal meningioma has been reported only once, and a mechanism for such metastases has not been investigated. We report a case of breast carcinoma metastatic to an epidural cervical meningioma, summarize the literature on metastases to central nervous system meningiomas, and suggest a possible mechanism. Our patient, a 55-year-old woman, presented with difficulty walking, back pain, and quadriparesis. Magnetic resonance imaging revealed an enhancing C3-4 epidural lesion and an L4 compression fracture. Because of concern that the fracture and epidural lesion might represent metastases, we performed a metastatic work-up, which revealed a right breast mass. The patient underwent C3-C4 laminectomies and an epidural lesion was encountered. Intraoperative frozen section revealed mixed meningioma and breast adenocarcinoma. A gross total resection was achieved and the patient subsequently received spinal irradiation and hormonal therapy. Whereas a literature review revealed numerous reports of metastases to cranial meningiomas, this represents only the second reported case of such pathology in the spine. Mechanisms of this unusual process likely include meningiomas' vascularity, meningiomas' slow growth providing nutrient availability, and perhaps, as suggested by our analysis, E-cadherin expression by both meningiomas and breast cancer. Metastasis to meningioma must be considered in an epidural spinal lesion in all patients with a known malignancy, with surgical aggressiveness tailored to the intraoperative pathologic diagnosis.

  16. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

  17. Localisation of malignant glioma by a radiolabelled human monoclonal antibody.

    PubMed Central

    Phillips, J; Alderson, T; Sikora, K; Watson, J

    1983-01-01

    Human monoclonal antibodies were produced by fusing intratumoral lymphocytes from patients with malignant gliomas with a human myeloma line. One antibody was selected for further study after screening for binding activity to glioma cell lines. The patient from whom it was derived developed recurrent glioma. 1 mg of antibody was purified, radiolabelled with 131I, and administered intravenously. The distribution of antibody was determined in the blood, CSF and tumour cyst fluid and compared with that of a control human monoclonal immunoglobulin. Antibody localisation in the tumour was observed and confirmed by external scintiscanning. Images PMID:6101173

  18. Paraneoplastic symptoms caused by extracranial meningioma metastases?

    PubMed Central

    Mindermann, Thomas

    2016-01-01

    Background: There are only few reports on distant metastases of cranial meningiomas WHO I. In one-third of the cases, distant metastases seem to be clinically silent. This is the first case of distant metastases which may have manifested with a paraneoplastic syndrome. Case Description: A 52-year-old white male patient was diagnosed with distant metastases to the bones and liver 11 and 12 years following craniotomy and removal of a tentorial meningioma WHO I. At that time, the patient had developed paresthesia, unsteady gait, and a slight cognitive impairment, which in retrospect had no other explanation than that of a paraneoplastic syndrome. Eighteen years following craniotomy, a small intracranial tumor rest is under control following two single session radiosurgery treatments. At present, the patient has a multitude of bone and liver metastases, which seem to cause his paraneoplastic symptoms. Conclusion: Screening for malignancies in patients with paraneoplastic symptoms and a history of cranial meningioma should include screening for distant metastases from the meningioma. PMID:28168092

  19. Eliminating malignant contamination from therapeutic human spermatogonial stem cells

    PubMed Central

    Dovey, Serena L.; Valli, Hanna; Hermann, Brian P.; Sukhwani, Meena; Donohue, Julia; Castro, Carlos A.; Chu, Tianjiao; Sanfilippo, Joseph S.; Orwig, Kyle E.

    2013-01-01

    Spermatogonial stem cell (SSC) transplantation has been shown to restore fertility in several species and may have application for treating some cases of male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich SSCs from human testis cell suspensions and also remove malignant contamination. We used flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT-4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not expressed on human spermatogonia. A multiparameter sort of MOLT-4–contaminated human testicular cell suspensions was performed to isolate EpCAM+/HLA-ABC–/CD49e– (putative spermatogonia) and EpCAM–/HLA-ABC+/CD49e+ (putative MOLT-4) cell fractions. The EpCAM+/HLA-ABC–/CD49e– fraction was enriched for spermatogonial colonizing activity and did not form tumors following human-to–nude mouse xenotransplantation. The EpCAM–/HLA-ABC+/CD49e+ fraction produced tumors following xenotransplantation. This approach could be generalized with slight modification to also remove contaminating TF-1a leukemia cells. Thus, FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression. PMID:23549087

  20. Disseminated extracranial metastatic meningioma.

    PubMed

    Chua, Felicia H Z; Low, Sharon Y Y; Tham, Chee K; Ding, Cristine; Wong, Chin F; Nolan, Colum P

    2016-11-01

    Meningiomas are usually low-grade, solitary lesions that rarely metastasize. In this group of central nervous system tumours, the higher grade subtypes are notorious for resistance to conventional chemo-radiation therapies. Recent studies have shown efficacy in the use of bevacizumab in patients with recurrent and, or progressive anaplastic meningioma. The authors report a case of a young patient with recurrent anaplastic meningioma who despite being treated with bevacizumab, progressed with disease dissemination to multiple extracranial sites. Although the majority of meningiomas are amendable to treatment, the higher grade subtypes remain therapeutically challenging. The unexpected resistance to anti-angiogenic therapy in this patient adds another layer of complexity to an elusive subset of a supposedly benign disease. This patient report reflects the need for in-depth studies, molecular characterization and overall, better disease understanding in order to improve prognosis for affected patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Lechpammer, Mirna

    2016-07-15

    Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed.

  2. Management of Spinal Meningiomas.

    PubMed

    Ravindra, Vijay M; Schmidt, Meic H

    2016-04-01

    Spinal meningiomas are the most common spinal tumors encountered in adults, and account for 6.5% of all craniospinal tumors. The treatment for these lesions is primarily surgical, but emerging modalities may include chemotherapy and radiosurgery. In this article, the current management of spinal meningiomas and the body of literature surrounding conventional treatment is reviewed and discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A successful case of an anaplastic meningioma treated with chemotherapy for soft tissue sarcomas.

    PubMed

    Lucchesi, Maurizio; Buccoliero, Anna M; Scoccianti, Silvia; Guidi, Milena; Farina, Silvia; Fonte, Carla; Favre, Claudio; Genitori, Lorenzo; Sardi, Iacopo

    2016-07-01

    Malignant meningioma has a bad prognosis. Surgery and radiotherapy are the most effective therapeutic options, without an established role for chemotherapy. We report a case of 2-year-old male child with diagnosis of postoperative relapse of a malignant meningioma. Considering the rapid progression, the young age and the lack of effective therapeutic alternatives, the patient underwent multidisciplinary anticancer treatment with a protocol made for soft tissue sarcomas (EpSSG NRSSTS 2005 protocol), with positive outcome. This case represents a successful management of an anaplastic meningioma with a multimodal treatment, including chemotherapy, in a pediatric patient.

  4. Percoll density gradient separation of cells from human malignant effusions.

    PubMed Central

    Hamburger, A. W.; Dunn, F. E.; White, C. P.

    1985-01-01

    A simple method is described for the separation of cells derived from effusions of patients with adenocarcinomas in discontinuous density gradients of Percoll. After separation, cells from different fractions were analyzed by morphologic, histochemical and immunologic criteria. Total cell recovery from 27 experiments was 67 +/- 4%. Macrophages (82%) were recovered in the intermediate density fraction (1.056-1.067 g ml-1) with a purity of 90%. Recovered lymphocytes (98%) were found in the high density fraction (1.067-1.077 g ml-1) with a purity of 92%. The majority of the lymphocytes recovered were T cells. Malignant adenocarcinoma cells (90%) were recovered in the lowest density fractions (up to 1.056 g ml-1) with a purity of 79%. Use of effective cell separation procedures should facilitate the analysis of the functional capacities of both normal and neoplastic cells derived from human malignant effusions. PMID:2981542

  5. Fractal Analysis May Improve the Preoperative Identification of Atypical Meningiomas.

    PubMed

    Czyz, Marcin; Radwan, Hesham; Li, Jian Y; Filippi, Christopher G; Tykocki, Tomasz; Schulder, Michael

    2017-02-01

    There is no objective and readily accessible method for the preoperative determination of atypical characteristics of a meningioma grade. To evaluate the feasibility of using fractal analysis as an adjunctive tool to conventional radiological techniques in visualizing histopathological features of meningiomas. A group of 27 patients diagnosed with atypical (WHO grade II) meningioma and a second group of 27 patients with benign (WHO grade I) meningioma were enrolled in the study. Preoperative brain magnetic resonance (MR) studies (T1-wieghted, post-gadolinium) were processed and analyzed to determine the average fractal dimension (FDa) and maximum fractal dimension (FDm) of the contrast-enhancing region of the tumor using box-count method. FDa and FDm as well as particular radiological features were included in the logistic regression model as possible predictors of malignancy. The cohort consisted of 34 women and 20 men, mean age of 62 ± 15 yr. Fractal analysis showed good interobserver reproducibility (Kappa >0.70). Both FDa and FDm were significantly higher in the atypical compared to the benign meningioma group (P < .0001). Multivariate logistic regression model reached statistical significance with P = .0001 and AUC = 0.87. The FDm, which was greater than 1.31 (odds ratio [OR], 12.30; P = .039), and nonskull base localization (OR, .052; P = .015) were confirmed to be statistically significant predictors of the atypical phenotype. Fractal analysis of preoperative MR images appears to be a feasible adjunctive diagnostic tool in identifying meningiomas with potentially aggressive clinical behavior.

  6. [Expression and significance of ABCG2 in human malignant glioma].

    PubMed

    Chu, Liang; Huang, Qiang; Zhai, De-Zhong; Zhu, Qing; Huo, Hong-Mei; Dong, Jun; Qian, Zhi-Yuan; Wang, Ai-Dong; Lan, Qing; Gao, Yi-Lu

    2007-10-01

    ATP-binding cassette transporter protein ABCG2 is a marker derived from hematopoietic stem cells. However, its role in tumorigenesis and malignant progression of glioma is unclear. This study was to investigate the expression and significance of ABCG2 in gliomas of different malignant grades. A microarray chip containing glioma tissues of different malignant grades, implanted glioma xenografts in nude mice, spheroids of glioma cell lines and glioma stem cells was prepared and examined for the expression of ABCG2 with immunohistochemical staining. The positive rate of ABCG2 was 26.8% in the 71 specimens of human glioma tissues, with 11.1% in grade I gliomas, 8% in grade II gliomas, 43.5% in grade III gliomas, and 42.9% in grade IV gliomas; it was significantly higher in grade III-IV gliomas than in grade I-II gliomas (chi2=10.710, P=0.001). The positive rate of ABCG2 was 100% in implanted glioma xenografts in nude mice, gliomas stem cells, and neural stem cells. It was also expressed in some normal tissues. The positive cells surrounded and invaded into vessels in glioma tissues. ABCG2 is overexpressed in glioma stem cells, glioma tissues of higher grades, and implanted glioma xenografts. The positive cells distribute around vessels in glioma tissues.

  7. Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma

    PubMed Central

    Du, Ziming; Abedalthagafi, Malak; Aizer, Ayal A.; McHenry, Allison R.; Sun, Heather H.; Bray, Mark-Anthony; Viramontes, Omar; Machaidze, Revaz; Brastianos, Priscilla K.; Reardon, David A.; Dunn, Ian F.; Freeman, Gordon J.; Ligon, Keith L.; Carpenter, Anne E.; Alexander, Brian M.; Agar, Nathalie Y.; Rodig, Scott J.; Bradshaw, Elizabeth M.; Santagata, Sandro

    2015-01-01

    There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma – both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors. PMID:25609200

  8. Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma.

    PubMed

    Du, Ziming; Abedalthagafi, Malak; Aizer, Ayal A; McHenry, Allison R; Sun, Heather H; Bray, Mark-Anthony; Viramontes, Omar; Machaidze, Revaz; Brastianos, Priscilla K; Reardon, David A; Dunn, Ian F; Freeman, Gordon J; Ligon, Keith L; Carpenter, Anne E; Alexander, Brian M; Agar, Nathalie Y; Rodig, Scott J; Bradshaw, Elizabeth M; Santagata, Sandro

    2015-03-10

    There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma - both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.

  9. Treatment recommendations for primary extradural meningiomas.

    PubMed

    Mattox, Austin; Hughes, Betsy; Oleson, James; Reardon, David; McLendon, Roger; Adamson, Cory

    2011-01-01

    Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors.

  10. Lipomatous meningioma: A rare subtype of benign metaplastic meningiomas

    PubMed Central

    Yüksel, Mehmet Onur; Gürbüz, Mehmet Sabri; Tanrıverdi, Osman; Özmen, Sevilay Akalp

    2017-01-01

    Lipomatous meningiomas are extremely rare subtypes of benign meningiomas and are classified as metaplastic meningioma in the World Health Organization classification. We present a 77-year-old man presented with the history of a gradually intensifying headache for the last 3 months. A right frontoparietal mass was detected on his cranial magnetic resonance imaging. The patient was operated on via a right frontoparietal craniotomy, and histopathological diagnosis was lipomatous meningioma. Distinctive characteristics of lipomatous meningiomas were discussed with special emphasis to importance of immunohistochemical examinations, particularly for its differentiation from the tumors showing similar histology though having more aggressive character. PMID:28149104

  11. The Potential Involvement of E-cadherin and β-catenins in Meningioma

    PubMed Central

    Zhou, Keiyu; Wang, Guangtao; Wang, Yirong; Jin, Hanghuang; Yang, Shuxu; Liu, Chibo

    2010-01-01

    Objective To investigate the potential involvements of E-cadherin and β-catenin in meningioma. Methods Immunohistochemistry staining was performed on samples from patients with meningioma. The results were graded according to the positive ratio and intensity of tissue immunoreactivity. The expression of E-cadherin and β-catenin in meningioma was analyzed by its relationship with WHO2007 grading, invasion, peritumoral edema and postoperative recurrence. Results The positive rates of E-cadherin in meningioma WHO I, II, III were 92.69%, 33.33% and 0, respectively, (P<0.05); while the positive rates of β-catenin in meningioma WHO I, II, III were 82.93%, 33.33% and 20.00%, respectively, (P<0.05). The positive rate of E-cadherin in meningioma without invasion (94.12%) was higher than that with invasion (46.67%) (P<0.05). The difference in the positive rate of β-catenin between meningioma without invasion (88.24%) and meningioma with invasion (33.33%, P<0.05) was also statically significant. The positive rates of E-cadherin in meningioma with peritumoral edema 0, 1, 2, 3 were 93.75%, 85.71%, 60.00% and 0 respectively, (P<0.05); the positive rates of β-catenin in meningioma with peritumoral edema 0, 1, 2, 3 were 87.50%, 85.71%, 30.00% and 0 respectively, (P<0.01). The positive rates of E- cadherin in meningioma with postoperative recurrence were 33.33%, and the positive rate with postoperative non-recurrence was 90.00% (P<0.01). The positive rates of β-catenin in meningioma with postoperative recurrence and non-recurrence were 11.11%, 85.00%, respectively (P<0.01). Conclusion The expression levels of E- cadherin and β-catenin correlated closely to the WHO 2007 grading criteria for meningioma. In atypical or malignant meningioma, the expression levels of E-cadherin and β-catenin were significantly lower. The expression levels of E- cadherin and β-catenin were also closely correlated with the invasion status of meningioma, the size of the peritumoral edema and the

  12. Papillary meningioma: an aggressive variant meningioma with clinical features and treatment: a retrospective study of 10 cases.

    PubMed

    Li, Bin; Tao, Bangbao; Bai, Hongmin; Zhong, Jun; Wu, Xiangru; Shi, Juanhong; Sun, Hui; Li, Shiting

    2016-10-01

    Papillary meningioma is a rare subtype of malignant meningiomas. The aim of this retrospective study was to investigate the clinical, radiological, histopathological features and prognosis for papillary meningioma at our institutions. Ten patients with clinically, radiologically and histopathologically confirmed papillary meningiomas were treated at our hospitals. The clinical data, imaging characteristics, histopathological features, surgical treatment and postoperative follow-up, were analyzed retrospectively. The patients with a mean age of 36.9 years at the time of their initial operations. The papillary meningiomas were predominantly located in the convexity (n = 6). At their initial operation, six patients underwent gross total resection and four patients underwent subtotal resection. The mean post-operative follow-up period was 42.6 months (range: 12-90 months). Six patients underwent multiple surgical resections. The mean time to first recurrence was 21.5 months. On magnetic resonance imaging scan, marked enhancements and dural tail signs were displayed in all lesions. All lesions showed peritumoral edema. Cysts were seen in four lesions. Bone hyperostosis or destruction was seen in six lesions. Cerebrospinal fluid dissemination was seen in three lesions. Incomplete surgical resection was associated with recurrence. MIB-1 labeling index was associated with progression-free survival for patients (p = 0.0442). Papillary meningioma has a tendency to present in middle-aged patients, and it has specific clinical and histopathological characteristics. MIB-1 labeling index and the extent of resection might predict the recurrence. Cystic formation, peritumoral edema, osseous change and CSF dissemination might be neuroimaging characteristics of papillary meningioma, especially in recurrence papillary meningioma.

  13. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells.

    PubMed

    Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2016-04-01

    Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells.

  14. Primary pulmonary meningioma

    PubMed Central

    Huang, Shucheng; Chen, Li; Mao, Yuping; Tong, Hongwei

    2017-01-01

    Abstract Rationale: Primary extracranial meningiomas are rare outside the head and neck region. Patient concerns: A 44-year-old female patient had chest pain for more than 1 year. Diagnoses: Preoperative chest computed tomography (CT) scan revealed a nodule in the right lower lobe, 1.8 cm in diameter. Tumor tissues were examined by immunohistochemistry for vimentin and S-100. Interventions: Histopathologically, the tumor was characterized by whorled nests of spindle-shaped cells accompanied by psammoma bodies. Immunohistochemistry demonstrated tumor cell positivity for vimentin and S-100. This case was diagnosed as a primary pulmonary meningioma. The tumor was removed by a thoracoscopic pulmonary wedge resection. Outcomes: Postoperative cranial and spinal CT scan did not show any intracranial or spinal mass. No recurrence of the tumor was reported at the time of writing up this case report. Lessons: A primary pulmonary meningioma should be considered in the differential diagnosis workup of pulmonary nodules. PMID:28489736

  15. Definitive Embolization of Meningiomas

    PubMed Central

    Bateman, B.T.; Lin, E.; Pile-Spellman, J.

    2005-01-01

    Summary This review examines the possible role for definitive embolization as a primary therapy for intracranial meningiomas. Surgery or radiosurgery are currently considered the standard of care for most benign meningiomas. However, each of these carries substantial risks. The perioperative mortality for surgical resection, as reported in large series, is between 3.7-9.4%; these studies report a similarly high rate of new neurological deficits following surgery. The rate of complications from radiosurgery is reported between 2-16% and it may take months to years before improvement in symptoms occurs following this therapy. There are a few reports of treating meningiomas by embolization without subsequent surgery. While these studies include small numbers of patients and have limited follow-up, the initial results are very promising. Given the risks and limitations of surgery and radiosurgery, prospective trials are now needed to determine the safety and efficacy of definitive embolization. PMID:20584499

  16. Meningiomas of Meckel's cave.

    PubMed

    Nijensohn, D E; Araujo, J C; MacCarty, C S

    1975-08-01

    A retrospective review of 12 cases of meningioma of Meckel's cave involving the Gasserian ganglion or the trigeminal posterior root (or both) seen at the Mayo Clinic during a 20-year period suggested three clearly defined clinical groups. One group (the largest) had typical trigeminal neuralgia and an excellent prognosis after the removal of the easily detachable mass that was impinging on the ganglion. A second group, with meningiomas en plaque embedded in the ganglion, had a history of atypical trigeminal face pain without neurological deficit, but the prognosis for pain relief was not as good as in the previous group. A third group had a history of face dysesthesias and pain, objective trigeminal sensory loss, and multiple cranial nerve deficit; these patients had meningiomas with histological signs of mitotic activity and a poor prognosis, with return of intractable pain and recurrence of the tumor.

  17. Felix Platter and a historical perspective of the meningioma.

    PubMed

    Bir, Shyamal C; Maiti, Tanmoy Kumar; Bollam, Papireddy; Nanda, Anil

    2015-07-01

    Felix Platter is one of the pioneer anatomists and physicians of the 16th century who described various human diseases including meningioma. In this historical article, we present the details of Platter's life and his pioneering work on meningioma. In 1614, Dr. Platter described the first case of meningioma. He described the tumor as a round, fleshy mass shaped like an acorn and as large as a medium-sized apple, and full of holes. The tumor was covered with its own membrane, had no connection with the matters of the brain, and left behind a cavity after removal. This first clear description of an intracranial tumor is most consistent with encapsulated meningioma. The succeeding scholar, Harvey Cushing, coined the term "meningioma" for this tumor; neurosurgeons today describe the tumor as "parasagittal or falcine meningioma." In addition to his contribution to meningioma study, Dr. Platter was also the first to describe Dupuytren's disease, hypertrophy of the thalamus, and the retina as the sensory organ of the eye. He contributed to the germ theory of disease and gave substantial accounts of mental illnesses, gynecological disorders, and certain dermatological conditions. Dr. Platter published numerous accounts on various diseases. In 1614 he reported the case of meningioma in the book entitled "Platerus Observations in Hominis". Additionally, Dr. Platter published his work, 'Praxeos Medicae,' which contains his most important contribution on psychiatry and his classification of psychiatric diseases. Because of his many contributions to neuroscience, particularly his identification of meningioma, Dr. Platter should be highly credited as a pioneer in the field of neurosurgery. Published by Elsevier B.V.

  18. Experience with 5-Aminolevulinic Acid in Fluorescence-Guided Resection of a Deep Sylvian Meningioma

    PubMed Central

    Chae, Michael P; Song, Sang Woo; Park, Sung-Hye

    2012-01-01

    The 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a useful intraoperative marker for the diagnosis and the detection of various malignancies, but its use in meningioma is only reported infrequently. In meningioma, a complete resection of the tumor mass is crucial for the prevention of recurrence and postoperative morbidities. Deep sylvian meningioma is a rare type of meningioma where complete tumor removal is complicated by its deep anatomical location and close involvement with the middle cerebral artery. From our experience, 5-ALA-mediated fluorescence facilitated a safe excision whilst preserving critical neurovascular structures. To our best knowledge, this is first report from use of 5-ALA in a deep sylvian meningioma. PMID:23346330

  19. Experience with 5-aminolevulinic Acid in fluorescence-guided resection of a deep sylvian meningioma.

    PubMed

    Chae, Michael P; Song, Sang Woo; Park, Sung-Hye; Park, Chul-Kee

    2012-12-01

    The 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a useful intraoperative marker for the diagnosis and the detection of various malignancies, but its use in meningioma is only reported infrequently. In meningioma, a complete resection of the tumor mass is crucial for the prevention of recurrence and postoperative morbidities. Deep sylvian meningioma is a rare type of meningioma where complete tumor removal is complicated by its deep anatomical location and close involvement with the middle cerebral artery. From our experience, 5-ALA-mediated fluorescence facilitated a safe excision whilst preserving critical neurovascular structures. To our best knowledge, this is first report from use of 5-ALA in a deep sylvian meningioma.

  20. The Role of Osteopontin in the Malignancy of Human Breast Carcinoma

    DTIC Science & Technology

    1997-07-01

    DAMD17-96-1-6075 TITLE: The Role of Osteopontin in the Malignancy of Human Breast Carcinoma PRINCIPAL INVESTIGATION: Dr. Frances O’Malley Alan B. Tuck...1997 Annual (I Jun 96 - 31 May 97) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS The Role of Osteopontin in the Malignancy of Human Breast Carcinoma DAMD17...OPN in the malignancy of human breast cancer will be of potential importance not only in the interpretation of prognostic information gained through

  1. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    PubMed Central

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  2. Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.

    PubMed

    Jahns, Franziska; Wilhelm, Anne; Jablonowski, Nadja; Mothes, Henning; Greulich, Karl Otto; Glei, Michael

    2015-04-01

    The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.

  3. Clinicopathologic features of aggressive meningioma emphasizing the role of radiotherapy in treatment.

    PubMed

    Engenhart-Cabillic, Rita; Farhoud, Ahmed; Sure, Ulrich; Heinze, Stefan; Henzel, Martin; Mennel, Hans-Dieter; Bertalanffy, Helmut

    2006-11-01

    Although meningiomas are typically benign, they occasionally behave in an aggressive fashion and carry a less favorable prognosis. The aim of this study was to review the clinical, radiologic and histopathologic features of these aggressive variants as well as the outcome after multimodality therapy. 16 patients with atypical meningiomas (n = 11) and anaplastic meningiomas (n = 5) were treated in the Departments of Neurosurgery and Radiation Oncology at the University Hospital of Philipps University Marburg, Germany, between 1997 and 2003. Tumor grading was based on new WHO criteria. There were eleven men and five women with a mean age of 54 years. The median follow-up period was 34 months. A total of 24 surgical procedures were performed for these 16 patients. Only seven patients underwent postoperative fractionated stereotactic radiotherapy. Patients with atypical meningioma received radiotherapy only for the recurrent disease. Six patients (37.5%) experienced tumor recurrence after a mean period of 27.2 months in spite of gross total resection. Radiographic findings suggestive of aggressiveness were observed mostly with WHO grade III meningiomas. By comparing the proliferation rate in four cases with atypical meningioma operated twice, the recurrent tumor had a higher proliferation rate than the first tumor in three cases. A special proliferation pattern was noticed in MIB-1 with anaplastic meningiomas. The mean overall survival period was 66.5 months. There was no mortality among patients with atypical meningioma, while four out of five patients with anaplastic meningioma died during follow-up. Considering the higher rate of recurrence in aggressive meningiomas even after radical surgical excision and the possibility that the recurrent tumor is more aggressive than the original one, surgery should be combined with postoperative fractionated radiotherapy to improve local tumor control. The peculiar focal expression patterns of anaplastic meningioma in MIB-1

  4. The role of human papilloma virus in urological malignancies.

    PubMed

    Heidegger, Isabel; Borena, Wegene; Pichler, Renate

    2015-05-01

    Human papillomavirus (HPV) is associated with cancer of the cervix uteri, penis, vulva, vagina, anus and oropharynx. However, the role of HPV infection in urological tumors is not yet clarified. HPV appears not to play a major causative role in renal and testicular carcinogenesis. However, HPV infection should be kept in mind regarding cases of prostate cancer, as well as in a sub-group of patients with bladder cancer with squamous differentiation. Concerning the role of HPV in penile cancer incidence, it is a recognized risk factor proven in a large number of studies. This short review provides an update regarding recent literature on HPV in urological malignancies, thereby, also discussing possible limitations on HPV detection in urological cancer.

  5. Raman spectroscopic identification of normal and malignant human stomach cells

    NASA Astrophysics Data System (ADS)

    Yang, Jipeng; Guo, Jianyu; Wu, Liangping; Sun, Zhenrong; Cai, Weiying; Wang, Zugeng

    2005-12-01

    Micro-Raman spectroscopy is employed to identify the normal and malignant human stomach cells. For the cancer cell, the reduced intensity of the Raman peak at 1250 cm^(-1) indicates that the protein secondary structure transforms from ?-sheet or disordered structures to ?-helical, while the increased intensity of the symmetric PO2 stretching vibration mode at 1094 cm^(-1) shows the increased DNA content. The ratio of the intensity at 1315 cm^(-1) to that at 1340 cm^(-1) reduces from 1.8 for the normal cell to 1.1 for the cancer cell in the course of canceration, and the ratio of the intensity at 1655 cm^(-1) to that at 1450 cm^(-1) increases from 1.00 for the cancer cell to 1.26 for the normal cell which indicates that the canceration of stomach cell may induce saturation of the lipid chain.

  6. Multimodal optical analysis of meningioma and comparison with histopathology.

    PubMed

    Zanello, Marc; Poulon, Fanny; Varlet, Pascale; Chretien, Fabrice; Andreiuolo, Felipe; Pages, Mélanie; Ibrahim, Ali; Pallud, Johan; Dezamis, Edouard; Abi-Lahoud, Georges; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi-Haidar, Darine

    2017-02-01

    Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real-time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real-time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one- and two-photon excitation and the second-harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second-harmonic generation signal delineated the collagen background and two-photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration. Correspondence between H&E staining (top pictures) and the two-photon fluorescence imaging (bottom pictures).

  7. Surgical Treatment for Falcotentorial Meningiomas

    PubMed Central

    Hong, Chang Ki; Hong, Je Beom; Park, Hunho; Moon, Ju Hyung; Chang, Jong Hee; Lee, Kyu Sung

    2016-01-01

    Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience. PMID:27189300

  8. Diagnosing necrotic meningioma: a distinctive imaging pattern in diffusion MRI and MR spectroscopy.

    PubMed

    Ben-Arie, Gal; Serlin, Yonatan; Ivens, Sebastian; Benifla, Mony; Cagnano, Emanuela; Melamed, Israel; Merkin, Vladimir; Shelef, Ilan

    2017-02-01

    The differential diagnosis of necrotic meningiomas includes brain abscess and malignant neoplasms. We report and discuss hereby the work-up of two patients diagnosed with necrotic meningioma using diffusion-weighted imaging, magnetic resonance spectroscopy, resective surgery, and histopathology. The purpose of the present article is to add to the scant literature on the use of advanced imaging modalities in the routine investigation of brain lesions and their utility in arriving at the final diagnosis.

  9. Radiosensitization effect of zidovudine on human malignant glioma cells

    SciTech Connect

    Zhou Fuxiang; Liao Zhengkai; Dai Jing; Xiong Jie; Xie CongHua; Luo Zhiguo; Liu Shiquan; Zhou Yunfeng . E-mail: yfzhouwhu@163.com

    2007-03-09

    Telomeres are shortened with each cell division and play an important role in maintaining chromosomal integrity and function. Telomerase, responsible for telomere synthesis, is activated in 90% of human tumor cells but seldom in normal somatic cells. Zidovudine (AZT) is a reverse transcriptase inhibitor. In this study, we have investigated the effects of {gamma}-radiation in combination with AZT on telomerase activity (TA), telomere length, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and the changes in radiosensitivity of human malignant glioma cell line U251. The results showed that the TA was suppressed by AZT but enhanced by irradiation, resulting in a deceleration of restored rate of shortened telomere, decreased repair rate of DNA strand breaks, and increased radiosensitivity of U251 cells. Our results suggested that telomerase activity and telomere length may serve as markers for estimating the efficacy of cancer radiotherapy and reverse transcriptase inhibitors, such as AZT, may be used clinically as a new radiosensitizer in cancer radiotherapy.

  10. Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls

    NASA Astrophysics Data System (ADS)

    Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H.; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

  11. Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls

    PubMed Central

    Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H.; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; Di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

    2017-01-01

    Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins. PMID:28150726

  12. Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls.

    PubMed

    Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; Di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-02

    Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

  13. Epidural Cystic Spinal Meningioma

    PubMed Central

    Zhang, Ji; Chen, Zheng-he; Wang, Zi-feng; Sun, Peng; Jin, Jie-tian; Zhang, Xiang-heng; Zhao, Yi-ying; Wang, Jian; Mou, Yong-gao; Chen, Zhong-ping

    2016-01-01

    Abstract Cystic spinal meningioma (CSM) is an uncommon meningioma variant. Extradural CSMs are particularly rare and difficult to distinguish from other intraaxial tumors. This study presents a case of a 36-year-old woman with intraspinal extradual CSM at the thoracolumbar spine. She experienced persistent weakness, progressive numbness, and sensory disturbance in the right lower limb. Magnetic resonance imaging (MRI) of the patient revealed an irregular cystic mass at the thoracic 11 to lumbar 3 levels dorsally. This case was misdiagnosed as other neoplasms prior to surgery because of the atypical radiographic features and location of the tumor. Extradural CSMs should be considered in the differential diagnosis of intraspinal extradural cystic neoplasms. Complete removal of cystic wall provides an optimal outcome, rendering the lesion curable. PMID:26986119

  14. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    SciTech Connect

    McCormick, J.J.

    1992-01-01

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  15. Third ventricular meningiomas.

    PubMed

    Li, Puxian; Diao, Xingtao; Bi, Zhiyong; Hao, Shuyu; Ren, Xiaohui; Zhang, Junting; Xing, Jun

    2015-11-01

    We report 13 patients with third ventricular meningiomas (TVM) and discuss the clinical, radiological, pathological and surgical features, as well as follow-up of these tumors. TVM are rare intracranial tumors, and because of this, there are few reports in the literature. Of 11,600 intracranial meningiomas that were surgically treated and pathologically confirmed at Beijing Tian Tan Hospital over a period of 10 years (2003-2013), 13 TVM were selected for a retrospective review. We recorded the clinical, radiological, pathological, and surgical data and statistically analyzed the preoperative, postoperative and 6 month postoperative Karnofsky performance scale (KPS) scores. TVM represented 0.11% of intracranial meningiomas. Radiologically, TVM were divided into three groups: anterior (n=3), posterior (n=3), and entire third ventricle (n=7). Three patients (23.1%) were misdiagnosed preoperatively. Total removal was achieved in 61.5% (8/13) of patients, and subtotal resection was achieved in 38.5% (5/13). Pathologically, the tumors were World Health Organization (WHO) Grade I in 11 patients (84.6%) and WHO Grade II in two (15.6%). There were no statistically significant differences in the preoperative, postoperative, or 6 month postoperative KPS scores (F=0.814; p=0.401). TVM without dural attachments are rare neoplasms that should be differentiated from choroid plexus papilloma, craniopharyngioma, and pineocytoma. Surgery is the optimal treatment and may result in a favorable prognosis, and understanding of the radiological subtype can help with the choice of surgical approach.

  16. Meningioma in Down Syndrome.

    PubMed

    Yamamoto, Takahiro; Shinojima, Naoki; Todaka, Tatemi; Nishikawa, Shigeyuki; Yano, Shigetoshi; Kuratsu, Jun-ichi

    2015-09-01

    Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21. There is epidemiologic evidence that individuals with Down syndrome are at decreased risk for solid tumors including brain tumors. It has been suggested that some genes expressed on the extra copy of chromosome 21 act as tumor suppressor genes and contribute to protection against tumorigenesis. We report the first case to our knowledge of a patient with Down syndrome, an 8-year-old boy, with an intracranial meningioma, in which the status of chromosome 21 was examined. The diagnosis was based on histologic examination of the surgically resected tumor. Postoperatively, the patient's neurologic status improved, and there was no tumor regrowth in the next 2 years. Fluorescence in situ hybridization for chromosome 22 confirmed high allele loss involving the neurofibromin 2 gene locus, a finding typical in meningiomas. Fluorescence in situ hybridization also revealed chromosome 21 heterogeneity in tumor cells; not only cells with trisomy 21 but also cells with disomy and monosomy 21 were present. All blood cells from the patient manifested trisomy 21. Deletion of the chromosome 21 allele may be associated with tumorigenesis of meningioma in Down syndrome. This supports the hypothesis that some genes whose expression is increased on the extra copy of chromosome 21 function as tumor suppressor genes and that they contribute to the reduced tumor incidence in individuals with Down syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Involvement of NANOG upregulation in malignant progression of human cells.

    PubMed

    Li, Yang; Higashiyama, Shinji; Shimakage, Misuzu; Kawahara, Kunimitsu; Yutsudo, Masuo; Watari, Akihiro

    2013-03-01

    Previously, we isolated cell lines that display various degrees of transformed phenotypes from a single-cell population of human diploid fibroblasts (RB) containing a large deletion (13q14-22) in one copy of chromosome 13. They included a cell line transfected with SV40 early genes (RBSV), an immortalized cell line (RBI), an anchorage-independent cell line (RBS), and a tumorigenic cell line (RBT). Here, we analyzed gene expression profiles in these cell lines and showed that expression of some fibroblast-specified or mesenchyme-specified genes were downregulated, and those of stem cell-specified genes, including NANOG, were upregulated during malignant progression. When NANOG expression was knocked down with a short hairpin NANOG expression vector (shNANOG vector) in the RBS and RBT cells, the anchorage independency and tumorigenicity were repressed. We next examined various cancer cell lines for NANOG expression and showed that some cancer cell lines expressed a high level of normal and/or variant NANOG proteins. Overexpression of NANOG mRNA in lung adenocarcinoma was also shown by in situ hybridization. All these data indicate the involvement of NANOG in tumorigenesis.

  18. Altered expression of E-Cadherin-related transcription factors indicates partial epithelial-mesenchymal transition in aggressive meningiomas.

    PubMed

    Wallesch, Maren; Pachow, Doreen; Blücher, Christina; Firsching, Raimund; Warnke, Jan-Peter; Braunsdorf, Werner E K; Kirches, Elmar; Mawrin, Christian

    2017-09-15

    E-Cadherin has been suggested to be involved in meningioma progression but is also known as a key player of epithelial to mesenchymal transition (EMT). We wondered whether the adherens junction protein E-Cadherin, the tight junction protein Zo-1, and transcription factors suppressing E-Cadherin expression (Slug, Snail, Twist, Zeb-1) are differentially expressed between histopathological subtypes of meningioma, and if the expression of these factors is related to biological features of meningiomas. Analyzing 85 meningiomas of various histopathological subtypes and grades of malignancy by immunohistochemistry and 50 of them in addition by real-Time-PCR, we observed significantly reduced expression of Zeb-1, Twist and Slug, together with slightly increased expression levels for E-Cadherin and Zo- 1 in fibroblastic WHO-grade I tumors compared to meningothelial WHO grade I tumors, contradicting the hypothesis of EMT in the fibroblastic meningiomas characterized by mesenchymal appearance. However, comparing aggressive WHO grade II or III meningiomas with WHO-grade I tumors, we observed altered expression levels (loss of E-Cadherin and Zo-1, increased expression of Zeb-1 and Slug) indicating molecular features of EMT in aggressive meningiomas. This was supported by reduced E-Cadherin and increased Slug levels in recurrent compared to non-recurrent meningiomas. The expression levels of E-cadherin and Zo-1 were positively correlated with expression of NF2 mRNA. In primary meningioma cultures and IOMM-Lee meningioma cells, EMT induction by TGF-ß resulted in altered morphology and increased expression of EMT associated transcription factors. Meningioma cells with allelic losses of NF2 showed generally higher levels of various EMT relevant proteins, but were unresponsive to TGF-ß treatment. Our data indicate that aggressive meningiomas of WHO grade II/III are characterized by molecular alterations indicating partial EMT. This might contribute to the aggressive biology of

  19. Epidemiology and etiology of meningioma

    PubMed Central

    Wrensch, Margaret; Claus, Elizabeth B.

    2010-01-01

    Although most meningiomas are encapsulated and benign tumors with limited numbers of genetic aberrations, their intracranial location often leads to serious and potentially lethal consequences. They are the most frequently diagnosed primary brain tumor accounting for 33.8% of all primary brain and central nervous system tumors reported in the United States between 2002 and 2006. Inherited susceptibility to meningioma is suggested both by family history and candidate gene studies in DNA repair genes. People with certain mutations in the neurofibromatosis gene (NF2) have a very substantial increased risk for meningioma. High dose ionizing radiation exposure is an established risk factor for meningioma, and lower doses may also increase risk, but which types and doses are controversial or understudied. Because women are twice as likely as men to develop meningiomas and these tumors harbor hormone receptors, an etiologic role for hormones (both endogenous and exogenous) has been hypothesized. The extent to which immunologic factors influence meningioma etiology has been largely unexplored. Growing emphasis on brain tumor research coupled with the advent of new genetic and molecular epidemiologic tools in genetic and molecular epidemiology promise hope for advancing knowledge about the causes of intra-cranial meningioma. In this review, we highlight current knowledge about meningioma epidemiology and etiology and suggest future research directions. PMID:20821343

  20. Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

    ClinicalTrials.gov

    2017-03-01

    Acoustic Schwannoma; Adult Anaplastic Meningioma; Adult Ependymoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Meningeal Hemangiopericytoma; Adult Papillary Meningioma; Neurofibromatosis Type 1; Neurofibromatosis Type 2; Recurrent Adult Brain Tumor

  1. Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma*

    PubMed Central

    Locasale, Jason W.; Melman, Tamar; Song, Susan; Yang, Xuemei; Swanson, Kenneth D.; Cantley, Lewis C.; Wong, Eric T.; Asara, John M.

    2012-01-01

    Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the identification of biomarkers and classification of neurological diseases. PMID:22240505

  2. Osseous metaplastic meningioma in the thoracic spine mimicking osteosarcoma: a case report.

    PubMed

    Mannoji, Chikato; Koda, Masao; Murakami, Masazumi; Kubosawa, Hitoshi; Yamazaki, Masashi; Okawa, Akihiko; Furuya, Takeo; Takahashi, Kazuhisa

    2013-05-01

    Case report. We describe a case of osseous metaplastic meningioma in the thoracic spine that pathologically mimicked osteosarcoma. As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically. The patient's medical records, imaging results, and pathological findings were reviewed, as was the relevant literature. A 20-year-old woman with a 6-month history of lumbago and right sciatica was referred to our hospital because magnetic resonance imaging (MRI) showed a tumor compressing her spinal cord at the T11 vertebra level. Computed tomography (CT) showed calcification of the tumor, and the preoperative diagnosis was meningioma. Surgery was performed and the tumor was entirely removed. The tumor was very hard, and pathological findings suggested atypical meningioma with massive ossification. Some parts of the tumor seemed malignant, as spindle cells with a high nucleocytoplasmic ratio were highly concentrated, which led to the possibility of osteosarcoma. The tumor was conclusively diagnosed as osseous metaplastic meningioma based not only on the pathology, but also on CT and MRI findings and the postoperative course. As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically. Results of imaging studies including CT and MRI, as well as patients' postoperative course, should be considered when making a final diagnosis of meningioma. N/A.

  3. Idiotype vaccines for human B-cell malignancies.

    PubMed

    Inoges, S; de Cerio, A Lopez-Diaz; Soria, E; Villanueva, H; Pastor, F; Bendandi, M

    2010-01-01

    After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma. Potentially applicable to all B-cell malignancies whose cells express a clonal immunoglobulin or its epitopes on their surface, this treatment is designed to prevent disease recurrence or progression. Mostly used in follicular lymphoma patients so far, idiotype vaccines have clearly shown biological efficacy, clinical efficacy and clinical benefit in this setting, although no study aiming at regulatory approval of the procedure has been able to meet its main clinical endpoints. In mantle cell lymphoma, only biological efficacy has been proven for idiotypic vaccination, while in multiple myeloma a limited number of studies support the notion of biological and perhaps even clinical efficacy, although no credible evidence of clinical benefit has still emerged. Idiotype vaccines have been produced and administered in a number of substantially different manners. Therefore, the results of most clinical trials cannot be easily compared, and even less pooled together in meaningful meta-analyses. A more creative and yet scientifically sound way to design clinical trials of customized active immunotherapies will be key to the future development of idiotype vaccines, particularly considering that we currently lack any clinical or biological indicator to possibly predict which patients are more likely to respond to idiotypic vaccination from an immunologic point of view. This review aims at summarizing the multifaceted success achieved by idiotype vaccines, as well as at outlining the challenges awaiting them in the near future: how to improve feasibility, immunogenicity and efficacy, as well as how to confirm benefit and gain regulatory approval.

  4. Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review

    PubMed Central

    Chaudhary, Ajay Kumar; Singh, Mamta; Sundaram, Shanthy; Mehrotra, Ravi

    2009-01-01

    Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil® (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix® (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here. PMID:19555477

  5. Recurrent lumbosacral metastases from intracranial meningioma. Report of a case and review of the literature.

    PubMed

    Conrad, M D; Schonauer, C; Pelissou-Guyotat, I; Morel, C; Madarassy, G; Deruty, R

    2001-09-01

    We report a case of a 31 year-old woman who in 1991 presented a clinical history of headaches, nausea and vomiting. CT scan showed a right frontotemporal meningioma. The first operation achieved a macroscopically complete resection. The tumour was histologically classified as a transitional meningioma. There were recurrences of the intracranial meningioma in 1994, 1996, 1997 and 1998. These recurrences were accompanied by differentiation to atypical and anaplastic meningioma. In all of these operations, a macroscopically complete resection of the tumour was performed. In 1996 adjuvant radiation therapy was given. In 1998 therapy with bromocriptine was adopted. In April 1999, the patient presented with lumbosacral pain associated with L5 bilateral sciatica. MRI showed a gadolinium enhancing mass lesion at L5-S1 level. Complete tumour resection was performed. The histological findings were the same as in 1998. In December 1999 the patient presented with perineal pain and MRI showed a L4 and S3 recurrence and the tumour was resected. The histological findings were those of a malignant meningioma. In February 2000 an intracranial recurrence was detected and operated on. The histological diagnosis was malignant meningioma. A review of the literature was undertake and is discussed.

  6. Group I Paks as therapeutic targets in NF2-deficient meningioma

    PubMed Central

    Duron, Sergio G.; Campbell, David A.; Ong, Christy C.; Hoeflich, Klaus P.; Chang, Long-Sheng; Welling, D. Bradley; Yang, Zeng-jie; Chernoff, Jonathan

    2015-01-01

    Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of NF2 is found in 40–60% of sporadic meningiomas, but the molecular mechanisms underlying malignant changes of meningioma cells remain unclear. Because group I p21-activated kinases (Paks) bind to and are inhibited by the NF2-encoded protein Merlin, we assessed the signaling and anti-tumor effects of three group-I specific Pak inhibitors - Frax597, 716 and 1036 - in NF2−/− meningiomas in vitro and in an orthotopic mouse model. We found that these Pak inhibitors suppressed the proliferation and motility of both benign (Ben-Men1) and malignant (KT21-MG1) meningiomas cells. In addition, we found a strong reduction in phosphorylation of Mek and S6, and decreased cyclin D1 expression in both cell lines after treatment with Pak inhibitors. Using intracranial xenografts of luciferase-expressing KT21-MG1 cells, we found that treated mice showed significant tumor suppression for all three Pak inhibitors. Similar effects were observed in Ben-Men1 cells. Tumors dissected from treated animals exhibited an increase in apoptosis without notable change in proliferation. Collectively, these results suggest that Pak inhibitors might be useful agents in treating NF2-deficient meningiomas. PMID:25596744

  7. Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma

    PubMed Central

    Kanno, Hiromi; Nishihara, Hiroshi; Wang, Lei; Yuzawa, Sayaka; Kobayashi, Hiroyuki; Tsuda, Masumi; Kimura, Taichi; Tanino, Mishie; Terasaka, Shunsuke; Tanaka, Shinya

    2013-01-01

    Background CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. Methods First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. Results Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Conclusions To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma. PMID:23539121

  8. Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma.

    PubMed

    Kanno, Hiromi; Nishihara, Hiroshi; Wang, Lei; Yuzawa, Sayaka; Kobayashi, Hiroyuki; Tsuda, Masumi; Kimura, Taichi; Tanino, Mishie; Terasaka, Shunsuke; Tanaka, Shinya

    2013-07-01

    CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.

  9. A microRNA expression signature predicts meningioma recurrence.

    PubMed

    Zhi, Feng; Zhou, Guangxin; Wang, Suinuan; Shi, Yimin; Peng, Ya; Shao, Naiyuan; Guan, Wei; Qu, Hongtao; Zhang, Yi; Wang, Qiang; Yang, Changchun; Wang, Rong; Wu, Sujia; Xia, Xiwei; Yang, Yilin

    2013-01-01

    The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan-Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two-phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14-miRNA profile differed between tumor and NAT samples. Downregulation of miR-29c-3p and miR-219-5p were found to be associated with advanced clinical stages of meningioma. Kaplan-Meier analysis showed that high expression of miR-190a and low expression of miR-29c-3p and miR-219-5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR-190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes. Copyright © 2012 UICC.

  10. Metastasis to a spinal meningioma.

    PubMed

    Bansil, Rohit; Walia, Bipin S; Khan, Zahid; Abrari, Andleeb

    2017-01-01

    Metastasis of one cancer to another is rare. Here, we report a spinal meningioma that was infiltrated by metastatic deposits from another cancer. A 62-year-old male presented with a progressive spastic paraparesis. Magnetic resonance (MR) imaging of the spine suggested a well-defined intradural extramedullary (IDEM) T8 mass in the dorsal spinal canal. When excised, it proved histologically to be a meningothelial meningioma infiltrated by metastatic deposits from an adenocarcinoma. Tumor to tumor metastasis rarely occurs, and meningioma, owing to its biological character and increased vascularity, is one of the most common recipients of a metastases from other lesions.

  11. Frontal cutaneous meningioma - Case report*

    PubMed Central

    Ramos, Leonor; Coutinho, Ines; Cardoso, José Carlos; Garcia, Helena; Cordeiro, Margarida Robalo

    2015-01-01

    Cutaneous meningiomas are rare tumors most commonly located on the scalp. We report the case of a 55-year-old male who presented with a 2x3 cm tumoral lesion on the forehead. The lesion was hard, adherent and covered by normal skin. Incisional biopsy revelead a proliferation of monomorphic round cells, organized in nests and focally forming pseudovascular spaces. Immunohistochemical study revealed positivity for epithelial antigen membrane and vimentin. Vascular markers, cytokeratins and S100 protein were negative. A brain CT scan did not show any evidence of intracranial meningioma. The authors describe the case of a cutaneous frontal meningioma in probable relation with previous cranioencephalic trauma. PMID:26312695

  12. RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

    ClinicalTrials.gov

    2015-09-28

    Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

  13. Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5 years of clinical practice.

    PubMed

    Abdelaziz, Osama S; Kandil, Alaa; El-Assaal, Shaaban; Abdelaziz, Amro; Rostom, Yosry; Rashed, Yaser

    2011-01-01

    Meningiomas are mostly benign but some are atypical or malignant. Surgical resection is curative when complete removal of benign meningiomas is contemplated. Incompletely excised and recurrent tumors are frequently treated with fractionated radiation therapy or stereotactic radiosurgery. The purpose of this study is to evaluate the short-term radiological and functional outcomes of a single center using linear accelerator (Linac) stereotactic radiosurgery for the treatment of intracranial meningiomas. Twenty-nine patients (12 males and 17 females) with 30 meningiomas, in different brain locations (skull base and non-skull base meningiomas), were treated with Linac-based stereotactic radiosurgery. The mean tumor volume was 6.3 cm³, and the mean tumor marginal and maximum doses were 10.9 and 15 Gy, respectively. The median prescribed isodose line was 80%. The patients were followed-up for a minimum of 3 years. Regarding radiological outcome, nine (30%) meningiomas demonstrated evident volume reduction, 19 (63.3%) meningiomas remained unchanged, and two (6.7%) meningiomas increased in size after radiosurgery. The local tumor control rates for skull base meningiomas and non-skull base meningiomas after radiosurgery were 90.9% and 100%, respectively. Regarding functional outcomes, 64% of patients presenting with cranial neuropathies showed improvement of their cranial nerve functions and 29% of patients remained unchanged. One patient had temporary trigeminal neuropathy. Although radiosurgery for meningiomas is generally effective and quite safe in achieving high control rates with minimum morbidity over short- and intermediate-term periods of follow-up, tumor progression might occur in a delayed manner after initial apparent control for few years. We recommend continued follow-up for longer periods to better assess the long-term outcomes.

  14. Microenvironment-dependent growth of pre-neoplastic and malignant plasma cells in humanized mice

    PubMed Central

    Das, Rituparna; Strowig, Till; Verma, Rakesh; Koduru, Srinivas; Hafemann, Anja; Hopf, Stephanie; Kocoglu, Mehmet H.; Borsotti, Chiara; Zhang, Lin; Branagan, Andrew; Eynon, Elizabeth; Manz, Markus G.; Flavell, Richard A.; Dhodapkar, Madhav V.

    2016-01-01

    Most human cancers including myeloma are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human pre-neoplastic and malignant plasma cells together with non-malignant cells in vivo [?]. Growth was largely restricted to the bone marrow, mirroring the pattern in patients. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes. Moreover, xenografts from patients with preneoplastic gammopathy showed progressive growth, suggesting that the clinical stability of these lesions may in part be due to growth controls extrinsic to tumor cells. These data demonstrate a new approach to investigate the entire spectrum of human plasma cell neoplasia and illustrate the utility of humanized models for understanding the functional diversity of human tumors [?]. PMID:27723723

  15. [Operation of lateral ventricular meningiomas of the trigone].

    PubMed

    Li, Xue-zhen; Zhao, Ji-zong

    2006-09-05

    To summarize the surgical treatment of intraventricular trigonal meningiomas. 64 cases of intraventricular trigonal meningiomas were retrospectively analyzed. 40 tumors were located in the left trigone and 24 tumors in the right. Pathological diagnosis included 35 fibrous, 10 mixed, 8 endothelial, 3 transitional, 1 secretion and 1 malignant meningioma. The remaining 6 cases cannot be classified into any type. The tumors ranged in diameter from 2 cm to 15 cm (median 4.8 cm). Microscopic complete removal was achieved in all cases. Postoperatively, hemiparalysis occurred in 4 cases, aphasia in 14, hemianopia in 2, persistent fever (last more than 7 days) in 30 and focal hydrocephalus in 4. There was no mortality. The incidence of postoperative aphasia was correlated with operational approach (Pearson correlation coefficient = 0.404, P = 0.001), tumor side (Pearson correlation coefficient = 0.012, P = 0.012) and size (Pearson correlation coefficient = 0.284, P = 0.023). Postoperative persistent fever was correlated with size (Pearson correlation coefficient = 0.367, P = 0.003) and resection method (Pearson correlation coefficient = 0.537, P = 0.000). In cases of diameter > or = 4 cm, length of stay was not correlated with ventricular drainage (Pearson correlation coefficient = 0.047, P = 0.748). Transcortical parieto-occipital approach and Transcortical temporo-parieto-occipital approaches are applicable for intraventricular trigonal meningiomas. The key points to avoid postoperative complications are to decrease damage to surrounding brain tissue and pollution to ventricles.

  16. Rectal carcinoid tumor metastasis to a skull base meningioma

    PubMed Central

    Huang, Jennifer; Gupta, Amit; Badve, Chaitra; Cohen, Mark L; Wolansky, Leo J

    2016-01-01

    Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently develop in the gastrointestinal tract or lungs and have high potential for metastasis. Metastasis to the brain is rare, but to another intracranial tumor is extremely rare. Of the intracranial tumors, meningiomas are the most common to host metastases, which may be related to its rich vascularity and E-cadherin expression. We describe the case of a 65-year-old female with active chemotherapy-treated neuroendocrine carcinoma who presented with left-sided facial numbness, headaches, and blurry vision. Initial imaging revealed a 1 cm irregular dural-based left petrous apex mass suggestive of a meningioma that was re-imaged four months later as a rapidly enlarging, extra-axial, mass extending into the cavernous sinus, effacing Meckel’s cave that resembled a trigeminal schwannoma. Pathology revealed a carcinoid tumor metastatic to meningioma. While the mass displayed characteristic imaging findings of a schwannoma, rapid growth in the setting of known active malignancy should prompt the clinician to consider mixed pathology from metastatic disease or a more aggressive meningioma. PMID:26825133

  17. Posterior Fossa Meningioma

    PubMed Central

    Saleh, Essam A.; Taibah, Abdel Kader; Achilli, Vittorio; Aristegui, Miguel; Mazzoni, Antonio; Sanna, Mario

    1994-01-01

    Posterior fossa meningioma is the second most common tumor in the cerebellopontine angle. It has a higher rate of postoperative morbidity and mortality compared to acoustic neuroma. Forty posterior fossa meningioma patients managed in our centers were reviewed. Thirty-nine patients were managed surgically with 42 surgical procedures. The approaches used were the translabyrinthine approach in 18 patients (43%), the modified transcochlear in 11 cases (26%), the petro-occipital transsigmoid in 5 cases (12%), the suboccipital in 4 cases (10%), the petro-occipital trassigmoid transcervical in 2 cases (5%), the petro-occipital transsigmoid transtentorial in 1 case (2%), and a subtemporal transtentorial for another case (2%). Facial nerve anatomical integrity was preserved in 87% of procedures but was interrupted in 5 cases, with 4 of the latter subsequently repaired. Total tumor removal was accomplished in 38 cases. A second-stage total tumor removal is planned for the remaining case. There was only one case of perioperative death and no cases of radiological recurrence so far. ImagesFigure 1Figure 2Figure 3Figure 4p206-bFigure 5p207-bFigure 5 PMID:17171173

  18. Natural History of Meningioma Development in Mice Reveals: A Synergy of Nf2 and p16Ink4a Mutations

    PubMed Central

    Kalamarides, Michel; Stemmer-Rachamimov, Anat O; Takahashi, Masaya; Han, Zhi-Yan; Chareyre, Fabrice; Niwa-Kawakita, Michiko; Black, Peter M; Carroll, Rona S; Giovannini, Marco

    2008-01-01

    Meningiomas account for approximately 30% of all primary central nervous system tumors and are found in half of neurofibromatosis type 2 patients often causing significant morbidity. Although most meningiomas are benign, 10% are classified as atypical or anaplastic, displaying aggressive clinical behavior. Biallelic inactivation of the neurofibromatosis 2 (NF2) tumor suppressor is associated with meningioma formation in all NF2 patients and 60% of sporadic meningiomas. Deletion of the p16INK4a/p14ARF locus is found in both benign and malignant meningiomas, while mutation of the p53 tumor suppressor gene is uncommon. Previously, we inactivated Nf2 in homozygous conditional knockout mice by adenoviral Cre delivery and showed that Nf2 loss in arachnoid cells is rate-limiting for meningioma formation. Here, we report that additional nullizygosity for p16Ink4a increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. In addition, by using magnetic resonance imaging (MRI) to screen a large cohort of mutant mice, we were able to detect meningothelial proliferation and meningioma development opening the way to future studies in which therapeutic interventions can be tested as preclinical assessment of their potential clinical application. PMID:17924978

  19. Microcystic meningioma with late-phase accumulation on thallium-201 single-photon emission computed tomography: case report.

    PubMed

    Matano, Fumihiro; Adachi, Koji; Murai, Yasuo; Kitamura, Takayuki; Ohashi, Ryuji; Teramoto, Akira; Morita, Akio

    2014-01-01

    Microcystic meningiomas are rare but benign brain tumors. Previous reports have shown that Thallium-201 single-photon emission computed tomography ((201)Tl SPECT) demonstrated a higher late-phase accumulation of (201)Tl in malignant or recurrent meningiomas than in nonaggressive meningiomas. No study has reported (201)Tl SPECT findings in microcystic meningiomas. We here describe a case of a microcystic meningioma with a high (201)Tl SPECT retention rate in a 62-year-old woman who complained of headache. Computed tomography revealed an intracranial tumor in the right frontal lobe. Moreover, (201)Tl SPECT revealed a high uptake of (201)Tl in the tumor, which was particularly prominent in the delayed phase. The uptake index on an early image was 1.46 and that on a delayed image was 1.35. Therefore, the retention index was 0.92. After 2 years of tumor growth, we performed successful radical resection, and histological examination revealed the presence of a microcystic meningioma. Therefore, we concluded that (201)Tl SPECT may be useful for the preoperative diagnosis of microcystic meningiomas and that late-phase accumulation of (201)Tl is not a specific finding of malignant brain tumors. Therefore, we need to be careful in the evaluation and judgment of high retention in a delayed image of (201)Tl SPECT.

  20. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  1. Giant sacrolumbar meningioma. Case report.

    PubMed

    Feldenzer, J A; McGillicuddy, J E; Hopkins, J W

    1990-06-01

    A case of giant sacral meningioma with presacral and lumbar extension is presented. The difficulties in diagnosis and management are emphasized including the staged multidisciplinary surgical approaches and preoperative tumor embolization.

  2. [Chronic epidural haematoma mimicking meningioma].

    PubMed

    Beculić, Hakija; Skomorac, Rasim; Jusić, Aldin; Mekić-Abazović, Alma; Bajtarević, Alma

    2011-02-01

    The study presents a rare case of organised chronic epidural haematoma that imitated a meningioma. A patient was admitted to the Department of Neurology of the Cantonal Hospital Zenica due to loss of consciousness and right hemiparesis. Non-contrast Computed Tomography (CT) scan had shown an expansive intracranial process in the left parietal region which was radiologically diagnosed as a meningioma. During the operation a linear skull fracture and organised chronic epidural haematoma were found.

  3. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    PubMed Central

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM. PMID:27512676

  4. Oncolytic virotherapy for human malignant mesothelioma: recent advances.

    PubMed

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM.

  5. Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

    PubMed Central

    Kushwah, Rahul; Guezguez, Borhane; Lee, Jung Bok; Hopkins, Claudia I; Bhatia, Mickie

    2014-01-01

    The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation. PMID:25252682

  6. Giving AXL the axe: targeting AXL in human malignancy.

    PubMed

    Gay, Carl M; Balaji, Kavitha; Byers, Lauren Averett

    2017-02-14

    The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation.

  7. Giving AXL the axe: targeting AXL in human malignancy

    PubMed Central

    Gay, Carl M; Balaji, Kavitha; Byers, Lauren Averett

    2017-01-01

    The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation. PMID:28072762

  8. Intraparenchymal Angiomatous Meningioma: A Diagnostic Dilemma

    PubMed Central

    Bansal, Divya; Gogoi, Priyanka; Nazir, Wazid; Tandon, Anupama

    2015-01-01

    Meningioma arises from the arachnoid cap cells of the cerebrum. Intraparenchymal meningiomas or meningiomas without dural attachment are rare. We report a case of 40-year-old male who presented with a history of headache, dizziness and gradual loss of vision since one year. Clinicoradiological diagnosis of a high grade glioma was considered. Tumour was excised and haematoxylin and eosin stained sections revealed a tumour comprised predominantly of variable sized blood vessels showing hyalinization in a background of plump spindle cells with oval vesicular nuclei. In view of these features angiomatous meningioma was suspected. However, to confirm the diagnosis, a panel of immunohistochemical markers including vimentin, EMA and GFAP was done and a final diagnosis of angiomatous meningioma was offered. Angiomatous meningioma is a rare variant of meningioma and even much rarer in the intraparenchymal location. Angiomatous meningioma should be considered in the differential diagnosis of highly vascular intraparenchymal brain tumours. PMID:26557529

  9. Intraparenchymal Angiomatous Meningioma: A Diagnostic Dilemma.

    PubMed

    Bansal, Divya; Diwaker, Preeti; Gogoi, Priyanka; Nazir, Wazid; Tandon, Anupama

    2015-10-01

    Meningioma arises from the arachnoid cap cells of the cerebrum. Intraparenchymal meningiomas or meningiomas without dural attachment are rare. We report a case of 40-year-old male who presented with a history of headache, dizziness and gradual loss of vision since one year. Clinicoradiological diagnosis of a high grade glioma was considered. Tumour was excised and haematoxylin and eosin stained sections revealed a tumour comprised predominantly of variable sized blood vessels showing hyalinization in a background of plump spindle cells with oval vesicular nuclei. In view of these features angiomatous meningioma was suspected. However, to confirm the diagnosis, a panel of immunohistochemical markers including vimentin, EMA and GFAP was done and a final diagnosis of angiomatous meningioma was offered. Angiomatous meningioma is a rare variant of meningioma and even much rarer in the intraparenchymal location. Angiomatous meningioma should be considered in the differential diagnosis of highly vascular intraparenchymal brain tumours.

  10. In vitro measurements of ultraweak luminescence of human malignant tumors and healthy tissues

    NASA Astrophysics Data System (ADS)

    Chwirot, B. W.; Chwirot, S.; Jedrzejczyk, W.; Pozniak, V.; Dziczek, D.; Michniewicz, Z.; Jackowski, M.; Raczynska, A. M.; Winczakiewicz, J.

    2001-07-01

    In vitro measurements of levels of ultraweak luminescence were carried out using healthy and malignant tissues obtained from 63 patients undergoing surgical operations for cancers of colon, stomach and breast. The results obtained support recent reports that there is a difference in mean intensities of the ultraweak luminescence emitted from healthy and malignant tissues. This work demonstrates, however, that because of a large scatter among the intensities detected for samples obtained from different patients the differences found for the mean intensities cannot serve as a parameter for differentiating between the malignant and normal human tissues.

  11. A Pilocytic Astrocytoma Mimicking a Clinoidal Meningioma

    PubMed Central

    Hong, Christopher S.; Lehman, Norman L.; Sauvageau, Eric

    2014-01-01

    Pilocytic astrocytomas and meningiomas are benign, primary brain tumors that may involve the optic tract. Classically, the presence of a dural “tail” sign may differentiate a meningioma from other intracranial lesions. In this report, we describe a mass with the typical appearance of a clinoidal meningioma on magnetic resonance imaging (MRI) but postoperatively diagnosed as a pilocytic astrocytoma. This case illustrates the rare occurrence of a pilocytic astrocytoma mimicking a meningioma on MRI. PMID:24744944

  12. Oxidative stress-induced epigenetic changes associated with malignant transformation of human kidney epithelial cells.

    PubMed

    Mahalingaiah, Prathap Kumar S; Ponnusamy, Logeswari; Singh, Kamaleshwar P

    2017-02-14

    Renal Cell Carcinoma (RCC) in humans is positively influenced by oxidative stress status in kidneys. We recently reported that adaptive response to low level of chronic oxidative stress induces malignant transformation of immortalized human renal tubular epithelial cells. Epigenetic alterations in human RCC are well documented, but its role in oxidative stress-induced malignant transformation of kidney cells is not known. Therefore, the objective of this study was to evaluate the potential role of epigenetic changes in chronic oxidative stress-induced malignant transformation of HK-2, human renal tubular epithelial cells. The results revealed aberrant expression of epigenetic regulatory genes involved in DNA methylation (DNMT1, DNMT3a and MBD4) and histone modifications (HDAC1, HMT1 and HAT1) in HK-2 cells malignantly transformed by chronic oxidative stress. Additionally, both in vitro soft agar assay and in vivo nude mice study showing decreased tumorigenic potential of malignantly transformed HK-2 cells following treatment with DNA de-methylating agent 5-aza 2' dC further confirmed the crucial role of DNA hypermethyaltion in oxidative stress-induced malignant transformation. Changes observed in global histone H3 acetylation (H3K9, H3K18, H3K27 and H3K14) and decrease in phospho-H2AX (Ser139) also suggest potential role of histone modifications in increased survival and malignant transformation of HK-2 cells by oxidative stress. In summary, the results of this study suggest that epigenetic reprogramming induced by low levels of oxidative stress act as driver for malignant transformation of kidney epithelial cells. Findings of this study are highly relevant in potential clinical application of epigenetic-based therapeutics for treatments of kidney cancers.

  13. Optic Nerve Sheath Meningiomas.

    PubMed

    Radhakrishnan, Sunita; Lee, Michael S

    2005-01-01

    Optic nerve sheath meningiomas (ONSMs) grow slowly and, if untreated, patients may have stable visual function for up to several years. Treatment of an ONSM may lead to vision loss (radiation retinopathy or optic neuropathy). Therefore, observation is recommended for a patient with ONSM and relatively preserved visual acuity, color vision, pupils, and visual fields. Follow-up every 4 to 6 months initially is recommended extending to annual examinations if visual function and tumor size remain stable for a few years. Neuroimaging can be repeated every 12 months. An undisputed decline in visual function or any intracranial extension warrants treatment of the ONSM. The treatment of choice for a tumor confined to the orbit is stereotactic fractionated radiation. Stereotactic fractionated radiation uses multiple small doses of radiation using tight margins. A reasonable alternative, three-dimensional conformal fractionated radiation uses computed tomography-guided planning but usually requires wider margins. Conventional radiation uses much wider margins and would not be recommended for treatment of ONSM. The radiation can be administered during 5 to 6 weeks in 28 daily fractions of 1.8 to 2 Gy/fraction to a total of 50.4 to 56 Gy. Many patients have improvement or stabilization of their visual function. Gamma knife radiosurgery does not have a role in ONSM because the required dose is toxic to the optic nerve. A tumor that extends intracranially may be treated with fractionated radiation if any vision remains. Surgical excision can be considered for significant intracranial extension but this often leads to complete vision loss in the ipsilateral eye. A blind, disfigured eye also may be treated with en bloc surgical resection of the meningioma.

  14. Meningiomas of Meckel's cave.

    PubMed

    Delfini, R; Innocenzi, G; Ciappetta, P; Domenicucci, M; Cantore, G

    1992-12-01

    A series of 16 patients with meningiomas of Meckel's cave is reported. Trigeminal neuralgia, typical or atypical, was the initial symptom in 10 patients (62.5%). At admission, trigeminal signs and symptoms were present in 15 patients (93.7%); in 7 patients (43.7%), trigeminal dysfunction was combined with the impairment of other cranial nerves. On retrospective analysis, these patients fall into two clinical groups that differ also in prognosis. Group 1 comprises eight patients with trigeminal signs and symptoms only. These patients had small meningiomas strictly affecting Meckel's cave. Total removal of the tumor was achieved in seven of eight patients, without adjunctive postoperative neurological deficits. In this group, there were no tumor recurrences. Group 2 comprises the other eight patients in whom trigeminal dysfunction was combined with impairment of other cranial nerves. These patients had large tumors arising from Meckel's cave and secondarily invading the cavernous sinus (five patients) or extending into the posterior fossa (two patients) or largely growing into the middle fossa (one patient). Total removal was achieved in only one patient, and a worsening of the preoperative neurological status was observed in four patients; there were three cases of tumor progression. A subtemporal intradural approach (used in the past in every case) is still used for the small tumors of Group 1 with good results. Since 1985, for tumors involving the cavernous sinus, we have employed a frontotemporal craniotomy with extradural clinoidectomy and superior and lateral approach to the cavernous sinus. When the tumor extends toward the posterior fossa, we use a combined temporosuboccipital-transpetrosal approach.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. REIC/Dkk-3 induces cell death in human malignant glioma.

    PubMed

    Mizobuchi, Yoshifumi; Matsuzaki, Kazuhito; Kuwayama, Kazuyuki; Kitazato, Keiko; Mure, Hideo; Kageji, Teruyoshi; Nagahiro, Shinji

    2008-06-01

    The progression of glioma to more malignant phenotypes results from the stepwise accumulation of genetic alterations and the consequent disruption of the apoptotic pathway and augmentation of survival signaling. REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of the growth of several human cancers; however, to date it has not been identified in brain tumors. We compared the gene and protein expression of REIC/Dkk-3 in human malignant glioma and normal brain tissues using quantitative real-time PCR, Western blotting, and immunohistochemistry. We also performed small interfering REIC/Dkk-3 (siREIC/Dkk-3) knockdown and REIC/Dkk-3 overexpression experiments to examine the role of REIC/Dkk-3 in human malignant glioma cells in vitro. In brain tissue from patients with malignant glioma, the gene and protein expression of REIC/Dkk-3 was lower than in normal brain tissue and was related to the malignancy grade. In the primary glioblastoma cell line, REIC/Dkk-3 transfection led to apoptosis owing to the activation of phosphorylated JUN, caspase-9, and caspase-3 and the reduction of beta-catenin; in REIC/Dkk-3 knockdown experiments, cell growth was augmented. Our results suggest that REIC/Dkk-3 regulates the growth and survival of these cells in a caspase-dependent and -independent way via modification of the Wnt signaling pathway. Our work is the first documentation that the gene and protein expression of REIC/Dkk-3 is down-regulated in human malignant glioma. Our demonstration of the mechanisms underlying REIC/Dkk-3-induced cell death indicates that REIC/Dkk-3 plays a pivotal role in the biology of human malignant glioma and suggests that REIC/Dkk-3 is a promising candidate for molecular target therapy.

  16. CHIP: A new modulator of human malignant disorders

    PubMed Central

    Shao, Qianqian; Yang, Gang; Zheng, Lianfang; Zhang, Taiping; Zhao, Yupei

    2016-01-01

    Carboxyl terminus of Hsc70-interacting protein (CHIP) is known as a chaperone-associated E3 for a variety of protein substrates. It acts as a link between molecular chaperones and ubiquitin–proteasome system. Involved in the process of protein clearance, CHIP plays a critical role in maintaining protein homeostasis in diverse conditions. Here, we provide a comprehensive review of our current understanding of CHIP and summarize recent advances in CHIP biology, with a focus on CHIP in the setting of malignancies. PMID:27007160

  17. CHIP: A new modulator of human malignant disorders.

    PubMed

    Cao, Zhe; Li, Guanqiao; Shao, Qianqian; Yang, Gang; Zheng, Lianfang; Zhang, Taiping; Zhao, Yupei

    2016-05-17

    Carboxyl terminus of Hsc70-interacting protein (CHIP) is known as a chaperone-associated E3 for a variety of protein substrates. It acts as a link between molecular chaperones and ubiquitin-proteasome system. Involved in the process of protein clearance, CHIP plays a critical role in maintaining protein homeostasis in diverse conditions. Here, we provide a comprehensive review of our current understanding of CHIP and summarize recent advances in CHIP biology, with a focus on CHIP in the setting of malignancies.

  18. Pediatric intracranial meningiomas--do they differ from their counterparts in adults?

    PubMed

    Arivazhagan, A; Devi, B Indira; Kolluri, Sastry V R; Abraham, R G; Sampath, S; Chandramouli, B A

    2008-01-01

    Meningiomas are very rare in children comprising only 0.44.1% of pediatric age tumors and only 1.5-1.8% of all intracranial neoplasms. We analyzed the clinical, pathological and management profile of these rare tumors and elucidated their differences from meningiomas in adults. From 1990 to 2005, 33 patients belonging to the pediatric age group with intracranial meningiomas were treated in NIMHANS. There were 19 male and 14 female children. The duration of symptoms ranged from 1 to 60 months. The study had a mean follow-up of 23.4 months. The commonest presenting symptoms were headache (90.9%) and visual disturbances (51.5%). Three patients had associated neurofibromatosis. Calcification was noticed in 22% of the tumors. Intraventricular meningiomas were the commonest (24.2%). Gross total or near total resection was possible in 22 out of 33 patients. Nine patients had reversible postoperative motor deficits. Fibrous meningioma was the commonest histological subtype (24.2%). Five patients had atypical or anaplastic subtypes. Adjuvant radiotherapy was administered in 4 patients. Six patients had recurrences and underwent surgery. Ten patients required either staged procedures or multiple surgeries for the recurrence/residual tumors. Pediatric meningiomas are rare tumors and differ from those in adults by their male predominance, atypical locations, higher rates of malignant subtypes, recurrence and association with neurofibromatosis. Surgical management is challenging because of atypical location. (c) 2008 S. Karger AG, Basel.

  19. Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

    SciTech Connect

    Yang, Yingbin; Cai, Shaoxi; Yang, Li; Yu, Shuhui; Jiang, Jiahuan; Yan, Xiaoqing; Zhang, Haoxing; Liu, Lan; Liu, Qun; Du, Jun; Cai, Shaohui; Sung, K.L. Paul

    2010-12-10

    Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

  20. Intracranial Meningioma with Leptomeningeal Dissemination : Retrospective Study with Review of the Literature

    PubMed Central

    Park, Ki-Su; Kim, Ki-Hong; Park, Seong-Hyun; Lee, Dong-Hyun

    2015-01-01

    Objective The purposes of this article are to present 5 cases of intracranial meningioma with leptomeningeal dissemination (LD) and investigate the characteristics of this disease. Methods We present a retrospective case series of 5 females at our institutions (age ranged 21-72 years, mean 54.6 years) diagnosed with LD of an intracranial meningioma after surgery between 1998 and 2013. A database search revealed 45 cases with LD of meningioma in the English literature. Characteristic features were analyzed and compared. Results The incidence rate at our institutions of LD of meningioma was 0.9% (5/534). World Health Organization (WHO) grade was distributed as follows: I : 2, II : 2, and III : 1. Time to LD ranged from 2.5 months to 6.9 years; the patient with WHO grade III had the shortest interval to LD. The patient with an intraventricular meningioma (WHO grade II) had the second shortest interval to LD (1.7 years), and simultaneously revealed both LD and extraneuronal metastases. Four of 5 patients showed a disease progression, with the survival ranging from 1 month to 3.8 years after LD. Based on the literature, the initial tumor was an intraventricular meningioma in 9 patients, and their time to LD was shorter on average (mean 1.9 years). Histologically, 26 of 45 (58%) were initially diagnosed with a WHO grade II or III meningioma, and 6 of 19 patients (32%) with WHO grade I revealed malignant transformation. Conclusion This study shows that intraventricular location and histologically aggressive features seem to increase the chance of LD of meningioma. PMID:25932292

  1. A case of an anaplastic meningioma metastasizing to the mediastinal lymph nodes

    PubMed Central

    Nishida, Norihiro; Kanchiku, Tsukasa; Imajo, Yasuaki; Suzuki, Hidenori; Yoshida, Yuichiro; Kato, Yoshihiko; Hoshii, Yoshinobu; Taguchi, Toshihiko

    2016-01-01

    Context Grade II and III (World Health Organization classification) meningiomas rarely develop in the spinal cord. However, we experienced a case with an anaplastic meningioma that developed in the spinal cord at the cervicothoracic junction and metastasized to the mediastinal lymph nodes. No such cases have previously been reported. Findings The patient was a 68-year-old man who developed back pain that did not affect his daily living. He developed left lower limb paralysis, and was admitted after magnetic resonance imaging (MRI) revealed an intramedullary tumor at the level of cervical vertebra 7 and thoracic vertebra 1. Positron emission tomography revealed tracer uptake in the intramedullary tumor and the mediastinal lymph nodes, suggesting a metastatic spinal cord tumor or malignant lymphoma. A lymph node biopsy was then performed. Although the tumor was highly malignant, its primary site was not identified. Detailed examinations by several other departments revealed no abnormalities. On hospital day 30, his left lower limb paralysis deteriorated, and MRI revealed that the tumor had grown. Thus, laminaplasty, laminectomy, and tumor resection were performed. The tumor was an anaplastic meningioma that resembled mediastinal lymph node tissue, and other tumor lesions were not found. These findings suggested that an anaplastic meningioma had metastasized to the mediastinal lymph nodes. The patient did not respond to radiotherapy, and he was transferred to another hospital. Conclusion In cases of intramedullary spinal tumors with metastasis without other potential primary tumor lesions, early diagnosis and treatment should be performed while considering anaplastic meningioma. PMID:25738779

  2. AR-Signaling in Human Malignancies: Prostate Cancer and Beyond

    PubMed Central

    Schweizer, Michael T.; Yu, Evan Y.

    2017-01-01

    In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR) has remained the main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types. PMID:28085048

  3. AR-Signaling in Human Malignancies: Prostate Cancer and Beyond.

    PubMed

    Schweizer, Michael T; Yu, Evan Y

    2017-01-11

    In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR) has remained the main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types.

  4. Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

    PubMed Central

    Pećina-Šlaus, Nives; Kafka, Anja; Lechpammer, Mirna

    2016-01-01

    Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed. PMID:27429002

  5. Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

    PubMed

    Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

    2015-04-01

    Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.

  6. Genomic landscape of high-grade meningiomas

    PubMed Central

    Bi, Wenya Linda; Greenwald, Noah F.; Abedalthagafi, Malak; Wala, Jeremiah; Gibson, Will J.; Agarwalla, Pankaj K.; Horowitz, Peleg; Schumacher, Steven E.; Esaulova, Ekaterina; Mei, Yu; Chevalier, Aaron; Ducar, Matthew; Thorner, Aaron R.; van Hummelen, Paul; Stemmer-Rachamimov, Anat; Artyomov, Maksym; Al-Mefty, Ossama; Dunn, Gavin P.; Santagata, Sandro; Dunn, Ian F.; Beroukhim, Rameen

    2017-01-01

    High-grade meningiomas frequently recur and are associated with high rates of morbidity and mortality. To determine the factors that promote the development and evolution of these tumors, we analyzed the genomes of 134 high-grade meningiomas and compared this information with data from 587 previously published meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any statistically significant mutated genes aside from NF2. High-grade meningiomas also possessed significantly elevated rates of chromosomal gains and losses, especially among tumors with monosomy 22. Meningiomas previously treated with adjuvant radiation had significantly more copy number alterations than radiation-induced or radiation-naïve meningiomas. Across serial recurrences, genomic disruption preceded the emergence of nearly all mutations, remained largely uniform across time, and when present in low-grade meningiomas, correlated with subsequent progression to a higher grade. In contrast to the largely stable copy number alterations, mutations were strikingly heterogeneous across tumor recurrences, likely due to extensive geographic heterogeneity in the primary tumor. While high-grade meningiomas harbored significantly fewer overtly targetable alterations than low-grade meningiomas, they contained numerous mutations that are predicted to be neoantigens, suggesting that immunologic targeting may be of therapeutic value. PMID:28713588

  7. Surgical Resectability of Skull Base Meningiomas

    PubMed Central

    GOTO, Takeo; OHATA, Kenji

    2016-01-01

    With recent advances in surgical technology such as preoperative imaging, neuro-monitoring, and surgical instruments, the surgical resectability of intracranial meningiomas has increased over the last two decades. This study reviewed clinical articles regarding the surgical treatment of meningiomas to clarify the role of surgical excision, with a focus on skull base meningiomas. We sub-classified clinical articles about skull base meningiomas into two categories (anterior and middle fossa meningiomas; and posterior fossa meningiomas) and reviewed papers in each category. In cases with anterior and middle fossa meningiomas, surgical resectability has reached a sufficient level to maximize functional preservation. In cases of posterior fossa meningioma, however, surgical respectability remains insufficient even with full use of recent surgical modalities. Continuous refining of operative procedures is required to obtain more satisfactory outcomes, especially for posterior fossa meningioma. In addition, recent long-term outcomes of stereotactic radiosurgery (SRS) were acceptable for controlling the skull base meningiomas. Therefore, combination with surgical excision and SRS should be considered in complicated skull base meningiomas. PMID:27076382

  8. Favorable Outcomes of Pediatric Patients Treated With Radiotherapy to the Central Nervous System Who Develop Radiation-Induced Meningiomas

    SciTech Connect

    Galloway, Thomas J.; Indelicato, Daniel J.; Amdur, Robert J.; Swanson, Erika L.; Morris, Christopher G.; Marcus, Robert B.

    2011-01-01

    Purpose: To report the outcome of patients treated at the University of Florida who developed meningiomas after radiation to the central nervous system (CNS) for childhood cancer. Methods and Materials: We retrospectively identified 10 patients aged {<=}19 years who received radiotherapy to sites in the craniospinal axis and subsequently developed a meningioma. We report the histology of the radiation-induced meningioma, treatment received, and ultimate outcome among this cohort of patients. Results: Meningioma was diagnosed at a median of 23.5 years after completion of the primary radiation. Fifty percent of second meningiomas were World Health Organization Grade 2 (atypical) or higher. All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). The actuarial event-free survival and overall survival rate at 5 years after treatment for a radiation-induced meningioma was 89%. Three patients who underwent resection for retreatment experienced a Grade 3 toxicity. Conclusions: Radiation-induced meningiomas after treatment of pediatric CNS tumors are effectively managed with single-modality therapy. Such late-effect data inform the overall therapeutic ratio and support the continued role of selective irradiation in managing pediatric CNS malignancies.

  9. Growth retardation and bilateral cataracts followed by anaplastic meningioma 23 years after high-dose cranial and whole-body irradiation for acute lymphoblastic leukemia: case report and review of the literature.

    PubMed

    Korenkov, Alexei I; Imhof, Hans G; Brandner, Sebastian; Taub, Ethan; Huguenin, Pia U; Gaab, Michael R; Yonekawa, Yasuhiro

    2005-09-01

    We report a case of meningioma diagnosed 23 years after high-dose cranial and whole-body irradiation for the treatment of acute lymphocytic leukemia (ALL). Radiotherapy in this case also caused early radiation injury to the lenses and the pituitary gland, with growth retardation and mineralizing angiopathy. Radiation-induced meningiomas are more commonly malignant, more commonly multiple, and more likely to recur after resection than non-radiation-induced meningiomas. Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs, such as the lens and pituitary gland, and for the later development of a radiation-induced meningioma.

  10. Totally ossified metaplastic spinal meningioma.

    PubMed

    Ju, Chang Il; Hida, Kazutoshi; Yamauchi, Tomohiro; Houkin, Kiyohiro

    2013-09-01

    A 61-year-old woman with a very rare case of totally ossified large thoracic spinal metaplastic meningioma, showing progressing myelopathy is presented. Computed tomographic images showed a large totally ossfied intradural round mass occupying the spinal canal on T9-10 level. Magnetic resonance imaging revealed a large T9-10 intradural extramedullary mass that was hypointense to spinal cord on T1- and T2-weighted sequences, partial enhancement was apparent after Gadolinium administration. The spinal cord was severely compressed and displaced toward the right at the level of T9-10. Surgical removal of the tumor was successfully accomplished via the posterior midline approach and the histological diagnosis verified an ossified metaplastic meningioma. The clinical neurological symptoms of patient were improved postoperatively. In this article we discuss the surgical and pathological aspects of rare case of spinal totally ossified metaplastic meningioma.

  11. Totally Ossified Metaplastic Spinal Meningioma

    PubMed Central

    Hida, Kazutoshi; Yamauchi, Tomohiro; Houkin, Kiyohiro

    2013-01-01

    A 61-year-old woman with a very rare case of totally ossified large thoracic spinal metaplastic meningioma, showing progressing myelopathy is presented. Computed tomographic images showed a large totally ossfied intradural round mass occupying the spinal canal on T9-10 level. Magnetic resonance imaging revealed a large T9-10 intradural extramedullary mass that was hypointense to spinal cord on T1- and T2-weighted sequences, partial enhancement was apparent after Gadolinium administration. The spinal cord was severely compressed and displaced toward the right at the level of T9-10. Surgical removal of the tumor was successfully accomplished via the posterior midline approach and the histological diagnosis verified an ossified metaplastic meningioma. The clinical neurological symptoms of patient were improved postoperatively. In this article we discuss the surgical and pathological aspects of rare case of spinal totally ossified metaplastic meningioma. PMID:24278660

  12. Immature mesenchymal stem cell-like pericytes as mediators of immunosuppression in human malignant glioma.

    PubMed

    Ochs, Katharina; Sahm, Felix; Opitz, Christiane A; Lanz, Tobias V; Oezen, Iris; Couraud, Pierre-Olivier; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

    2013-12-15

    Malignant gliomas are primary brain tumors characterized by profound local immunosuppression. While the remarkable plasticity of perivascular cells - resembling mesenchymal stem cells (MSC) - in malignant gliomas and their contribution to angiogenesis is increasingly recognized, their role as potential mediators of immunosuppression is unknown. Here we demonstrate that FACS-sorted malignant glioma-derived pericytes (HMGP) were characterized by the expression of CD90, CD248, and platelet-derived growth factor receptor-β (PDGFR-β). HMGP shared this expression profile with human brain vascular pericytes (HBVP) and human MSC (HMSC) but not human cerebral microvascular endothelial cells (HCMEC). CD90+PDGFR-β+perivascular cells distinct from CD31+ endothelial cells accumulated in human gliomas with increasing degree of malignancy and negatively correlated with the presence of blood vessel-associated leukocytes and CD8+ T cells. Cultured CD90+PDGFR-β+HBVP were equally capable of suppressing allogeneic or mitogen-activated T cell responses as human MSC. HMGP, HBVP and HMSC expressed prostaglandin E synthase (PGES), inducible nitric oxide synthase (iNOS), human leukocyte antigen-G (HLA-G), hepatocyte growth factor (HGF) and transforming growth factor-β (TGF-β). These factors but not indoleamine 2,3-dioxygenase-mediated conversion of tryptophan to kynurenine functionally contributed to immunosuppression of immature pericytes. Our data provide evidence that human cerebral CD90+ perivascular cells possess T cell inhibitory capability comparable to human MSC and suggest that these cells, besides their critical role in tumor vascularization, also promote local immunosuppression in malignant gliomas and possibly other brain diseases.

  13. Inactivation of glyceraldehyde-3-phosphate dehydrogenase of human malignant cells by methylglyoxal.

    PubMed

    Ray, M; Basu, N; Ray, S

    1997-12-01

    The effect of methylglyoxal on the activity of glyceraldehyde-3-phosphate dehydrogenase (GA3PD) of several normal human tissues and benign and malignant tumors has been tested. Methylglyoxal inactivated GA3PD of all the malignant cells (47 samples) and the degree of inactivation was in the range of 25-90%, but it had no inhibitory effect on this enzyme from several normal cells (24 samples) and benign tumors (13 samples). When the effect of methylglyoxal on other two dehydrogenases namely glucose 6-phosphate dehydrogenase (G6PD) and L-lactic dehydrogenase (LDH) of similar cells was tested as controls it has been observed that methylglyoxal has some inactivating effect on G6PD of all the normal, benign and malignant samples tested, whereas, LDH remained completely unaffected. These studies indicate that the inactivating effect of methylglyoxal on GA3PD specifically of the malignant cells may be a common feature of all the malignant cells, and this phenomenon can be used as a simple and rapid device for the detection of malignancy.

  14. Imaging of Meningioma Progression by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

    PubMed Central

    Agar, Nathalie Y.R.; Malcolm, James G.; Mohan, Vandana; Yang, Hong W.; Johnson, Mark D.; Tannenbaum, Allen; Agar, Jeffrey N.; Black, Peter M.

    2010-01-01

    Often considered benign, meningiomas represent 32% of intracranial tumors with 3 grades of malignancy defined by the WHO histology based classification. Malignant meningiomas are associated with less than 2 years median survival. The inability to predict recurrence and progression of meningiomas induces significant anxiety for patients and limits physicians in implementing prophylactic treatment approaches. This report presents an analytical approach to tissue characterization based on MALDI TOF mass spectrometry imaging (MSI) which is introduced in an attempt to develop a reference database for predictive classification of brain tumors. This pilot study was designed to evaluate the potential of such approach and to begin to address limitations of the current methodology. Five recurrent and progressive meningiomas for which surgical specimens were available from the original and progressed grades were selected and tested against non-progressive high-grade meningiomas, high-grade gliomas, and non-tumor brain specimens. The common profiling approach of data acquisition was compared to imaging and revealed significant benefits in spatially resolved acquisition for improved spectral definition. A preliminary classifier based on support vector machine showed the ability to distinguish meningioma image spectra from non-tumor brain and from gliomas, a different type of brain tumors, and to enable class imaging of surgical tissue. Although the development of classifiers was shown to be sensitive to data preparation parameters such as recalibration and peak picking criteria, it also suggested the potential for maturing into a predictive algorithm if provided with larger series of well-defined cases. PMID:20196536

  15. Human immunodeficiency virus infection and female lower genital tract malignancy.

    PubMed

    Kuhn, L; Sun, X W; Wright, T C

    1999-02-01

    The risk of lower genital tract neoplasia is increased in women infected with HIV. This has been best demonstrated in cervical squamous intraepithelial lesions, but has also been observed in vulvar and perianal intraepithelial lesions in some studies. Alterations in the prevalence and natural history of human papillomavirus infections of the lower genital tract appear to account for much of the increase. HIV-infected women are approximately four times more likely to be infected with human papillomavirus (including infection with high oncogenic risk human papillomavirus types) than are HIV-uninfected women, and these infections are more likely to be persistent. Human papilomavirus-associated lesions may be more difficult to treat in HIV-infected women. These data highlight the need to develop effective cervical cancer prevention programs for HIV-infected women.

  16. Metastatic meningioma: The role of whole‑body diffusion-weighted imaging

    PubMed Central

    Cabada, Teresa; Bermejo, Rebeca; Bacaicoa, Carmen; Martínez-Peñuela, Ana

    2011-01-01

    We report the case of a 74-year-old male patient with a completely resected anaplastic meningioma who developed multiple metastases two years later (subcutaneous tissue near the surgical area, cervical lymph nodes, lung, pleura and bones). The primary tumor and all of the metastases showed a significant restricted diffusion. Whole‑body diffusion-weighted imaging (DWI) was performed for assessment of the metastases. This case demonstrated the usefulness of this technique in screening extracranial metastases in patients with malignant meningiomas. PMID:22866153

  17. Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma.

    PubMed

    Wu, Licun; Allo, Ghassan; John, Thomas; Li, Ming; Tagawa, Tetsuzo; Opitz, Isabelle; Anraku, Masaki; Yun, Zhihong; Pintilie, Melania; Pitcher, Bethany; Liu, Geoffrey; Feld, Ron; Johnston, Michael R; de Perrot, Marc; Tsao, Ming-Sound

    2017-02-15

    Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor-stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1-5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies. Clin Cancer Res; 23(4); 1060-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. High-dose radiation-induced meningiomas. Report of five cases and critical review of the literature.

    PubMed

    Salvati, Maurizio; Caroli, Emanuela; Brogna, Cristian; Orlando, Epimenio Ramundo; Delfini, Roberto

    2003-01-01

    Radiotherapy is an important modality for the treatment of tumors and arteriovenous malformations affecting the central nervous system, even though several significant side effects have been described (radionecrosis, tumors, etc.). Meningiomas induced by high-dose radiation therapy are uncommon. In this study we describe five cases treated at our institute and review all previously published reports of meningioma occurring after high-dose radiotherapy. These tumors develop mainly in patients irradiated in childhood; their incidence peaks in the second decade of life, there is a predominance in females and a high frequency of malignant forms. Although rare, meningiomas may represent a late complication of radiation treatment. The behavior of the radiation-induced variety of meningioma seems to differ from that of its "spontaneous" counterpart. The use of radiotherapy should be carefully evaluated for relatively benign or congenital lesions which generally affect young patients with a long life expectancy.

  19. Pulmonary metastases from benign calvarial meningioma: a case report.

    PubMed

    Cho, Byung-Rae; Yoon, Wan-Soo

    2017-04-01

    The most common intracranial tumour is meningioma, which rarely presents with extracranial metastasis, especially in benign cases. We report a case of meningioma recurrence with multiple pulmonary metastases in a patient who had a benign meningioma removed 12 years prior.

  20. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report

    PubMed Central

    Ramanathan, Nithya; Kamaruddin, Khairul Azmi; Othman, Aizzat; Mustafa, Fadhli; Awang, Mohamed Saufi

    2016-01-01

    Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma. PMID:27418876

  1. Loss of p53 expression is accompanied by upregulation of beta-catenin in meningiomas: a concomitant reciprocal expression.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Vladušić, Tomislav; Tomas, Davor; Logara, Monika; Skoko, Josip; Hrašćan, Reno

    2016-04-01

    Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.

  2. Myosin VI contributes to malignant proliferation of human glioma cells

    PubMed Central

    Xu, Rong; Fang, Xu-hao

    2016-01-01

    Previously characterized as a backward motor, myosin VI (MYO6), which belongs to myosin family, moves toward the minus end of the actin track, a direction opposite to all other known myosin members. Recent researches have illuminated the role of MYO6 in human cancers, particularly in prostate cancer. However, the role of MYO6 in glioma has not yet been determined. In this study, to explore the role of MYO6 in human glioma, lentivirus-delivered short hairpin RNA (shRNA) targeting MYO6 was designed to stably down-regulate its endogenous expression in glioblastoma cells U251. Knockdown of MYO6 signifi cantly inhibited viability and proliferation of U251 cells in vitro. Moreover, the cell cycle of U251 cells was arrested at G0/G1 phase with the absence of MYO6, which could contribute to the suppression of cell proliferation. In conclusion, we firstly identified the crucial involvement of MYO6 in human glioma. The inhibition of MYO6 by shRNA might be a potential therapeutic method in human glioma. PMID:26937209

  3. Effects of sex on the incidence and prognosis of spinal meningiomas: a Surveillance, Epidemiology, and End Results study.

    PubMed

    Westwick, Harrison J; Shamji, Mohammed F

    2015-09-01

    Most spinal meningiomas are intradural lesions in the thoracic spine that present with both local pain and myelopathy. By using the large prospective Surveillance, Epidemiology, and End Results (SEER) database, the authors studied the incidence of spinal meningiomas and examined demographic and treatment factors predictive of death. Using SEER*Stat software, the authors queried the SEER database for cases of spinal meningioma between 2000 and 2010. From the results, tumor incidence and demographic statistics were computed; incidence was analyzed as a function of tumor location, pathology, age, sex, and malignancy code. Survival was analyzed by using a Cox proportional hazards ratio in SPSS for age, sex, marital status, primary site, size quartile, treatment modality, and malignancy code. In this analysis, significance was set at a p value of 0.05. The 1709 spinal meningiomas reported in the SEER database represented 30.7% of all primary intradural spinal tumors and 7.9% of all meningiomas. These meningiomas occurred at an age-adjusted incidence of 0.193 (95% CI 0.183-0.202) per 100,000 population and were closely related to sex (337 [19.7%] male patients and 1372 [80.3%] female patients). The Cox hazard function for mortality in males was higher (2.4 [95% CI1.7-3.5]) and statistically significant, despite the lower lesion incidence in males. All-cause survival was lowest in patients older than 80 years. Primary site and treatment modality were not significant predictors of mortality. Spinal meningiomas represent a significant fraction of all primary intradural spinal tumors and of all meningiomas. The results of this study establish the association of lesion incidence and survival with sex, with a less frequent incidence in but greater mortality among males.

  4. A novel mutation of the FAT2 gene in spinal meningioma

    PubMed Central

    Tate, Genshu; Kishimoto, Koji; Mitsuya, Toshiyuki

    2016-01-01

    Meningiomas may be classified as neurofibromin 2 (NF2)-associated and non-NF2 meningiomas depending on the presence or absence of molecular alterations in the NF2 gene. One of the characteristic histological features of meningiomas is the whorl formation of neoplastic arachnoid cells. NF2 is a human homolog of the Drosophila gene, Merlin (Mer). In humans, NF2 is the gene responsible for the disease neurofibromatosis type II, which results in the development of brain tumors, including acoustic neurinoma and meningioma. The present study aimed to investigate the molecular pathogenesis of spinal meningioma. It was hypothesized that the whorl formation of meningiomas may occur as a result of a disturbance in the planar cell polarity (PCP) of arachnoid cells, thus, genes understood to govern PCP signaling were analyzed for alterations. Whole exome sequencing followed by Sanger sequencing validation was performed for the analysis of spinal meningioma tissue obtained from a 42-year-old Japanese female. The sequencing identified a nonsynonymous mutation of c.3597G>C, resulting in p.Q1199H, in the FAT atypical cadherin 2 (FAT2) gene. FAT2 is homologous to the Drosophila Fat (Ft) gene, which belongs to the cadherin superfamily. Drosophila Fat is involved in PCP, tumor suppression and Hippo (Hpo) signaling, which is associated with Mer. Taken together, the results of the present study concluded that human FAT2 may function as a key molecule that governs not only PCP, but also NF2-Hpo signaling in arachnoid cells; thus, a mutation in this gene may result in spinal meningioma. PMID:27900010

  5. A novel mutation of the FAT2 gene in spinal meningioma.

    PubMed

    Tate, Genshu; Kishimoto, Koji; Mitsuya, Toshiyuki

    2016-11-01

    Meningiomas may be classified as neurofibromin 2 (NF2)-associated and non-NF2 meningiomas depending on the presence or absence of molecular alterations in the NF2 gene. One of the characteristic histological features of meningiomas is the whorl formation of neoplastic arachnoid cells. NF2 is a human homolog of the Drosophila gene, Merlin (Mer). In humans, NF2 is the gene responsible for the disease neurofibromatosis type II, which results in the development of brain tumors, including acoustic neurinoma and meningioma. The present study aimed to investigate the molecular pathogenesis of spinal meningioma. It was hypothesized that the whorl formation of meningiomas may occur as a result of a disturbance in the planar cell polarity (PCP) of arachnoid cells, thus, genes understood to govern PCP signaling were analyzed for alterations. Whole exome sequencing followed by Sanger sequencing validation was performed for the analysis of spinal meningioma tissue obtained from a 42-year-old Japanese female. The sequencing identified a nonsynonymous mutation of c.3597G>C, resulting in p.Q1199H, in the FAT atypical cadherin 2 (FAT2) gene. FAT2 is homologous to the Drosophila Fat (Ft) gene, which belongs to the cadherin superfamily. Drosophila Fat is involved in PCP, tumor suppression and Hippo (Hpo) signaling, which is associated with Mer. Taken together, the results of the present study concluded that human FAT2 may function as a key molecule that governs not only PCP, but also NF2-Hpo signaling in arachnoid cells; thus, a mutation in this gene may result in spinal meningioma.

  6. Malignant Transformation of Hymenolepis nana in a Human Host.

    PubMed

    Muehlenbachs, Atis; Bhatnagar, Julu; Agudelo, Carlos A; Hidron, Alicia; Eberhard, Mark L; Mathison, Blaine A; Frace, Michael A; Ito, Akira; Metcalfe, Maureen G; Rollin, Dominique C; Visvesvara, Govinda S; Pham, Cau D; Jones, Tara L; Greer, Patricia W; Vélez Hoyos, Alejandro; Olson, Peter D; Diazgranados, Lucy R; Zaki, Sherif R

    2015-11-05

    Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

  7. Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma

    PubMed Central

    Norden, Andrew D.; Ligon, Keith L.; Hammond, Samantha N.; Muzikansky, Alona; Reardon, David A.; Kaley, Thomas J.; Batchelor, Tracy T.; Plotkin, Scott R.; Raizer, Jeffrey J.; Wong, Eric T.; Drappatz, Jan; Lesser, Glenn J.; Haidar, Sam; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gaffey, Sarah C.; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Phuphanich, Surasak

    2015-01-01

    Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8–20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12–43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor–1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. PMID:25527270

  8. Nuclear magnetic resonance in cancer, XII: Application of NMR malignancy index to human lung tumours.

    PubMed Central

    Goldsmith, M.; Koutcher, J. A.; Damadian, R.

    1977-01-01

    Sixty specimens of human lung tissue from 52 individuals were inspected at 22.5 MHz by proton magnetic resonance techniques. The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique for the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice (T1) and spin-spin (T2) relaxation times) into a malignancy index yielded 3 cases of overlap between the two populations of tissue. The mean and standard deviations obtained were 1.966 +/- 0.262 for normal tissue, and 2.925 +/- 0.864 for malignant specimens. In addition, analysis of the electrolyte and water content of the tissues confirm that factors other than specimen water content influence the relaxation time. PMID:911662

  9. Radiation-induced meningiomas in pediatric patients

    SciTech Connect

    Moss, S.D.; Rockswold, G.L.; Chou, S.N.; Yock, D.; Berger, M.S.

    1988-04-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

  10. Recurrent spinal meningioma: a case report.

    PubMed

    Choi, Hoi Jung; Paeng, Sung Hwa; Kim, Sung Tae; Jung, Yong Tae

    2012-09-01

    Meningiomas are the second most common intradural spinal tumors accounting for 25% of all spinal tumors. Being a slow growing and invariably benign tumor, it responds favorably to surgical excision. In addition, spinal meningioma has low recurrence rates. However, we experienced a case of intradural extramedullary spinal meningioma which recurred 16 years after the initial surgery on a 64-year-old woman. She presented with progressive neurological symptoms and had a surgical history of removal of thoracic spinal meningioma 16 years ago due to bilateral low leg weakness. She underwent a second operation at the same site and a pale yellowish tumor was excised, which was histopathologically confirmed as meningothelial meningioma, compared with previously transitional type. she showed neurological recovery after the operation. We, therefore, report the good results of this recurrent intradural spinal meningioma case developed after 16 years with literature review.

  11. Radiation-induced meningiomas in pediatric patients.

    PubMed

    Moss, S D; Rockswold, G L; Chou, S N; Yock, D; Berger, M S

    1988-04-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

  12. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis.

    PubMed

    Lazarov, Mirella; Kubo, Yoshiaki; Cai, Ti; Dajee, Maya; Tarutani, Masahito; Lin, Qun; Fang, Min; Tao, Shiying; Green, Cheryl L; Khavari, Paul A

    2002-10-01

    Ras acts with other proteins to induce neoplasia. By itself, however, strong Ras signaling can suppress proliferation of normal cells. In primary epidermal cells, we found that oncogenic Ras transiently decreases cyclin-dependent kinase (CDK) 4 expression in association with cell cycle arrest in G1 phase. CDK4 co-expression circumvents Ras growth suppression and induces invasive human neoplasia resembling squamous cell carcinoma. Tumorigenesis is dependent on CDK4 kinase function, with cyclin D1 required but not sufficient for this process. In facilitating escape from G1 growth restraints, Ras and CDK4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK4 cyclin-dependent kinase inhibitors. These data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth.

  13. Confocal reflectance imaging of excised malignant human bladder biopsies

    NASA Astrophysics Data System (ADS)

    Daniltchenko, Dmitri I.; Kastein, Albrecht; Koenig, Frank; Sachs, Markus; Schnorr, Dietmar; Al-Shukri, Salman; Loening, Stefan A.

    2004-08-01

    To evaluate the potential of reflectance confocal scanning laser microscopy (CM) for rapid imaging of non-processed freshly excised human bladder biopsies and cystectomy specimens. Freshly excised bladder tumors from three cystectomy specimens and random biopsies from twenty patients with a history of superficial bladder tumors were imaged with CM. Additional acetic acid washing prior to CM imaging was performed in some of the samples. Confocal images were compared to corresponding routine histologic sections. CM allows imaging of unprocessed bladder tissue at a subcellular resolution. Urothelial cell layers, collagen, vessels and muscle fibers can be rapidly visualized, in native state. In this regard, umbrella cells, basement membrane elucidated. Besides obvious limitations partly due to non-use of exogenous dyes, CM imaging offers several advantages: rapid imaging of the tissue in its native state like the basement membrane, normally seen only by using immunohistopathology. Reflectance CM opens a new avenue for imaging bladder cancer.

  14. p120 GAP requirement in normal and malignant human hematopoiesis

    PubMed Central

    1993-01-01

    There is evidence to suggest that the p120 GAP (GAP), originally described as an inhibitor of p21ras, may also serve as a downstream effector of ras-regulated signal transduction. To determine whether GAP expression is required for the growth of human normal and leukemic hematopoietic cells, we used GAP antisense oligodeoxynucleotides to inhibit it and analyzed the effects of this inhibition on the colony- forming ability of nonadherent, T lymphocyte-depleted mononuclear cells and of highly purified progenitors (CD34+ MNC) obtained from the bone marrow and peripheral blood of healthy volunteers or chronic myeloid leukemia (CML, bcr-abl-positive) patients. The acute myelogenous leukemia cell line MO7, the Philadelphia BV173 cell line, and the acute promyelocytic leukemia NB4 and HL-60 cell lines were similarly examined. GAP antisense treatment inhibited colony formation from normal myelo-, erythro-, and megakaryopoietic progenitor cells as well as from CML progenitor cells. Proliferation of MO7 (growth factor- dependent) and BV173 (bcr-abl-dependent) cells, but not that of NB4 and HL-60 (growth factor-independent) cells, was also inhibited, even though a specific downregulation of GAP was observed in each cell line, as analyzed by either or both mRNA and protein expression. Stimulation of MO7 cells with hematopoietic growth factors increased the expression of GAP as well as the levels of active GTP-bound p21ras. Stimulation of GAP expression was inhibited upon GAP antisense treatment. These data indicate that p120 GAP is involved in human normal and leukemic hemopoiesis and strongly suggest that GAP is not only a p21ras inhibitor (signal terminator), but also a positive signal transducer. PMID:8245773

  15. Primary cutaneous extravertebral meningioma. Case report.

    PubMed

    Zaaroor, M; Borovich, B; Bassan, L; Doron, Y; Gruszkiewicz, J

    1984-05-01

    A case of cutaneous extravertebral meningioma is presented. It was diagnosed in infancy as a lumbar meningocele. Operation was initially refused but was subsequently demanded for cosmetic reasons. The findings were a very thick corrugated skin and a cutaneous meningioma connected by a fibrous tract to the dura mater. The presence of a fibrous stalk linking the tumor to the dura mater might have been the pathogenetic connection between the meningocele and cutaneous meningioma.

  16. O6.09PROSTAGLANDIN E RECEPTOR-4 ACTIVATION REGULATES TRYPTOPHAN METABOLISM IN HUMAN MALIGNANT GLIOMAS

    PubMed Central

    Ochs, K.; Ott, M.; Rauschenbach, K.J.; Sahm, F.; Opitz, C.A.; von Deimling, A.; Wick, W.; Platten, M.

    2014-01-01

    Malignant gliomas generate a local immunosuppressive microenvironment as well as systemic immunosuppression. Tryptophan-2,3-dioxygenase (TDO)-mediated tryptophan metabolism and the production of immunosuppressive prostaglandins relevantly contribute to this inhibition of anti-glioma immune responses. We now connect these two critical immunosuppressive pathways by demonstrating that prostaglandins enhance TDO expression and enzymatic activity in malignant gliomas via activation of prostaglandin E receptor-4 (EP4). Stimulation with prostaglandin E2 (PGE2) concentration-dependently upregulates TDO-mediated kynurenine release in human glioma cell lines, while knockdown of the PGE2 receptor EP4 inhibits TDO expression and activity. In tissue of human malignant gliomas expression of the PGE2-producing enzyme cyclooxygenase-2 (COX-2) and its receptor EP4 are associated with TDO expression both on transcript and protein level. Of clinical relevance, high expression of EP4 correlates with poor survival in patients with gliomas of the WHO grades III and IV. Importantly, treatment of glioma cells with an EP4 inhibitor decreased TDO expression and activity. In summary targeting EP4 may inhibit both immunosuppressive COX-2 signaling as well as tryptophan degradation and thus could provide a novel immunotherapeutic avenue for the treatment of malignant gliomas.

  17. Spinal meningiomas: surgical management and outcome.

    PubMed

    Gottfried, Oren N; Gluf, Wayne; Quinones-Hinojosa, Alfredo; Kan, Peter; Schmidt, Meic H

    2003-06-15

    Advances in imaging and surgical technique have improved the treatment of spinal meningiomas; these include magnetic resonance imaging, intraoperative ultrasonography, neuromonitoring, the operative microscope, and ultrasonic cavitation aspirators. This study is a retrospective review of all patients treated at a single institution and with a pathologically confirmed diagnosis of spinal meningioma. Additionally the authors analyze data obtained in 556 patients reported in six large series in the literature, evaluating surgical techniques, results, and functional outcomes. Overall, surgical treatment of spinal meningiomas is associated with favorable outcomes. Spinal meningiomas can be completely resected, are associated with postoperative functional improvement, and the rate of recurrence is low.

  18. Clinical and Radiological Characteristics of Angiomatous Meningiomas

    PubMed Central

    Hwang, Juyoung; Kong, Doo-Sik; Seol, Ho Jun; Nam, Do-Hyun; Lee, Jung-Il

    2016-01-01

    Background Angiomatous meningioma is a rare histological subtype of meningioma. Therefore, this specific medical condition is rarely reviewed in the literature. In the present work, we report the clinical and radiological features with postoperative outcomes of angiomatous meningioma. Methods This retrospective study included the patients who were pathologically diagnosed with angiomatous meningioma after surgical resection between February 2010 and September 2015 in our institute. We analyzed the clinical data, radiological manifestation, treatment and prognosis of all patients. Results The 15 patients (5 males and 10 females) were diagnosed with angiomatous meningioma during the study period. The median age of patients at the time of surgery was 63 years (range: 40 to 80 years). According to Simpson classification, 7, 5, and 3 patients achieved Simpson grade I, II, and IV resection, respectively. In the follow-up period, recurrence was noted in one patient. Ten out of the 15 patients showed homogeneous enhancement. Two patients demonstrated cystic changes. There was no occurrence of calcification or hemorrhage in our patients. Characteristically, 14 out of 15 patients showed signal voids of vessels. Significant peritumoral edema was observed in the majority of tumors (67%). Conclusion Angiomatous meningiomas are rare benign meningioma. Brain images of angiomatous meningioma usually demonstrate signal void signs and peritumoral edema. In the present study, angiomatous meningiomas showed good prognosis after surgical resection. PMID:27867918

  19. Human rgr: transforming activity and alteration in T-cell malignancies.

    PubMed

    Leonardi, Peter; Kassin, Ezra; Hernandez-Muñoz, Inmaculada; Diaz, Roberto; Inghirami, Giorgio; Pellicer, Angel

    2002-08-01

    We have previously identified the oncogene rgr (ralGDS related) in DNA derived from a rabbit squamous cell carcinoma. Here we describe the identification of the human orthologue of the rabbit rgr gene termed hrgr (human ralGDS related). Four alternatively spliced full-length hrgr transcripts were isolated from normal human testes and liver libraries. Truncation of hrgr confers transforming ability to its cDNA. Using a RT-PCR assay we have been able to detect the expression of an abnormally truncated transcript in several human T-cell lymphoma lines, and in fresh tissue samples of patients with T-cell malignancies. In the DHL cell line, an Anaplastic Large Cell Lymphoma (ALCL) line, a DNA rearrangement was detected within the hrgr gene region. We propose that these T-cell lymphomas, at least in part, owe their malignant phenotypes to genetic alterations of the hrgr gene. These findings also raise the possibility that mutations in the hrgr gene are involved in other malignancies.

  20. Nanomelatonin triggers superior anticancer functionality in a human malignant glioblastoma cell line

    NASA Astrophysics Data System (ADS)

    Yadav, Sanjeev Kumar; Srivastava, Anup Kumar; Dev, Atul; Kaundal, Babita; Choudhury, Subhasree Roy; Karmakar, Surajit

    2017-09-01

    Melatonin (MEL) has promising medicinal value as an anticancer agent in a variety of malignancies, but there are difficulties in achieving a therapeutic dose due to its short half-life, low bioavailability, poor solubility and extensive first-pass metabolism. In this study chitosan/tripolyphosphate (TPP) nanoparticles were prepared by an ionic gelation method to overcome the therapeutic challenges of melatonin and to improve its anticancer efficacy. Characterization of the melatonin-loaded chitosan (MEL-CS) nanoformulation was performed using transmission and scanning electron microscopies, dynamic light scattering, Fourier transform infrared spectroscopy, Raman spectroscopy and x-ray diffraction. In vitro release, cellular uptake and efficacy studies were tested for their enhanced anticancer potential in human U87MG glioblastoma cells. Confocal studies revealed higher cellular uptake of MEL-CS nanoparticles and enhanced anticancer efficacy in human malignant glioblastoma cancer cells than in healthy non-malignant human HEK293T cells in mono- and co-culture models. Our study has shown for the first time that MEL-CS nanocomposites are therapeutically more effective as compared to free MEL at inducing functional anticancer efficacy in the human brain tumour U87MG cell line.

  1. From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

    NASA Astrophysics Data System (ADS)

    Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

    2004-04-01

    The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

  2. Modeling normal and malignant human hematopoiesis in vivo through newborn NSG xenotransplantation.

    PubMed

    Ishikawa, Fumihiko

    2013-12-01

    Various strains of immune-compromised mice have been developed to investigate human normal and malignant stem cells in vivo. NOD/SCID mice harboring complete null mutation of Il2rg (NSG mice) lack T cells, B cells, and NK cells, and support high levels of engraftment by human cord blood hematopoietic stem cells (CB HSCs) and acute myeloid leukemia stem cells (AML LSCs). In addition to achieving high levels of human hematopoietic cell engraftment, use of newborn NSG mice as recipients has enabled the investigation into how human CB HSCs generate mature immune subsets in vivo. Moreover, through establishing an in vivo model of human primary AML by xenotransplantation of human LSCs into newborn NSG mice, functional properties of human AML such as cell cycle, location, and self-renewal capacity can be examined in vivo. Newborn NSG xenogeneic transplantation model may facilitate the understanding of human normal and malignant hematopoiesis and contribute to the development of novel therapies against hematologic diseases.

  3. Spinal meningiomas in dogs: Description of 8 cases including a novel radiological and histopathological presentation

    PubMed Central

    José-López, Roberto; de la Fuente, Cristian; Pumarola, Martí; Añor, Sonia

    2013-01-01

    Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis. PMID:24155414

  4. Aldosterone and progesterone-secreting adrenocortical adenocarcinoma in a cat with a concurrent meningioma

    PubMed Central

    Leshinsky, Jana; Beatty, Julia A; Fawcett, Anne; Voss, Katja; Makara, Mariano; Krockenberger, Mark B; Barrs, Vanessa R

    2016-01-01

    Case summary A 12-year-old, male neutered domestic shorthair cat was referred for investigation of suspected hyperaldosteronism due to persistent hypokalaemia, hindlimb ataxia, weakness of 1 month’s duration and a left adrenal mass that was detected on abdominal ultrasound. Neurological examination findings at referral were suggestive of a concurrent left forebrain lesion. Hyperaldosteronism and concurrent hyperprogesteronism were confirmed on endocrine testing. On computed tomography (CT) of the abdomen and thorax there was no evidence of local vascular invasion by the adrenal mass or of metastatic disease. CT and magnetic resonance imaging featured a large, focal rim-enhancing extra-axial left forebrain lesion consistent with a meningioma. Surgical excision of the forebrain mass was followed by adrenalectomy 2 weeks later. The tumours were classified on histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma, respectively. Immunohistochemical staining of the meningioma confirmed the presence of progesterone receptors. The cat remains well 2 years later. Relevance and novel information In humans, elevated serum progesterone levels have been associated with rapid growth of meningiomas due to the presence of progesterone receptors on the tumour. This is the first report of a cat with a progesterone and aldosterone-secreting adrenocortical adenocarcinoma and a concurrent meningioma. Clinicians should be aware of the potential effect of elevated progesterone on meningiomas in cats. PMID:28491405

  5. Mutational Analysis of Recurrent Meningioma Progressing From Atypical to Rhabdoid Subtype.

    PubMed

    Bujko, Mateusz; Machnicki, Marcin M; Grecka, Emilia; Rusetska, Nataliia; Matyja, Ewa; Kober, Paulina; Mandat, Tomasz; Rydzanicz, Małgorzata; Płoski, Rafał; Krajewski, Romuald; Bonicki, Wieslaw; Stokłosa, Tomasz; Siedlecki, Janusz A

    2017-01-01

    Rhabdoid meningioma is rare aggressive meningioma histological subtype that develops predominantly through progression from less malignant tumors. Owing to its low incidence, this tumor's biological background is unknown. The aim of this study was to profile somatic mutations in 4 meningioma samples from the same patient, derived previously from 4 subsequent tumor resections. A 58-year-old woman presented with recurrent meningioma progressing from atypical to rhabdoid subtype. Four tumor samples that represent a primary tumor (atypical GII) and 3 recurrent tumors that were subsequently removed (anaplastic GIII, rhabdoid GIII, and anaplastic/rhabdoid GIII) from this patient were subjected to mutational analysis of coding sequences of 952 tumor-related genes. Three mutations were identified in all tumor samples exhibiting a high allelic frequency: ARID1A frameshift deletion, NF2 in-frame deletion, and missense variant of SRSF2. The predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining of tumor sections in which a high proportion of cells lacked protein expression. Additional low-allelic-fraction mutations were observed in all tumor samples, likely representing "passenger," low-effect mutations that reflect a clonal selection of tumor cells through malignant progression of the meningioma. The mutation of ARID1A that encodes the subunit of the SWI/SNF complex represents the most likely driver of the tumor's malignant potential. It also may be involved in the acquisition of the rhabdoid phenotype, given that mutations in chromatin remodeling proteins are the hallmark of atypical teratoid/rhabdoid tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype.

    PubMed

    Benbrahim-Tallaa, Lamia; Tokar, Erik J; Diwan, Bhalchandra A; Dill, Anna L; Coppin, Jean-François; Waalkes, Michael P

    2009-12-01

    Breast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation. Cells were continuously exposed to low-level cadmium (2.5 muM) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer. Over 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metalloproteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including ER-alpha negativity and HER2 (human epidermal growth factor receptor 2) negativity, reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell markers, were prominently overexpressed in CTBE cell mounds, indicative of persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc and k-ras overexpression, typical in aggressive breast cancers. CTBE cell xenograft tumors were also ER-alpha negative. Cadmium malignantly transforms normal human breast epithelial cells-through a mechanism not requiring ER-alpha-into a basal-like cancer phenotype. Direct cadmium induction of a malignant phenotype in human breast epithelial cells strongly fortifies a potential role in breast cancer.

  7. The softening of human bladder cancer cells happens at an early stage of the malignancy process

    PubMed Central

    Ramos, Jorge R; Pabijan, Joanna

    2014-01-01

    Summary Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  8. Fourier component imaging of water resonance in the human breast provides markers for malignancy

    NASA Astrophysics Data System (ADS)

    Medved, Milica; Newstead, Gillian M.; Fan, Xiaobing; Du, Yiping P.; Olopade, Olufunmilayo I.; Shimauchi, Akiko; Zamora, Marta A.; Karczmar, Gregory S.

    2009-10-01

    The purpose of this paper is to demonstrate that voxels with inhomogeneously broadened water resonances, as revealed by high spectral and spatial resolution (HiSS) MRI, correlate with underlying tumor pathology findings, and thus carry diagnostically useful information. Thirty-four women with mammographically suspicious breast lesions were imaged at 1.5 T, using high-resolution echo-planar spectroscopic imaging. Fourier component images (FCIs) of the off-peak spectral signal were generated, and clusters of voxels with significant inhomogeneous broadening (broadened clusters) were identified and correlated to biopsy results. Inhomogeneously broadened clusters were found significantly more frequently in malignant than in benign lesions. A larger percentage of broadened cluster voxels were found inside the malignant versus benign lesions. The high statistical significance for separation of benign and malignant lesions was robust over a large range of post-processing parameters, with a maximum ROC area under curve of 0.83. In the human breast, an inhomogeneously broadened water resonance can serve as a correlate marker for malignancy and is likely to reflect the underlying anatomy or physiology.

  9. Regulatory landscape and clinical implication of MBD3 in human malignant glioma

    PubMed Central

    Weng, Ling; Wirbisky, Sara E.; Freeman, Jennifer L.; Liu, Jingping; Liu, Qing; Yuan, Xianrui; Irudayaraj, Joseph

    2016-01-01

    In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma. PMID:27835581

  10. The softening of human bladder cancer cells happens at an early stage of the malignancy process.

    PubMed

    Ramos, Jorge R; Pabijan, Joanna; Garcia, Ricardo; Lekka, Malgorzata

    2014-01-01

    Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young's modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force.

  11. TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma.

    PubMed

    Chen, Jingkao; Dou, Yunling; Zheng, Xiaoke; Leng, Tiandong; Lu, Xiaofang; Ouyang, Ying; Sun, Huawei; Xing, Fan; Mai, Jialuo; Gu, Jiayu; Lu, Bingzheng; Yan, Guangmei; Lin, Jun; Zhu, Wenbo

    2016-11-01

    The melastatin-like transient receptor potential 7 (TRPM7) has been implicated in proliferation or apoptosis of some cancers, indicating the potential of TRPM7 as an anti-anaplastic target. Here, we identified the characteristic TRPM7 channel currents in human malignant glioma MGR2 cells, which could be blocked by a pharmacologic inhibitor Gd(3+). We mined the clinical sample data from Oncomine Database and found that human malignant glioma tissues expressed higher TRPM7 mRNA than normal brain ones. Importantly, we identified a widely used clinical anesthetic midazolam as a TRPM7 inhibitor. Midazolam treatment for seconds suppressed the TRPM7 currents and calcium influx, and treatment for 48 h inhibited the TRPM7 expression. The inhibitory effect on TRPM7 accounts for the proliferation loss and G0/G1 phase cell cycle arrest induced by midazolam. Our data demonstrates that midazolam represses proliferation of human malignant glioma cells through inhibiting TRPM7 currents, which may be further potentiated by suppressing the expression of TRPM7. Our result indicates midazolam as a pharmacologic lead compound with brain-blood barrier permeability for targeting TRPM7 in the glioma.

  12. Enhancement of drug sensitivity of human malignancies by epidermal growth factor.

    PubMed Central

    Kröning, R.; Jones, J. A.; Hom, D. K.; Chuang, C. C.; Sanga, R.; Los, G.; Howell, S. B.; Christen, R. D.

    1995-01-01

    We have previously shown that epidermal growth factor (EGF) enhances the in vitro and in vivo sensitivity of human ovarian carcinoma 2008 cells to cisplatin. EGF was found to enhance selectively the in vivo toxicity of cisplatin to 2008 cell xenografts without altering the toxicity of cisplatin to non-malignant target tissues such as the kidney or bone marrow. We now show that recombinant human EGF (rhEGF) enhances the cisplatin sensitivity of cell lines representative of many other types of malignancies in addition to ovarian carcinoma, including cancers of the head and neck, cervix, colon, pancreas and prostate, as well as non-small-cell carcinoma of the lung. In addition, rhEGF was found to sensitise cells to other platinum-containing drugs and several other classes of chemotherapeutic agents. rhEGF sensitised 2008 cells not only to cisplatin, but also to carboplatin and tetraplatin, as well as taxol, melphalan and 5-fluorouracil. We conclude that modulation of drug sensitivity by rhEGF is observed in cell lines representative of many human malignancies and for multiple classes of chemotherapeutic agents, indicating that it alters one or more components of the cellular damage response that are both common between cell lines and classes of drugs and fundamental to survival. Images Figure 2 PMID:7669570

  13. A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

    PubMed Central

    2014-01-01

    Background While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. Methods Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. Results Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. Conclusion Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated

  14. Thioredoxin-Interact ing-Pro t e in [TXNIP] and Transglutaminase 2 [TGM2] Expression in Meningiomas of Different Grades and the Role of Their Expression in Meningioma Recurrence and Prognosis

    PubMed

    Harb, Ola A; Elsayed, Walid SH; Ismail, Eman I; Toam, Mostafa M; Ammar, Mohamed G

    2017-08-27

    Background: Meningiomas are common central nervous system (CNS) tumors that account for thirty percent of primary intracranial tumors.. The accuracy of predicting meningioma recurrence and progression is not enough. So, there is a real need for discovering recent factors for identification of the relapse risk, progression rates, which patients will need aggressive treatment and predicting and improving patients’ survival. Thioredoxin-interacting-protein [TXNIP] is an alpha-arrestin-protein family member that is mapped on chromosome 1-q21–22 and is found to participate in cellular redox reactions regulations and control. Transglutaminase 2 (TGM2) is a transglutaminase enzyme family member that is found in many human cells, it may act as an enzyme, a structural protein and also has multiple roles in many cellular activities. Aim of our study: It was to explore the expression of TXNIP, TGM2 and Ki-67 using immunohistochemistry in different pathological grades of meningiomas, and to investigate the relevance between their expressions, clinicopathological criteria, disease recurrence and prognosis of meningioma patients. Methods: we included 50 cases of meningioma of different pathological grades; all patients were managed according to their grade by surgery alone, with radiotherapy or combined modalities. Sections from paraffin blocks prepared from samples of all patients stained by TXNIP, TGM2 and Ki-67 using immunohistochemistry. Results: high expression of TXNIP in 28 out of 50 (56%) cases of meningioma of different pathological grades and was positively correlated with meningioma lower grade, low KI labeling index (p=0.000), adequacy of resection, negatively correlated with high incidence of recurrence after surgery and it was negatively correlated with meningioma higher pathological grades (p=0.000). We detected high expression of TGM2 in 21 out of 50 (42%) cases of meningioma and it was positively correlated with meningioma higher grade (p= 0.002), high KI

  15. The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review.

    PubMed

    Motekallemi, Arash; Jeltema, Hanne-Rinck; Metzemaekers, Jan D M; van Dam, Gooitzen M; Crane, Lucy M A; Groen, Rob J M

    2015-10-01

    Meningiomas are the second most common primary tumors affecting the central nervous system. Surgical treatment can be curative in case of complete resection. 5-aminolevulinic acid (5-ALA) has been established as an intraoperative tool in malignant glioma surgery. A number of studies have tried to outline the merits of 5-ALA for the resection of intracranial meningiomas. In the present paper, we review the existing literature about the application of 5-ALA as an intraoperative tool for the resection of intracranial meningiomas. PubMed was used as the database for search tasks. We included articles published in English without limitations regarding publication date. Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study.

  16. Prediction of High-Grade Pediatric Meningiomas: Magnetic Resonance Imaging Features Based on T1-Weighted, T2-Weighted, and Contrast-Enhanced T1-Weighted Images.

    PubMed

    Li, Hao; Zhao, Meng; Jiao, Yuming; Ge, Peicong; Li, Zhicen; Ma, Ji; Wang, Shuo; Cao, Yong; Zhao, Jizong

    2016-07-01

    Prediction of high-grade meningiomas before surgery is essential to determine optimal treatment strategies; however, the relationship between radiologic features and malignancy of meningiomas in pediatric patients has not been clearly demonstrated. The aim of this study was to identify preoperative magnetic resonance imaging features that are significantly correlated with high risk of high-grade pediatric meningiomas. We retrospectively reviewed preoperative magnetic resonance imaging features and histopathologic diagnosis according to the 2007 World Health Organization classification system for intracranial tumors of 79 pediatric meningiomas from 2005 to 2015. World Health Organization grade II and III meningiomas were defined as high-grade meningiomas. The relationship between the radiologic findings and incidence of high-grade meningiomas was assessed initially with univariate analysis and then corrected by multivariate analysis. According to univariate analysis, heterogeneous tumor enhancement, an unclear tumor-brain interface, tumor cyst, type of dural attachment, lateral location, positive capsular enhancement, and irregular shape of tumor were strong predictive factors for high-grade meningiomas. When corrected by multivariate analysis, an unclear tumor-brain interface (P < 0.001; odds ratio = 10.4; 95% confidence interval, 3.0-37.0), lateral location (P = 0.014; odds ratio = 4.9; 95% confidence interval, 1.4-17.6), and narrow base (P = 0.001; odds ratio = 8.3; 95% confidence interval, 2.5-27.1) were strong independent predictive factors for high-grade meningiomas. In pediatric patients, meningiomas with an unclear tumor-brain interface, lateral location, and narrow base on preoperative magnetic resonance imaging are more likely to be high-grade meningiomas. Our results may be helpful in decision making regarding therapeutic strategies for pediatric patients with meningiomas. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Overabundance of Putative Cancer Stem Cells in Human Skin Keratinocyte Cells Malignantly Transformed by Arsenic

    PubMed Central

    Sun, Yang; Tokar, Erik J.; Waalkes, Michael P.

    2012-01-01

    Arsenic is a human skin carcinogen. Cancer is probably a disease driven by stem cells (SCs), and SCs are likely a key target during arsenic oncogenesis. In utero arsenic exposure predisposes mice to skin cancers that overproduce cancer SCs (CSCs) and have distorted CSC signaling and population dynamics. Therefore, we hypothesized CSC accumulation may occur during arsenic-induced malignant transformation in vitro of human skin keratinocytes. Thus, the HaCaT cell line, malignantly transformed by arsenite (100nM, 30 weeks; termed As-TM cells) in prior work, was further studied for the quantity and nature of SCs after this transformation. SCs were isolated from passage-matched control and As-TM cells by a magnetic bead system that enriches for CD34-positive cells. There were 2.5 times more SCs isolated from As-TM cells than control. Holoclone production from As-TM putative CSCs was 2.5-fold higher by 1 week and 3.5-fold higher by 2 weeks than control SCs. Potential malignant phenotype was assessed in isolated SC/CSCs. Transcript level of SC/CSC markers were elevated in both isolated As-TM CSCs and control SCs compared with parental cells, but compared with control SCs, As-TM putative CSCs had elevated CD34, K5, K14, K15, and K19 transcripts and dramatically stronger staining for p63, Rac1, K5, Notch1, and K19. As-TM putative CSCs also showed markedly elevated MMP-9 secretion and colony formation, indicators of cancer phenotype, even compared with total population of As-TM cells. Thus, malignant phenotype is particularly pronounced in CSCs after arsenic-induced transformation of human skin cells and occurs concurrently with a potential overproduction of these cells. PMID:22011395

  18. Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas.

    PubMed

    Graillon, Thomas; Defilles, Céline; Mohamed, Amira; Lisbonis, Christophe; Germanetti, Anne-Laure; Chinot, Olivier; Figarella-Branger, Dominique; Roche, Pierre-Hugues; Adetchessi, Tarek; Fuentes, Stéphane; Metellus, Philippe; Dufour, Henry; Enjalbert, Alain; Barlier, Anne

    2015-08-01

    Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial.

  19. Coexistent intracerebral metastatic melanoma and meningioma.

    PubMed

    Shinde, Sweety V; Shenoy, Asha S; Savant, Hemant V; Balasubramaniam, Srikant B

    2017-01-01

    Coexistence of multifocal neural crest tumors, namely meningioma, melanoma, and nerve sheath tumors, is termed as neurocristopathy. Neurofibromatosis is the commonest form of neurocristopathy. We report a rare case of frontal lobe metastatic melanoma coexistent with a parietal lobe meningioma, in the absence of any stigmata of neurofibromatosis.

  20. Osteoblastic meningioma of the fourth ventricle.

    PubMed

    Johnson, M D; Tulipan, N; Whetsell, W O

    1989-04-01

    Meningiomas of the fourth ventricle are rare neoplasms. Only meningothelial and fibroblastic subtypes, purportedly arising from the tela choroidea, have been described. In this report we describe clinical, neuroradiological and pathological findings in a 52-year-old man with mild hydrocephalus produced by a large, calcified, osteoblastic meningioma of the fourth ventricle.

  1. Acute recurrent haemorrhage of an intracranial meningioma.

    PubMed

    Bellut, David; Nern, Christian; Burkhardt, Jan-Karl; Könü, Dilek; Bertalanffy, Helmut; Krayenbühl, Niklaus

    2011-07-01

    Meningioma-associated haemorrhages are rare. To our knowledge this is the first report of a patient with an acute two-stage haemorrhage of a benign intracranial meningioma (World Health Organization grade I) verified by cranial CT scan and histopathological examination. Early surgery with complete tumour removal led to a good outcome for the patient. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Diffusion-Weighted Imaging in Meningioma: Prediction of Tumor Grade and Association with Histopathological Parameters.

    PubMed

    Surov, Alexey; Gottschling, Sebastian; Mawrin, Christian; Prell, Julian; Spielmann, Rolf Peter; Wienke, Andreas; Fiedler, Eckhard

    2015-12-01

    To analyze diffusion-weighted imaging (DWI) findings of meningiomas and to compare them with tumor grade, cell count, and proliferation index and to test a possibility of use of apparent diffusion coefficient (ADC) to differentiate benign from atypical/malignant tumors. Forty-nine meningiomas were analyzed. DWI was done using a multislice single-shot echo-planar imaging sequence. A polygonal region of interest was drawn on ADC maps around the margin of the lesion. In all lesions, minimal ADC values (ADCmin) and mean ADC values (ADCmean) were estimated. Normalized ADC (NADC) was calculated in every case as a ratio ADCmean meningioma/ADCmean white matter. All meningiomas were surgically resected and analyzed histopathologically. The tumor proliferation index was estimated on Ki-67 antigen-stained specimens. Cell density was calculated. Collected data were evaluated by means of descriptive statistics. Analyses of ADC/NADC values were performed by means of two-sided t tests. The mean ADCmean value was higher in grade I meningiomas in comparison to grade II/III tumors (0.96 vs 0.80 × 10(-3) mm(2)s(-1), P = .006). Grade II/III meningiomas showed lower NADC values in comparison to grade I tumors (1.05 vs 1.26, P = .015). There was no significant difference in ADCmin values between grade I and II/III tumors (0.69 vs 0.63 × 10(-3) mm(2)s(-1), P = .539). The estimated cell count varied from 486 to 2091 (mean value, 1158.20 ± 333.74; median value, 1108). There were no significant differences in cell count between grade I and grade II/III tumors (1163.93 vs 1123.86 cells, P = .77). The mean level of the proliferation index was 4.78 ± 5.08%, the range was 1% to 18%, and the median value was 2%. The proliferation index was statistically significant higher in grade II/III meningiomas in comparison to grade I tumors (15.43% vs 3.00%, P = .001). Ki-67 was negatively associated with ADCmean (r = -0.61, P < .001) and NADC (r = -0.60, P < .001). No significant correlations between

  3. Ectopic orbital meningioma: Fact or fiction?

    PubMed

    Tan, Lee Teak; Stewart, Christopher M; Sheerin, Fintan; MacDonald, Brendan; Silva, Priy; Norris, Jonathan H

    2017-06-01

    Primary intraorbital ectopic meningiomas are rare and their existence remains controversial. We present a 30-year-old female with painless, non-axial proptosis and a palpable superomedial mass. The MRI demonstrated that the mass had no optic nerve sheath or sphenoid wing involvement and was initially reported to have no intracranial extension. The patient was initially thought to have an ectopic orbital meningioma. Subsequent multidisciplinary team (MDT) consultation and further specialist review of the MRI revealed a subtle dural tail connecting to an enhancing mass in the olfactory groove. Biopsy revealed a WHO Grade 1 transitional meningioma with an infiltrative pattern. We argue that some previously reported cases of ectopic meningioma may lack the requisite imaging to discover the primary disease. Our report highlights the importance of MRI in this group of patients and the role of a skull-base MDT with specialist neuroradiology input to determine the true origin and extent of these extradural orbital meningiomas.

  4. Paraventricular meningioma revealed by mental disorder

    PubMed Central

    Hilmani, Said; Houass, Yassine; El Azhari, Abdessamad

    2016-01-01

    Background: Ventricular meningioma constitutes 2% of intracranial meningioma, representing a challenging disease for neurosurgeons. Although cognitive impairment is one of the major symptoms of ventricular tumors, few studies have reported the details of cognitive impairment before and after their surgical removal. The expected effects on cognitive function should also be considered when choosing a surgical approach. Case Descriptions: We report the case of a large lateral ventricle meningioma revealed by cognitive dysfunction and moderate intellectual disability. The patient underwent subtotal resection of the tumor which had partial improvement in cognitive disorders. It is important to precisely assess neuropsychological function in patients with large brain tumors, and judicious preoperative plan, adequate knowledge of anatomy, and use of correct microsurgical techniques are fundamental in achieving complete resection of paraventricular meningioma with low morbidity. Conclusion: Pre and postoperative precise neuropsychological examinations may identify the potential cognitive impairment and beneficial effects of surgery in patients with large lateral ventricle meningiomas. PMID:28144473

  5. Toxicogenomics of A375 human malignant melanoma cells treated with arbutin.

    PubMed

    Cheng, Sun-Long; Liu, Rosa Huang; Sheu, Jin-Nan; Chen, Shui-Tein; Sinchaikul, Supachok; Tsay, Gregory Jiazer

    2007-01-01

    Although arbutin is a natural product and widely used as an ingredient in skin care products, its effect on the gene expression level of human skin with malignant melanoma cells is rarely reported. We aim to investigate the genotoxic effect of arbutin on the differential gene expression profiling in A375 human malignant melanoma cells through its effect on tumorigenesis and related side-effect. The DNA microarray analysis provided the differential gene expression pattern of arbutin-treated A375 cells with the significant changes of 324 differentially expressed genes, containing 88 up-regulated genes and 236 down-regulated genes. The gene ontology of differentially expressed genes was classified as belonging to cellular component, molecular function and biological process. In addition, four down-regulated genes of AKT1, CLECSF7, FGFR3, and LRP6 served as candidate genes and correlated to suppress the biological processes in the cell cycle of cancer progression and in the downstream signaling pathways of malignancy of melanocytic tumorigenesis.

  6. Dielectric spectroscopy of normal and malignant human lung cells at ultra-high frequencies.

    PubMed

    Egot-Lemaire, S; Pijanka, J; Sulé-Suso, J; Semenov, S

    2009-04-21

    Microwave techniques for biomedical applications aimed at cancer treatment or diagnosis, either by imaging or spectroscopy, are promising. Their use relies on knowledge of the dielectric properties of tissues, especially on a detectable difference between malignant and normal tissues. As most studies investigated the dielectric properties of ex vivo tissues, there is a need for better biophysical understanding of human tissues in their living state. As an essential component of tissues, cells represent valuable objects of analysis. The approach developed in this study is an investigation at cell level. Its aim was to compare human lung normal and malignant cells by dielectric spectroscopy in the beginning of the microwave range, where such information is of substantial biomedical importance. These cells were embedded in small and low-conductivity agarose hydrogels and laid on an open-ended coaxial probe connected to a vector network analyser operated from 200 MHz to 2 GHz. The comparison between normal and malignant cells was drawn using the variation of measured dielectric properties and fitting the measurements using the Maxwell-Wagner equation. Both methods revealed slight differences between the two cell lines, which were statistically significant regarding conductivities of composite gels and cells.

  7. Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

    2008-02-01

    Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

  8. 5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk.

    PubMed

    Zhang, Jun; Zhou, Yan-Wen; Shi, Hua-Ping; Wang, Yan-Zhong; Li, Gui-Ling; Yu, Hai-Tao; Xie, Xin-You

    2013-11-01

    The causes of meningiomas are not well understood. Folate metabolism gene polymorphisms have been shown to be associated with various human cancers. It is still controversial and ambiguous between the functional polymorphisms of folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) and risk of adult meningioma. A population-based case–control study involving 600 meningioma patients (World Health Organization [WHO] Grade I, 391 cases; WHO Grade II, 167 cases; WHO Grade III, 42 cases) and 600 controls was done for the MTHFR C677T and A1298C, MTRR A66G, and MTR A2756G variants in Chinese Han population. The folate metabolism gene polymorphisms were determined by using a polymerase chain reaction–restriction fragment length polymorphism assay. Meningioma cases had a significantly lower frequency of MTHFR 677 TT genotype [odds ratio (OR) = 0.49, 95 % confidence interval (CI) 0.33–0.74; P = 0.001] and T allele (OR = 0.80, 95 % CI 0.67–0.95; P = 0.01) than controls. A significant association between risk of meningioma and MTRR 66 GG (OR = 1.41, 95 % CI 1.02–1.96; P = 0.04) was also observed. When stratifying by the WHO grade of meningioma, no association was found. Our study suggested that MTHFR C677T and MTRR A66G variants may affect the risk of adult meningioma in Chinese Han population.

  9. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    PubMed Central

    Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

    2011-01-01

    Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = −0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold). Conclusion Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

  10. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    PubMed

    Ryan, James; Curran, Catherine E; Hennessy, Emer; Newell, John; Morris, John C; Kerin, Michael J; Dwyer, Roisin M

    2011-01-19

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log(10) Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log(10)RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log(10)RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r =  0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold). Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  11. High prevelance of human parvovirus infection in patients with malignant tumors

    PubMed Central

    LI, YASHA; DONG, YANMING; JIANG, JUN; YANG, YONGBO; LIU, KAIYU; LI, YI

    2012-01-01

    It is well known that the immunity of patients with malignant tumors decreases significantly. An increased parvovirus B19 (B19) infection rate has been observed in immunocompromised hosts. However, only a small amount of literature regarding the risk of human parvovirus infection in patients with malignant tumors is available. To evaluate the correlation of human parvovirus infection with malignant tumors, 288 serum samples from patients with malignant tumors were screened for B19 DNA by nested-PCR. The serum samples, 156 of which were from known clinicopathological cancer patients, were subjected to analysis of the seropositive rate of human bocavirus (HBoV), hepatitis B virus (HBV) and transfusion transmitted virus (TTV) by PCR. A total of 800 normal population sera and 941 aspirate samples from children with respiratory tract infections were used as controls for the detection of B19 and HBoV, respectively. Pairwise comparison between cancerous serum and control samples, and the correlation between parvovirus infection and clinicopathological variables, including gender and cancer type, were evaluated using the χ2 test, Fisher’s exact test or the t-test. P<0.05 was considered to indicate a statistically significant difference. The overall prevalence of B19 DNA in cancer patients was 50.69% (146/288), which was significantly higher than that of the healthy controls with 4.5% (36/800) (χ2 test, P<0.0001). Similar results were obtained for HBoV with a 39.74% (62/156) prevalence in cancer patients. However, the infection prevalence of HBV and TTV in the cancer patients was 5.13 (8/156) and 6.41% (10/156), respectively (P<0.0001), which was much less than that of B19 and HBoV. These results revealed that a high risk of B19 and HBoV infection occurred in cancer patients, and a potential correlation exists between parvovirus infection and occurrence of malignant tumors. PMID:22740966

  12. Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas

    SciTech Connect

    Yamaguchi, F.; Saya, H.; Bruner, J.M.; Morrison, R.S. )

    1994-01-18

    Malignant astrocytomas, which are highly invasive, vascular neoplasms, compose the majority of nervous system tumors in humans. Elevated expression of fibroblast growth factors (FGFs) in astrocytomas has implicated the FGF family of mitogens in the initiation and progression of astrocyte-derived tumors. In this study, the authors demonstrated that human astrocytomas undergo parallel changes in FGF-receptor (FGFR) expression during their progression from a benign to a malignant phenotype. FGFR type 2 (BEK) expression was abundant in normal white matter and in all low-grade astrocytomas but was not seen in malignant astrocytomas. Conversely, FGFR type 1 (FLG) expression was absent or barely detectable in normal white matter but was significantly elevated in malignant astrocytomas. Malignant astrocytomas also expressed an alternatively spliced form of FGFR-1 (FGFR-1[beta]) containing two immunoglobulin-like disulfide loops, whereas normal human adult and fetal brains expressed a receptor form (FGFR-1[alpha]) containing three immunoglobulin-like disulfide loops. Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-1[beta] as they progressed from benign to malignant phenotype. These results suggest that differential expression and alternative splicing of FGFRs may be critical in the malignant progression of astrocytic tumors.

  13. Association of human papilloma virus with atypical and malignant oral papillary lesions.

    PubMed

    McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; Muhanna, Nidal; Irish, Jonathan; Leong, Iona; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace

    2014-06-01

    This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Expression of cyclin D1 correlates with malignancy in human ovarian tumours.

    PubMed Central

    Barbieri, F.; Cagnoli, M.; Ragni, N.; Pedullà, F.; Foglia, G.; Alama, A.

    1997-01-01

    Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to play a relevant role in the pathogenesis of several human cancer types. In the current study, the expression of cyclin D1 has been investigated in a series of 33 patients, with benign (10 patients), borderline (five patients) and malignant (18 patients) ovarian disease. Cyclin D1 protein and mRNA content were analysed by Western blotting and reverse transcriptase polymerase chain reaction respectively. The levels of cyclin D1 protein were undetectable in patients with benign disease, detectable in the majority of patients with borderline disease and elevated in those with ovarian carcinomas, being significantly related to the degree of malignancy (carcinoma vs benign, P = 0.0001; benign vs borderline, P = 0.0238). A significant relationship between cyclin D1 expression and tumour proliferative activity was also found (P = 0.000001). Moreover, eight benign lesions, two borderline tumours and 11 carcinomas proved to be suitable for the analysis of cyclin D1 transcript, and emerging data demonstrated significant agreement between protein abundance and mRNA expression. Results from the current study suggest that cyclin D1 expression is associated with the degree of transformation and most probably plays a role in the early development of ovarian malignancy. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9155044

  15. Malignancies and infection due to the human immunodeficiency virus. Are these emerging diseases?

    PubMed

    Valencia Ortega, M E

    2017-09-02

    Since the start of the human immunodeficiency virus (HIV) epidemic, tumour disease among patients has been significant. The collection of malignancies can be divided primarily into 2 groups: those associated with HIV (all of which are related to viral diseases) and those not associated with HIV (only some of which are associated with viral diseases). The origin of these malignancies is multifactorial, and the main causes that have led to an increase in tumour disease are immunosuppression, coinfection with oncogenic viruses and life prolongation secondary to the use of antiretroviral therapy. Establishing the general characteristics of the undiagnosed AIDS tumours is difficult, mainly because they are a highly heterogeneous group formed by malignancies of a diverse nature. The treatments do not differ from those used in the general population, although the management can be more difficult due to the late diagnosis, drug interactions and associated comorbidities. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  16. Dynamic holographic endoscopy--ex vivo investigations of malignant tumors in the human stomach.

    PubMed

    Avenhaus, Wolfgang; Kemper, Björn; Knoche, Sabine; Domagk, Dirk; Poremba, Christopher; von Bally, Gert; Domschke, Wolfram

    2005-01-01

    Laser holographic interferometry is based on the superimposition of the holograms of different motional states of an object on a single holographic storing medium. Using a combination of holographic interferometry and endoscopic imaging, we tried to detect areas of focally disturbed tissue elasticity in gastric cancer preparations. By connecting a mobile electronic speckle pattern interferometry (ESPI) camera system (light source: double frequency Nd:YAG laser, lambda = 532 nm) to different types of endoscopes, ex vivo experiments were performed on ten formalin fixed human stomachs, nine containing adenocarcinomas and one with a gastric lymphoma. Linking the endoscopic ESPI camera complex to a fast image processing system, the method of double pulse exposure image subtraction was applied at a video frame rate of 12.5 Hz. Speckle correlation patterns and corresponding phase difference distributions resulting from gastric wall deformation by gentle touch with a guide wire were analyzed. Tumor-free gastric areas showed high-contrast concentric fringes around the point of stimulation. In contrast, fringe patterns and filtered phase difference distributions corresponding to the areas of malignancy in all the cases were characterized by largely parallel lines, indicating that stimulation of rigid tumor tissue primarily led to tilting. Our ex vivo investigations of malignant gastric tumors show that the application of dynamic holographic endoscopy makes it possible to distinguish areas of malignancy from surrounding healthy tissue based on the differences in tissue elasticity.

  17. SPECT and PET Imaging of Meningiomas

    PubMed Central

    Valotassiou, Varvara; Leondi, Anastasia; Angelidis, George; Psimadas, Dimitrios; Georgoulias, Panagiotis

    2012-01-01

    Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO) criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical) and grade III (anaplastic) meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue. PMID:22623896

  18. SPECT and PET imaging of meningiomas.

    PubMed

    Valotassiou, Varvara; Leondi, Anastasia; Angelidis, George; Psimadas, Dimitrios; Georgoulias, Panagiotis

    2012-01-01

    Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO) criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical) and grade III (anaplastic) meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue.

  19. Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: evidence for multiple estrogen binding sites

    SciTech Connect

    Lesch, K.P.; Schott, W.; Gross, S.

    1987-09-01

    The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using /sup 125/I-labeled estradiol (/sup 125/I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the Kd for /sup 125/I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.

  20. Primary leptomeningeal melanoma of the cervical spine mimicking a meningioma-a case report.

    PubMed

    Marx, Sascha; Fleck, Steffen K; Manwaring, Jotham; Vogelgesang, Silke; Langner, Soenke; Schroeder, Henry W S

    2014-08-01

    Background and Importance Primary leptomeningeal melanoma (PLM) is highly malignant and exceedingly rare. Due to its rarity, diagnostic and treatment paradigms have been slow to evolve. We report the first case of a PLM that mimics a cervical spine meningioma and then discuss the current clinical, radiologic, and pathologic diagnostic methodologies as well as expected outcomes related to this disease. Clinical Presentation A 54-year-old woman presented a dural-based extramedullary solid mass ventral to the C2-C3 spinal cord causing spinal cord compression without cord signal changes, characteristic of meningioma. Intraoperative microscopic inspection revealed numerous black spots littering the surface of the dura; the tumor itself was yellow in appearance and had a soft consistency. Pathologic analysis of the specimen revealed a malignant melanin-containing tumor. No primary site was found, so a diagnosis of primary leptomeningeal melanoma was made, and the patient subsequently received interferon therapy. To date (2 years postoperatively), no local or systemic recurrence of the tumor has been identified. Conclusion As with most rare tumors, case reports constitute the vast majority of references to PLM. Only an increased awareness and an extensive report of each individual case can help diagnose and clarify the nature of PLM. Clinicians need to be aware of such malignant conditions when diagnosing benign tumoral lesions of the spine such as meningiomas.

  1. Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations

    PubMed Central

    Sato, Mitsuo; Larsen, Jill E.; Lee, Woochang; Sun, Han; Shames, David S.; Dalvi, Maithili P.; Ramirez, Ruben D.; Tang, Hao; DiMaio, J. Michael; Gao, Boning; Xie, Yang; Wistuba, Ignacio I.; Gazdar, Adi F.; Shay, Jerry W.; Minna, John D.

    2013-01-01

    We used CDK4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, MYC) and followed the stepwise transformation of HBECs to full malignancy. This model demonstrated that: 1) the combination of five genetic alterations (CDK4, hTERT, sh-p53, KRASV12, and c-MYC) is sufficient for full tumorigenic conversion of HBECs; 2) genetically-identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation; 3) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; 4) high levels of KRASV12 are required for full malignant transformation of HBECs, however prior loss of p53 function is required to prevent oncogene-induced senescence; 5) over-expression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; 6) growth of parental HBECs in serum-containing medium induces differentiation while growth of oncogenically manipulated HBECs in serum increases in vivo tumorigenicity, decreases tumor latency, produces more undifferentiated tumors, and induces epithelial-to-mesenchymal transition (EMT); 7) oncogenic transformation of HBECs leads to increased sensitivity to standard chemotherapy doublets; 8) an mRNA signature derived by comparing tumorigenic vs. non-tumorigenic clones was predictive of outcome in lung cancer patients. Collectively, our findings demonstrate this HBEC model system can be used to study the effect of oncogenic mutations, their expression levels, and serum-derived environmental effects in malignant transformation, while also providing clinically translatable applications such as development of prognostic signatures and drug response phenotypes. PMID:23449933

  2. Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations.

    PubMed

    Sato, Mitsuo; Larsen, Jill E; Lee, Woochang; Sun, Han; Shames, David S; Dalvi, Maithili P; Ramirez, Ruben D; Tang, Hao; DiMaio, John Michael; Gao, Boning; Xie, Yang; Wistuba, Ignacio I; Gazdar, Adi F; Shay, Jerry W; Minna, John D

    2013-06-01

    We used CDK4/hTERT-immortalized normal human bronchial epithelial cells (HBEC) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, and MYC) and followed the stepwise transformation of HBECs to full malignancy. This model showed that: (i) the combination of five genetic alterations (CDK4, hTERT, sh-p53, KRAS(V12), and c-MYC) is sufficient for full tumorigenic conversion of HBECs; (ii) genetically identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation; (iii) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; (iv) high levels of KRAS(V12) are required for full malignant transformation of HBECs, however, prior loss of p53 function is required to prevent oncogene-induced senescence; (v) overexpression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRAS(V12); (vi) growth of parental HBECs in serum-containing medium induces differentiation, whereas growth of oncogenically manipulated HBECs in serum increases in vivo tumorigenicity, decreases tumor latency, produces more undifferentiated tumors, and induces epithelial-to-mesenchymal transition (EMT); (vii) oncogenic transformation of HBECs leads to increased sensitivity to standard chemotherapy doublets; (viii) an mRNA signature derived by comparing tumorigenic versus nontumorigenic clones was predictive of outcome in patients with lung cancer. Collectively, our findings show that this HBEC model system can be used to study the effect of oncogenic mutations, their expression levels, and serum-derived environmental effects in malignant transformation, while also providing clinically translatable applications such as development of prognostic signatures and drug response phenotypes. ©2013 AACR.

  3. Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma.

    PubMed

    Olar, Adriana; Wani, Khalida M; Wilson, Charmaine D; Zadeh, Gelareh; DeMonte, Franco; Jones, David T W; Pfister, Stefan M; Sulman, Erik P; Aldape, Kenneth D

    2017-03-01

    Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p = 0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p < 0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence

  4. Prognostic significance of AMPK in human malignancies: A meta-analysis

    PubMed Central

    Cheng, Ji; Shuai, Xiaoming; Gao, Jinbo; Cai, Ming; Wang, Guobin; Tao, Kaixiong

    2016-01-01

    Background AMPK is a well-investigated kinase mediating cellular metabolism and stress responses. However, its indicative role in survival prognosis remains ill-defined. Therefore we performed this meta-analysis in order to clarify the prognostic impact of AMPK expression in human malignancies. Methods Literatures were retrieved via searching databases of PubMed, Web of Science, Embase and Cochrane Library. Studies comparing the prognostic significance between different AMPK levels among human malignancies were included into the pooled analysis. The statistical procedures were conducted by Review Manager 5.3 and the effect size was displayed by model of odds ratio. Subgroup analyses were additionally implemented to disclose the potential confounding elements. The outcome stability was examined by sensitivity analysis, and both Begg's test and Egger's test were utilized to detect the publication bias across the included studies. Results 21 retrospective cohorts were eventually obtained with a total sample-size of 9987 participants. Patients with higher AMPK expression had better outcomes of 3-year overall survival (P<0.0001), 5-year overall survival (P<0.0001), 10-year overall survival (P<0.0001), 3-year disease free survival (P<0.0001), 5-year disease free survival (P=0.002) and 10-year disease free survival (P=0.0004). Moreover, the majority of subgroup results also verified the favorably prognostic significance of AMPK over-expression. The outcome stability was confirmed by sensitivity analysis. Results of Begg's (P=0.76) and Egger's test (P=0.09) suggested that there was no publication bias within the included trials. Conclusions Higher expression of AMPK significantly indicates better prognosis in human malignancies. PMID:27716618

  5. Isolation and Characterization of Fast-Migrating Human Glioma Cells in the Progression of Malignant Gliomas.

    PubMed

    Adamski, Vivian; Schmitt, Anne Dorothée; Flüh, Charlotte; Synowitz, Michael; Hattermann, Kirsten; Held-Feindt, Janka

    2017-03-13

    Gliomas are the most common primary brain tumors. The most malignant form, the glioblastoma multiforme (GBM; WHO IV), is characterized by an invasive phenotype, which enables the tumor cells to infiltrate into adjacent brain tissue. When investigating GBM migration and invasion properties in vitro, in most cases GBM cell lines were analyzed. Comprehensive investigations focusing on progression-dependent characteristics of migration processes using fresh human glioma samples of different malignancy grades do not exist. Thus, we isolated fast-migrating tumor cells from fresh human glioma samples of different malignancy grades (astrocytomas WHO grade II, grade III, GBM, and GBM recurrences) and characterized them with regard to the transcription of genes involved in the migration and invasion, tumor progression, epithelial-to-mesenchymal transition, and stemness. In addition, we transferred our results to GBM cell lines and glioma stem-like cells and examined the influence of temozolomide on the expression of the above-mentioned genes in relation to migratory potential. Our results indicate that "evolutionary-like" expression alterations occur during glioma progression when comparing slow- and fast-migrating cells of fresh human gliomas. Furthermore, a close relation between migratory and stemness properties seems to be most likely. Variations in gene expression were also identified in GBM cell lines, not only when comparing fast- and slow-migrating cells but also regarding temozolomide-treated and untreated cells. Moreover, these differences coincided with the expression of stem cell markers and their migratory potential. Expression of migration-related genes in fast-migrating glioma cells is not only regulated in a progression-dependent manner, but these cells are also characterized by specific stem cell-like features.

  6. Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3.

    PubMed

    Shibuya, Hidenobu; Hamamura, Kazunori; Hotta, Hiroshi; Matsumoto, Yasuyuki; Nishida, Yoshihiro; Hattori, Hisashi; Furukawa, Keiko; Ueda, Minoru; Furukawa, Koichi

    2012-09-01

    The expression and implications of gangliosides in human osteosarcomas have not been systematically analyzed. In this study, we showed that gangliosides GD3 and GD2 are highly expressed in the majority of human osteosarcoma cell lines derived from oral cavity regions. Introduction of GD3 synthase cDNA into a GD3/GD2-negative (GD3/GD2-) human osteosarcoma subline resulted in the establishment of GD3/GD2+ transfectant cells. They showed increased cell migration and invasion activities in wound healing and Boyden chamber invasion assays, respectively, compared to the control cells. When treated with serum, GD3/GD2+ cells showed stronger tyrosine phosphorylation of p130Cas, focal adhesion kinase, and paxillin than GD3/GD2- cells. In particular, paxillin underwent much stronger phosphorylation, suggesting its role in cell motility. Furthermore, we tried to dissect the roles of GD3 and GD2 in the malignant properties of the transfectant cells by establishing single ganglioside-expressing cells, that is, either GD3 or GD2. Although GD3/GD2+ cells showed the most malignant properties, GD2+ cells showed almost equivalent levels to GD3/GD2+ cells in invasion and migration activities, and in the intensities of tyrosine phosphorylation of paxillin. Among Src family kinases, Lyn was expressed predominantly, and was involved in the invasion and motility of GD3- and/or GD2-expressing transfectants. Furthermore, it was elucidated by gene silencing that Lyn was located in a different pathway from that of FAK to eventually lead paxillin activation. These results suggested that GD2/GD3 are responsible for the enhancement of the malignant features of osteosarcomas, and might be candidate targets in molecular-targeted therapy. © 2012 Japanese Cancer Association.

  7. Meningiomas of the cerebellopontine angle.

    PubMed

    Matthies, C; Carvalho, G; Tatagiba, M; Lima, M; Samii, M

    1996-01-01

    Meningiomas of the cerebellopontine angle (CPA) represent a clinically and surgically interesting entity. The opportunity of complete surgical excision and the incidence of impairment of nerval structures largely depend on the tumour biology that either leads to displacement of surrounding structures by an expansive type of growth or to an enveloping of nerval and vascular structures by an en plaque type of growth. As the origin and the direction of growth are very variable, the exact tumour extension in relation to the nerval structures and the tumour origin can be identified sometimes only at the time of surgery. Out of a series of 230 meningiomas of the posterior skull base operated between 1978 and 1993, data of 134 meningiomas involving the cerebellopontine angle are presented. There were 20% male and 80% female patients, age at the time of surgery ranging from 18 to 76 years, on the average 51 years. The clinical presentation was characterized by a predominant disturbance of the cranial nerves V (19%), VII (11%), VIII (67%) and the caudal cranial nerves (6%) and signs of ataxia (28%). 80% of the meningiomas were larger than 30 mm in diameter, 53% led to evident brainstem compression or dislocation and 85% extended anteriorly to the internal auditory canal. Using the lateral suboccipital approach in the majority of cases and a combined presigmoidal or combined suboccipital and subtemporal approaches in either sequence in 5%, complete tumour removal (Simpson I and II) was accomplished in 95% and subtotal tumour removal in 5%. Histologically the meningiotheliomatous type was most common (49%) followed by the mixed type (19%), fibroblastic (16%), psammomatous (7%), hemangioblastic (7%) and anaplastic (2%) types. Major post-operative complications were CSF leakage (8%) requiring surgical revision in 2% and hemorrhage (3%) requiring revision in 2%. While the majority of neurological disturbances showed signs of recovery, facial nerve paresis or paralysis was

  8. Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model

    PubMed Central

    Hillegass, Jedd M.; Shukla, Arti; Lathrop, Sherrill A.; MacPherson, Maximilian B.; Beuschel, Stacie L.; Butnor, Kelly J.; Testa, Joseph R.; Pass, Harvey I.; Carbone, Michele; Steele, Chad; Mossman, Brooke T.

    2010-01-01

    Asbestos fibers cause chronic inflammation that may be critical to the development of malignant mesothelioma (MM). Two human MM cell lines (Hmeso, PPM Mill) were used in a SCID mouse xenograft model to assess time-dependent patterns of inflammation and tumor formation. After intraperitoneal (IP) injection of MM cells, mice were euthanized at 7, 14, and 30 days, and peritoneal lavage fluid (PLF) was examined for immune cell profiles and human and mouse cytokines. Increases in human MM-derived IL-6, IL-8, bFGF, and VEGF were observed in mice at 7 days postinjection of either MM line, and a striking neutrophilia was observed at all time points. Free-floating tumor spheroids developed in mice at 14 days, and both spheroids and adherent MM tumor masses occurred in all mice at 30 days. Results suggest that inflammation and cytokine production precede and may be critical to the development of MMs. PMID:20716277

  9. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells

    PubMed Central

    Mezzapelle, Rosanna; Rrapaj, Eltjona; Gatti, Elena; Ceriotti, Chiara; Marchis, Francesco De; Preti, Alessandro; Spinelli, Antonello E.; Perani, Laura; Venturini, Massimo; Valtorta, Silvia; Moresco, Rosa Maria; Pecciarini, Lorenza; Doglioni, Claudio; Frenquelli, Michela; Crippa, Luca; Recordati, Camilla; Scanziani, Eugenio; de Vries, Hilda; Berns, Anton; Frapolli, Roberta; Boldorini, Renzo; D’Incalci, Maurizio; Bianchi, Marco E.; Crippa, Massimo P.

    2016-01-01

    Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment. PMID:26961782

  10. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

    PubMed Central

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  11. Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

    PubMed Central

    Bekelis, Kimon; Valdés, Pablo A.; Erkmen, Kadir; Leblond, Frederic; Kim, Anthony; Wilson, Brian C.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection. Methods A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches. Results The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological

  12. Postpartum Regression of a Presumed Cavernous Meningioma

    PubMed Central

    Phang, See Yung; Whitfield, Peter

    2016-01-01

    Meningiomas are known to be more common in females than males. They are also known in rare cases to grow in size during pregnancy, which can complicate its management. We describe a 31-year-old Caucasian woman who presented with blurring of her vision and diplopia during the third trimester of her pregnancy. Magnetic resonance imaging (MRI) showed a small left cavernous sinus meningioma. The patient was treated conservatively until her uncomplicated delivery. A postpartum MRI scan showed complete regression of the suspected meningioma. Currently the patient is contemplating a further pregnancy. PMID:27066285

  13. Frontal cutaneous meningioma--Case report.

    PubMed

    Ramos, Leonor; Coutinho, Ines; Cardoso, José Carlos; Garcia, Helena; Cordeiro, Margarida Robalo

    2015-01-01

    Cutaneous meningiomas are rare tumors most commonly located on the scalp. We report the case of a 55-year-old male who presented with a 2 x 3 cm tumoral lesion on the forehead. The lesion was hard, adherent and covered by normal skin. Incisional biopsy revealed a proliferation of monomorphic round cells, organized in nests and focally forming pseudovascular spaces. Immunohistochemical study revealed positivity for epithelial antigen membrane and vimentin. Vascular markers, cytokeratins and S100 protein were negative. A brain CT scan did not show any evidence of intracranial meningioma. The authors describe the case of a cutaneous frontal meningioma in probable relation with previous cranioencephalic trauma.

  14. Meckel's cave meningiomas with subarachnoid hemorrhage.

    PubMed

    Rosenberg, G A; Herz, D A; Leeds, N; Strully, K

    1975-06-01

    Two patients with Meckel's Cave meningiomas were initially hospitalized as a result of subarachnoid hemorrhage. Four-vessel angiography was necessary to exclude other causes of bleeding while demonstrating these lesions. Apoplectic presentation in both cases led to early diagnosis and successful surgical therapy. A review of the literature reveals subarachnoid hemorrhage to be a rarity in association with meningiomas. The two patients currently reported are believed to be the only examples on record of hemorrhagic meningiomas arising from the region of Meckel's Cave.

  15. Meningioma with metastasis from follicular carcinoma thyroid.

    PubMed

    Chaturvedi, Sujata; Gupta, Sanjeev; Kumari, Rima

    2010-01-01

    A 45-year-old female presented with loss of vision in the left eye, numbness on left half of face and left-sided hemicrania for two months. On the basis of radiological investigations, provisional diagnosis of basal meningioma was made. Tissue sent for histopathological evaluation revealed a dual tumor-meningioma with metastasis from follicular carcinoma, thyroid. To the best of authors' knowledge, this is the first report of a tumor metastasizing to another tumor, where a follicular carcinoma thyroid metastasized to meningioma.

  16. ETM study of electroporation influence on cell morphology in human malignant melanoma and human primary gingival fibroblast cells.

    PubMed

    Skolucka, Nina; Daczewska, Malgorzata; Saczko, Jolanta; Chwilkowska, Agnieszka; Choromanska, Anna; Kotulska, Malgorzata; Kaminska, Iwona; Kulbacka, Julita

    2011-04-01

    To estimate electroporation (EP) influence on malignant and normal cells. Two cell lines including human malignant melanoma (Me-45) and normal human gingival fibroblast (HGFs) were used. EP parameters were the following: 250, 1 000, 1 750, 2 500 V/cm; 50 µs by 5 impulses for every case. The viability of cells after EP was estimated by MTT assay. The ultrastructural analysis was observed by transmission electron microscope (Zeiss EM 900). In the current study we observed the intracellular effect following EP on Me-45 and HGF cells. At the conditions applied, we did not observe any significant damage of mitochondrial activity in both cell lines treated by EP. Conversely, we showed that EP in some conditions can stimulate cells to proliferation. Some changes induced by EP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters of EP (250 and 1 000 V/cm). After applying higher electric field intensities (2 500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications after EP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters of EP. We can claim that EP conditions are cell line dependent. In terms of the intracellular morphology, human fibroblasts are more sensitive to electric field as compared with melanoma cells. Optimal conditions should be determined for each cell line. Summarizing our study, we can conclude that EP is not an invasive method for human normal and malignant cells. This technique can be safely applied in chemotherapy for delivering drugs into tumor cells.

  17. ETM study of electroporation influence on cell morphology in human malignant melanoma and human primary gingival fibroblast cells

    PubMed Central

    Skolucka, Nina; Daczewska, Malgorzata; Saczko, Jolanta; Chwilkowska, Agnieszka; Choromanska, Anna; Kotulska, Malgorzata; Kaminska, Iwona; Kulbacka, Julita

    2011-01-01

    Objective To estimate electroporation (EP) influence on malignant and normal cells. Methods Two cell lines including human malignant melanoma (Me-45) and normal human gingival fibroblast (HGFs) were used. EP parameters were the following: 250, 1 000, 1 750, 2 500 V/cm; 50 µs by 5 impulses for every case. The viability of cells after EP was estimated by MTT assay. The ultrastructural analysis was observed by transmission electron microscope (Zeiss EM 900). Results In the current study we observed the intracellular effect following EP on Me-45 and HGF cells. At the conditions applied, we did not observe any significant damage of mitochondrial activity in both cell lines treated by EP. Conversely, we showed that EP in some conditions can stimulate cells to proliferation. Some changes induced by EP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters of EP (250 and 1 000 V/cm). After applying higher electric field intensities (2 500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications after EP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters of EP. Conclusions We can claim that EP conditions are cell line dependent. In terms of the intracellular morphology, human fibroblasts are more sensitive to electric field as compared with melanoma cells. Optimal conditions should be determined for each cell line. Summarizing our study, we can conclude that EP is not an invasive method for human normal and malignant cells. This technique can be safely applied in chemotherapy for delivering drugs into tumor cells. PMID:23569735

  18. Selective growth inhibition of human malignant melanoma cells by syringic acid-derived proteasome inhibitors

    PubMed Central

    2013-01-01

    Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide boronic acid derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid, 1), a known phenolic acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic acid and its proposed derivatives to 20S proteasome were studied. Several derivatives were virtually proposed, however, five derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5) and 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results Derivatives 2, 5, and 6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p ≤ 0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2

  19. MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells

    PubMed Central

    Ogawa, Hisataka; Wu, Xin; Kawamoto, Koichi; Nishida, Naohiro; Konno, Masamitsu; Koseki, Jun; Matsui, Hidetoshi; Noguchi, Kozou; Gotoh, Noriko; Yamamoto, Tsuyoshi; Miyata, Kanjiro; Nishiyama, Nobuhiro; Nagano, Hiroaki; Yamamoto, Hirofumi; Obika, Satoshi; Kataoka, Kazunori; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2015-01-01

    Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors. PMID:25970424

  20. Impact of 1p/19q codeletion on the diagnosis and prognosis of different grades of meningioma.

    PubMed

    Basaran, Recep; Uslu, Serap; Gucluer, Berrin; Onoz, Mustafa; Isik, Nejat; Tiryaki, Mehmet; Yakicier, Cengiz; Sav, Aydin; Elmaci, Ilhan

    2016-10-01

    Meningiomas are one of the most common tumours to affect the central nervous system. Genetic mutations are important in meningeal tumourigenesis, progression and prognosis. In this study, we aimed to examine the effect of 1p/19q deletion on the diagnosis and prognosis of meningioma subtypes using the fluorescence in situ hybridization (FISH) method. Twenty-four patients with meningioma were retrospectively studied. Tumour samples were obtained from 10 typical, 11 atypical and three anaplastic malignant meningiomas. The most representative tumour sections were screened for 1p/19q deletion using the FISH method. Of the 24 patients, eight were women (33.3%) and 16 (66.7%) were men. The mean age was 56.6 years. The higher-grade meningioma was usually seen in males and had a higher rate of deletion on 1p (p = 0.001). There was a statistically significant difference between the grades and the rate of deletion on 19q (p = 0.042) and between the grades and the rates of polysomy, monosomy and amplification on 19q (p = 0.002; p = 0.001; p = 0.002, respectively). There was no statistical difference between 1p/19q codeletion and the grades of meningioma (p > 0.05). We detected higher level of Ki-67 in the condition of codeletion but did not find a statistical difference (p = 0.0553). Deletion on 1p, as well as deletion, polysomy, monosomy and amplification on 19q, are detected more frequently in high grade meningiomas. This amplification is most likely due to the amplification of oncogenes.

  1. Expression of p21/sup ras/ in normal and malignant human tissues: lack of association with proliferation and malignancy

    SciTech Connect

    Chesa, P.G.; Rettig, W.J.; Melamed, M.R.; Old, L.J.; Niman, H.L.

    1987-05-01

    Proteins encoded by cellular ras oncogenes (p21/sup ras) are expressed in a wide variety of malignant tumors, including carcinomas, lymphomas, and neuroectodermal tumors. The function of p21/sup ras/ in these tumors and the distribution and role of p21/sup ras/ in corresponding normal tissues are unclear. This immunohistochemical study examined the relationship between p21/sup ras/ expression and malignant transformation, cellular differentiation, and proliferative activity in vivo. p21/sup ras/ was found to be widely expressed in normal tissues, but within those tissues expression was often sharply restricted to cells at specific stages of differentiation; terminally differentiated cells generally showed stronger reactivity with antibodies to p21/sup ras/ than did rapidly proliferating cells. Fetal and adult tissues had corresponding patterns of p21/sup ras/ expression, and the distribution of p21/sup ras/ in neoplasms paralleled the pattern in normal tissue from which they were derived. Thus, p21/ras/ seems to play a role in many fully differentiated cell types, and levels of p21/sup ras/ expression do not correlate with proliferative activity in normal cells or, in contrast to past reports, with the transformed phenotype.

  2. Discrimination analysis of human lung cancer cells associated with histological type and malignancy using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Yusuke; Shinzawa, Hideyuki; Takenaka, Tatsuji; Furihata, Chie; Sato, Hidetoshi

    2010-01-01

    The Raman spectroscopic technique enables the observation of intracellular molecules without fixation or labeling procedures in situ. Raman spectroscopy is a promising technology for diagnosing cancers-especially lung cancer, one of the most common cancers in humans-and other diseases. The purpose of this study was to find an effective marker for the identification of cancer cells and their malignancy using Raman spectroscopy. We demonstrate a classification of cultured human lung cancer cells using Raman spectroscopy, principal component analysis (PCA), and linear discrimination analysis (LDA). Raman spectra of single, normal lung cells, along with four cancer cells with different pathological types, were successfully obtained with an excitation laser at 532 nm. The strong appearance of bands due to cytochrome c (cyt-c) indicates that spectra are resonant and enhanced via the Q-band near 550 nm with excitation light. The PCA loading plot suggests a large contribution of cyt-c in discriminating normal cells from cancer cells. The PCA results reflect the nature of the original cancer, such as its histological type and malignancy. The five cells were successfully discriminated by the LDA.

  3. Overexpression of leucine aminopeptidase 3 contributes to malignant development of human esophageal squamous cell carcinoma.

    PubMed

    Zhang, Shu; Yang, Xiaojing; Shi, Hui; Li, Mei; Xue, Qun; Ren, Hanru; Yao, Li; Chen, Xueyu; Zhang, Jianguo; Wang, Huijie

    2014-06-01

    Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. We aimed to examine the biological function of LAP3 in esophageal squamous cell carcinoma (ESCC). LAP3 expressions were examined in human ESCC tissue and cell lines ECA109 and TE1 cells. Recombinant pSilencer4.1-LAP3-shRNA was transfected into ECA109 cells to silence LAP3 expression. The effects of LAP3 silencing on ECA109 cell proliferation in vitro were evaluated. Flow cytometry profiling was used to detect the differentiate cell cycle distribution in LAP3-silenced ECA109 cells. Wound-healing assay and transwell assay were used to examine the activities of migration and invasion in LAP3-silenced ECA109 cells. We overexpressed LAP3 in TE1 cells to find out the corresponding results. LAP3 expression level was abundance in ESCC tissue. LAP3 silencing significantly reduced ECA109 cell proliferation and colony formation. The knockdown of LAP3 resulted in cell cycle arrest at G1-phase. Moreover, over expression of LAP3 favors TE1 cell proliferation and invasiveness which also confirms its contribution in malignant development. We came to the conclusion that LAP3 contributed to ESCC progression by overcoming cell cycle arrest. The proliferative and migration effects of LAP3 might contribute to malignant development of human ESCC.

  4. Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells

    PubMed Central

    Shishkin, Sergey; Eremina, Lidia; Pashintseva, Natalya; Kovalev, Leonid; Kovaleva, Marina

    2016-01-01

    Identification of actin-depolymerizing factor homology (ADF-H) domains in the structures of several related proteins led first to the formation of the ADF/cofilin family, which then expanded to the ADF/cofilin superfamily. This superfamily includes the well-studied cofilin-1 (Cfl-1) and about a dozen different human proteins that interact directly or indirectly with the actin cytoskeleton, provide its remodeling, and alter cell motility. According to some data, Cfl-1 is contained in various human malignant cells (HMCs) and is involved in the formation of malignant properties, including invasiveness, metastatic potential, and resistance to chemotherapeutic drugs. The presence of other ADF/cofilin superfamily proteins in HMCs and their involvement in the regulation of cell motility were discovered with the use of various OMICS technologies. In our review, we discuss the results of the study of Cfl-1 and other ADF/cofilin superfamily proteins, which may be of interest for solving different problems of molecular oncology, as well as for the prospects of further investigations of these proteins in HMCs. PMID:28025492

  5. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

    PubMed

    Halder, Babli; Singh, Shruti; Thakur, Suman S

    2015-01-01

    In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

  6. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells

    PubMed Central

    Halder, Babli; Singh, Shruti; Thakur, Suman S.

    2015-01-01

    In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells. PMID:26334881

  7. Cyclooxygenase-2 is associated with malignant phenotypes in human lung cancer

    PubMed Central

    Li, Weiying; Yue, Wentao; Wang, Hui; Lai, Baitang; Yang, Xuehui; Zhang, Chunyan; Wang, Yue; Gu, Meng

    2016-01-01

    The objective of the present study was to investigate whether cyclooxygenase-2 (COX-2) is associated with malignancy, and to investigate its molecular mechanisms in human lung cancer tumor malignancy. The present study used RNA interference (RNAi) methodology and celecoxib, a COX-2 inhibitor, to investigate the effect of COX-2 knockdown on the proliferation and invasion abilities of lung cancer cells and the molecular mechanisms involved. Human lung adenocarcinoma A549-si10 and LTEP-A2 cells transfected with a specific small interfering RNA (A549-si10 and LTEP-A2-si10, respectively) grew more slowly compared with parental cell lines and cells transfected with pU6. The colony formation of A549-si10 and LTEP-A2-si10 cells was also reduced. In addition, A549-si10 and LTEP-A2-si10 cells were characterized by decreased metastatic and invasive abilities. The proliferation and invasive potential of parental A549 and LTEP-A2 cells was inhibited following treatment with celecoxib. In vivo, a COX-2 knockdown resulted in a decrease of proliferation and reduction of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and endothelial growth factor receptor (EGFR) expression in A549 xenografts. In conclusion, the present study revealed that COX-2 plays a extremely important role in tumor growth, infiltration and metastasis via the regulation of VEGF, MMP-2 and EGRF expression. Therefore, COX-2 is a potential therapeutic target for lung cancer. PMID:27895738

  8. Spontaneous Regression of an Incidental Spinal Meningioma.

    PubMed

    Yilmaz, Ali; Kizilay, Zahir; Sair, Ahmet; Avcil, Mucahit; Ozkul, Ayca

    2016-03-15

    The regression of meningioma has been reported in literature before. In spite of the fact that the regression may be involved by hemorrhage, calcification or some drugs withdrawal, it is rarely observed spontaneously. We report a 17 year old man with a cervical meningioma which was incidentally detected. In his cervical MRI an extradural, cranio-caudal contrast enchanced lesion at C2-C3 levels of the cervical spinal cord was detected. Despite the slight compression towards the spinal cord, he had no symptoms and refused any kind of surgical approach. The meningioma was followed by control MRI and it spontaneously regressed within six months. There were no signs of hemorrhage or calcification. Although it is a rare condition, the clinicians should consider that meningiomas especially incidentally diagnosed may be regressed spontaneously.

  9. Meningioma with hemorrhagic onset: two case reports.

    PubMed

    Vij, Mukul; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Kumar, Sheo; Behari, Sanjay

    2012-01-01

    Haemorrhage is a rare complication of meningiomas that can occur spontaneously, after embolization, stereotactic radiation and perioperatively. Our first case was a 16 year old male, admitted with spastic quadriparesis, and retention of urine. Magnetic Resonance Imaging (MRI) revealed anteriorly placed cervical intradural extramedullary mass. Patient underwent emergency surgery following sudden worsening of neurological symptoms and intratumoral bleed was noted peroperatively. Tumor was labeled as angiomatous meningioma with hemorrhage. The second case was of a 45 year female who presented with history of sudden onset weakness in right upper and lower limb followed by unconsciousness. MRI revealed heterogeneous lesion in left parasagittal area with intratumoral bleed. Left frontal craniotomy with tumour decompression was performed. Tumour was labelled as meningothelial meningioma with haemorrhage. Meningiomas with hemorrhagic onset remain rare, and pathophysiology is still incompletely understood. Prevention and outcome of intratumoral haemorrhage highly depends on early diagnosis and adequate treatment.

  10. Primary extracranial meningioma of the mandible.

    PubMed

    Mosqueda-Taylor, Adalberto; Domínguez-Malagon, Hugo; Cano-Valdez, Ana-Maria; Montiel-Hernandez, Ana-Maria

    2009-04-01

    Meningiomas are benign tumors of mesodermal origin that arise from arachnoid cell clusters that penetrate the dura to form arachnoid villi. These neoplasms represent one of the most common neoplasms developing within the central nervous system and are usually located at points of entry of vessels and nerves through the dura. Extracranial meningiomas (EM) comprise only 2% of all meningiomas, and only six cases of primary EM of the jawbones have been described to date. They may arise as an extension of intracranial meningiomas or as primary tumors and may be clinically indistinguishable from other benign tumours of the jaws, as they usually present as a well-delineated unencapsulated tumors. In this article a case of primary intramandibular primary EM that appeared as a well-defined osteolytic radiolucent lesion of the jaw is reported. The salient clinico-pathological features of this case is compared to those previously reported in the literature and differential diagnosis and therapeutic considerations are discussed.

  11. Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines.

    PubMed

    Kim, H-A; Kim, M-C; Kim, N-Y; Kim, Y

    2015-08-01

    Deregulation of crucial embryonic pathways, including hedgehog signaling, has been frequently implicated in a variety of human cancers and is emerging as an important target for anticancer therapy. This study evaluated the potential anticancer effects of cyclopamine, a chemical inhibitor of hedgehog signaling, in human malignant mesothelioma (HMM) cell lines. Cyclopamine treatment significantly decreased the proliferation of HMM cells by promoting apoptosis and shifting the cell cycle toward dormant phase. The clonogenicity and mobility of HMM cells were significantly decreased by cyclopamine treatment. Treatment of HMM cells with cyclopamine significantly reduced the abundance of side population cells, which were measured using an assay composed of Hoechst 33342 dye staining and subsequent flow cytometry. Furthermore, the expression levels of stemness-related genes were significantly affected by cyclopamine treatment. Taken together, the present study showed that targeting hedgehog signaling could reduce a more aggressive subpopulation of the cancer cells, suggesting an alternative approach for HMM therapy.

  12. Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines

    PubMed Central

    Kim, H-A; Kim, M-C; Kim, N-Y; Kim, Y

    2015-01-01

    Deregulation of crucial embryonic pathways, including hedgehog signaling, has been frequently implicated in a variety of human cancers and is emerging as an important target for anticancer therapy. This study evaluated the potential anticancer effects of cyclopamine, a chemical inhibitor of hedgehog signaling, in human malignant mesothelioma (HMM) cell lines. Cyclopamine treatment significantly decreased the proliferation of HMM cells by promoting apoptosis and shifting the cell cycle toward dormant phase. The clonogenicity and mobility of HMM cells were significantly decreased by cyclopamine treatment. Treatment of HMM cells with cyclopamine significantly reduced the abundance of side population cells, which were measured using an assay composed of Hoechst 33342 dye staining and subsequent flow cytometry. Furthermore, the expression levels of stemness-related genes were significantly affected by cyclopamine treatment. Taken together, the present study showed that targeting hedgehog signaling could reduce a more aggressive subpopulation of the cancer cells, suggesting an alternative approach for HMM therapy. PMID:26206198

  13. Imaging of meningioma progression by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    PubMed

    Agar, Nathalie Y R; Malcolm, James G; Mohan, Vandana; Yang, Hong W; Johnson, Mark D; Tannenbaum, Allen; Agar, Jeffrey N; Black, Peter M

    2010-04-01

    Often considered benign, meningiomas represent 32% of intracranial tumors with three grades of malignancy defined by the World Health Organization (WHO) histology based classification. Malignant meningiomas are associated with less than 2 years median survival. The inability to predict recurrence and progression of meningiomas induces significant anxiety for patients and limits physicians in implementing prophylactic treatment approaches. This report presents an analytical approach to tissue characterization based on matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry imaging (MSI) which is introduced in an attempt to develop a reference database for predictive classification of brain tumors. This pilot study was designed to evaluate the potential of such an approach and to begin to address limitations of the current methodology. Five recurrent and progressive meningiomas for which surgical specimens were available from the original and progressed grades were selected and tested against nonprogressive high-grade meningiomas, high-grade gliomas, and nontumor brain specimens. The common profiling approach of data acquisition was compared to imaging and revealed significant benefits in spatially resolved acquisition for improved spectral definition. A preliminary classifier based on the support vector machine showed the ability to distinguish meningioma image spectra from the nontumor brain and from gliomas, a different type of brain tumor, and to enable class imaging of surgical tissue. Although the development of classifiers was shown to be sensitive to data preparation parameters such as recalibration and peak picking criteria, it also suggested the potential for maturing into a predictive algorithm if provided with a larger series of well-defined cases.

  14. The embryonic morphogen, Nodal, is associated with channel-like structures in human malignant melanoma xenografts.

    PubMed

    McAllister, Josephine C; Zhan, Qian; Weishaupt, Carsten; Hsu, Mei-Yu; Murphy, George F

    2010-04-01

    Formation of channel-like structures, also termed vasculogenic mimicry (VM), describes the ability of aggressive melanoma cells to form PAS-positive anastomosing structures that correlate with tumor virulence. This phenomenon may indicate differentiation plasticity, a feature melanoma cells may share with stem cells in the developing embryo. Recent studies have indicated that VM and tumorigenicity of human malignant melanoma may depend on the signaling pathways of an embryonic morphogen, Nodal. However, given the secretory nature of Nodal protein and melanoma cell heterogeneity, it remains unclear whether the Nodal-expressing cells participate directly or indirectly in VM that is potentially related to tumorigenic growth. We have developed a humanized murine xenograft model in which developing human melanomas may be sequentially studied during early stages of tumorigenic growth within a physiological human dermal microenvironment. Nodal protein localized diffusely to melanoma cell membranes, with occasional foci of accentuated reactivity in patterns suggestive of channel formation. Similar findings were detected in a limited number of patient-derived tumors. In situ hybridization confirmed Nodal mRNA to be restricted to tumor cells within xenografts that formed arborizing networks in patterns consistent with VM. These data indicate that Nodal gene expression is associated with formation of VM-like structures in a physiologically relevant model of human melanoma tumorigenesis, and further support a key role for Nodal expression in the formation of channel-like structures. The humanized xenograft model should be useful in future studies to define the mechanistic pathways responsible for VM and melanoma progression.

  15. Jugular fossa meningioma: presentation and treatment options.

    PubMed

    Rutt, Amy L; Chen, Xiaoli; Sataloff, Robert T

    2009-10-01

    Primary jugular fossa meningiomas are among the rarest subtypes of meningioma. They are intimately related to the lower cranial nerves, the jugular bulb and vein, and the temporal bone, and they have a tendency to extend both intra- and extracranially. The most common morbidity associated with jugular fossa lesions is lower cranial nerve deficits. In these cases, the differential diagnosis and preoperative radiographic diagnosis are very important because preoperative management and operative planning for the jugular fossa subtype differ considerably from those of other types of meningioma. Because of the rarity of this condition, our understanding of its treatment, long-term follow-up, and recurrence is limited. As experience with radiosurgical treatment of all meningiomas is accumulating, we may find that radiosurgery of jugular fossa meningiomas is appropriate. In the meantime, cure is still possible with complete surgical resection, and surgical morbidity can be minimized through meticulous planning and surgical technique. We describe a case of primary jugular fossa meningioma in a 45-year-old man who presented with complaints of chronic left aural fullness, hearing loss, and difficulty understanding voices. Imaging revealed the presence of a destructive jugular fossa mass. The patient underwent surgical resection without complication, and he was free of recurrence at 1 year of follow-up.

  16. Atypical Growth Pattern of an Intraparenchymal Meningioma

    PubMed Central

    Chen, Xiaoxi

    2016-01-01

    Meningiomas are the most common primary nonneuroglial extra-axial neoplasms, which commonly present as spherical or oval masses with a dural attachment. Meningiomas without dural attachment are rare and, according to their locations, are classified into 5 varieties, including intraventricular, deep Sylvain fissure, pineal region, intraparenchymal, or subcortical meningiomas. To the best of our knowledge, intraparenchymal meningioma with cerebriform pattern has never been reported. In this paper, we report a 34-year-old Chinese male patient who presented with paroxysmal headaches and progressive loss of vision for 10 months and blindness for 2 weeks. A thorough physical examination revealed loss of bilateral direct and indirect light reflex. No other relevant medical history and neurologic deficits were noted. Computed tomography and magnetic resonance imaging scans showed an irregular mass with a unique cerebriform pattern and extensive peritumoral edema in the parietal-occipital-temporal region of the right cerebral hemisphere. The initial diagnosis was lymphoma. Intraoperatively, the tumor was completely buried in a sulcus in the parietal-occipital-temporal region without connecting to the dura. The histological diagnosis was intracranial meningioma based on pathological examination. Therefore, when an unusual cerebriform growth pattern of a tumor is encountered, an intraparenchymal meningioma should be considered as a differential diagnosis. PMID:27752384

  17. Comparative Analysis of the Magnetic Resonance Imaging Features Between Anaplastic Meningioma and Atypical Meningioma.

    PubMed

    Liu, Hong; Zhou, Junlin; Li, Wenyi; Liu, Guangyao

    2016-05-01

    The aim of the study was to investigate the differences in the imaging feature between anaplastic meningioma (World Health Organization grade III) and atypical meningioma (World Health Organization grade II), summarize its specificity of image features, and provide the basis for accurate preoperative diagnosis. The magnetic resonance imaging features of 20 patients of anaplastic meningioma were compared with those of 30 patients of atypical meningioma retrospectively, all of which were confirmed by surgery and pathology. The imaging features of the 2 groups of tumors were statistically analyzed using χ tests. The 2 tumor types differed in several features, including lobulated or irregular shape (P < 0.05), cystic and necrotic changes (P < 0.05), peritumoral edema (P < 0.05), and brain-tumor interface (P < 0.01). There were no significant differences in hemorrhage, homogeneous enhancement of the tumor, dural tail sign, or adjacent bone change (P > 0.05). Differences in the imaging feature between anaplastic meningioma and atypical meningioma can improve the differential diagnosis and allow a more appropriate approach to therapy. The article focuses on examining the differences of the magnetic resonance imaging features between anaplastic meningiomas and atypical meningiomas have been examined in only a few studies.

  18. Physical interaction between human ribonucleotide reductase large subunit and thioredoxin increases colorectal cancer malignancy.

    PubMed

    Lou, Meng; Liu, Qian; Ren, Guoping; Zeng, Jiling; Xiang, Xueping; Ding, Yongfeng; Lin, Qinghui; Zhong, Tingting; Liu, Xia; Zhu, Lijun; Qi, Hongyan; Shen, Jing; Li, Haoran; Shao, Jimin

    2017-04-14

    Ribonucleotide reductase (RR) is the rate-limiting enzyme in DNA synthesis by catalyzing the reduction of ribonucleotides to deoxyribonucleotides. During each enzymatic turnover, reduction of the active site disulfide in the catalytic large subunit is performed by a pair of shuttle cysteine residues in its C-terminal tail. Thioredoxin (Trx) and Glutaredoxin (Grx) are ubiquitous redox proteins, catalyzing thiol-disulfide exchange reactions. Here, immunohistochemical examination of clinical colorectal cancer (CRC) specimens revealed that human thioredoxin1 (hTrx1), but not human glutaredoxin1 (hGrx1), was upregulated along with human RR large subunit (RRM1) in cancer tissues, and the expression levels of both proteins were correlated with cancer malignancy stage. Ectopically expressed hTrx1 significantly increased RR activity, DNA synthesis, and cell proliferation and migration. Importantly, inhibition of both hTrx1 and RRM1 produced a synergistic anti-cancer effect in CRC cells and xenograft mice. Furthermore, hTrx1 rather than hGrx1 was the efficient reductase for RRM1 regeneration. We also observed a direct protein-protein interaction between RRM1 and hTrx1 in CRC cells. Interestingly, besides the known two conserved cysteines, a third one (Cys779) in the RRM1 C-terminus was essential for RRM1 regeneration and binding to hTrx1, while both Cys32 and Cys35 in hTrx1 played a counterpart role. Our findings suggest that the upregulated RRM1 and hTrx1 in CRC directly interact with each other and promote RR activity, resulting in enhanced DNA synthesis and cancer malignancy. We propose that the RRM1-hTrx1 interaction might be a novel potential therapeutic target for cancer treatment.

  19. Intracellular ionized calcium concentration in muscles from humans with malignant hyperthermia.

    PubMed

    López, J R; Alamo, L; Caputo, C; Wikinski, J; Ledezma, D

    1985-06-01

    Ca2+ selective microelectrodes have been used to determine the free myoplasmic [Ca2+] in human skeletal muscle obtained from patients who had developed early signs associated with malignant hyperthermia (MH) during anesthesia. Intercostal muscle biopsies were performed under local anesthesia in four MH patients 15 days to 4 months after developing the MH crisis and in three control subjects. We used only microelectrodes that showed a Nernstian response between pCa3 and pCa7 (30.5 mV per decade at 37 degrees C). Membrane resting potential (V(m)) and calcium potential (V(Ca)) were obtained from superficial fibers. The free cytosolic [Ca2+] was 0.39 +/- 0.1 microM (mean +/- SEM, n = 18) in muscle fibers obtained from malignant hyperthermic patients, whereas in control subjects it was 0.11 +/- 0.02 microM (n = 10). These results suggest that this syndrome might be related to an abnormally high myoplasmic free resting calcium concentration, probably due to a defective function of the plasma membrane or the sarcoplasmic reticulum.

  20. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease

    PubMed Central

    Hieken, Tina J.; Chen, Jun; Hoskin, Tanya L.; Walther-Antonio, Marina; Johnson, Stephen; Ramaker, Sheri; Xiao, Jian; Radisky, Derek C.; Knutson, Keith L.; Kalari, Krishna R.; Yao, Janet Z.; Baddour, Larry M.; Chia, Nicholas; Degnim, Amy C.

    2016-01-01

    Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention. PMID:27485780

  1. P16INK4a MEDIATED SUPPRESSION OF TELOMERASE IN NORMAL AND MALIGNANT HUMAN BREAST CELLS

    PubMed Central

    Bazarov, Alexey V.; van Sluis, Marjolein; Hines, Curtis; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W.; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

    2010-01-01

    Summary The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal. PMID:20569236

  2. Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in Cervical Malignancies.

    PubMed

    Husain, R S Akram; Ramakrishnan, V

    2015-01-01

    Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Human pregnane X receptor compromises the function of p53 and promotes malignant transformation

    PubMed Central

    Robbins, D; Cherian, M; Wu, J; Chen, T

    2016-01-01

    The pregnane X receptor (PXR) is well established as a nuclear receptor that has a central role in xenobiotic metabolism and disposition. However, emerging evidence suggests that PXR is also a regulator of apoptosis, promoting a malignant phenotype both in vitro and in vivo. The tumor suppressor p53 can be activated in the presence of DNA damage and induce cell cycle arrest to allow for DNA repair or, ultimately, apoptosis to suppress tumor formation. We previously identified p53 as a novel PXR-associated protein by using a mass spectrometric approach. In the current study, we identified a novel inhibitory effect of PXR on p53, revealing an anti-apoptotic function of PXR in colon carcinogenesis. PXR expression reduced p53 transactivation and the expression of its downstream target genes involved in cell cycle arrest and apoptosis by decreasing p53 recruitment to the promoter regions of these genes. Consistent with the inhibitory effect of PXR on p53, elevated PXR levels decreased doxorubicin- or nutlin-3a-mediated toxicity and promoted malignant transformation in colon cancer cells. Our findings show for the first time that PXR expression modulates p53 target gene promoter binding and contributes to the downregulation of p53 function in human colon cancer cells. These results define the functional significance of PXR expression in modulating p53-mediated mechanisms of tumor suppression. PMID:27547448

  4. p16(INK4a) -mediated suppression of telomerase in normal and malignant human breast cells.

    PubMed

    Bazarov, Alexey V; Van Sluis, Marjolein; Hines, William C; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

    2010-10-01

    The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.

  5. Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

    PubMed Central

    Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

    2013-01-01

    Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

  6. Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Bukovac, Anja; Vladušić, Tomislav; Tomas, Davor; Hrašćan, Reno

    2017-07-01

    Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ(2) = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

  7. Immunocytochemical analysis of glucose transporter protein-1 (GLUT-1) in typical, brain invasive, atypical and anaplastic meningioma.

    PubMed

    van de Nes, Johannes A P; Griewank, Klaus G; Schmid, Kurt-Werner; Grabellus, Florian

    2015-02-01

    Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and "spontaneous" necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1-4) and to be consistently strong in WHO grade III meningiomas (IRS = 6-12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS = 1-9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS = 0-4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) "Spontaneous" necrosis and small cell change typically occurred away from the intratumoral capillary

  8. NY-ESO-1 expression in meningioma suggests a rationale for new immunotherapeutic approaches.

    PubMed

    Baia, Gilson S; Caballero, Otavia L; Ho, Janelle S Y; Zhao, Qi; Cohen, Tzeela; Binder, Zev A; Salmasi, Vafi; Gallia, Gary L; Quinones-Hinojosa, Alfredo; Olivi, Alessandro; Brem, Henry; Burger, Peter; Strausberg, Robert L; Simpson, Andrew J G; Eberhart, Charles G; Riggins, Gregory J

    2013-11-01

    Meningiomas are the most common primary intracranial tumors. Surgical resection remains the treatment of choice for these tumors. However, a significant number of tumors are not surgically accessible, recur, or become malignant, necessitating the repetition of surgery and sometimes radiation. Chemotherapy is rarely used and is generally not recognized as an effective treatment. Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in patients with cancer and this feature makes them attractive targets for immunotherapy-based approaches. We analyzed mRNA expression of 37 testis-restricted CT genes in a discovery set of 18 meningiomas by reverse transcription PCR. The overall frequency of expression of CT genes ranged from 5.6% to 27.8%. The most frequently expressed was NY-ESO-1, in 5 patients (27.8%). We subsequently analyzed NY-ESO-1 protein expression in a larger set of meningiomas by immunohistochemistry and found expression in 108 of 110 cases. In some cases, NY-ESO-1 expression was diffused and homogenous, but in most instances it was heterogeneous. Importantly, NY-ESO-1 expression was positively correlated with higher grade and patients presenting with higher levels of NY-ESO-1 staining had significantly worse disease-free and overall survival. We have also shown that NY-ESO-1 expression may lead to humoral immune response in patients with meningioma. Considering the limited treatment options for patients with meningioma, the potential of NY-ESO-1-based immunotherapy should be explored. ©2013 AACR.

  9. Receptor tyrosine kinase inhibition by regorafenib/sorafenib inhibits growth and invasion of meningioma cells.

    PubMed

    Tuchen, Marcus; Wilisch-Neumann, Annette; Daniel, Evelyn A; Baldauf, Lisa; Pachow, Doreen; Scholz, Johannes; Angenstein, Frank; Stork, Oliver; Kirches, Elmar; Mawrin, Christian

    2017-03-01

    Systemic chemotherapeutic treatment for unresectable and/or aggressive meningiomas is still unsatisfying. PDGF receptor (PDGFR)-mediated activation of mitogenic signalling has been shown to be active in meningiomas. Therefore, we evaluate in vitro and in vivo the effects of inhibiting PDGFR using the clinically well-characterised tyrosine kinase inhibitors sorafenib or regorafenib in meningioma models. IOMM-Lee meningioma cells were used to assess cytotoxic effects, inhibition of proliferation, induction of apoptosis, as well as inhibition of migration and motility by sorafenib and regorafenib. Using an orthotopic mouse xenograft model, growth inhibition as monitored by magnetic resonance imaging, and overall survival of sorafenib- or regorafenib-treated mice compared with control animals was determined. Treatment of malignant IOMM-Lee cells resulted in significantly reduced cell survival and induction of apoptosis following regorafenib and sorafenib treatment. Western blots showed that both drugs target phosphorylation of p44/42 ERK via downregulation of the PDGFR. Both drugs additionally showed significant inhibition of cell motility and invasion. In vivo, mice with orthotopic meningioma xenografts showed a reduced volume (n.s.) of signal enhancement in MRI (mainly tumour) following sorafenib and regorafenib treatment. This was translated in a significantly increased overall survival time (p ≤ 0.05) for regorafenib-treated mice. Analyses of in vivo-grown tumours demonstrated again reduced PDGFR expression and expression/phosphorylation of p44/42. Sorafenib and regorafenib show antitumour activity in vitro and in vivo by targeting PDGFR and p44/42 ERK signalling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Meningiomas with Rhabdoid or Papillary Components : Prognosis and Comparison with Anaplastic Meningiomas

    PubMed Central

    Kim, Jeong-Kwon; Jung, Shin; Lee, Kyung-Hwa; Kim, Seul-Kee; Lee, Eun Jung

    2016-01-01

    Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (<50%) rhabdoid or papillary component (group B2). Homogeneous enhancement on MRI was associated with improved PFS compared to heterogeneous enhancement (p=0.025). Depending on pathology, the mean PFS was 134.9±31.6 months for group A, 46.6±13.4 months for group B1, and 118.7±19.2 months for group B2. The mean OS was 138.5±24.6 months for group A and 59.7±16.8 months for group B1. All recurrent tumors were of the previously diagnosed pathology, except for one tumor from group B1, which recurred as an atypical meningioma without a papillary component. Group B1 tumors showed a more aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. PMID:27446516

  11. Comparison of multiple assays for detecting human antibodies directed against surface antigens on normal and malignant human tissue culture cells.

    PubMed

    Rosenberg, S A; Schwarz, S; Anding, H; Hyatt, C; Williams, G M

    1977-01-01

    Four separate assays of human antibody reactivity to four separate normal and malignant human tissue culture cell lines from two patients have been evaluated using a single highly-reactive allogeneic serum. The visual and end-point cytolysis assay and the 51Chromium release assay were equally sensitive in measuring complement mediated antibody cytoxicity and both were far more sensitive than a trypan blue dye exclusion assay. The assay of antibody reactivity by hemadsorption technique was about 10 times more sensitive than any of the cytotoxicity assays. This latter assay measures only IgG antibody however. These assays showed that cell lines from different patients may differ greatly in 'reactivity' to an allogeneic serum and emphasized the importance of utilizing tumor and normal cells from the same patient when using tissue culture cells to search for tumor specific reactivity. These observations emphasize the importance of utilizing multiple assays against paired normal and malignant cells from the same patient to be certain of the specificity and magnitude of the measured antibody.

  12. Lin28 Enhances Tumorigenesis and is Associated With Advanced Human Malignancies

    PubMed Central

    Viswanathan, Srinivas R.; Powers, John T.; Einhorn, William; Hoshida, Yujin; Ng, Tony; Toffanin, Sara; O'Sullivan, Maureen; Lu, Jun; Philips, Letha A.; Lockhart, Victoria L.; Shah, Samar P.; Tanwar, Pradeep S.; Mermel, Craig H.; Beroukhim, Rameen; Azam, Mohammad; Teixeira, Jose; Meyerson, Matthew; Hughes, Timothy P.; Llovet, Josep M; Radich, Jerald; Mullighan, Charles G.; Golub, Todd R.; Sorensen, Poul H.; Daley, George Q.

    2009-01-01

    Multiple members of the let-7 family of miRNAs are often repressed in human cancers1,2, thereby promoting oncogenesis by de-repressing the targets K-Ras, c-Myc, and HMGA2 3,4. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins Lin28 and Lin28B block let-7 precursors from being processed to mature miRNAs5–8, suggesting that over-expression of Lin28/Lin28B might promote malignancy via repression of let-7. Here we show that LIN28 and LIN28B are over-expressed in primary human tumors and human cancer cell lines (overall frequency ∼15%), and that over-expression is linked to repression of let-7 family miRNAs and de-repression of let-7 targets. Lin28/Lin28B facilitate cellular transformation in vitro, and over-expression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28/LIN28B with poor clinical prognosis. PMID:19483683

  13. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse

    PubMed Central

    Clappier, Emmanuelle; Gerby, Bastien; Sigaux, François; Delord, Marc; Touzri, Farah; Hernandez, Lucie; Ballerini, Paola; Baruchel, André

    2011-01-01

    Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA–mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle– and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse. PMID:21464223

  14. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse.

    PubMed

    Clappier, Emmanuelle; Gerby, Bastien; Sigaux, François; Delord, Marc; Touzri, Farah; Hernandez, Lucie; Ballerini, Paola; Baruchel, André; Pflumio, Françoise; Soulier, Jean

    2011-04-11

    Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA-mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle- and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse.

  15. The bone morphogenetic protein antagonist Gremlin is overexpressed in human malignant mesothelioma.

    PubMed

    Wang, Dian-Jun; Zhi, Xiu-Yi; Zhang, Shu-Cai; Jiang, Miao; Liu, Peng; Han, Xing-Peng; Li, Jun; Chen, Zhao; Wang, Chang-Li

    2012-01-01

    Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family and its antagonistic effect is likely through direct binding to BMP proteins. As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body patterning and tissue differentiation. Recent studies have shown a deregulation of Gremlin in several types of human cancers. However, the role of Gremlin in human malignant mesothelioma (MM) is still unknown. In this study, we investigated the expression of Gremlin in human MM. We found that Gremlin mRNA and protein were both overexpressed in the majority of primary MM tissue samples that we examined. We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell lines. Consistently, we found that the Gremlin promoter activity was significantly elevated in those MM cell lines expressing the Gremlin gene. On the other hand, no activity of the Gremlin promoter was detected in the two MM cell lines lacking Gremlin expression. Moreover, to examine the functional significance of the Gremlin overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell lines expressing Gremlin and found that inhibition of Gremlin expression significantly suppressed proliferation of those MM cells. Taken together, our results suggest that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation of Gremlin may play a critical role in the tumorigenesis of human MM.

  16. Spinal drop metastases from a papillary meningioma: a case report and review of the literature: utility of CSF sampling.

    PubMed

    Erkutlu, Ibrahim; Buyukhatipoglu, Hakan; Alptekin, Mehmet; Berkyurek, Eser; Tutar, Ediz; Gok, Abdulvahap

    2009-01-01

    In this paper, we report a rare case of a 29-year-old boy who presented with papillary meningioma originating from the posterior fossa meninges. After a long, disease-free period, however, spinal drop metastases occurred 32 months after resection of the primary tumor. The primary and metastatic lesions had a similar histological appearance, meaning that multiple spinal metastatic lesions occurred through CSF route even after a gross total resection of the tumor. Tumor seeding during surgery is the evident reason for spinal metastasis, although we strictly adhered to the standard precautions for operations for malignant tumors such as obstruction of the cisterna magna with cotton paddies, and changing surgical gloves and instruments during the operation. In this report, we briefly discuss an exceedingly rare variant of meningioma, the papillary variant, and suggest a new approach, a CSF sampling, in the management of both malignant and benign meningiomas. CSF sampling allows for the early detection of metastasis and of tumor cells before metastasis has occurred, thus allowing treatment to begin as soon as possible. This early detection and management is possibly associated with longer survival. Furthermore, we discussed that meningiomas are tumors that are not as benign as initially thought.

  17. Elevated expression of serine/threonine phosphatase type 5 correlates with malignant proliferation in human osteosarcoma.

    PubMed

    Han, Kun; Gan, Zhihua; Lin, Shuchen; Hu, Haiyan; Shen, Zan; Min, Daliu

    2017-01-01

    Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells. Moreover, FACS analysis showed that knockdown of PP5 expression induced a significant arrest in the G0/G1 phase of the cell cycle, which was associated with the inhibition of cell proliferation. Therefore, knockdown of PP5 is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

  18. FTIR microscopic comparative study on normal, premalignant, and malignant tissues of human intenstine

    NASA Astrophysics Data System (ADS)

    Mordechai, Shaul; Argov, Shmuel; Salman, Ahmad O.; Cohen, Beny; Ramesh, Jagannathan; Erukhimovitch, Vitaly; Goldstein, Jed; Sinelnikov, Igor

    2000-07-01

    Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The biological systems we have studied include normal, premalignant (polyp) and malignant human colonic tissues from three patients. Our method is based on microscopic infrared study (FTIR-microscopy) of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a `gold' reference. The normal intestine tissue has a stronger absorption than polyp and cancerous types over a wide region in all three cases. The detailed analysis showed that there is a significant decrease in total phosphate and creatine contents for polyp and cancerous tissue types in comparison to the controls.

  19. Frequency analysis of multispectral photoacoustic images for differentiating malignant region from normal region in excised human prostate

    NASA Astrophysics Data System (ADS)

    Sinha, Saugata; Rao, Navalgund A.; Valluru, Keerthi S.; Chinni, Bhargava K.; Dogra, Vikram S.; Helguera, Maria

    2014-03-01

    Frequency domain analysis of the photoacoustic (PA) radio frequency signals can potentially be used as a tool for characterizing microstructure of absorbers in tissue. This study investigates the feasibility of analyzing the spectrum of multiwavelength PA signals generated by excised human prostate tissue samples to differentiate between malignant and normal prostate regions. Photoacoustic imaging at five different wavelengths, corresponding to peak absorption coefficients of deoxyhemoglobin, whole blood, oxyhemoglobin, water and lipid in the near infrared (NIR) (700 nm - 1000 nm) region, was performed on freshly excised prostate specimens taken from patients undergoing prostatectomy for biopsy confirmed prostate cancer. The PA images were co-registered with the histopathology images of the prostate specimens to determine the region of interest (ROI) corresponding to malignant and normal tissue. The calibrated power spectrum of each PA signal from a selected ROI was fit to a linear model to extract the corresponding slope, midband fit and intercept parameters. The mean value of each parameter corresponding to malignant and adjacent normal prostate ROI was calculated for each of the five wavelengths. The results obtained for 9 different human prostate specimens, show that the mean values of midband fit and intercept are significantly different between malignant and normal regions. In addition, the average midband fit and intercept values show a decreasing trend with increasing wavelength. These preliminary results suggest that frequency analysis of multispectral PA signals can be used to differentiate malignant region from the adjacent normal region in human prostate tissue.

  20. Six1 promotes epithelial–mesenchymal transition and malignant conversion in human papillomavirus type 16-immortalized human keratinocytes

    PubMed Central

    Creek, Kim E.

    2014-01-01

    Six1, a member of the Six family of homeodomain transcription factors, is overexpressed in various human cancers, and SIX1 overexpression is associated with tumor progression and metastasis. Six1 messenger RNA levels increase during in vitro progression of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we show that HKc/DR-overexpressing Six1 exhibited a more mesenchymal phenotype, as characterized by a fibroblastic appearance and increased invasion. We utilized Whole Human Genome Microarrays to explore the gene expression changes associated with Six1 overexpression in HKc/DR. We found that overexpression of Six1 downregulated epithelial-related genes and upregulated mesenchymal-related genes, which suggests that Six1 overexpression induces epithelial–mesenchymal transition (EMT). Pathway analysis of the microarray data showed alterations in the transforming growth factor-beta (TGF-β) pathway, including enhanced expression of the TGF-β receptor type II (TβRII), and activation of the mitogen-activated protein kinase (MAPK) pathway in HKc/DR-overexpressing Six1, suggesting that Smad-independent pathways of TGF-β signaling may be involved in Six1-mediated EMT. p38 MAPK activation was required for sustained Six1-induced EMT and TβRII overexpression. Finally, we determined that Six1 overexpression in HKc/DR resulted in malignant conversion and increased the cancer stem cell (CSC)-like population. Thus, Six1 overexpression promotes EMT, CSCs properties and malignant conversion in HKc/DR through MAPK activation, which supports the possible use of p38-TβRII inhibitors for the treatment of cancers overexpressing Six1. PMID:24574515

  1. A B-Cell Superantigen Induces the Apoptosis of Murine and Human Malignant B Cells

    PubMed Central

    Lorenzo, Daniela; Duarte, Alejandra; Mundiñano, Juliana; Berguer, Paula; Nepomnaschy, Irene; Piazzon, Isabel

    2016-01-01

    B-cell superantigens (Sags) bind to conserved sites of the VH or VL regions of immunoglobulin molecules outside their complementarity-determining regions causing the apoptosis of normal cognate B cells. No attempts to investigate whether B-cell Sags are able to induce the apoptosis of cognate malignant B cells were reported. In the present study we show that protein L (PpL), secreted by Finegoldia magna, a B-cell Sag which interacts with κ+ bearing cells, induces the apoptosis of murine and human κ+ lymphoma B cells both in vitro and in vivo. Apoptosis was not altered by caspase-8 inhibitor. No alterations in the levels of Bid, Fas and Fas-L were found suggesting that PpL does not activate the extrinsic pathway of apoptosis. The involvement of the intrinsic pathway was clearly indicated by: i) alterations in mitochondrial membrane potential (ΔΨm) both in murine and human lymphoma cells exposed to PpL; ii) decreased levels of apoptosis in the presence of caspase-9 inhibitor; iii) significant increases of Bim and Bax protein levels and downregulation of Bcl-2; iv) the translocation from the cytoplasm to the mitochondria of Bax and Bim pro-apoptotic proteins and its inhibition by caspase-9 inhibitor but not by caspase-8 inhibitor and v) the translocation of Bcl-2 protein from the mitochondria to the cytosol and its inhibition by caspase-9 inhibitor but not by caspase-8 inhibitor. The possibility of a therapeutic use of Sags in lymphoma/leukemia B cell malignancies is discussed. PMID:27603942

  2. Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function

    PubMed Central

    Szalontay, Luca; Schally, Andrew V; Popovics, Petra; Vidaurre, Irving; Krishan, Awtar; Zarandi, Marta; Cai, Ren-Zhi; Klukovits, Anna; Block, Norman L; Rick, Ferenc G

    2014-01-01

    Malignant melanoma is the deadliest form of skin cancer; the treatment of advanced and recurrent forms remains a challenge. It has recently been reported that growth hormone-releasing hormone (GHRH) receptor is involved in the pathogenesis of melanoma. Therefore, we investigated the effects of our new GHRH antagonists on a human melanoma cancer cell line. Antiproliferative effects of GHRH antagonists, MIA-602, MIA-606 and MIA-690, on the human melanoma cell line, A-375, were studied in vitro using the MTS assay. The effect of MIA-690 (5 μg/day 28 d) was further evaluated in vivo in nude mice bearing xenografts of A-375. Subcellular localization of p27 was detected with Western blot and immunofluorescent staining. MIA-690 inhibited the proliferation of A-375 cells in a dose-dependent manner (33% at 10 μM, and 19.2% at 5 μM, P < 0 .05 vs. control), and suppressed the growth of xenografted tumors by 70.45% (P < 0.05). Flow cytometric analysis of cell cycle effects following the administration of MIA-690 revealed a decrease in the number of cells in G2/M phase (from 19.7% to 12.9%, P < 0.001). Additionally, Western blot and immunofluorescent studies showed that exposure of A-375 cells to MIA-690 triggered the nuclear accumulation of p27. MIA-690 inhibited tumor growth in vitro and in vivo, and increased the translocation of p27 into the nucleus thus inhibiting progression of the cell cycle. Our findings indicate that patients with malignant melanoma could benefit from treatment regimens, which combine existing chemotherapy agents and novel GHRH-antagonists. PMID:25486366

  3. Role of malignant ascites on human mesothelial cells and their gene expression profiles

    PubMed Central

    2014-01-01

    Background Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions The results of this study not only provide evidence supporting the importance of the interplay between cancer

  4. Ossified spinal meningiomas: Clinical and surgical features.

    PubMed

    Alafaci, Concetta; Grasso, Giovanni; Granata, Francesca; Salpietro, Francesco M; Tomasello, Francesco

    2016-03-01

    Meningiomas constitute 25% of primary spinal tumors and predominantly involve the thoracic spinal cord. Although calcifications are commonly seen in intracranial meningiomas, gross calcifications are observed in only 1-5% of all spinal meningiomas. We report the clinical findings, surgical strategy and histological features of 9 patients with ossified spinal meningiomas (OSMs). Clinical and surgical features of 9 patients with ossified spinal meningiomas were retrospectively reviewed. There were 8 women and 1 man with a mean age of 59 years. In 7 patients, the lesions were localized in the thoracic segment of the spine while in 2 patients in the lower cervical segment. All patients presented with weakness of the lower limbs and hypoesthesia below the site level of the lesion. Only 2 patients presented with urinary incontinence. Gross-total resection of the tumor was achieved in 6 patients while in 3 a subtotal removal of the meningioma was obtained. In all patients the postoperative course was uneventful. Six patients presented with a significant neurological improvement while in 3 patients a mild improvement was observed. Microscopically, all tumors showed typical histological pattern of ossified meningioma. OSMs are amenable to surgery if the complete removal can be achieved. Because of their hard-rock consistency complete resection can be challenging. In difficult cases, subtotal removal can be advised and follow-up imaging is mandatory. Overall, the risk of long-term recurrence of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Prevalence of human papillomavirus in archival samples obtained from patients with cervical pre-malignant and malignant lesions from Northeast Brazil

    PubMed Central

    2010-01-01

    Background Human Papillomavirus (HPV) is considered as a necessary, but not sufficient, cause of cervical cancer. In this study, we aimed to assess the prevalence of HPV in a series of pre-malignant and malignant cervical lesion cases, to identify the virus genotypes, and to assess their distribution pattern according to lesion type, age range, and other considered variables. The samples were submitted to histopathological revision examination and analysed by polymerase chain reaction (PCR) for the presence of HPV DNA, followed by HPV typing by dot blot hybridisation. Findings Of the analysed samples, 53.7% showed pre-malignant cervical lesions, and 46.3% presented with cervical cancer. Most cancer samples (84.1%) were classified as invasive carcinoma. The mean age of these cancer patients was 47.3 years. The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cancer patients. HPV 16 was the most prevalent type, followed by HPV 18 and 58, including both single and double infections. Double infection was detected in 11.6% of the samples, and the most common combination was HPV 16+18. Conclusions Cervical cancer appears to occur in women in a lower age range in the studied area, compared to the situation in other Brazilian regions. Furthermore, among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women with more than one sexual partner, smokers, and individuals with less than an elementary education, relative to their counterparts. Findings The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cervical cancer patients from Northeast Brazil. HPV 16 was the most prevalent type, followed by HPV 18 and 58. The most common double infection was HPV 16+18. Cervical cancer appears to occur in women in a lower age range in the Northeast Brazil. Among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women

  6. Syntenic Relationships between Genomic Profiles of Fiber-Induced Murine and Human Malignant Mesothelioma

    PubMed Central

    Jean, Didier; Thomas, Emilie; Manié, Elodie; Renier, Annie; de Reynies, Aurélien; Lecomte, Céline; Andujar, Pascal; Fleury-Feith, Jocelyne; Galateau-Sallé, Françoise; Giovannini, Marco; Zucman-Rossi, Jessica; Stern, Marc-Henri; Jaurand, Marie-Claude

    2011-01-01

    Malignant mesothelioma (MM) is an aggressive tumor with a poor prognosis mainly linked to past asbestos exposure. Murine models of MM based on fiber exposure have been developed to elucidate the mechanism of mesothelioma formation. Genomic alterations in murine MM have now been partially characterized. To gain insight into the pathophysiology of mesothelioma, 16 murine and 35 human mesotheliomas were characterized by array-comparative genomic hybridization and were screened for common genomic alterations. Alteration of the 9p21 human region, often by biallelic deletion, was the most frequent alteration in both species, in agreement with the CDKN2A/CDKN2B locus deletion in human disease and murine models. Other shared aberrations were losses of 1p36.3–p35 and 13q14–q33 and gains of 5p15.3–p13 regions. However, some differences were noted, such as absence of recurrent alterations in mouse regions corresponding to human chromosome 22. Comparison between altered recurrent regions in asbestos-exposed and non–asbestos-exposed patients showed a significant difference in the 14q11.2–q21 region, which was also lost in fiber-induced murine mesothelioma. A correlation was also demonstrated between genomic instability and tumorigenicity of human mesothelioma xenografts in nude mice. Overall, these data show similarities between murine and human disease, and contribute to the understanding of the influence of fibers in the pathogenesis of mesothelioma and validation of the murine model for preclinical testing. PMID:21281820

  7. Malignant progression of an SV40-transformed human epidermal keratinocyte cell line.

    PubMed Central

    Brown, K. W.; Gallimore, P. H.

    1987-01-01

    Human foetal keratinocytes were transfected with a recombinant plasmid (pSV6-1) which contained an origin defective SV40 genome. The resulting transformed cell line had many properties in common with previously described SV40-transformed keratinocytes, including expression of simple epithelial-type keratins. It was non-tumourigenic in nude mice at early passages, forming small benign cysts, however, after approximately 46 in vitro passages, these transformed keratinocytes formed invasive squamous cell carcinomas in athymic nude mice. Several in vitro changes were associated with this acquisition of tumourigenicity (a) an alteration in cellular morphology, (b) development of a cytogenetically marked clone and (c) loss of cell surface fibronectin. The loss of fibronectin was also observed in vivo; cysts formed by SV6-1 Bam/HFK produced human fibronectin whereas tumours did not, although both tumours and cysts were laminin- and keratin-positive. These results indicate that the spontaneous development of secondary events in immortalised human cells may lead to the acquisition of a malignant phenotype. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2447927

  8. Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

    PubMed

    Dickinson, P J; Surace, E I; Cambell, M; Higgins, R J; Leutenegger, C M; Bollen, A W; LeCouteur, R A; Gutmann, D H

    2009-09-01

    Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

  9. Coexistence of cervico-thoracic extradural en-plaque meningioma with multiple intracranial meningiomas.

    PubMed

    Kale, Aydemir; Akyol, Cetin; Keskin, Emrah; Aydoğmuş, Evren; Aydın, Hasan Ali; Barut, Figen; Gül, Sanser; Kalaycı, Murat

    2014-01-01

    Meningioma is one of the most common tumors in the spinal cord. Extradural and en-plaque variety of meningioma occur less frequently. A 47-year-old woman is presented with radiculopathy signs. Magnetic resonance imaging revealed a lesion from C6 through T3 vertebral levels compressing the cord both anteriorly and posteriorly. Subtotally excision was performed and histopathologic signs showed transitional type of meningioma (WHO Grade 1). Post operatively, she had good neurological recovery. Intraoperative findings point out that the en-plaque meningioma was pure extradural. Twelve cases of pure extradural en-plaque meningioma have been reported in the literature. Besides, to the best our knowledge coexistence of "en plaque" spinal epidural meningioma with meningiomas in cranial cavity has not been reported. Complete resection is mandatory to prevent recurrence. Moreover, it is considerably difficult to remove the parts of tumor over anterior of the dura without complication. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy

    PubMed Central

    2010-01-01

    Background The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. Results To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Conclusions Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation. PMID:20630075

  11. Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

    PubMed Central

    Arena, Vincenzo; Arena, Manuel; Arena, Goffredo Orazio

    2017-01-01

    The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells. PMID:28068409

  12. Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment.

    PubMed

    Zhou, Shufeng; Abdouh, Mohamed; Arena, Vincenzo; Arena, Manuel; Arena, Goffredo Orazio

    2017-01-01

    The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells.

  13. c-RET Molecule in Malignant Melanoma from Oncogenic RET-Carrying Transgenic Mice and Human Cell Lines

    PubMed Central

    Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

    2010-01-01

    Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma. PMID:20422010

  14. Radiation therapy for primary optic nerve meningiomas.

    PubMed

    Smith, J L; Vuksanovic, M M; Yates, B M; Bienfang, D C

    1981-06-01

    Optic nerve sheath meningiomas, formerly thought to be rare, have been encountered with surprising frequency since the widespread use of computed tomography. Early diagnosis led to an enthusiastic surgical approach to these lesions, but this has been tempered by the realization that even in the best of hands, blindness followed such surgery with distressing frequency. Optic nerve sheath meningiomas may be divided into primary, secondary, and multiple meningioma groups. Five patients with primary optic nerve sheath meningiomas treated with irradiation therapy are presented in this report. Improvement in visual acuity, stabilization to increase in the visual field, and decrease in size to total regression of optociliary veins, have been documented following irradiation therapy of the posterior orbital and intracanalicular portions of the optic nerve in some of these cases. Although each patient must be carefully individualized, there is no question that visual palliation can be achieved in some cases of optic nerve sheath meningioma. Further investigation of this therapeutic modality in selected cases in advised.

  15. Transformation of a meningioma with atypical imaging

    PubMed Central

    Kumar, Ashish; Deopujari, Chandrashekhar; Karmarkar, Vikram

    2016-01-01

    Meningiomas are benign tumors of the central nervous system. They have long term curability if they are excised completely. If not, they can recur after a prolonged period and can lead to increased morbidity during re-surgery. Recurrence is rarely associated with invasiveness. Usually de-differentiation in case of meningiomas is uncommon without any predisposing factors including different genetic mutations or radiation to the involved region. We report a case of a 38-year-old female who was operated for a benign para-sagittal meningioma 8 years back and subsequently developed an invasive recurrence off late. Also this time, the imaging morphology was slightly different for a meningioma and gross as well as microscopic findings were very atypical. Awareness for such cases must be there while dealing with recurrent meningiomas as invasiveness may not always be associated with adverse predisposing factors like radiation. As invasiveness is always a histopathological diagnosis, picking up such features on imaging is a daunting task and if done, can help neurosurgeons prognosticate such invasive recurrences in a better fashion. PMID:27366271

  16. [Ptosis secondary to cavernous sinus meningioma].

    PubMed

    Louis, M; Goga, D; François, P; Laure, B

    2013-12-01

    Meningiomas of the cavernous sinus are often the cause of neuro-ophthalmologic manifestations. Fifty percent of affected patients present with ptosis. We report a case of ptosis acquired during the first year of life due to oculomotor nerve palsy secondary to a cavernous sinus meningioma. We then discuss the causes of third cranial nerve palsy and treatment options for ptosis associated with CN III palsy. A fifteen-year-old female patient presented with ptosis due to a third cranial nerve palsy appearing within the first year of life. Magnetic resonance imaging (MRI) revealed a cavernous sinus meningioma. The ptosis was treated by frontalis suspension using autologous temporalis fascia. The meningioma required regular follow-up. Ptosis due to third cranial nerve palsy is rare in children. The most common etiologies are congenital and represent 33 to 40% of cases in various studies. Other etiologies are traumatic, tumoral, vascular and infectious. The cause needs to be found by imaging over the entire course of the nerve. Cavernous sinus meningioma is one cause of third cranial nerve palsy. The surgical treatment of ptosis due to third cranial nerve palsy is levator resection or frontalis suspension with a strip of fascia lata or temporalis fascia. Copyright © 2013. Published by Elsevier Masson SAS.

  17. Dorsal spinal epidural psammomatous meningioma in an adult male

    PubMed Central

    Pandey, Sharad; Singh, Kulwant; Sharma, Vivek; Ghosh, Amrita; Suman, Saurabh

    2016-01-01

    Meningiomas are benign in nature and arise from the arachnoid cells. They are mostly situated in the intracranial compartment, whereas spinal meningiomas are rare. Approximately, in 10% of cases, an extradural component is seen but an exclusively extradural meningioma is quite uncommon. However, WHO Grade II (atypical) and Grade III (anaplastic) tumors can behave aggressively. We reported a case of purely extradural psammomatous meningioma in an adult male affecting the dorsal spine although uncommon meningiomas should be included in the differential diagnosis of extradural intraspinal masses. PMID:26933358

  18. Dorsal spinal epidural psammomatous meningioma in an adult male.

    PubMed

    Pandey, Sharad; Singh, Kulwant; Sharma, Vivek; Ghosh, Amrita; Suman, Saurabh

    2016-01-01

    Meningiomas are benign in nature and arise from the arachnoid cells. They are mostly situated in the intracranial compartment, whereas spinal meningiomas are rare. Approximately, in 10% of cases, an extradural component is seen but an exclusively extradural meningioma is quite uncommon. However, WHO Grade II (atypical) and Grade III (anaplastic) tumors can behave aggressively. We reported a case of purely extradural psammomatous meningioma in an adult male affecting the dorsal spine although uncommon meningiomas should be included in the differential diagnosis of extradural intraspinal masses.

  19. Intraventricular meningioma after cranial irradiation for childhood leukemia.

    PubMed

    Ney, Douglas E; Huse, Jason T; Dunkel, Ira J; Steinherz, Peter G; Haque, Sofia; Khakoo, Yasmin

    2010-10-01

    Meningiomas are among the most common brain tumors in adults. They are most commonly located over the cerebral convexities and are infrequently found in an intraventricular location. Ionizing cranial radiation is a risk factor for late occurrence of meningiomas within the radiation field. While pathologic grading of meningiomas is straightforward, significant variability often exists between pathologists in applying standard grading criteria. This has implications for prognosis. Radiation-induced meningiomas may also have predilection to recur. The authors describe a case of an intraventricular meningioma occurring 23 years after cranial irradiation for childhood acute lymphoblastic leukemia.

  20. Influence of zinc deficiency on AKT-MDM2-P53 signaling axes in normal and malignant human prostate cells

    USDA-ARS?s Scientific Manuscript database

    With prostate being the highest zinc-accumulating tissue before the onset of cancer, the effects of physiologic levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined. Cells were cultured for 6 d in...

  1. Peroxisome proliferator-activated receptor- gamma expression in human malignant and normal brain, breast and prostate-derived cells.

    PubMed

    Nwankwo, J O; Robbins, M E

    2001-01-01

    The constitutive and gamma -linolenic acid (GLA)-induced expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) immunoreactive protein in a panel of human malignant brain (U87MG, T98G); breast (MCF-7, MB MDA-231, MB MDA 435) and prostate (ALVA, DU-145, LNCaP, PC3) cell lines have been compared with those for their normal cell counterparts, the human normal astrocyte (NHA), mammary epithelial (HMEC) and prostate epithelial (PrEC) cells, respectively. Constitutive levels of expression for PPAR gamma protein were significantly higher in the malignant cell lines relative to their normal cells. GLA supplementation did not affect the protein expression in malignant cells but caused 6- and 3-fold increases in normal breast and prostate cells, respectively. Since activation of PPAR gamma protein in some human malignant cell lines has been demonstrated to induce tumour cell death, these findings signal the need to exploit the significantly elevated expression of this protein in the therapy of human cancer. Copyright 2001 Harcourt Publishers Ltd.

  2. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

    PubMed Central

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-01-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. PMID:22289125

  3. Human beta-defensin-2 controls cell cycle in malignant epithelial cells: in vitro study.

    PubMed

    Zhuravel, E; Shestakova, T; Efanova, O; Yusefovich, Yu; Lytvin, D; Soldatkina, M; Pogrebnoy, P

    2011-09-01

    In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 μM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)(2)D(3) has shown similar cell growth suppression effect of native endogenously produced hBD-2. The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB.

  4. Maternally Expressed Gene 3, an imprinted non-coding RNA gene, is associated with meningioma pathogenesis and progression

    PubMed Central

    Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A.; Zhou, Yunli; Cheunsuchon, Pornsuk; Louis, David N.; Klibanski, Anne

    2010-01-01

    Meningiomas are common tumors, representing 15-25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. Chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore it has been proposed that an as yet unidentified tumor suppressor is present at this locus. MEG3 is an imprinted gene located at 14q32 that encodes a non-coding RNA with an anti-proliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by approximately 60% in BrdU incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by approximately 80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a non-coding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism. PMID:20179190

  5. Involvement of F-BOX proteins in progression and development of human malignancies.

    PubMed

    Uddin, Shahab; Bhat, Ajaz A; Krishnankutty, Roopesh; Mir, Fayaz; Kulinski, Michal; Mohammad, Ramzi M

    2016-02-01

    The Ubiquitin Proteasome System (UPS) is a core regulator with various protein components (ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, ubiquitin-protein E3 ligases, and the 26S proteasome) which work together in a coordinated fashion to ensure the appropriate and efficient proteolysis of target substrates. E3 ubiquitin ligases are essential components of the UPS machinery, working with E1 and E2 enzymes to bind substrates and assist the transport of ubiquitin molecules onto the target protein. As the UPS controls the degradation of several oncogenes and tumor suppressors, dysregulation of this pathway leads to several human malignancies. A major category of E3 Ub ligases, the SCF (Skp-Cullin-F-box) complex, is composed of four principal components: Skp1, Cul1/Cdc53, Roc1/Rbx1/Hrt1, and an F-box protein (FBP). FBPs are the substrate recognition components of SCF complexes and function as adaptors that bring substrates into physical proximity with the rest of the SCF. Besides acting as a component of SCF complexes, FBPs are involved in DNA replication, transcription, cell differentiation and cell death. This review will highlight the recent literature on three well characterized FBPs SKP2, Fbw7, and beta-TRCP. In particular, we will focus on the involvement of these deregulated FBPs in the progression and development of various human cancers. We will also highlight some novel substrates recently identified for these FBPs.

  6. Radiosurgical planning of meningiomas: compromises with conformity.

    PubMed

    Rowe, Jeremy G; Walton, Lee; Vaughan, Paul; Malik, Irfan; Radatz, Matthias; Kemeny, Andras

    2004-01-01

    The radiosurgical planning of meningiomas frequently necessitates compromises between irradiating tumour and risking damage to adjacent structures. In selected cases, we resolved this by excluding part of the tumour from the prescription isodose volume. Most of these compromises or 'suboptimal' plans achieved growth control. Growth control could not be related to conformity indices or to various measures of the radiation dose received by the meningioma. Examining recurrences, 75% arose from dura outside the original treatment field. These findings are discussed in terms of dose prescription protocols and the use of conformity indices in planning. The importance of the dural origin of meningiomas is well established in surgical practice, as reflected by Simpson's grades, but may be equally significant in radiosurgical practice.

  7. Pediatric spinal clear cell meningioma. Case report.

    PubMed

    Colen, Chaim B; Rayes, Mahmoud; McClendon, Jamal; Rabah, Raja; Ham, Steven D

    2009-01-01

    In this report the authors describe a unique case of spinal clear cell meningioma in a 13-year-old girl. Clear cell meningiomas (CCMs) are not uncommon. To the authors' knowledge, 14 cases of pediatric CCM occurring in the spinal canal have been reported. Factors lending resistance to meningioma initiation and invasion are analyzed. This 13-year-old girl presented with pain radiating down her left leg. Admission MR imaging showed an inhomogeneous enhancing intradural-extramedullary mass at the L4-5 level. Resection revealed a CCM, and radiotherapy was subsequently administered. Postoperatively there has been no recurrence in > 2 years. In this paper the authors report a case of CCM and provide a comprehensive literature review on this disease. Current recommendations for its management are still debatable, especially in the pediatric population, and the authors propose an algorithm for its treatment and surveillance.

  8. Cervical spinal extradural meningioma: Case report.

    PubMed

    Benzagmout, M; Azzal, F; Bitar, A; El Faïz Chaoui, M; Van Effenterre, R

    2010-10-01

    Extradural meningiomas account for approximately 7% of all spinal meningiomas and are most commonly located in the thoracic spine. Although rare, they should be included in the differential diagnosis of an extradural contrast-enhancing mass. Prognosis depends greatly on the extent of surgical resection. If considered safe, complete resection should be attempted to decrease the risk of recurrence. We report a case of spinal epidural meningioma diagnosed in an elderly woman complaining of right cervicobrachial pain of several years duration, associated with diffuse paresthesia and permanent numbness of her right index finger. The surgical removal of the tumor was incomplete because of the deep lateral extension of the lesion. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  9. Spinal subdural hematoma following meningioma removal operation.

    PubMed

    Jun, Hyo Sub; Oh, Jae Keun; Park, Young Seok; Song, Joon Ho

    2014-03-01

    Although blood contamination of cerebrospinal fluid (CSF) after an intracranial operation can occur, the development of a symptomatic spinal hematoma after craniotomy has been anecdotally reported and it is uncommon reported after a supratentorial meningioma removal operation. We report a case of spinal subdural hematoma following a supratentorial meningioma removal operation and discuss the mechanism of spinal subdural hematoma (SSDH) development. A 54-year-old woman presented with lumbago and radicular pain on both legs 4 days after a right parietooccipital craniotomy for meningioma removal. Only the straight leg raising sign was positive on neurologic examination but the magnetic resonance imaging (MRI) demonstrated a lumbosacral spinal subdural hematoma. The patient received serial lumbar tapping, after which her symptoms showed improvement.

  10. Spinal Subdural Hematoma Following Meningioma Removal Operation

    PubMed Central

    Jun, Hyo Sub; Oh, Jae Keun; Park, Young Seok

    2014-01-01

    Although blood contamination of cerebrospinal fluid (CSF) after an intracranial operation can occur, the development of a symptomatic spinal hematoma after craniotomy has been anecdotally reported and it is uncommon reported after a supratentorial meningioma removal operation. We report a case of spinal subdural hematoma following a supratentorial meningioma removal operation and discuss the mechanism of spinal subdural hematoma (SSDH) development. A 54-year-old woman presented with lumbago and radicular pain on both legs 4 days after a right parietooccipital craniotomy for meningioma removal. Only the straight leg raising sign was positive on neurologic examination but the magnetic resonance imaging (MRI) demonstrated a lumbosacral spinal subdural hematoma. The patient received serial lumbar tapping, after which her symptoms showed improvement. PMID:24891866

  11. Primary pulmonary meningioma: A case report.

    PubMed

    Huang, Shucheng; Chen, Li; Mao, Yuping; Tong, Hongwei

    2017-05-01

    Primary extracranial meningiomas are rare outside the head and neck region. A 44-year-old female patient had chest pain for more than 1 year. Preoperative chest computed tomography (CT) scan revealed a nodule in the right lower lobe, 1.8 cm in diameter. Tumor tissues were examined by immunohistochemistry for vimentin and S-100. Histopathologically, the tumor was characterized by whorled nests of spindle-shaped cells accompanied by psammoma bodies. Immunohistochemistry demonstrated tumor cell positivity for vimentin and S-100. This case was diagnosed as a primary pulmonary meningioma. The tumor was removed by a thoracoscopic pulmonary wedge resection. Postoperative cranial and spinal CT scan did not show any intracranial or spinal mass. No recurrence of the tumor was reported at the time of writing up this case report. A primary pulmonary meningioma should be considered in the differential diagnosis workup of pulmonary nodules.

  12. Posterior approach to ventrally located spinal meningiomas

    PubMed Central

    Voulgaris, Spyridon; Mihos, Evaggelos; Karagiorgiadis, Dimitrios; Zigouris, Andreas; Fotakopoulos, George; Drosos, Dimitrios; Pahaturidis, Dimitrios

    2010-01-01

    For the resection of anteriorly located meningiomas, various approaches have been used. Posterior approach is less invasive and demanding; however, it has been associated with increased risk of spinal cord injury. We evaluated ten consecutive patients that underwent surgery for spinal meningiomas. All patients were preoperative assessed by neurological examination, computed tomography and magnetic resonance imaging. All tumors were ventrally located and removed via a posterior approach. Transcranial motor-evoked potentials (TcMEPs), somatosensory-evoked potential (SSEP) and free running electromyography (EMG) were monitored intraoperative. Postoperative all patients had regular follow-up examinations. There were four males and six females. The mean age was 68.2 years (range 39–82 years). In nine out of ten cases, the tumor was located in the thoracic spine. A case of a lumbar meningioma was recorded. The most common presenting symptom was motor and sensory deficits and unsteady gait, whereas no patient presented with paraplegia. All meningiomas were operated using a microsurgical technique via a posterior approach. During the operation, free running EMG monitoring prompted a surgical alert in case of irritation, whereas TcMEP and SSEP amplitudes remained unchanged. Histopathology revealed the presence of typical (World Health Organisation grade I) meningiomas. The mean Ki-67/MIB-1 index was 2.75% (range 0.5–7). None of our patients sustained a transient or permanent motor deficit. After a mean follow-up period of 26 months (range 56–16 months), no tumor recurrence and no instability were found. Posterior approach for anteriorly located meningiomas is a safe procedure with the use of intraoperative monitoring, less invasive and well-tolerated especially in older patients. Complete tumor excision can be performed with satisfactory results. PMID:20127494

  13. Posterior approach to ventrally located spinal meningiomas.

    PubMed

    Voulgaris, Spyridon; Alexiou, George A; Mihos, Evaggelos; Karagiorgiadis, Dimitrios; Zigouris, Andreas; Fotakopoulos, George; Drosos, Dimitrios; Pahaturidis, Dimitrios

    2010-07-01

    For the resection of anteriorly located meningiomas, various approaches have been used. Posterior approach is less invasive and demanding; however, it has been associated with increased risk of spinal cord injury. We evaluated ten consecutive patients that underwent surgery for spinal meningiomas. All patients were preoperative assessed by neurological examination, computed tomography and magnetic resonance imaging. All tumors were ventrally located and removed via a posterior approach. Transcranial motor-evoked potentials (TcMEPs), somatosensory-evoked potential (SSEP) and free running electromyography (EMG) were monitored intraoperative. Postoperative all patients had regular follow-up examinations. There were four males and six females. The mean age was 68.2 years (range 39-82 years). In nine out of ten cases, the tumor was located in the thoracic spine. A case of a lumbar meningioma was recorded. The most common presenting symptom was motor and sensory deficits and unsteady gait, whereas no patient presented with paraplegia. All meningiomas were operated using a microsurgical technique via a posterior approach. During the operation, free running EMG monitoring prompted a surgical alert in case of irritation, whereas TcMEP and SSEP amplitudes remained unchanged. Histopathology revealed the presence of typical (World Health Organisation grade I) meningiomas. The mean Ki-67/MIB-1 index was 2.75% (range 0.5-7). None of our patients sustained a transient or permanent motor deficit. After a mean follow-up period of 26 months (range 56-16 months), no tumor recurrence and no instability were found. Posterior approach for anteriorly located meningiomas is a safe procedure with the use of intraoperative monitoring, less invasive and well-tolerated especially in older patients. Complete tumor excision can be performed with satisfactory results.

  14. Glioblastoma Mimicking Meningioma: Report of 2 Cases.

    PubMed

    Patel, Mohit; Nguyen, Ha Son; Doan, Ninh; Gelsomino, Michael; Shabani, Saman; Mueller, Wade

    2016-11-01

    Glioblastoma can mimic various pathologies, including arteriovenous malformation, hemorrhage from ischemic stroke, cerebral contusion, metastatic disease, lymphoma, and infection. The literature is limited regarding diagnostic confusion with meningioma. Herein, we present 2 patients that exhibited imaging, including cerebral angiography during preoperative embolization, which was consistent with meningioma, but where final surgical diagnosis revealed glioblastoma. Case 1 was a 57-year-old woman presenting with headache, ataxia, and memory lapses for the past month. Brain magnetic resonance imaging (MRI) demonstrated a heterogeneous-enhancing right temporoparietal mass with broad contact along the right tentorium, cerebrospinal fluid (CSF) cleft sign, and dural tail sign-consistent with meningioma. Patient underwent angiography with successful polyvinyl alcohol foam (PVA) particle embolization of the petrosquamosal branch of the right middle meningeal artery (MMA) and meningeal branch of the right occipital artery, resulting in significant devascularization of the tumor blush. Subsequently, the patient underwent tumor resection, where pathology revealed glioblastoma. Case 2 was a 60-year-old man presenting with right hemiparesis. Brain MRI demonstrated a left parasagittal, heterogeneous-enhancing mass abutting the falx with a dural tail sign-consistent with meningioma. Patient underwent angiography with successful PVA particle embolization of the left MMA, resulting in significant devascularization of the tumor blush. Patient underwent a tumor resection where pathology revealed glioblastoma. Glioblastoma can mimic meningioma on MRI with dural tail sign, CSF cleft sign, and broad dural contact. Moreover, cerebral angiography can reveal tumor feeders commonly associated with meningioma. These features can contribute to diagnostic confusion. Based on these 2 cases, preoperative embolization of tumor feeders is possible with glioblastoma. Copyright © 2016 The Author

  15. Ectopic over-expression of oncogene Pim-2 induce malignant transformation of nontumorous human liver cell line L02.

    PubMed

    Ren, Ke; Duan, Wentao; Shi, Yujun; Li, Bo; Liu, Zuojin; Gong, Jiangping

    2010-07-01

    In order to prove that ectopic over-expression of Pim-2 could induce malignant transformation of human liver cell line L02, three groups of cells were set up including human liver cell line L02 (L02), L02 cells transfected with Pim-2 gene (L02/Pim-2) and L02 cells transfected with empty-vector (L02/Vector). Pim-2 expression levels were detected. The morphology, proliferation level, apoptosis rate and migration ability of the cells were detected respectively. Then the cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed. Compared with the controls, Pim-2 expression levels were significantly higher in L02/Pim-2 cells (P<0.05), and their morphology had obvious malignant changes. They also showed a significantly increased proliferation rate (P<0.05) and migration capacity (P<0.05), as well as a significantly decreased apoptosis rate (P<0.05). Only the athymic mice inoculated with L02/Pim-2 cells could generate neoplasm, and the morphology of the neoplasm coincided with that of the hepatoma. The results manifest that ectopic Pim-2 gene could be stably expressed in L02/Pim-2 cells. Both the morphological and biological changes of L02/Pim-2 cells demonstrate the trend of malignant transformation. L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02.

  16. Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject

    SciTech Connect

    Fishkin, J.B.; Coquoz, O.; Anderson, E.R.; Brenner, M.; Tromberg, B.J. |

    1997-01-01

    A 1-GHz multifrequency, multiwavelength frequency-domain photon migration instrument is used to measure quantitatively the optical absorption ({mu}{sub a}) and effective optical scattering ({mu}{sub s}{sup {prime}}) of normal and malignant tissues in a human subject. Large ellipsoidal ({approximately}10-cm major axis, {approximately}6-cm minor axes) subcutaneous malignant lesions were compared with adjacent normal sites in the abdomen and back. Absorption coefficients recorded at 674, 811, 849, and 956 nm were used to calculate tissue hemoglobin concentration (oxyhemoglobin, deoxyhemoglobin, and total), water concentration, hemoglobin oxygen saturation, and blood volume fraction {ital in vivo}. Our results show that the normal and the malignant tissues measured in the patient have clearly resolvable optical and physiological property differences that may be broadly useful in identifying and characterizing tumors.{copyright} 1997 Optical Society of America

  17. Contemporary Endovascular Embolotherapy for Meningioma

    PubMed Central

    Dubel, Gregory J.; Ahn, Sun Ho; Soares, Gregory M.

    2013-01-01

    Preoperative endovascular tumor embolization has been used for 40 years. Meningiomas are the most common benign intracranial tumor in which preoperative embolization has been most extensively described in the literature. Advocates of embolization report that it reduces operative blood-loss, and softens the tumor, thus making surgery safer and easier. Opponents suggest that it adds additional risk and cost for patients without controlled studies showing conclusive benefit. The literature suggests a 3 to 6% neurological complication rate related to embolization. The combined external and internal carotid artery blood supply and complex anastomoses of the meninges can make embolization challenging. Positive outcomes require thorough knowledge of the pertinent vascular anatomy, familiarity with the neurovascular equipment and embolics, and meticulous technique. There remains debate on several aspects of embolization, including tumors most appropriate for embolization, embolic agent of choice, ideal size of embolic, and the choice of vessel(s) to embolize. This detailed review of pertinent vascular anatomy, embolization technique, results, and complications should allow practitioners to maximize treatment outcomes in this setting. PMID:24436548

  18. Meningioma after radiotherapy for Hodgkin's disease.

    PubMed

    Deutsch, M; Rosenstein, M; Figura, J H

    1999-08-01

    The most common second primary tumors after treatment of childhood Hodgkin's disease are leukemia, lymphoma, breast cancer, soft tissue sarcoma, and thyroid cancer. Although intracranial meningioma has been reported after radiotherapy to the scalp for benign conditions and for intracranial primary brain tumors, this appears to be an extremely rare sequelae of treatment for Hodgkin's disease. The authors describe a 15-year-old boy who underwent radiotherapy for Hodgkin's disease and in whom a meningioma developed in the posterior fossa 27 years later.

  19. Predicting Meningioma Consistency on Preoperative Neuroimaging Studies

    PubMed Central

    Shiroishi, Mark S.; Cen, Steven Y.; Tamrazi, Benita; D'Amore, Francesco; Lerner, Alexander; King, Kevin S.; Kim, Paul E.; Law, Meng; Hwang, Darryl H.; Boyko, Orest B.; Liu, C. Jason

    2016-01-01

    Synopsis This article provides an overview of the neuroimaging literature focused on pre-operative prediction of meningioma consistency. A validated, non-invasive neuroimaging method to predict tumor consistency can provide valuable information regarding neurosurgical planning and patient counseling. Most of the neuroimaging literature indicates conventional MRI using T2-weighted imaging (T2WI) may be helpful to predict meningioma consistency, however, further rigorous validation is necessary. Much less is known about advanced MRI techniques such as diffusion MRI, MR elastography (MRE) and MR spectroscopy (MRS). Of these methods, MRE and DTI appear particularly promising. PMID:27012379

  20. Meningiomas of the velum interpositum: surgical considerations.

    PubMed

    Lozier, Alan P; Bruce, Jeffrey N

    2003-07-15

    Meningiomas of the third ventricle are a rare subtype of pineal region tumor that arise from the posterior portion of the velum interpositum, the double layer of pia mater that forms the roof of the third ventricle. The authors review the literature concerning these meningiomas and present a case in which the lesion was resected via the supracerebellar-infratentorial approach. The relationship of the tumor to the deep venous system and the splenium of the corpus callosum guides the selection of the most advantageous surgical approach. Posterior displacement of the internal cerebral veins demonstrated on preoperative imaging provides a strong rationale for use of the supracerebellar-infratentorial approach.

  1. Giant velum interpositum meningioma in a child.

    PubMed

    Moiyadi, Aliasgar V; Shetty, Prakash

    2012-07-01

    Intraventricular meningiomas are rare, but are relatively more often seen in children. Large size at presentation often obscures anatomical details. A particular subset of such tumors arising from the velum interpositum pose a significant surgical challenge. Thorough preoperative imaging, especially with respect to the course of the deep venous structures, provides useful evidence as to the origin. Preservation of venous anatomy at surgery is vital. We describe a 3-year-old girl with a giant velum interpositum meningioma that was completely excised with excellent outcome. This is probably the youngest such case reported.

  2. Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo.

    PubMed

    Wang, Hao; Yang, Yifei; Wang, Wei; Guan, Bing; Xun, Meng; Zhang, Hai; Wang, Ziling; Zhao, Yong

    2017-05-01

    Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

  3. Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies

    PubMed Central

    Johnson, Benny; Mahadevan, Daruka

    2015-01-01

    Background: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of the CEA family of cell adhesion proteins that belong to the immunoglobulin superfamily. CEACAM6 is normally expressed on the surface of myeloid (CD66c) and epithelial surfaces. Stiochiomertic expression of members of the CEA family (CEACAM1, 5, 6, 7) on epithelia maintains normal tissue architecture through homo-and hetero-philic interactions. Dysregulated over-expression of CEACAM6 is oncogenic, is associated with anoikis resistance and an invasive phenotype mediated by excessive TGFβ, AKT, FAK and SRC signaling in human malignancies. Methods: Extensive literature review through PubMed was conducted to identify relevant preclinical and clinical research publications regarding CEACAM6 over the last decade and was summarized in this manuscript. Results: CEACAM5 and 6 are over-expressed in nearly 70% of epithelial malignancies including colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDA), hepatobiliary, gastric, breast, non-small cell lung and head/neck cancers. Importantly, CEACAM6 is a poor prognostic marker in CRC, while its expression correlates with tumor stage, metastasis and post-operative survival in PDA. CEACAM6 appears to be an immune checkpoint suppressor in hematologic malignancies including acute lymphoblastic leukemia and multiple myeloma. Several therapeutic monoclonal antibodies or antibody fragments targeting CEACAM6 have been designed and developed as a targeted therapy for human malignancies. A Llama antibody targeting CEACAM6 is being evaluated in early phase clinical trials. Conclusion: This review focuses on the role of CEACAM6 in the pathogenesis and signaling of the malignant phenotype in solid and hematologic malignancies and highlights its potential as a therapeutic target for anti-cancer therapy. PMID:27595061

  4. Clinical Significance of EphB4 and EphB6 Expression in Human Malignant and Benign Thyroid Lesions.

    PubMed

    Giaginis, Constantinos; Alexandrou, Paraskevi; Poulaki, Elpida; Delladetsima, Ioanna; Troungos, Constantinos; Patsouris, Efstratios; Theocharis, Stamatios

    2016-04-01

    Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of EphB4 and EphB6 protein expression in human malignant and benign thyroid lesions. EphB4 and EphB6 protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 127 patients with benign (n = 71) and malignant (n = 56) thyroid lesions. Enhanced EphB4 and EphB6 expression was more frequently observed in malignant compared to benign thyroid lesions (p = 0.0508 and p = 0.0006, respectively). EphB4 and EphB6 expression also provided a distinct discrimination between papillary carcinoma and hyperplastic nodules (p = 0.0302 and p = 0.0013, respectively). In malignant thyroid lesions, enhanced EphB4 expression was significantly associated with larger tumor size (p = 0.0366). Enhanced EphB6 expression was significantly associated with larger tumor size (p = 0.0366), the presence of lymph node metastases (p = 0.0023), the presence of capsular (p = 0.0038), lymphatic (p = 0.0053) and vascular invasion (p = 0.0018) and increased risk of recurrence rate (p = 0.0038). The present study supported evidence that EphB4 and mainly EphB6 may participate in the malignant thyroid transformation, reinforcing their utility as useful biomarkers and possible therapeutic targets in this type of neoplasia.

  5. On the growth rates of human malignant tumors: implications for medical decision making.

    PubMed

    Friberg, S; Mattson, S

    1997-08-01

    Testicular carcinomas, pediatric tumors, and some mesenchymal tumors are examples of rapidly proliferating cell populations, for which the tumor volume doubling time (TVDT) can be counted in days. Cancers from the breast, prostate, and colon are frequently slow-growing, displaying a TVDT of months or years. Irrespective of their growth rates, most human tumors have been found: to start from one single cell, to have a long subclinical period, to grow at constant rates for long periods of time, to start to metastasize often even before the primary is detected, and to have metastases that often grow at approximately the same rate as the primary tumor. The recognition of basic facts in tumor cell kinetics is essential in the evaluation of important present-day strategies in oncology. Among the facts emphasized in this review are: (1) Screening programs. Most tumors are several years old when detectable by present-day diagnostic methods. This makes the term "early detection" questionable. (2) Legal trials. The importance of so-called doctor's delay is often discussed, but the prognostic value of "early" detection is overestimated. (3) Analyses of clinical trials. Such analysis may be differentiated depending on the growth rates of the type of tumor studied. Furthermore, uncritical analysis of survival data may be misleading if the TVDT is not taken into consideration. (4) Analyses of epidemiological data. If causes of malignant tumors in humans are searched for, the time of exposure must be extended far back in the subject's history. (5) Risk estimations by insurance companies. For the majority of human cancers, the 5-year survival rate is not a valid measurement for cure. Thus, basic knowledge of tumor kinetics may have important implications for political health programs, legal trials, medical science, and insurance policies.

  6. Lack of Decorin Expression by Human Bladder Cancer Cells Offers New Tools in the Therapy of Urothelial Malignancies

    PubMed Central

    Lund, Riikka; Vuorikoski, Sanna; Boström, Pia; Laato, Matti; Boström, Peter J.; Järveläinen, Hannu

    2013-01-01

    Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demonstrated using the publicly available GeneSapiens databank that decorin gene expression is present in both normal and malignant human bladder tissues. However, when we applied in situ hybridization with digoxigenin-labeled RNA probes for decorin on human bladder carcinoma tissue samples derived from a large radical cystectomy patient cohort (n = 199), we unambiguously demonstrated that invasive and non-invasive bladder carcinoma cells completely lack decorin mRNA. The cancer cells were also negative for decorin immunoreactivity. Instead, decorin expression was localized solely to original non-malignant stromal areas of bladder tissue. In accordance with the aforementioned results, human bladder cancer cells in vitro were also negative for decorin expression as shown by RT-qPCR analyses. The lack of decorin expression by bladder cancer cells was shown not to be due to the methylation of the proximal promoter region of the decorin gene. When bladder cancer cells were transfected with a decorin adenoviral vector, their proliferation was significantly decreased. In conclusion, we have shown that human bladder cancer cells are totally devoid of decorin expression. We have also shown that adenovirus-mediated decorin gene transduction of human bladder cancer cell lines markedly inhibits their proliferation. Thus, decorin gene delivery offers new potential therapeutic tools in urothelial malignancies. PMID:24146840

  7. Involvement of human beta-defensin-2 in regulation of malignant potential of cultured human melanoma cells.

    PubMed

    Gerashchenko, O; Zhuravel, E; Skachkova, O; Khranovska, N; Pushkarev, V; Pogrebnoy, P; Soldatkina, M

    2014-03-01

    Human beta-defensin-2 (hBD-2) is an antimicrobial cationic peptide capable to control human carcinoma cell growth via cell cycle regulation. The present study was aimed on determination of hBD-2 influence on the growth patterns and malignant potential of cultured human melanoma cells. The study was performed on cultured human melanoma cells of mel Z and mel Is lines treated with recombinant hBD-2 (rec-hBD-2); cell viability, proliferation, cell cycle distribution, and anchorage-independent growth were analyzed using MTT test, direct cell counting, flow cytometry, and colony forming assay respectively. Expression and/or phosphorylation levels of proteins involved in cell cycle control were evaluated by Western blotting. The treatment of mel Z and mel Is cells with rec-hBD-2 in a concentration range of 100-1000 nM resulted in a concentration-dependent suppression of cell proliferation, viability, and colony forming activity. It has been shown that rec-hBD-2 exerts its growth suppression effects via significant downregulation of B-Raf expression, activation of pRB and upregulation of p21(WAF1) expression, downregulation of cyclin D1 and cyclin E resulting in cell cycle arrest at G1/S checkpoint. According to obtained results, hBD-2 exerts its growth suppression effect toward human melanoma cells via downregulation of B-Raf, cyclin D1 and cyclin E expression, upregulation of p21(WAF1) expression and activation of pRB.

  8. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  9. Discrimination between spinal extradural meningioma and both intra and extradural meningioma: Case Report.

    PubMed

    Ito, Kenyu; Imagama, Shiro; Ando, Kei; Kobayashi, Kazuyoshi; Hida, Tetsuro; Tsushima, Mikito; Matsumoto, Akiyuki; Morozumi, Masayoshi; Tanaka, Satoshi; Nishida, Yoshihiro; Ishiguro, Naoki

    2017-02-01

    Meningiomas are common spinal tumor and mostly located at intradura. Recurrence rate after surgery for extradural meningioma was higher than intradural meningioma. A patient with intra and extradural spinal meningioma was treated and discussed its features and clinical management. A 41-year-old woman noted numbness of bilateral legs, gait disturbance, and mild bladder disturbance for over the two-month period. Magnetic resonance imaging revealed an epidural mass at T8-9 involving the dura mater from the left side. Intraoperatively, ultrasonography showed extradural tumor suppress the dura from the left side and no subarachnoid space. Therefore, it was difficult to diagnose the tumor was located at only extradural or both intra and extradural. The extradural tumor was resected as much as possible, then ultrasonography was performed for the second time. The spinal cord was decompressed and subarachnoid space was appeared with intradural tumor. The dura mater was opened in the midline for intradural exploration, and the intradural tumor appeared beside the spinal cord. The dura mater with attachment to the tumor was rescected. To prevent a recurrence, ultrasonography after removing extradural tumor is recommended to detect intra dural tumor and invasion of tumor into dura mater. In such case, removing only extradural meningioma is not enough, and gross total resection including intradural meningioma and dura mater is required.

  10. Discrimination between spinal extradural meningioma and both intra and extradural meningioma: Case Report

    PubMed Central

    Ito, Kenyu; Imagama, Shiro; Ando, Kei; Kobayashi, Kazuyoshi; Hida, Tetsuro; Tsushima, Mikito; Matsumoto, Akiyuki; Morozumi, Masayoshi; Tanaka, Satoshi; Nishida, Yoshihiro; Ishiguro, Naoki

    2017-01-01

    ABSTRACT Meningiomas are common spinal tumor and mostly located at intradura. Recurrence rate after surgery for extradural meningioma was higher than intradural meningioma. A patient with intra and extradural spinal meningioma was treated and discussed its features and clinical management. A 41-year-old woman noted numbness of bilateral legs, gait disturbance, and mild bladder disturbance for over the two-month period. Magnetic resonance imaging revealed an epidural mass at T8-9 involving the dura mater from the left side. Intraoperatively, ultrasonography showed extradural tumor suppress the dura from the left side and no subarachnoid space. Therefore, it was difficult to diagnose the tumor was located at only extradural or both intra and extradural. The extradural tumor was resected as much as possible, then ultrasonography was performed for the second time. The spinal cord was decompressed and subarachnoid space was appeared with intradural tumor. The dura mater was opened in the midline for intradural exploration, and the intradural tumor appeared beside the spinal cord. The dura mater with attachment to the tumor was rescected. To prevent a recurrence, ultrasonography after removing extradural tumor is recommended to detect intra dural tumor and invasion of tumor into dura mater. In such case, removing only extradural meningioma is not enough, and gross total resection including intradural meningioma and dura mater is required. PMID:28303070

  11. Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment.

    PubMed

    Nawarak, Jiraporn; Huang-Liu, Rosa; Kao, Shao-Hsuan; Liao, Hsien-Hua; Sinchaikul, Supachok; Chen, Shui-Tein; Cheng, Sun-Long

    2009-02-01

    Although the toxicogenomics of A375 human malignant melanoma cells treated with arbutin have been elucidated using DNA microarray, the proteomics of the cellular response to this compound are still poorly understood. In this study, we performed proteomic analyses to investigate the anticancer effect of arbutin on the protein expression profile in A375 cells. After treatment with arbutin (8 microg/ml) for 24, 48 and 72 h, the proteomic profiles of control and arbutin-treated A375 cells were compared, and 26 differentially expressed proteins (7 upregulated and 19 downregulated proteins) were identified by MALDI-Q-TOF MS and MS/MS. Among these proteins, 13 isoforms of six identical proteins were observed. Bioinformatic tools were used to search for protein function and to predict protein interactions. The interaction network of 14 differentially expressed proteins was found to be correlated with the downstream regulation of p53 tumor suppressor and cell apoptosis. In addition, three upregulated proteins (14-3-3G, VDAC-1 and p53) and five downregulated proteins (ENPL, ENOA, IMDH2, PRDX1 and VIME) in arbutin-treated A375 cells were validated by RT-PCR analysis. These proteins were found to play important roles in the suppression of cancer development.

  12. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells

    PubMed Central

    Kluz, Thomas; Cohen, Lisa; Shen, Steven S.; Costa, Max

    2016-01-01

    Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress. PMID:27186882

  13. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    PubMed

    Cartularo, Laura; Kluz, Thomas; Cohen, Lisa; Shen, Steven S; Costa, Max

    2016-01-01

    Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  14. Preliminary micro-Raman images of normal and malignant human skin cells

    NASA Astrophysics Data System (ADS)

    Short, Michael A.; Lui, Harvey; McLean, David I.; Zeng, Haishan; Chen, Michael X.

    2006-02-01

    Micro-Raman spectroscopy covering a frequency range from 200 to 4000 cm -1 was used to image human skin melanocytes and keratinocytes with a spatial resolution of 0.5 μm. The cells were either cultivated on glass microscope slides or were located within thin sections of skin biopsies mounted on low fluorescence BaF II. A commercially available system was used to obtain the spectra utilizing a x100 long working distance objective with a numerical aperture of 0.8, and a cooled CCD. Both 633 and 515 nm excitations were tried, although the latter proved to be more effcient at producing Raman emission mostly due to the 1/λ 4 dependence in light scattering. Fluorescence emission from the cells was surprisingly low. The excitation power at the sample was kept below about 2 mW to avoid damaging the cells; this was the limiting factor on how quickly a Raman image could be obtained. Despite this diffculty we were able to obtain Raman images with rich information about the spectroscopic and structural features within the cytoplasm and cell nuclei. Differences were observed between the Raman images of normal and malignant cells. Spectra from purified DNA, RNA, lipids, proteins and melanin were obtained and these spectra were compared with the skin cell spectra with the aim of understanding how they are distributed over a cell and how the distribution changes between different cells.

  15. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

    PubMed

    Washimi, Kota; Yokose, Tomoyuki; Yamashita, Makiko; Kageyama, Taihei; Suzuki, Katsuo; Yoshihara, Mitsuyo; Miyagi, Yohei; Hayashi, Hiroyuki; Tsuji, Shoutaro

    2012-01-01

    Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

  16. Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

    PubMed Central

    Washimi, Kota; Yokose, Tomoyuki; Yamashita, Makiko; Kageyama, Taihei; Suzuki, Katsuo; Yoshihara, Mitsuyo; Miyagi, Yohei; Hayashi, Hiroyuki; Tsuji, Shoutaro

    2012-01-01

    Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM. PMID:22768319

  17. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy.

    PubMed

    Hunter, Chris; Smith, Raffaella; Cahill, Daniel P; Stephens, Philip; Stevens, Claire; Teague, Jon; Greenman, Chris; Edkins, Sarah; Bignell, Graham; Davies, Helen; O'Meara, Sarah; Parker, Adrian; Avis, Tim; Barthorpe, Syd; Brackenbury, Lisa; Buck, Gemma; Butler, Adam; Clements, Jody; Cole, Jennifer; Dicks, Ed; Forbes, Simon; Gorton, Matthew; Gray, Kristian; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Hinton, Jonathon; Jenkinson, Andy; Jones, David; Kosmidou, Vivienne; Laman, Ross; Lugg, Richard; Menzies, Andrew; Perry, Janet; Petty, Robert; Raine, Keiran; Richardson, David; Shepherd, Rebecca; Small, Alexandra; Solomon, Helen; Tofts, Calli; Varian, Jennifer; West, Sofie; Widaa, Sara; Yates, Andy; Easton, Douglas F; Riggins, Gregory; Roy, Jennifer E; Levine, Kymberly K; Mueller, Wolf; Batchelor, Tracy T; Louis, David N; Stratton, Michael R; Futreal, P Andrew; Wooster, Richard

    2006-04-15

    Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of 518 protein kinases in each of nine gliomas. Large numbers of somatic mutations were observed in two gliomas recurrent after alkylating agent treatment. The pattern of mutations in these cases showed strong similarity to that induced by alkylating agents in experimental systems. Further investigation revealed inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We propose that inactivating somatic mutations of MSH6 confer resistance to alkylating agents in gliomas in vivo and concurrently unleash accelerated mutagenesis in resistant clones as a consequence of continued exposure to alkylating agents in the presence of defective mismatch repair. The evidence therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents convert from induction of tumor cell death to promotion of neoplastic progression. These observations highlight the potential of large scale sequencing for revealing and elucidating mutagenic processes operative in individual human cancers.

  18. Characterization of Two Human Skeletal Calsequestrin Mutants Implicated in Malignant Hyperthermia and Vacuolar Aggregate Myopathy*

    PubMed Central

    Lewis, Kevin M.; Ronish, Leslie A.; Ríos, Eduardo; Kang, ChulHee

    2015-01-01

    Calsequestrin 1 is the principal Ca2+ storage protein of the sarcoplasmic reticulum of skeletal muscle. Its inheritable D244G mutation causes a myopathy with vacuolar aggregates, whereas its M87T “variant” is weakly associated with malignant hyperthermia. We characterized the consequences of these mutations with studies of the human proteins in vitro. Equilibrium dialysis and turbidity measurements showed that D244G and, to a lesser extent, M87T partially lose Ca2+ binding exhibited by wild type calsequestrin 1 at high Ca2+ concentrations. D244G aggregates abruptly and abnormally, a property that fully explains the protein inclusions that characterize its phenotype. D244G crystallized in low Ca2+ concentrations lacks two Ca2+ ions normally present in wild type that weakens the hydrophobic core of Domain II. D244G crystallized in high Ca2+ concentrations regains its missing ions and Domain II order but shows a novel dimeric interaction. The M87T mutation causes a major shift of the α-helix bearing the mutated residue, significantly weakening the back-to-back interface essential for tetramerization. D244G exhibited the more severe structural and biophysical property changes, which matches the different pathophysiological impacts of these mutations. PMID:26416891

  19. Alterations of telomere length in human brain tumors.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mehdipour, Parvin

    2011-09-01

    Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100 bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

  20. Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1.

    PubMed

    Michelhaugh, Sharon K; Guastella, Anthony R; Varadarajan, Kaushik; Klinger, Neil V; Parajuli, Prahlad; Ahmad, Aamir; Sethi, Seema; Aboukameel, Amro; Kiousis, Sam; Zitron, Ian M; Ebrahim, Salah A; Polin, Lisa A; Sarkar, Fazlul H; Bollig-Fischer, Aliccia; Mittal, Sandeep

    2015-07-15

    There is a paucity of effective therapies for recurrent/aggressive meningiomas. Establishment of improved in vitro and in vivo meningioma models will facilitate development and testing of novel therapeutic approaches. A primary meningioma cell line was generated from a patient with an olfactory groove meningioma. The cell line was extensively characterized by performing analysis of growth kinetics, immunocytochemistry, telomerase activity, karyotype, and comparative genomic hybridization. Xenograft models using immunocompromised SCID mice were also developed. Histopathology of the patient tumor was consistent with a WHO grade I typical meningioma composed of meningothelial cells, whorls, and occasional psammoma bodies. The original tumor and the early passage primary cells shared the standard immunohistochemical profile consistent with low-grade, good prognosis meningioma. Low passage KCI-MENG1 cells were composed of two cell types with spindle and round morphologies, showed linear growth curve, had very low telomerase activity, and were composed of two distinct unrelated clones on cytogenetic analysis. In contrast, high passage cells were homogeneously round, rapidly growing, had high telomerase activity, and were composed of a single clone with a near triploid karyotype containing 64-66 chromosomes with numerous aberrations. Following subcutaneous and orthotopic transplantation of low passage cells into SCID mice, firm tumors positive for vimentin and progesterone receptor (PR) formed, while subcutaneous implant of high passage cells yielded vimentin-positive, PR-negative tumors, concordant with a high-grade meningioma. Although derived from a benign meningioma specimen, the newly-established spontaneously immortal KCI-MENG1 meningioma cell line can be utilized to generate xenograft tumor models with either low- or high-grade features, dependent on the cell passage number (likely due to the relative abundance of the round, near-triploid cells). These human

  1. Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

    PubMed Central

    Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

    2013-01-01

    Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

  2. Signals of apoptotic pathways in several types of meningioma.

    PubMed

    Sabbatini, Maurizio; Comi, Cristoforo; Chiocchetti, Annalisa; Piffanelli, Valentina; Car, Pier Giorgio; Dianzani, Umberto; Monaco, Francesco; Cannas, Mario

    2011-03-01

    Meningiomas are intracranial tumour derived from meningothelial cells, which aggressive behaviour has been frequently associated to cell apoptosis. In this paper activation of several factors involved in apoptosis has been investigated on biopsies of primary, non recurrent meningiomas. Benign (meningotheliomatous, transitional, fibrous, angiomatous), atypical and anaplastic meningiomas were analysed by immunohistochemistry and western blot, to visualize the occurring of different apoptotic pathways and their association with clinical grading. Apoptotic cell have been detected by a double colorimetric staining for TUNEL and caspase-3 active form. Apoptotic signal positive cells have been detected in all type of meningiomas analysed, with exception of meningotheliomatous meningiomas. Differences have been found in the activation of apoptotic pathways between several types of grade I meningiomas and among benign, anaplastic and atypical meningiomas. An intense expression of several apoptotic inhibitor occurred in grade I meningiomas. The correlation among expression of apoptotic and inhibitory factors and cell proliferation index may suggest that in grade I meningiomas apoptosis may be related to mechanisms involved into tumor cells surviving. Instead in grade II and III meningiomas the same correlation seems indicate an high turnover of tumor cells that might be useful as index of cell proliferation and tumor mass growth.

  3. [Cytogenetic aberrations in histologically benign infiltratively growing sphenoid wing meningiomas].

    PubMed

    Korshunov, A G; Cherekaev, V A; Bekiashev, A Kh; Sycheva, R V

    2007-01-01

    Meningiomas of the sphenoid wing (SW) frequently show an invasive pattern of growth and cause destruction of the adjacent structures. As a result, the rate of recurrent SW meningiomas is as high as 30%. Cytogenetic investigations showed no aberrations specific to invasively growing meningiomas. During this study, the authors evaluated 10 invasive and 5 non-invasive SW meningiomas via comparative genome hybridization (CGH) (matrix CGH), by using the gene chips of GenoSensor Array micromatrixes. The mean number of aberrations in the tumor cells was much greater in case of invasive meningiomas (67.4 versus 40.5 in case of non-invasive SW meningiomas. Furthermore, in invasive SW meningiomas, there were frequently losses in loci 1p, 6q, and 14q and gains in loci 15q and 10, which had been predetermined as molecular markers of stepwise progression of meningioma. Thus, the presence of a complex cytogenetic profile and progression-associated chromosome aberrations in benign SW meningiomas is linked with the increase of their invasive potential. Due to the fact that there are no well-defined adjuvant therapy regimens for recurring meningiomas at present, the revealed genomic aberrations may become potential targets for searching for drugs and a therapeutic intervention in future.

  4. Efficient isolation of human metapneumovirus using MNT-1, a human malignant melanoma cell line exhibiting early and distinct cytopathic effect.

    PubMed

    Sato, Ko; Watanabe, Oshi; Ohmiya, Suguru; Chiba, Fumiko; Suzuki, Akira; Okamoto, Michiko; Younghuang, Jiang; Hata, Akihiro; Nonaka, Hiroyuki; Kitaoka, Setsuko; Nagai, Yukio; Kawamura, Kazuhisa; Hayashi, Masahiro; Kumaki, Satoru; Suzuki, Tamio; Kawakami, Kazuyoshi; Nishimura, Hidekazu

    2017-09-20

    Isolation of human metapneumovirus (HMPV) from clinical specimens is currently inefficient due to the lack of a cell culture system exhibiting a distinct cytopathic effect (CPE). The cell lines LLC-MK2, Vero, and Vero E6 are used for isolation of HMPV; however, the CPE in these cell lines is subtle and usually requires a long observation period and sometimes blind passages. Thus, a cell line that exhibits an early and distinct CPE following HMPV inoculation is highly desired by clinical virology laboratories. We demonstrate that the human malignant melanoma cell line MNT-1 shows obvious syncytium formation shortly after inoculation with HMPV-positive clinical specimens. In addition, the growth and isolation efficiency of HMPV was higher using MNT-1 than any other conventional cell line. Addition of this cell line to our routine viral isolation system for clinical specimens markedly enhanced isolation frequency, allowing isolation-based surveillance. MNT-1 has the potential to facilitate clinical and epidemiological studies of HMPV. © 2017 The Societies and Wiley Publishing Asia Pty Ltd.

  5. Targeting autophagy enhances BO-1051-induced apoptosis in human malignant glioma cells.

    PubMed

    Chu, Pei-Ming; Chen, Li-Hsin; Chen, Ming-Teh; Ma, Hsin-I; Su, Tsann-Long; Hsieh, Pei-Chen; Chien, Chian-Shiu; Jiang, Bo-Hua; Chen, Yu-Chih; Lin, Yi-Hui; Shih, Yang-Hsin; Tu, Pang-Hsien; Chiou, Shih-Hwa

    2012-03-01

    BO-1051 is an N-mustard derivative that is conjugated with DNA-affinic 9-anilinoacridine. Since BO-1051 was reported to have strong anticancer activity, we investigated the effect and underlying mechanism of BO-1051 in human glioma cell lines. Human glioma cell lines U251MG and U87MG were studied with BO-1051 or the combination of BO-1051 and autophagic inhibitors. Growth inhibition was assessed by MTT assay. Apoptosis was measured by annexin V staining followed by flow cytometry and immunoblotting for apoptosis-related molecules. Induction of autophagy was detected by acridine orange labeling, electron microscopy, LC3 localization and its conversion. Transfection of shRNA was used to determine the involvement of Beclin1 in apoptotic cell death. MTT assay showed that BO-1051 suppressed the viability of four glioma cell lines (U251MG, U87MG, GBM-3 and DBTRG-05MG) in a dose-dependent manner. The IC(50) values of BO-1051 for the glioma cells were significantly lower than the values for primary neurons cultures and normal fibroblast cells. Moreover, BO-1051 not only induced apoptotic cell death, but also enhanced autophagic flux via inhibition of Akt/mTOR and activation of Erk1/2. Importantly, suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly increased BO-1051-induced apoptotic cell death in U251MG and U87MG cells. In addition, the proportion of apoptotic cells after BO-1051 treatment was enhanced by co-treatment with shRNA against Beclin1. BO-1051 induced both apoptosis and autophagy, and inhibition of autophagy significantly augmented the cytotoxic effect of BO-1051. Thus, a combination of BO-1051 and autophagic inhibitors offers a potentially new therapeutic modality for the treatment of malignant glioma.

  6. Molecular mechanism of inositol hexaphosphate-mediated apoptosis in human malignant glioblastoma T98G cells.

    PubMed

    Karmakar, Surajit; Banik, Naren L; Ray, Swapan K

    2007-12-01

    Glioblastoma is the deadliest brain tumor in humans. Current therapies are mostly ineffective and new agents need to be explored for controlling this devastating disease. Inositol hexaphosphate (IP6) is a phytochemical that is widely found in corns, cereals, nuts, and high fiber-content foods. Previous studies demonstrated anti-cancer properties of IP6 in several in vitro and in vivo tumor models. However, therapeutic efficacy of IP6 has not yet been evaluated in glioblastoma. Here, we explored the molecular mechanism of action of IP6 in human malignant glioblastoma T98G cells. The viability of T98G cells decreased following treatment with increasing doses of IP6. T98G cells exposed to 0.25, 0.5, and 1 mM IP6 for 24 h showed morphological and biochemical features of apoptosis. Western blotting indicated changes in expression of Bax and Bcl-2 proteins resulting in an increase in Bax:Bcl-2 ratio and upregulation of cytosolic levels of cytochrome c and Smac/Diablo, suggesting involvement of mitochondria-dependent caspase cascade in apoptosis. IP6 downregulated cell survival factors such as baculovirus inhibitor-of-apoptosis repeat containing-2 (BIRC-2) protein and telomerase to promote apoptosis. Upregulation of calpain and caspase-9 occurred in course of apoptosis. Increased activities of calpain and caspase-3 cleaved 270 kD alpha-spectrin at specific sites generating 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Increased caspase-3 activity also cleaved inhibitor of caspase-3-activated DNase and poly(ADP-ribose) polymerase. Collectively, our results demonstrated that IP6 down regulated the survival factors BIRC-2 and telomerase and upregulated calpain and caspase-3 activities for apoptosis in T98G cells.

  7. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    PubMed

    Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

    2014-07-01

    Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38α phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

  8. Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.

    PubMed

    Furukawa, Jun-ichi; Tsuda, Masumi; Okada, Kazue; Kimura, Taichi; Piao, Jinhua; Tanaka, Shinya; Shinohara, Yasuro

    2015-01-01

    Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.

  9. Downregulated MicroRNA-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/β-Catenin Signaling Pathway▿

    PubMed Central

    Saydam, Okay; Shen, Yiping; Würdinger, Thomas; Senol, Ozlem; Boke, Elvan; James, Marianne F.; Tannous, Bakhos A.; Stemmer-Rachamimov, Anat O.; Yi, Ming; Stephens, Robert M.; Fraefel, Cornel; Gusella, James F.; Krichevsky, Anna M.; Breakefield, Xandra O.

    2009-01-01

    Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of β-catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target β-catenin mRNA, thereby inhibiting its translation and blocking Wnt/β-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of β-catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/β-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas. PMID:19703993

  10. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

    PubMed Central

    Lakiotaki, Eleftheria; Giaginis, Constantinos; Tolia, Maria; Alexandrou, Paraskevi; Delladetsima, Ioanna; Giannopoulou, Ioanna; Kyrgias, George; Patsouris, Efstratios; Theocharis, Stamatios

    2015-01-01

    The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n = 43) and malignant (n = 44) lesions and was statistically analyzed with clinicopathological parameters, follicular cells' proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA) staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0010 and p = 0.0005, resp.). Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p = 0.0097 and p = 0.0110, resp.). In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p = 0.0301). Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p = 0.1165), lymphatic (p = 0.1989), and vascular invasion (p = 0.0555), as well as in those with increased risk of recurrence rate (p = 0.1165), at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia. PMID:26539529

  11. Cervical spinal meningioma mimicking intramedullary spinal tumor.

    PubMed

    Senturk, Senem; Guzel, Aslan; Guzel, Ebru; Bayrak, Aylin Hasanefendioğlu; Sav, Aydin

    2009-01-01

    Case report. To report a very unusual spinal meningioma, mimicking an intramedullary spinal tumor. Spinal meningiomas, usually associated with signs and symptoms of cord or nerve root compression, are generally encountered in women aged over 40. Radiologic diagnosis is often established by their intradural extramedullary location on magnetic resonance images. A 60-year-old woman had a 6-month history of progressive weakness in her upper extremities, difficulty in walking, and cervical pain radiating through both arms. Neurologic examination revealed motor strength deficiency in all her extremities, with extensor reflexes, clonus, and bilateral hyper-reflexiveness. A sensory deficit was present all over her body. Magnetic resonance images revealed that the spinal cord appeared expanded with an ill-defined, homogeneously contrast-enhanced, lobulated, eccentric mass at the C1-C3 level. The patient was operated with a preliminary diagnosis of an intramedullary tumor. At surgery, the mass was found to be extramedullary, and gross total resection was performed. Histopathological examination revealed a meningioma characterized by the presence of fibrous and meningothelial components. The patient was able to ambulate with a cane, and extremity strength and sensation improved 2 months after surgery. Spinal meningiomas can mimic intramedullary tumors, and should be considered in differential diagnosis of intradural tumors with atypical appearance.

  12. Intraventricular trigonal meningioma: Neuronavigation? No, thanks!

    PubMed Central

    Silva, Danilo O. A.; Matis, Georgios K.; Costa, Leonardo F.; Kitamura, Matheus A. P.; Birbilis, Theodossios A.; Azevedo Filho, Hildo R. C.

    2011-01-01

    Background: Most of the time meningiomas are benign brain tumors and surgical removal ensures cure in the vast majority of the cases. Thus, whenever possible, complete surgical resection should be the goal of the treatment. Methods: This is a report of our surgical technique for the operative resection of a trigonal meningioma in a resource-limited setting. The necessity of accurate and deep knowledge of the regional anatomy is outlined. Results: A 44-year-old male presented to our outpatient clinic complaining of cephalalgia increasing in frequency and intensity over the last month. His neurological exam was normal, yet a brain computed tomography scan revealed a lesion in the right trigone of the ventricular system. The diagnosis of possible meningioma was set. After thoroughly informing the patient, tumor resection was decided. An intraparietal sulcus approach was favored without the use of any modern technological aids such as intraoperative magnetic resonance imaging or neuronavigation. The postoperative course was uneventful and a postoperative computed tomography scan demonstrated the complete resection of the tumor. The patient was discharged two days later with no neurological deficits. In a two-year-follow-up he remains recurrence-free. Conclusion: In the current cost-effective era it is still possible to safely remove an intraventricular trigonal meningioma without the convenience of neuronavigation. Since the best neuronavigator is the profound neuroanatomical knowledge, no technological advancement could replace a well-educated and trained neurosurgeon. PMID:21886886

  13. Occipital Falcine Anaplastic Hemangiopericytoma Mimicking Meningioma

    PubMed Central

    Kanesen, Davendran; Kandasamy, Regunath; Idris, Zamzuri

    2016-01-01

    The rarity of hemangiopericytoma (HPC) and its controversial histological classification result in its frequent misdiagnosis and thus make the treatment quite challenging. It is often difficult to distinguish these tumors from meningiomas based on clinical features and radiological findings. This is a case report of a man, diagnosed clinically and radiologically as meningioma, which turned out to be anaplastic HPC on histological examination. A 30-year-old man presented with 3 months of progressively worsening of headache and blurring of vision. Clinical examination revealed the right homonymous hemianopia with reduced visual acuity and papilledema bilaterally. Magnetic resonance imaging revealed a multilobulated and heterogenous extraaxial lesion attached to the occipital falx. It measured 9.0 cm (AP) × 5.5 cm (W) × 5.8 cm (CC) and expands bilaterally with major bulk on the left. An occipital craniotomy followed by a subtotal tumor excision was only achieved due to profuse bleeding intraoperatively. Histopathology confirmed an anaplastic HPC (WHO Grade 3). The importance of differentiation between HPCs and meningiomas cannot be overemphasized. A preoperative correct diagnosis is difficult, but it is important that it should be made. Multilobulated (mushroom appearance), prominent internal signal voids, relatively narrow dural attachment, and lytic destruction without calcifications are useful findings to distinguish HPCs from meningiomas. PMID:28163517

  14. Occipital Falcine Anaplastic Hemangiopericytoma Mimicking Meningioma.

    PubMed

    Kanesen, Davendran; Kandasamy, Regunath; Idris, Zamzuri

    2016-12-01

    The rarity of hemangiopericytoma (HPC) and its controversial histological classification result in its frequent misdiagnosis and thus make the treatment quite challenging. It is often difficult to distinguish these tumors from meningiomas based on clinical features and radiological findings. This is a case report of a man, diagnosed clinically and radiologically as meningioma, which turned out to be anaplastic HPC on histological examination. A 30-year-old man presented with 3 months of progressively worsening of headache and blurring of vision. Clinical examination revealed the right homonymous hemianopia with reduced visual acuity and papilledema bilaterally. Magnetic resonance imaging revealed a multilobulated and heterogenous extraaxial lesion attached to the occipital falx. It measured 9.0 cm (AP) × 5.5 cm (W) × 5.8 cm (CC) and expands bilaterally with major bulk on the left. An occipital craniotomy followed by a subtotal tumor excision was only achieved due to profuse bleeding intraoperatively. Histopathology confirmed an anaplastic HPC (WHO Grade 3). The importance of differentiation between HPCs and meningiomas cannot be overemphasized. A preoperative correct diagnosis is difficult, but it is important that it should be made. Multilobulated (mushroom appearance), prominent internal signal voids, relatively narrow dural attachment, and lytic destruction without calcifications are useful findings to distinguish HPCs from meningiomas.

  15. Paraclinoid aneurysm concealed by sphenoid wing meningioma.

    PubMed

    Petrecca, Kevin; Sirhan, Denis

    2009-02-01

    The coexistence of brain tumours and aneurysms is rare. In all previously reported cases the aneurysm was detectable by angiography. We report here a case in which a paraclinoid internal carotid artery aneurysm was coexistent and concealed from angiographic detection by an adjacent parasellar meningioma.

  16. Metaplastic conus meningioma and its applied aspects

    PubMed Central

    Reddy, Srikanth; Pulligopu, Aneel Kumar; Kumar, Ashish; Sahu, Barada Prasad

    2015-01-01

    Cranial meningiomas may present with or without major deficits depending on their location and morphology. Spinal meningiomas account for 25% of all the spinal tumors. Most commonly encountered in the dorsal spine in middle-aged females, these intradural-extramedullary tumors can usually be excised without difficulty. Rarely, they can be encountered in the lumbar spine and may create many tactical problems for the surgical team especially if it is calcified and contains metaplastic bone. We report a 55-year-old patient who presented with backache and investigations revealed a calcified lesion at L1 level that was thought of as an ependymoma initially. Intraoperatively, the lesion was calcified in parts, and the histopathology revealed it to be a metaplastic meningioma with calcification. The patient had a transient hip weakness, which recovered completely later on. Calcification in meningiomas is common. However, frank bony metaplasia is extremely rare. More importantly, the applied aspect of their presence in the region of conus lies in the careful dissection to prevent damage to the surrounding neural structures. Awareness regarding the same may help us preventing complications in the future. PMID:25972958

  17. Metaplastic conus meningioma and its applied aspects.

    PubMed

    Reddy, Srikanth; Pulligopu, Aneel Kumar; Kumar, Ashish; Sahu, Barada Prasad

    2015-01-01

    Cranial meningiomas may present with or without major deficits depending on their location and morphology. Spinal meningiomas account for 25% of all the spinal tumors. Most commonly encountered in the dorsal spine in middle-aged females, these intradural-extramedullary tumors can usually be excised without difficulty. Rarely, they can be encountered in the lumbar spine and may create many tactical problems for the surgical team especially if it is calcified and contains metaplastic bone. We report a 55-year-old patient who presented with backache and investigations revealed a calcified lesion at L1 level that was thought of as an ependymoma initially. Intraoperatively, the lesion was calcified in parts, and the histopathology revealed it to be a metaplastic meningioma with calcification. The patient had a transient hip weakness, which recovered completely later on. Calcification in meningiomas is common. However, frank bony metaplasia is extremely rare. More importantly, the applied aspect of their presence in the region of conus lies in the careful dissection to prevent damage to the surrounding neural structures. Awareness regarding the same may help us preventing complications in the future.

  18. Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissues.

    PubMed

    D'Andrea, M R; Derian, C K; Santulli, R J; Andrade-Gordon, P

    2001-06-01

    The serine proteases thrombin and trypsin are among many factors that malignant cells secrete into the extracellular space to mediate metastatic processes such as cellular invasion, extracellular matrix degradation, angiogenesis, and tissue remodeling. The degree of protease secretion from malignant cells has been correlated to their metastatic potential. Protease activated receptors (PAR)-1 and -2, which are activated by thrombin and trypsin respectively, have not been extensively characterized in human tumors in situ. We investigated the presence of PAR-1 and PAR-2 in human normal, benign and malignant tissues using immunohistochemistry and in situ hybridization. Our results demonstrate PAR-1 and PAR-2 expression in the tumor cells, mast cells, macrophages, endothelial cells, and vascular smooth muscle cells of the metastatic tumor microenvironment. Most notably, an up-regulation of PAR-1 and PAR-2 observed in proliferating, smooth muscle actin (SMA)-positive stromal fibroblasts surrounding the carcinoma cells was not observed in normal or benign conditions. Furthermore, in vitro studies using proliferating, SMA-positive, human dermal fibroblasts, and scrape-wounded human dermal fibroblasts demonstrated the presence of PAR-1 and PAR-2 not detected in quiescent, SMA-negative cultures. PAR-1 and PAR-2 in the cells forming the tumor microenvironment suggest that these receptors mediate the signaling of secreted thrombin and trypsin in the processes of cellular metastasis.

  19. [Operative neurosurgery: personal view and historical backgrounds. (5) Meningioma].

    PubMed

    Yonekawa, Yasuhiro

    2009-01-01

    The author reports his experience of 410 surgeries of meningiomas on 365 cases during the last 13.5 years, including 51 surgeries on recurrent meningiomas and 8 surgeries with the change of initial approach on the same meningiomas. In the surgical management of meningiomas, following comments are to be emphasized: Appropriate approach and interruption of blood supply are of cardinal importance in surgical management of meningiomas. For the latter purpose, preoperative embolization of feeding arteries is recommended especially in deep seated and large meningiomas more than 3 cm in diameter for carrying out their surgical extirpation fast and radically. Olfactory groove meningiomas, planum sphenoidal meningiomas, tuberculum sellae meningiomas and sphenoid ridge meningiomas are managed with pterional approach. The latter two meningiomas may necessitate selective extradural anterior clinoidectomy SEAC. For the management of large midline meningiomas, combination with interhemispheric approach is necessary to manage pial supply appropriately for the preservation of circulation of the anterior cerebral artery ACA. Extension of the former two meningiomas to the other side can be managed with falcal incision and/or drilling out of the crista galli without performing a bifrontal approach. Reduction of exophthalmos due to sphenoid ridge meningiomas infiltrating Periorbita and extraocular muscles is hardly to be expected even after subtotal removal and extensive decompression of the orbita at the superior and lateral walls in combination with SEAC. Accidental compromise of the lenticulostriate arteries arising from M1 portion embraced by tumor nodules should be managed with oxycellulose and fibrin glue at first without their bipolar coagulation, as resulting infarction in the territory causes persistent hemiparesis. Meningiomas in the cavernous sinus should be observed as long as possible in case of no growth, as they remain the same in their size and extension mostly for a

  20. Uptake of AV-1451 in meningiomas.

    PubMed

    Bruinsma, Tyler J; Johnson, Derek R; Fang, Ping; Senjem, Matthew; Josephs, Keith A; Whitwell, Jennifer L; Boeve, Bradley F; Pandey, Mukesh K; Kantarci, Kejal; Jones, David T; Vemuri, Prashanthi; Murray, Melissa; Graff-Radford, Jonathan; Schwarz, Christopher G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Lowe, Val J

    2017-09-08

    AV-1451 is an imaging agent labeled with the positron-emitting radiolabel Fluorine-18. 18F-AV-1451 binds paired helical filament tau (PHF-tau), a pathology related to Alzheimer's disease. In our study of AV-1451 uptake in the brains of cognitively normal subjects, we noted a case of a meningioma with visually significant uptake of AV-1451. We initiated the present retrospective study to further examine cases of meningioma that underwent AV-1451 imaging. We searched the patient records of 650 patients who had undergone AV-1451 at our institution for the keyword "meningioma" to identify potential cases. PET/CT and MRI results were visually reviewed and semi-quantitative analysis of PET was performed. A paired student's t test was run between background and tumor standard uptake values. Fisher's exact test was used to examine the association between AV-1451 uptake and presence of calcifications on CT. We identified 12 cases of meningioma, 58% (7/12) of which demonstrated uptake greater than background using both visual analysis and tumor-to-normal cortex ratios (T/N + 1.90 ± 0.83). The paired student's t test revealed no statistically significant difference between background and tumor standard uptake values (p = 0.09); however, cases with a T/N ratio greater than one showed statistically higher uptake in tumor tissue (p = 0.01). A significant association was noted between AV-1451 uptake and presence of calcifications (p = 0.01). AV-1451 PET imaging should be reviewed concurrently with anatomic imaging to prevent misleading interpretations of PHF-tau distribution due to meningiomas.

  1. Meningioma in Breast Cancer Patients: Population-based Analysis of Clinicopathologic Characteristics.

    PubMed

    Milano, Michael T; Grossman, Craig E

    2017-02-01

    Although an association between meningioma and breast cancer (BC) has been postulated, clear mechanisms remain obscure. By conducting population-based analyses in women with both BC and meningioma, hypothesis-generating causal links were pursued. Using the US SEER 18 registry (2004 to 2009), clinicopathologic and demographic characteristics from cohorts of women with only BC (n=279,821) or meningioma (n=19,570) diagnoses were compared with 412 women with both diagnoses (BC-meningioma). BC diagnosis preceded meningioma by >2 months in 48% of women; 20% had synchronous (within 2 mo) disease. Median meningioma size was 1.9 and 2.4 cm in the BC-meningioma and meningioma cohorts, respectively (P=0.0009). Among BC-meningioma patients, meningioma size was similar whether diagnosed >2 months prior, synchronously, or >2 months after BC. Meningioma was pathologically confirmed in 38% of BC-meningioma and 51% of meningioma patients. Distribution of BC histologies was comparable in patients with and without meningioma, with ductal type predominating (80% in BC-meningioma, 83% in BC). Although hormone receptor status of invasive BC was not significantly different between BC-meningioma and BC groups, the BC-meningioma cohort had fewer women with ER+/PR+ in situ disease (P=0.006). BC stage among women with meningioma was more advanced versus women with BC only. Women with BC and meningioma have smaller-sized meningiomas and more advanced BCs compared with women having only 1 diagnosis. As there was no temporal relationship between size and latency between tumor diagnoses, the disparity in meningioma size between BC-meningioma and meningioma cohorts may have BC-associated biological components that warrant further study.

  2. Activation of Yes-Associated Protein in Low-Grade Meningiomas Is Regulated by Merlin, Cell Density, and Extracellular Matrix Stiffness.

    PubMed

    Tanahashi, Kuniaki; Natsume, Atsushi; Ohka, Fumiharu; Motomura, Kazuya; Alim, Adiljan; Tanaka, Ichidai; Senga, Takeshi; Harada, Ichiro; Fukuyama, Ryuichi; Sumiyoshi, Naoyuki; Sekido, Yoshitaka; Wakabayashi, Toshihiko

    2015-07-01

    The NF2 gene product Merlin is a protein containing ezrin, radixin, and moesin domains; it is a member of the 4.1 protein superfamily associated with the membrane cytoskeleton and also interacts with cell surface molecules. The mammalian Hippo cascade, a downstream signaling cascade of merlin, inactivates the Yes-associated protein (YAP). Yes-associated protein is activated by loss of the NF2 gene and functions as an oncogene in meningioma cells; however, the factors controlling YAP expression, phosphorylation, and subcellular localization in meningiomas have not been fully elucidated. Here, we demonstrate that merlin expression is heterogeneous in 1 NF2 gene-negative and 3 NF2 gene-positive World Health Organization grade I meningiomas. In the NF2 gene-positive meningiomas, regions with low levels of merlin (tumor rims) had greater numbers of cells with nuclear YAP versus regions with high merlin levels (tumor cores). Merlin expression and YAP phosphorylation were also affected by cell density in the IOMM-Lee and HKBMM human meningioma cell lines; nuclear localization of YAP was regulated by cell density and extracellular matrix (ECM) stiffness in IOMM-Lee cells. These results suggest that cell density and ECM stiffness may contribute to the heterogeneous loss of merlin and increased nuclear YAP expression in human meningiomas.

  3. Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

    PubMed Central

    2010-01-01

    Background Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Methods Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses. Results The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. Conclusion In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated

  4. 5-Aminolevulinic acid fluorescence-guided surgery for spinal meningioma.

    PubMed

    Muroi, Carl; Fandino, Javier; Coluccia, Daniel; Berkmann, Sven; Fathi, Ali-Reza; Landolt, Hans

    2013-01-01

    Fluorescence-guided surgery for cranial meningioma has been reported to be useful. There are no reports about spinal cases using this technique. We report on a meningioma of the cervical spine for which fluorescence-guided surgery was used. A 78-year-old female patient with a meningioma located in the cervical spine underwent surgery using fluorescence guidance. After complete removal of the meningioma and removal and coagulation of the dural attachment (equal to Simpson grade II resection), a fluorescence-positive remnant could be identified and successfully removed. The remnant was found to harbor meningioma tissue on histological examination. Fluorescence-guided microsurgery is helpful in achieving a total resection of spinal meningiomas, and might therefore reduce the risk of recurrence. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Meningioma involving Meckel's cave: transpetrosal surgical anatomy and clinical considerations.

    PubMed

    Choo, Daniel I; Steward, David L; Pensak, Myles L

    2002-09-01

    Meningiomas originating in Meckel's cave (MC) are uncommon lesions that represent 1% of all intracranial meningiomas. Innovations in skull base surgery have enabled resection of these lesions with less morbidity, but require an intimate knowledge of both lesional pathology and regional microneuroanatomy. To review the surgical and clinical considerations involved in the management of MC meningiomas, we retrospectively reviewed data from patients who underwent transpetrosal resection of primary MC meningiomas between 1984 and 1998. Of 146 patients who underwent transpetrosal removal of meningiomas, 7 were believed to have tumors originating in MC. All 7 patients presented with trigeminal dysfunction, facial pain, and/or headache. Complete tumor removal was achieved in 5 of the 7 patients. Facial hypoesthesia or anesthesia, paralysis of cranial nerve VI, and ophthalmoplegia were among the postoperative complications encountered. Meningiomas of MC represent treatable lesions whose diagnosis requires prompt imaging of patients with trigeminal dysfunction and symptoms of facial pain and headache.

  6. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    NASA Astrophysics Data System (ADS)

    Falzon, G.; Pearson, S.; Murison, R.; Hall, C.; Siu, K.; Round, A.; Schültke, E.; Kaye, A. H.; Lewis, R.

    2007-11-01

    Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma.

  7. Store-operated Ca2+ Entry in Malignant Hyperthermia-susceptible Human Skeletal Muscle*

    PubMed Central

    Duke, Adrian M.; Hopkins, Philip M.; Calaghan, Sarah C.; Halsall, Jane P.; Steele, Derek S.

    2010-01-01

    In malignant hyperthermia (MH), mutations in RyR1 underlie direct activation of the channel by volatile anesthetics, leading to muscle contracture and a life-threatening increase in core body temperature. The aim of the present study was to establish whether the associated depletion of sarcoplasmic reticulum (SR) Ca2+ triggers sarcolemmal Ca2+ influx via store-operated Ca2+ entry (SOCE). Samples of vastus medialis muscle were obtained from patients undergoing assessment for MH susceptibility using the in vitro contracture test. Single fibers were mechanically skinned, and confocal microscopy was used to detect changes in [Ca2+] either within the resealed t-system ([Ca2+]t-sys) or within the cytosol. In normal fibers, halothane (0.5 mm) failed to initiate SR Ca2+ release or Ca2+t-sys depletion. However, in MH-susceptible (MHS) fibers, halothane induced both SR Ca2+ release and Ca2+t-sys depletion, consistent with SOCE. In some MHS fibers, halothane-induced SR Ca2+ release took the form of a propagated wave, which was temporally coupled to a wave of Ca2+t-sys depletion. SOCE was potently inhibited by “extracellular” application of a STIM1 antibody trapped within the t-system but not when the antibody was denatured by heating. In conclusion, (i) in human MHS muscle, SR Ca2+ depletion induced by a level of volatile anesthetic within the clinical range is sufficient to induce SOCE, which is tightly coupled to SR Ca2+ release; (ii) sarcolemmal STIM1 has an important role in regulating SOCE; and (iii) sustained SOCE from an effectively infinite extracellular Ca2+ pool may contribute to the maintained rise in cytosolic [Ca2+] that underlies MH. PMID:20566647

  8. Store-operated Ca2+ entry in malignant hyperthermia-susceptible human skeletal muscle.

    PubMed

    Duke, Adrian M; Hopkins, Philip M; Calaghan, Sarah C; Halsall, Jane P; Steele, Derek S

    2010-08-13

    In malignant hyperthermia (MH), mutations in RyR1 underlie direct activation of the channel by volatile anesthetics, leading to muscle contracture and a life-threatening increase in core body temperature. The aim of the present study was to establish whether the associated depletion of sarcoplasmic reticulum (SR) Ca(2+) triggers sarcolemmal Ca(2+) influx via store-operated Ca(2+) entry (SOCE). Samples of vastus medialis muscle were obtained from patients undergoing assessment for MH susceptibility using the in vitro contracture test. Single fibers were mechanically skinned, and confocal microscopy was used to detect changes in [Ca(2+)] either within the resealed t-system ([Ca(2+)](t-sys)) or within the cytosol. In normal fibers, halothane (0.5 mM) failed to initiate SR Ca(2+) release or Ca(2+)(t-sys) depletion. However, in MH-susceptible (MHS) fibers, halothane induced both SR Ca(2+) release and Ca(2+)(t-sys) depletion, consistent with SOCE. In some MHS fibers, halothane-induced SR Ca(2+) release took the form of a propagated wave, which was temporally coupled to a wave of Ca(2+)(t-sys) depletion. SOCE was potently inhibited by "extracellular" application of a STIM1 antibody trapped within the t-system but not when the antibody was denatured by heating. In conclusion, (i) in human MHS muscle, SR Ca(2+) depletion induced by a level of volatile anesthetic within the clinical range is sufficient to induce SOCE, which is tightly coupled to SR Ca(2+) release; (ii) sarcolemmal STIM1 has an important role in regulating SOCE; and (iii) sustained SOCE from an effectively infinite extracellular Ca(2+) pool may contribute to the maintained rise in cytosolic [Ca(2+)] that underlies MH.

  9. Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in non-malignant human breast epithelial cells

    PubMed Central

    Venkatesha, Venkatasubbaiah A.; Venkataraman, Sujatha; Sarsour, Ehab H.; Kalen, Amanda L.; Buettner, Garry R.; Robertson, Larry W.; Lehmler, Hans-Joachim; Goswami, Prabhat C.

    2008-01-01

    Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human non-malignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3) significantly decreased cell number, MTS reduction, and increased the percentage of cells with sub G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pre-treated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox-cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX-phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing. PMID:18691649

  10. Enhanced antitumor therapy by inhibition of p21waf1 in human malignant mesothelioma.

    PubMed

    Lazzarini, Raffaella; Moretti, Simona; Orecchia, Sara; Betta, Pier-Giacomo; Procopio, Antonio; Catalano, Alfonso

    2008-08-15

    The p21 cyclin-dependent kinase inhibitor was frequently expressed in human malignant pleural mesothelioma (MPM) tissues as well as cell lines. Recent data indicate that p21 keeps tumor cells alive after DNA damage, favoring a survival advantage. In this study, we assessed the possibility of p21 suppression as a therapeutic target for MPM. We established two different MPM-derived (from H28 and H2052 cells) subclones using vector-based short hairpin RNA (shRNA). Then, chemosensitivity against low doses of antineoplastic DNA-damaging agents was investigated by colony formation assays, and furthermore, the type of cell response induced by these drugs was analyzed. To examine the effect of p21 shRNA on chemosensitivity in vivo, tumor formation assays in nude mice were done. In colony formation assay, the IC50 of doxorubicin was 33 +/- 3.0 nmol/L in p21 shRNA-transfected cells with respect to 125 +/- 10 nmol/L of control vector-transfected cells. This enhancement of growth inhibition was achieved by converting a senescence-like growth arrest to apoptosis in response to doxorubicin, etoposide, and CPT11. In the in vivo assays, CPT11 and loss-of-expression of p21 in combination led to considerable suppression of tumor growth associated with a substantially enhanced apoptotic response, whereas CPT11 alone was ineffective at inducing these responses. These results indicated that p21 might play an important role in chemosensitivity to anticancer agents, and the suppression of its expression might be a potential therapeutic target for MPM.

  11. Cellular distribution of Glut-1 and Glut-5 in benign and malignant human prostate tissue.

    PubMed

    Reinicke, Karin; Sotomayor, Paula; Cisterna, Pedro; Delgado, Carolina; Nualart, Francisco; Godoy, Alejandro

    2012-02-01

    Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common event in human malignancies. In prostate cancer (CaP), however, expression of Gluts has been characterized poorly. In this study, expression and distribution of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76 specimens of benign prostate, 10 specimens of high-grade intraepithelial neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut-2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however, localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN, Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5, were immunohistochemically undetectable. However, over-expression of GLUT1 was observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut-9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut-11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low levels of expression of Glut-1 protein in the majority of CaP could explain, at least in part, the limited clinical applicability of positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic substrate in HGPIN. Understanding the molecular mechanisms involved in regulation/dysregulation of Gluts in CaP could provide insight in the understanding of hexose metabolism in CaP.

  12. In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

    PubMed Central

    Feng, Mingqian; Zhang, Jingli; Anver, Miriam; Hassan, Raffit; Ho, Mitchell

    2011-01-01

    Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo. PMID:21479131

  13. Altered expression of G/sub 1/-specific genes in human malignant myeloid cells

    SciTech Connect

    Calabretta, B.; Venturelli, D.; Kaczmarek, L.; Narni, F.; Talpaz, M.; Anderson, B.; Beran, M.; Baserga, R.

    1986-03-01

    The authors have studied the expression of cell-cycle genes specific to the G/sub 1/ (2A9, 2F1, 4F1, c-myc) and S (histone H3) phases of the cell cycle in normal and malignant human myeloid cycling cells. The levels of expression were determined by measuring the amounts of specific RNA in blot hybridization assays. Levels of expression of the G/sub 1/ genes were compared to the level of expression of the S-phase-specific H3 gene. In a normal asynchronous system provided by the bone marrow cells of three normal donors, the expressions of the four G/sub 1/-specific genes 2A9, 2F1, 4F1, and c-myc, and of the S-phase-specific gene H3 were in ratios that differed little from one individual to another. In the total RNA of eight patients in the chronic phase of chronic myelogenous leukemia, a high level of expression of G/sub 1/ cell-cycle genes was paralleled by a high level of expression of the S-phase H3 gene, simply reflecting and increase in the fraction of proliferating cells. In patients with acute myelogenous leukemia (AML), the RNA levels of 2F1 and 4F1 paralleled the expression of H3. However, in 9 of 10 patients with AML they found that the expression of c-myc was elevated with respect to H3 expression. Two important conclusions can be drawn from these findings: (i) increased levels of a G/sub 1/-specific RNA in a tumor may not indicate overexpression of that gene but may instead simply reflect the fraction of proliferating cells; and (ii) in some patients with AML, however, the expression of certain G/sub 1/ genes is truly deregulated and might contribute to the impairment of proliferative control that is associated with this phenotype.

  14. p53 mutations in human lymphoid malignancies: Association with Burkitt lymphoma and chronic lymphocytic leukemia

    SciTech Connect

    Gaidano, G.; Ballerini, P.; Gong, J.Z.; Inghirami, G.; Knowles, D.M.; Dalla-Favera, R. ); Neri, A, Centro Malattie del Sangue G. Marcora, Milan ); Newcomb, E.W. ); Magrath, I.T. )

    1991-06-15

    The authors have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direst sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsoes; 17/27 cell lines) and its leukemic counterpart L{sub 3}-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (1) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (2) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (3) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemia form L{sub 3}-type B-cell acute lymphoblastic leukemia.

  15. Pharmacological and biochemical characterization of adenosine receptors in the human malignant melanoma A375 cell line

    PubMed Central

    Merighi, Stefania; Varani, Katia; Gessi, Stefania; Cattabriga, Elena; Iannotta, Valeria; Ulouglu, Canan; Leung, Edward; Borea, Pier Andrea

    2001-01-01

    The present work characterizes, from a pharmacological and biochemical point of view, adenosine receptors in the human malignant melanoma A375 cell line. Adenosine receptors were detected by RT – PCR experiments. A1 receptors were characterized using [3H]-DPCPX binding with a KD of 1.9±0.2 nM and Bmax of 23±7 fmol mg−1 of protein. A2A receptors were studied with [3H]-SCH 58261 binding and revealed a KD of 5.1±0.2 nM and a Bmax of 220±7 fmol mg−1 of protein. A3 receptors were studied with the new A3 adenosine receptor antagonist [3H]-MRE 3008F20, the only A3 selective radioligand currently available. Saturation experiments revealed a single high affinity binding site with KD of 3.3±0.7 nM and Bmax of 291±50 fmol mg−1 of protein. The pharmacological profile of radioligand binding on A375 cells was established using typical adenosine ligands which displayed a rank order of potency typical of the different adenosine receptor subtype. Thermodynamic data indicated that radioligand binding to adenosine receptor subtypes in A375 cells was entropy- and enthalpy-driven. In functional assays the high affinity A2A agonists HE-NECA, CGS 21680 and A2A – A2B agonist NECA were able to increase cyclic AMP accumulation in A375 cells whereas A3 agonists Cl-IB-MECA, IB-MECA and NECA were able to stimulate Ca2+ mobilization. In conclusion, all these data indicate, for the first time, that adenosine receptors with a pharmacological and biochemical profile typical of the A1, A2A, A2B and A3 receptor subtype are present on A375 melanoma cell line. PMID:11704641

  16. Monocular nasal hemianopia from atypical sphenoid wing meningioma.

    PubMed

    Stacy, Rebecca C; Jakobiec, Frederick A; Lessell, Simmons; Cestari, Dean M

    2010-06-01

    Neurogenic monocular nasal field defects respecting the vertical midline are quite uncommon. We report a case of a unilateral nasal hemianopia that was caused by compression of the left optic nerve by a sphenoid wing meningioma. Histological examination revealed that the pathology of the meningioma was consistent with that of an atypical meningioma, which carries a guarded prognosis with increased chance of recurrence. The tumor was debulked surgically, and the patient's visual field defect improved.

  17. Review of controversies in management of non-benign meningioma.

    PubMed

    Paldor, Iddo; Awad, Mohammed; Sufaro, Yuval Z; Kaye, Andrew H; Shoshan, Yigal

    2016-09-01

    Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several controversies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resection of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT following GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recurrence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elucidates recommendations for some of the controversies involving NBM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Clear cell meningioma: case report and review of the literature.

    PubMed

    Oviedo, Angelica; Pang, Dachling; Zovickian, John; Smith, Matthew

    2005-01-01

    Clear cell meningioma (CCM) is a rare variant of meningioma. Only 17 cases have been previously reported in children. Although it has bland cytologic features, it has a higher rate of recurrence than does conventional meningioma. This variant has been reported in sites such as spinal/intradural (lumbar and thoracic), cerebellopontine angle, and supratentorial. The differential diagnosis of CCM includes microcystic meningioma, hemangioblastoma, and clear cell ependymoma. The characteristic histology and immunohistochemistry leads to the diagnosis. We present a case of a 7-year-old boy with a CCM of the cauda equina and a review of pediatric CCM.

  19. Dural Tuberculoma Mimicking Meningioma: A Clinicoradiologic Review of Dural En-Plaque Lesions.

    PubMed

    Aggarwal, Ashish; Patra, Devi Prasad; Gupta, Kirti; Sodhi, Harsimrat Bir

    2016-04-01

    Tuberculosis has long been a major health concern in developing countries and now has troubled developed world as well, owing to increase in patients with human immunodeficiency virus and immigration. Central nervous system tuberculosis accounts for approximately 1% of cases of tuberculosis. The pathologic presentation is varied, with intraparenchymal tuberculomas and pachymeningitis being the most common. Being a great mimicker, it simulates numerous diseases radiologically, and this is best realized when atypical forms are encountered. Here an atypical case of dural en-plaque tuberculoma is presented with comprehensive review of dural en-plaque lesions with their differentiating features. A 20-year-old man presented with features of increased intracranial pressure. On imaging, there was an enhancing dural-based lesion in the left frontoparietal region. In view of herniation syndrome, urgent surgical decompression of the lesion was performed. Histopathology showed features of tuberculosis. The patient is now asymptomatic with antitubercular therapy without any residual lesion at 6 months of follow-up. Tuberculoma en-plaque is an unusual entity characterized by a plaque-like meningitic process without exudation. It is easily confused with meningiomas as can other dural-based lesions comprising benign to malignant neoplastic, infectious, and granulomatous lesions. A preoperative diagnosis is imperative to differentiate it at least from neoplastic lesions, which are usually curable with surgical intervention in contrast to tuberculosis, which needs only optimal chemotherapy in most of the cases. Knowledge of differentiating imaging features, in corroboration with clinical history and high index of suspicion, helps in a proper preoperative diagnosis and optimal patient treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Stereotactic radiotherapy of meningiomas compressing optical pathways

    SciTech Connect

    Hamm, Klaus-Detlef . E-mail: khamm@erfurt.helios-kliniken.de; Henzel, Martin; Gross, Markus W.; Surber, Gunnar; Kleinert, Gabriele; Engenhart-Cabillic, Rita

    2006-11-15

    Purpose: Microsurgical resection is usually the treatment of choice for meningiomas, especially for those that compress the optical pathways. However, in many cases of skull-base meningiomas a high risk of neurological deficits and recurrences exist in cases where the complete tumor removal was not possible. In such cases (fractionated) stereotactic radiotherapy (SRT) can offer an alternative treatment option. We evaluated the local control rate, symptomatology, and toxicity. Patients and Methods: Between 1997 and 2003, 183 patients with skull-base meningiomas were treated with SRT, among them were 65 patients with meningiomas that compressed optical pathways (64 benign, 1 atypical). Of these 65 cases, 20 were treated with SRT only, 27 were subtotally resected before SRT, and 18 underwent multiple tumor resections before SRT. We investigated the results until 2005, with a median follow-up of 45 months (range, 22-83 months). The tumor volume (TV = gross tumor volume) ranged from 0.61 to 90.20 cc (mean, 18.9 cc). Because of the risk of new visual disturbances, the dose per fraction was either 2 or 1.8 Gy for all patients, to a total dose of 50 to 60 Gy. Results: The overall survival and the progression-free survival rates for 5 years were assessed to 100% in this patient group. To date, no progression for these meningiomas have been observed. Quantitatively, tumor shrinkage of more than 20%, or more than 2 mm in diameter, was proved in 35 of the 65 cases after SRT. In 29 of the 65 patients, at least 1 of the symptoms improved. On application of the Common Toxicity Criteria (CTC), acute toxicity (Grade 3) was seen in 1 case (worsening of conjunctivitis). Another 2 patients developed late toxicity by LENT-SOMA score, 1 x Grade 1 and 1 x Grade 3 (field of vision loss). Conclusion: As a low-risk and effective treatment option for tumor control, SRT with 1.8 to 2.0 Gy per fraction can also be recommended in case of meningiomas that compress optical pathways. An

  1. Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy.

    PubMed

    Sakurai, Takuya; Kondoh, Nobuo; Arai, Massaki; Hamada, Jun-ichi; Yamada, Toshiyuki; Kihara-Negishi, Fumiko; Izawa, Tetsuya; Ohno, Hideki; Yamamoto, Mikio; Oikawa, Tsuneyuki

    2007-01-01

    The Ets family of transcription factors is implicated in malignant transformation and tumor progression, including invasion, metastasis and neo-angiogenesis. In the present study, we found that the Fli-1 gene, a member of the Ets family, was highly expressed in several breast cancer cell lines (MDA-MB231, MDA-MB436, BT-549 and HCC1395). To investigate the functional roles of Fli-1 in breast cancer malignancy, we introduced an expression plasmid containing full-length Fli-1 cDNA into MCF7 breast cancer cells in which endogenous expression of Fli-1 was barely detectable.Overexpression of Fli-1 in MCF7 cells led to inhibition of apoptosis induced by serum depletion or ultraviolet irradiation, although it did not affect cell growth rate in liquid media, colony formation in soft agar or the in vitro invasion capacity of the cells. Expression of Fli-1 and antiapoptotic bcl-2 was coordinately upregulated by serum depletion in MCF7 cells, and the upregulation was inhibited by treatment of the cells with a c-Jun-NH(2)-terminal kinase-specific inhibitor. Furthermore, expression of the bcl-2 gene and protein was enhanced in Fli-1-overexpressing MCF7 cells compared with mock-transfected cells. In addition, human bcl-2 promoter activity was transactivated by Fli-1. These results suggest that Fli-1 contributes to the malignancy of human breast cancer by inhibiting apoptosis through upregulated expression of the bcl-2 gene.

  2. Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma.

    PubMed

    Chae, Jung-Il; Cho, Jin Hyoung; Lee, Kyung-Ae; Choi, Nag-Jin; Seo, Kang Seok; Kim, Sang-Bum; Lee, Sang-Han; Shim, Jung-Hyun

    2012-10-01

    Quercetin (Qu) is found in plants, including red onions and in the skins of red apples, and induces the apoptosis of certain malignant cells. However, no report has been issued on the apoptotic effect of Qu on human malignant pleural mesothelioma. In the present study, it was found that MSTO-211H mesothelioma cell viability was reduced and apoptotic cell death was increased by Qu (20-80 µM), which was found to have an IC₅₀ of 58 µM. In addition, Qu increased the sub-G₁ cell population, and was found to interact with specificity protein 1 (Sp1) and significantly suppressed its expression at the protein and mRNA levels. Furthermore, Qu modulated the levels of Sp1 regulatory genes, such as cyclin D1, myeloid cell leukemia (Mcl)-1 and survivin in MSTO-211H cells. Apoptotic signaling cascades were activated by the cleavage of Bid, caspase-3 and PARP, and by the downregulation of Bcl-xL and the upregulation of Bax in MSTO-211H cells. Our results strongly suggest that Sp1 be considered as a novel molecular target of Qu in human malignant pleural mesothelioma.

  3. The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation.

    PubMed

    Serafino, A; Balestrieri, E; Pierimarchi, P; Matteucci, C; Moroni, G; Oricchio, E; Rasi, G; Mastino, A; Spadafora, C; Garaci, E; Vallebona, P Sinibaldi

    2009-03-10

    Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.

  4. The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

    SciTech Connect

    Serafino, A. Balestrieri, E.; Pierimarchi, P.; Matteucci, C.; Moroni, G.; Oricchio, E.; Rasi, G.; Mastino, A.; Spadafora, C.; Garaci, E.; Vallebona, P. Sinibaldi

    2009-03-10

    Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.

  5. Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

    PubMed Central

    Gupta, Shikha; Gupta, Sunita

    2015-01-01

    Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

  6. Shape-dependent regulation of proliferation in normal and malignant human cells and its alteration by interferon

    SciTech Connect

    Kulesh, D.A.; Greene, J.J.

    1986-06-01

    The relationship between cell morphology, proliferation, and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes by plating onto plastic surfaces coated with poly(2-hydroxyethyl methacrylate). Poly(2-hydroxyethyl methacrylate) can precisely vary the shape of cells without toxicity. Cell proliferation was quantitated by cell counts and labeling indices were determined by autoradiography. The normal JHU-1 foreskin fibroblasts and IMR-90 lung fibroblasts exhibited contact-inhibited growth with a saturation density of 2.9 X 10(5) and 2.0 X 10(5) cells/cm2, respectively. These cells also exhibited stringent dependency on cell shape with a mitotic index of less than 3% at poly(2-hydroxyethyl methacrylate) concentrations at which the cells were rounded versus a labeling index of 75-90% when the cells were flat. The malignant bladder carcinoma line RT-4 exhibited partial contact-inhibited growth. Its dependency on cell shape was less stringent than that of normal cells with a mitotic index of 37-40% when rounded and 79% when flat. The malignant fibrosarcoma line, HT1080, was not contact inhibited and was entirely shape independent with a mitotic index of 70-90% regardless of cell shape. Treatment of HT1080 cells with low concentration of human fibroblast interferon (less than 40 units/ml) restored shape-dependent proliferation while having little effect on normal cells. Subantiproliferative doses of interferon were also shown to restore contact-inhibited proliferation control to malignant cells previously lacking it.

  7. Olfactory groove meningiomas: approaches and complications.

    PubMed

    Aguiar, Paulo Henrique Pires de; Tahara, Adriana; Almeida, Antonio Nogueira; Simm, Renata; Silva, Arnaldo Neves da; Maldaun, Marcos Vinicius Calfatt; Panagopoulos, Alexandros Theodoros; Zicarelli, Carlos Alexandre; Silva, Pedro Gabriel

    2009-09-01

    Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial meningiomas. We report 21 patients with OGMs. Tumors were operated on using three surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%. The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%. We preferred to use the pterional approach, which provides quick access to the tumor with less brain exposure. It also allows complete drainage of cisternal cerebrospinal fluid, providing a good level of brain relaxation during surgery. However, for long, thin tumors, hemostasis can be difficult using this approach.

  8. Epidural Cystic Spinal Meningioma: A Case Report.

    PubMed

    Zhang, Ji; Chen, Zheng-he; Wang, Zi-feng; Sun, Peng; Jin, Jie-tian; Zhang, Xiang-heng; Zhao, Yi-ying; Wang, Jian; Mou, Yong-gao; Chen, Zhong-ping

    2016-03-01

    Cystic spinal meningioma (CSM) is an uncommon meningioma variant. Extradural CSMs are particularly rare and difficult to distinguish from other intraaxial tumors. This study presents a case of a 36-year-old woman with intraspinal extradual CSM at the thoracolumbar spine. She experienced persistent weakness, progressive numbness, and sensory disturbance in the right lower limb. Magnetic resonance imaging (MRI) of the patient revealed an irregular cystic mass at the thoracic 11 to lumbar 3 levels dorsally. This case was misdiagnosed as other neoplasms prior to surgery because of the atypical radiographic features and location of the tumor. Extradural CSMs should be considered in the differential diagnosis of intraspinal extradural cystic neoplasms. Complete removal of cystic wall provides an optimal outcome, rendering the lesion curable.

  9. PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling

    SciTech Connect

    Yamada, Tamaki; Tsuda, Masumi; Ohba, Yusuke Kawaguchi, Hideaki; Totsuka, Yasunori; Shindoh, Masanobu

    2008-04-11

    Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer.

  10. Primary extra-cranial meningioma of head and neck: clinical, histopathological and immunohistochemical study of three cases.

    PubMed

    Possanzini, P; Pipolo, C; Romagnoli, S; Falleni, M; Moneghini, L; Braidotti, P; Salvatori, P; Paradisi, S; Felisati, G

    2012-10-01

    Extracranial meningiomas of the head and neck region are rare neoplasms, the majority being a secondary location of a primary intracranial tumour. We herewith report three rare cases of extracranial meningiomas, located in the temporal muscle, parotid gland and nasal cavity, together with complete pathological, immunohistochemical and ultrastructural studies. Prognosis of this tumour is generally excellent. Surgical excision is the treatment of choice, with no need for further treatment; nevertheless, differential diagnosis must consider other more common tumours of the head and neck and be based on histopathologic examination and relative techniques, including examination of frozen sections. This procedure is particularly useful assessing surgical treatment and should be performed whenever possible to exclude the malignant nature of the lesion and avoid over-treatment. All three patients underwent surgery and are alive and disease-free.

  11. LINAC radiosurgery in skull base meningiomas.

    PubMed

    Deinsberger, R; Tidstrand, J; Sabitzer, H; Lanner, G

    2004-12-01

    LINAC radiosurgery has provided increasing access and changed treatment strategies in patients with benign skull base meningiomas in recent years. From January 1996 to January 2003, 37 patients with skull base meningiomas were treated with LINAC radiosurgery. A combination of the University of Florida system and the X Knife System, developed by Radionics, was used in all patients. Eight patients were treated by microsurgical resection before radiosurgery, in two patients tumor recurrence was treated and in 29 patients LINAC radiosurgery was the initial treatment procedure. The median treatment volume was 5.9 mL (0.7 to 22 mL) and the median given dose was 14.6 Gy (12.8 to 18 Gy) prescribed to the 80 percent isodose line. The follow-up period is between 12 and 96 months, median 66 months. 12 patients (32.4 %) showed a significant reduction in tumor size, in 11 patients (29.7 %) there was significantly less contrast enhancement and in 13 patients (35.1 %) the skull base meningioma was without any change. In one patient (2.8 %) there was tumor growth 48 months after radiosurgery, so the tumor control rate was 97.2 %. Two patients (5.6 %) showed neurological worsening after radiosurgery, whereas the symptoms were transient in one patient. LINAC radiosurgery offers us an effective treatment modality and changes treatment strategies in skull base meningiomas towards a less aggressive surgical approach. By combining microsurgery and radiosurgery we can achieve high tumor control rates with an acceptable low morbidity and a high level of quality of life.

  12. Management of Intracranial Meningiomas Using Keyhole Techniques

    PubMed Central

    Burks, Joshua D; Conner, Andrew K; Bonney, Phillip A; Archer, Jacob B; Christensen, Blake; Smith, Jacqueline; Safavi-Abbasi, Sam

    2016-01-01

    Background: Keyhole craniotomies are increasingly being used for lesions of the skull base. Here we review our recent experience with these approaches for resection of intracranial meningiomas. Methods: Clinical and operative data were gathered on all patients treated with keyhole approaches by the senior author from January 2012 to June 2013. Thirty-one meningiomas were resected in 27 patients, including 9 supratentorial, 5 anterior fossa, 7 middle fossa, 6 posterior fossa, and 4 complex skull base tumors. Twenty-nine tumors were WHO Grade I, and 2 were Grade II.  Results: The mean operative time was 8 hours, 22 minutes (range, 2:55-16:14) for skull-base tumors, and 4 hours, 27 minutes (range, 1:45-7:13) for supratentorial tumors. Simpson Resection grades were as follows: Grade I = 8, II = 8, III = 1, IV = 15, V = 0. The median postoperative hospital stay was 4 days (range, 1-20 days). In the 9 patients presenting with some degree of visual loss, 7 saw improvement or complete resolution. In the 6 patients presenting with cranial nerve palsies, 4 experienced improvement or resolution of the deficit postoperatively. Four patients experienced new neurologic deficits, all of which were improved or resolved at the time of the last follow-up. Technical aspects and surgical nuances of these approaches for management of intracranial meningiomas are discussed.  Conclusions: With careful preoperative evaluation, keyhole approaches can be utilized singly or in combination to manage meningiomas in a wide variety of locations with satisfactory results. PMID:27284496

  13. MED12 Alterations in Both Human Benign and Malignant Uterine Soft Tissue Tumors

    PubMed Central

    Pérot, Gaëlle; Croce, Sabrina; Ribeiro, Agnès; Lagarde, Pauline; Velasco, Valérie; Neuville, Agnès; Coindre, Jean-Michel; Stoeckle, Eberhard; Floquet, Anne; MacGrogan, Gaëtan; Chibon, Frédéric

    2012-01-01

    The relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously repo