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Sample records for malignant meningioma cell

  1. Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma.

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    Yin-Cheng Huang

    Full Text Available 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.

  2. Edema and malignancy in meningiomas

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    Mattei,Tobias Alécio; Mattei,Josias Alécio; Ramina,Ricardo; Aguiar,Paulo Henrique; Plese,José Pindaro; Marino Jr,Raul

    2005-01-01

    PURPOSE: In recent years there have been many attempts to define a subset of aggressive malignant meningiomas based on histopathology and imaging technologies. The purpose of this study was to evaluate the level of peritumoral edema and its volume using the imaging technologies, computer tomography and magnetic resonance imaging, and correlate these results with the histological WHO classification. Reported causes of tumoral edema and its relationships to the histological characteristics were...

  3. Clinical results of BNCT for malignant meningiomas

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    Miyatake, Shin-ichi; Tamura, Yoji; Kawabata, Shinji

    2006-01-01

    Malignant meningiomas is difficult pathology to be controlled as well as GBM. Since June of 2005, we applied BNCT for 7 cases of malignancy related meningiomas with 13 times neutron irradiation. Five were anaplastic, one was atypical meningiomas and one was sarcoma transformed from meningioma with cervical lymph node metastasis. All cases were introduced after repetitive surgeries and XRT or SRS. Follow-up images were available for 6 cases with observation duration between 2 to 9 months. We applied F-BPA-PET before BNCT in 6 out of 7 cases. One case was received methionine-PET. Five out of 6 cases who received BPA-PET study showed good BPA uptake more than 3 of T/N ratio. One atypical meningiomas cases showed 2.0 of T/N ratio. Original tumor sizes were between 9.2 to 92.7 ml. Two out of 5 anaplastic meningiomas showed CR and all six cases showed radiographic improvements. Clinical symptoms before BNCT such as hemiparesis and facial pain were improved after BNCT, except one case. An huge atypical meningiomas which arisen from tentorium and extended bilateral occipital lobes and brain stem, visual problems were worsened after repetitive BNCT with increase of peritumoral edema. Malignant meningiomas are seemed to be good candidate for BNCT. (author)

  4. Perfusion MR imaging for differentiation of benign and malignant meningiomas

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    Zhang, Hao; Rodiger, Lars A.; Shen, Tianzhen; Miao, Jingtao; Oudkerk, Matthijs

    Introduction Our purpose was to determine whether perfusion MR imaging can be used to differentiate benign and malignant meningiomas on the basis of the differences in perfusion of tumor parenchyma and/or peritumoral edema. Methods A total of 33 patients with preoperative meningiomas (25 benign and

  5. Rapid recurrence of a malignant meningioma: case report

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    Baran Oguz

    2017-06-01

    Full Text Available This short report presents a case that developed rapid recurrence of a malignant meningioma. The meningioma was located on the right temporal lobe and total removal (Simpson grade-II was performed. Radiotherapy was not given and the lesion recurred within four months. The MIB-1 (Ki-67 index was 30 % and the tumor fulfilled all the criteria of anaplasia. After the second surgery, patient was transferred to the Radiation Oncology for radiotherapy. Should we questioned the extent of surgery? Neurosurgeons should be careful and close follow-up the patients with malignant meningioma.

  6. Perfusion MR imaging for differentiation of benign and malignant meningiomas

    International Nuclear Information System (INIS)

    Zhang, Hao; Roediger, Lars A.; Oudkerk, Matthijs; Shen, Tianzhen; Miao, Jingtao

    2008-01-01

    Our purpose was to determine whether perfusion MR imaging can be used to differentiate benign and malignant meningiomas on the basis of the differences in perfusion of tumor parenchyma and/or peritumoral edema. A total of 33 patients with preoperative meningiomas (25 benign and 8 malignant) underwent conventional and dynamic susceptibility contrast perfusion MR imaging. Maximal relative cerebral blood volume (rCBV) and the corresponding relative mean time to enhance (rMTE) (relative to the contralateral normal white matter) in both tumor parenchyma and peritumoral edema were measured. The independent samples t-test was used to determine whether there was a statistically significant difference in the mean rCBV and rMTE ratios between benign and malignant meningiomas. The mean maximal rCBV values of benign and malignant meningiomas were 7.16±4.08 (mean±SD) and 5.89±3.86, respectively, in the parenchyma, and 1.05±0.96 and 3.82±1.39, respectively, in the peritumoral edema. The mean rMTE values were 1.16±0.24 and 1.30±0.32, respectively, in the parenchyma, and 0.91±0.25 and 1.24±0.35, respectively, in the peritumoral edema. The differences in rCBV and rMTE values between benign and malignant meningiomas were not statistically significant (P>0.05) in the parenchyma, but both were statistically significant (P<0.05) in the peritumoral edema. Perfusion MR imaging can provide useful information on meningioma vascularity which is not available from conventional MRI. Measurement of maximal rCBV and corresponding rMTE values in the peritumoral edema is useful in the preoperative differentiation between benign and malignant meningiomas. (orig.)

  7. Perfusion MR imaging for differentiation of benign and malignant meningiomas

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    Zhang, Hao [University of Groningen, Department of Radiology, University Medical Center Groningen, Groningen (Netherlands); Shanghai Jiaotong University, Department of Radiology, First People' s Hospital, Shanghai (China); Roediger, Lars A.; Oudkerk, Matthijs [University of Groningen, Department of Radiology, University Medical Center Groningen, Groningen (Netherlands); Shen, Tianzhen [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University, Department of Radiology, First People' s Hospital, Shanghai (China)

    2008-06-15

    Our purpose was to determine whether perfusion MR imaging can be used to differentiate benign and malignant meningiomas on the basis of the differences in perfusion of tumor parenchyma and/or peritumoral edema. A total of 33 patients with preoperative meningiomas (25 benign and 8 malignant) underwent conventional and dynamic susceptibility contrast perfusion MR imaging. Maximal relative cerebral blood volume (rCBV) and the corresponding relative mean time to enhance (rMTE) (relative to the contralateral normal white matter) in both tumor parenchyma and peritumoral edema were measured. The independent samples t-test was used to determine whether there was a statistically significant difference in the mean rCBV and rMTE ratios between benign and malignant meningiomas. The mean maximal rCBV values of benign and malignant meningiomas were 7.16{+-}4.08 (mean{+-}SD) and 5.89{+-}3.86, respectively, in the parenchyma, and 1.05{+-}0.96 and 3.82{+-}1.39, respectively, in the peritumoral edema. The mean rMTE values were 1.16{+-}0.24 and 1.30{+-}0.32, respectively, in the parenchyma, and 0.91{+-}0.25 and 1.24{+-}0.35, respectively, in the peritumoral edema. The differences in rCBV and rMTE values between benign and malignant meningiomas were not statistically significant (P>0.05) in the parenchyma, but both were statistically significant (P<0.05) in the peritumoral edema. Perfusion MR imaging can provide useful information on meningioma vascularity which is not available from conventional MRI. Measurement of maximal rCBV and corresponding rMTE values in the peritumoral edema is useful in the preoperative differentiation between benign and malignant meningiomas. (orig.)

  8. Meningioma

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    ... meningioma is a tumor that arises from the meninges — the membranes that surround your brain and spinal ... know that something alters some cells in your meninges to make them multiply out of control, leading ...

  9. Meningioma as second malignant neoplasm after oncological treatment during childhood

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    Mueller, H.L.; Gebhardt, U. [Klinikum Oldenburg (Germany). Dept. of Pediatric Hematology and Oncology; Warmuth-Metz, M. [University Hospital Wuerzburg (Germany). Dept. of Neuroradiology; Pietsch, T. [Bonn Univ. (Germany). Dept. of Neuropathology; Soerensen, N. [Evangelisches Krankenhaus, Oldenburg (Germany). Dept. of Neurosurgery; Kortmann, R.D. [University Hospital Leipzig (Germany). Dept. of Radiooncology

    2012-05-15

    A total of 38 patients (18 female/20 male) with childhood meningioma were recruited from the German registry HIT-Endo (1989-2009). In 5 cases meningioma occurred as second malignant neoplasm (SMN). Histologies were confirmed by reference assessment in all cases (SMN: 2 WHO I, 1 WHO II, 2 WHO III). The SMNs were diagnosed at a median age of 12.4 years with a median latency of 10.2 years after primary malignancy (PMN; 4 brain tumors, 1 lymphoblastic leukemia; median age at diagnosis 2.7 years). Meningioma occurred as SMN in the irradiated field of PMN (range 12-54 Gy). The outcome after treatment of SMN meningioma (surgery/irradiation) was favorable in terms of psychosocial status and functional capacity in 4 of 5 patients (1 death). We conclude that survivors of childhood cancer who were exposed to radiation therapy at young age harbor the risk of developing meningioma as a SMN at a particularly short latency period in case of high dose exposure. (orig.)

  10. Malignant Subdural Hematoma Associated with High-Grade Meningioma

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    Teramoto, Shinichiro; Tsunoda, Akira; Kawamura, Kaito; Sugiyama, Natsuki; Saito, Rikizo; Maruki, Chikashi

    2018-01-01

    A 70-year-old man, who had previously undergone surgical resection of left parasagittal meningioma involving the middle third of the superior sagittal sinus (SSS) two times, presented with recurrence of the tumor. We performed removal of the tumor combined with SSS resection as Simpson grade II. After tumor removal, since a left dominant bilateral chronic subdural hematoma (CSDH) appeared, it was treated by burr hole surgery. However, because the CSDH rapidly and repeatedly recurred and eventually changed to acute subdural hematoma, elimination of the hematoma with craniotomy was accomplished. The patient unfortunately died of worsening of general condition despite aggressive treatment. Histopathology of brain autopsy showed invasion of anaplastic meningioma cells spreading to the whole outer membrane of the subdural hematoma. Subdural hematoma is less commonly associated with meningioma. Our case indicates the possibility that subdural hematoma associated with meningioma is formed by a different mechanism from those reported previously. PMID:29896565

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

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

    2015-01-01

    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

  12. Radiotherapy for intracranial meningioma. Special reference to malignant and high risk benign meningioma

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    Shimizu, Teppei; Iijima, Mitsuharu; Tanaka, Yoshiaki

    1995-01-01

    Results of radiotherapy in 21 patients who had been treated for intracranial meningioma from April 1975 to March 1993 at Tokyo Metropolitan Komagome Hospital are presented. All patients were treated with 4 MV X-rays using conventional fractionation. The median tumor dose was 54.4 Gy (range 30 Gy to 70 Gy). Radiotherapy was delivered by conformation technique in 11, parallel opposed field in four and three ports technique in two. Of 21 meningiomas, 13 were histologically malignant and 8 were benign. The median follow-up period was 63 months. Overall survival rate at 5 years was 71% for benign and 63% for malignant meningiomas; the 5-year progression-free survival rates were 25% and 30%, respectively. Eight of 21 patients received 60 Gy or more, and the remaining 13 received less than 60 Gy. The 5-year overall survival rates for these two groups were 43% and 83% (p<0.05), respectively. Ten of 21 patients were treated with post-operative radiotherapy as initial treatment and eleven of 21 patients were treated with salvage therapy with or without surgical excision for recurrent lesions. The 5-year survival rates and progression-free survival rates of these two groups showed no significant differences. From analysis of the clinical course of the salvage therapy group, radiotherapy may prolong survival time and delay further tumor recurrence. According to the present study, radiotherapy (doses of 55 Gy to 60 Gy) after primary resection and at the time of recurrence are equally effective for prolongation of survival and delay of further tumor recurrence. (author)

  13. Computed tomography and angiography do not reliably discriminate malignant meningiomas from benign ones

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    Servo, A.; Porras, M.; Jaeaeskelaeinen, J.; Paetau, A.; Haltia, M.

    1990-01-01

    Histological anaplasia, found in up to 10% of meningiomas, is an important prognostic sign as it is associated with increased recurrence rate and volume growth rate. We studied in retrospect a series of 230 primary intracranial meningiomas to discover whether histological anaplasia can be reliably foreseen in CT scans and angiograms. 205 meningiomas were histologically benign, and 25 meningiomas were classified as malignant (atypical or anaplastic), with either incipient (20) or overt (5) signs of anaplasia. Of ten CT parameters tested, three were associated significantly more often with malignant meningiomas: Nodular contour (58.3% vs 26.7%); cysts (20.0% vs 4.4%) and absence of calcifications (92% vs 65.3%); none of these parameters was an absolute sign of anaplasia. 'Mushrooming', previously regarded as a definite sign of malignancy, was seen in 9% of benign meningiomas and in 21% of malignant ones. In angiography, no apparent differences between benign and malignant meningiomas were seen. The conclusion is that it is not possible to distinguish malignant meningiomas from benign ones with CT or angiography. (orig.)

  14. Meningioma

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    Windt, H.L. de.

    1981-01-01

    131 Cases of meningioma, of which 113 were intracranial and 18 intraspinal, are reviewed retrospectively on the basis of the clinical findings. In the first category the history and neurological findings are combined. In category II the following investigations are discussed. In evaluation of plain X-rays of sphenoid meningiomas, it appears that 66.7% are abnormal. The EEG investigation generally correlates with the hemisphere in which the tumor is located. The isotope investigation (test) appears to be of great value in screening for meningioma, and is almost 100% abnormal. The CT scan is a rather welcome contribution in the diagnostic procedure for evaluation of meningioma. Category III discusses findings upon operation. (Auth.)

  15. Primary Benign Intraosseous Meningioma on {sup 18}F-FDG PET/CT Mimicking Malignancy

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    Kim, Ho Seong; Kim, Seok Hwi; Kim, Hyung Jin; Kang, Se Woong; Kim, Soo Jeong; Lee, Joo Hee; Hong, Sun Pyo; Cho, Young Seok; Choi, Joon Young [Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    We present a case of primary benign intraosseous meningioma in the sphenoid bone mimicking malignancy. A 44-year-old female patient who had a protruding right eye and headache came to our hospital. MRI showed a large, destructive, heterogeneously well-enhancing soft tissue mass in the right sphenoid bone suggesting malignancy. {sup 18}F-FDG PET/CT showed a hypermetabolic mass in the same site with an SUV{sub max} of 9.1 The pathological diagnosis by surgery revealed that this tumor was a WHO grade I transitional meningioma. This case suggests that primary benign intraosseous meningioma may show high {sup 18}F-FDG uptake mimicking a malignancy.

  16. Synchronous meningioma and anaplastic large cell lymphoma.

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    Colen, Chaim B; Rayes, Mahmoud; Kupsky, William J; Guthikonda, Murali

    2010-06-01

    Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

  17. Long-Term Experience With World Health Organization Grade III (Malignant) Meningiomas at a Single Institution

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    Rosenberg, Lewis A.; Prayson, Richard A.; Lee, Joung; Reddy, Chandana; Chao, Samuel T.; Barnett, Gene H.; Vogelbaum, Michael A.; Suh, John H.

    2009-01-01

    Purpose: To evaluate the outcomes for patients with Grade III meningiomas as defined by the 2007 World Health Organization standards. Methods and Materials: The slides from patients who had been treated at the Cleveland Clinic for malignant meningiomas were reviewed by a single neuropathologist. The data from 13 patients treated between 1984 and 2006 satisfied the World Health Organization 2007 definition of Grade III meningioma. A total of 24 surgeries were performed, including 13 primary, 7 salvage, and 4 second salvage. Also, 14 courses of radiotherapy (RT) were administered, including fractionated RT in 3 patients after primary surgery, fractionated RT in 4 patients after salvage surgery, salvage stereotactic radiosurgery to six separate areas in 3 patients, and salvage intensity-modulated RT in 1 patient. Results: From the primary surgery, the median survival was 3.4 years, the 5-year survival rate was 47.2%, and the 8-year survival rate was 12.2%. The median time to recurrence was 9.6 months. A trend was seen toward longer survival for patients who had received adjuvant RT after initial surgery compared with those treated with surgery alone. Two patients developed radiation necrosis, and three had surgical complications. Conclusion: This is one of the few studies reporting the outcomes for malignant meningioma patients according to recent definitions. Our results are consistent with existing reports of the overall poor outcomes for atypical and malignant meningioma patients. From the available data, surgical resection followed by RT and salvage therapy can lead to extended survival.

  18. Fabry disease: Four case reports of meningioma and a review of the literature on other malignancies

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    Beth L. Thurberg, MD, PhD

    2017-06-01

    Full Text Available Fabry disease (FD is an X-linked lysosomal storage disorder caused by loss of function mutations in the GLA gene at Xq22 with subsequent functional deficiency of alpha-galactosidase A, resulting in the accumulation of globotriaosylceramide (GL-3 or Gb3 in multiple cells types throughout the body. As with other rare metabolic disorders, little is known about the incidence of malignancies in these populations and the relationship to the underlying disease, if any. We report the occurrence of meningioma in four female patients with Fabry disease. Two of the cases are from the same family and shared the same GLA mutation. All four patients underwent surgical excision of their tumor. High resolution light microscopy and electron microscopy examination of one case revealed extensive involvement of tumor cells and associated blood vessels by GL-3 accumulation. Because of the small number of Fabry-associated cancer cases reported in the literature, questions about a possible link between lysosomal storage disorders and the development of malignancy remain open.

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

    International Nuclear Information System (INIS)

    Baek, Byoung Joon; Shin, Jae–Min; Lee, Chi Kyou; Lee, Ji Hye; Lee, Koen Hyeong

    2012-01-01

    Primary extracranial meningiomas (PEMs) originating from the nasal septum are extremely rare, as are extracranial metastases of meningiomas. 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. 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

  20. Molecular signatures define two main classes of meningiomas

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    Costello Joseph F

    2007-10-01

    Full Text Available Abstract Background Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis. Results We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups. Conclusion Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.

  1. Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study

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    Bostroem, J.P. [University of Bonn Medical Center, Department of Neurosurgery, Bonn (Germany); MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); Seifert, M.; Greschus, S. [University of Bonn Medical Center, Department of Radiology, Bonn (Germany); Schaefer, N.; Herrlinger, U. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); Glas, M. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); University of Bonn Medical Center, Stem Cell Pathologies, Institute of Reconstructive Neurobiology, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Lammering, G. [MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Heinrich-Heine-University of Duesseldorf, Department of Radiotherapy and Radiation Oncology, Duesseldorf (Germany)

    2014-04-15

    Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma. (orig.) [German] In zwei aktuellen retrospektiven Kohortenstudien konnte eine Wirksamkeit von Bevacizumab bei Patienten mit rezidivierenden atypischen und

  2. [Multiple meningiomas].

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    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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

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    Werner, Tamara V.; Hart, Martin; Nickels, Ruth; Kim, Yoo-Jin; Menger, Michael D.; Bohle, Rainer M.; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

    2017-01-01

    Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype. Following in silico prediction of potential targets of miR-34a-3p, SMAD4, FRAT1, and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs. Disruption of the miR-34a-3p binding sites in the 3'UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro. We show that SMAD4, FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro. As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4, FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas. PMID:28340489

  4. Cathepsin L in human meningiomas

    International Nuclear Information System (INIS)

    Trinkaus, M.; Lah, T.T.; Vranic, A.; Dolenc, V.V.

    2003-01-01

    Background. Although meningiomas are considered as benign tumours, about 10% comprise a subgroup of a typical meningiomas, classified as WHO grade II, with greater likelihood of recurrences and/or aggressive behaviour, including the possibility of brain tissue invasion. The lysosomal cysteine endopeptidase cathepsin L plays a role in tumour cell invasion and malignant progression of cancer, and has been suggested as a prognostic marker for certain types of tumours. Results. In our study, we compared the expression of cathepsin L in 30 meningiomas with their clinical invasiveness. Cathepsin L was determined by immunohistochemical analysis, quantitative real-time RT-PCR and Northern blot. We showed that expression of cathepsin L protein was significantly higher (p=0.019) in 9 atypical than in 21 benign meningiomas. Within the group of benign meningiomas, expression of cathepsin L was significantly lower in the transitional histological subtype. We measured the levels of cathepsin LA type of RNA splicing variants: LA, LAI and LAII, but not LAIII and not the LB variant, the latter being several times lower than the LA type. In contrast to protein levels, the levels of cathepsin LA, AI, AII RNA variants did not differ between histological subtypes or between benign and a typical meningiomas. The expression of total measured cathepsin LA, AI, AII RNA variants in the samples, taken from the centre and the periphery of the tumours, also showed no statistically significant differences. Conclusions. These results indicate that cathepsin L protein over-expression may contribute to the development of the aggressive and possibly invasive character of a typical meningiomas and that it may be up regulated at the translational level. (author)

  5. Nevoid basal cell carcinoma syndrome with medulloblastoma and meningioma. Case report

    International Nuclear Information System (INIS)

    Fukushima, Yutaka; Oka, Hidehiro; Utsuki, Satoshi; Iwamoto, Kazuhisa; Fujii, Kiyotaka

    2004-01-01

    A 35-year-old man presented with a rare case of nevoid basal cell carcinoma syndrome, or Gorlin's syndrome, associated with both medulloblastoma and meningioma, manifesting as visual field constriction due to multiple parasellar tumors. He had undergone resection of a medulloblastoma at the age of 1 year 9 months, followed by adjunctive irradiation with a total dose of 40 Gy. He presented with multiple subcutaneous nodules on his face and neck. Histological examination of biopsy specimens established the diagnosis of nevoid basal cell carcinoma syndrome. Tuberculum sellae meningioma was removed through a craniotomy, and his symptoms improved. Meningioma is known to occur in the field of therapeutic irradiation, so chemotherapy may be a better option for medulloblastoma associated with nevoid basal cell carcinoma syndrome. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Hitoshi [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima (Japan); Natsume, Atsushi, E-mail: anatsume@med.nagoya-u.ac.jp [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Iwami, Kenichiro; Ohka, Fumiharu [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae [Department of Biomolecular Engineering, Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology, Yokohama (Japan); Ito, Kengo [National Center for Geriatrics and Gerontology, Aichi (Japan); Saito, Kiyoshi [Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima (Japan); Sugita, Sachi; Hoshino, Tsuneyoshi [MICRON Inc.Medical Facilities Support Department, Aichi (Japan); Wakabayashi, Toshihiko [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan)

    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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  8. MENINGIOMAS: A CLINICOPATHOLOGICAL STUDY

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    Shri Lakshmi S

    2015-10-01

    Full Text Available Introduction: Meningiomas are tumors that arise from the meningothelial cells. Most of these tumors are intracranial; some are intraspinal and few extra cranial. There are many histological variants classified into three grades depending on clinical behavior. Classification is important for determining the modality of treatment. Objectives: To study the incidence, location, sex and age predilection, histological variants and grading of meningiomas based on WHO 2007 classification and recurrence if present. Materials and methods: All128 cases of meningiomas. Based on Histological features, typing and grading of meningiomas was done as per the WHO 2007 classification of Meningiomas. Age, Sex incidence, Location of meningiomas were studied. Results: Meningiomas comprised 25.25% of all CNS tumors during the study period. Of 507 CNS tumors, 128 were meningiomas. Most of them were intracranial, predominantly involving the convexities of brain, females and the 41 – 50 age group. Of these, 116 were benign grade I tumors, 9 were grade II and 3 were grade III. The most common histological variant was fibroblastic and meningothelial. Intraspinal meningiomas were 16 (12.5% cases with the psammomatous variant being more common. Grade II and Grade III tumors located in parafalcine or parasagittal area commonly recurred. Conclusion: Meningiomas are slow growing tumors arising from the meningothelial cells accounting for 25.25% of all CNS neoplasms showing a variety of histological patterns, more common in women, predominantly Grade I tumors. Recurrence of tumors depends on histological grade and extent of surgery.

  9. Absolute choline concentration measured by quantitative proton MR spectroscopy correlates with cell density in meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Qiang [University of Tsukuba, Department of Neurosurgery, Institute of Clinical Medicine, Tsukuba Science City, Ibaraki (Japan)]|[West China Hospital of Sichuan University, Huaxi MR Research Center, Department of Radiology, Chengdu (China); Shibata, Yasushi; Kawamura, Hiraku; Matsumura, Akira [University of Tsukuba, Department of Neurosurgery, Institute of Clinical Medicine, Tsukuba Science City, Ibaraki (Japan); Isobe, Tomonori [Kitasato University, Department of Medical Technology, School of Allied Health Sciences, Minato, Tokyo (Japan); Anno, Izumi [University of Tsukuba, Department of Radiology, Institute of Clinical Medicine, Tsukuba, Ibaraki (Japan); Gong, Qi-Yong [West China Hospital of Sichuan University, Huaxi MR Research Center, Department of Radiology, Chengdu (China)]|[University of Liverpool, Division of Medical Imaging, Faculty of Medicine, Liverpool (United Kingdom)

    2009-01-15

    This study was aimed to investigate the relationship between quantitative proton magnetic resonance spectroscopy (1H-MRS) and pathological changes in meningioma. Twenty-two meningioma cases underwent single voxel 1H-MRS (point-resolved spectroscopy sequence, repetition time/echo time = 2,000 ms/68, 136, 272 ms). Absolute choline (Cho) concentration was calculated using tissue water as the internal reference and corrected according to intra-voxel cystic/necrotic parts. Pathological specimens were stained with MIB-1 antibody to measure cell density and proliferation index. Correlation analysis was performed between absolute Cho concentration and cell density and MIB-1 labeled proliferation index. Average Cho concentration of all meningiomas before correction was 2.95 {+-} 0.86 mmol/kg wet weight. It was increased to 3.23 {+-} 1.15 mmol/kg wet weight after correction. Average cell density of all meningiomas was 333 {+-} 119 cells/HPF, and average proliferation index was 2.93 {+-} 5.72%. A linear, positive correlation between cell density and Cho concentration was observed (r = 0.650, P = 0.001). After correction of Cho concentration, the correlation became more significant (r = 0.737, P < 0.001). However, no significant correlation between Cho concentration and proliferation index was found. There seemed to be a positive correlation trend after correction of Cho concentration but did not reach significant level. Absolute Cho concentration, especially Cho concentration corrected according to intra-voxel cystic/necrotic parts, reflects cell density of meningioma. (orig.)

  10. The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP

    Directory of Open Access Journals (Sweden)

    Katherine Striedinger

    2008-11-01

    Full Text Available Neurofibromatosis type 2 (NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas. In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein (YAP, the mammalian homolog of Yorkie. NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Finally, siRNA-mediated reduction of YAP in NF2-deficient meningioma cells rescued the effects of merlin loss on cell proliferation and S-phase entry. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.

  11. A rare case of multiple meningiomas with different histology

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    Toma I. Papacocea

    2017-11-01

    Full Text Available Meningiomas are generally benign tumors but sometimes they manifest tendency to progress towards malignancy. It is not yet clear if anaplastic meningiomas have an innate malignancy characteristic, or an initially beginning histological appearance that degenerates malignantly in time. According to literature data, the risk of a benign meningioma to progress towards malignant phenotype is about 0.16-2%, such malignant transformation occurring after a variable period of time (2-16 years. A still unanswered question is how many of the malignant meningiomas present this appearance as an innate feature and how many of them originate from benign meningiomas. Multiple meningiomas are defined as the presence of two or more distinct meningiomas. They occur in 6-10% of all patients that present meningiomas. Multiple meningiomas with a distinct histological appearance are rarely discovered. They support the theory of meningiomas that develop independently in the same patient. Different histology of multiple meningiomas is found in less than a third of the patients who suffer from this pathology. We are presenting the case of a patient with multiple meningiomas with distinct histology, one being benign and the other malignant. In connection with this case we are raising a question of therapeutic management in patients diagnosed with malignant meningiomas, namely if other possible small/ benign meningiomas should be also entirely resected.

  12. An intraventricular clear cell meningioma revealed by an inflammatory syndrome in a male adult: a case report.

    Science.gov (United States)

    Cassereau, J; Lavigne, C; Michalak-Provost, S; Ghali, A; Dubas, F; Fournier, H D

    2008-07-01

    Intraventricular meningiomas are infrequent intracranial tumors. Clinical symptoms are mainly due to an increased intracranial pressure or a direct pressure on the surrounding brain structures. Inflammatory syndrome was described in some patients with chordoid meningiomas. Here we report a case of right intraventricular clear cell meningioma in a 50-year-old man who presented with fever, headache, and inflammatory syndrome. Clinical and biological normalization was rapidly obtained after tumor removal. Immunohistochemical examination showed tumor cells and lymphocytes positivity for the pyrogenic cytokine interleukin-6, with a same intensity. To our knowledge, this is the first case described in the literature concerning an adult man with an intraventricular clear cell meningioma associated with a systemic inflammatory syndrome.

  13. Anaplastic meningioma: The dark side of meningiomas

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    Andreea Cioca

    2017-06-01

    Full Text Available Anaplastic meningioma is a rare malignant tumor of the meninges, with a very aggressive behavior and a grim prognosis. Here we report a case of a 64-year old man which presented to the neurosurgery department with motor deficit in the right hemi–body, loss of speech and disorientation. Magnetic resonance imaging detected a mass located in the left frontal lobe that measured 7/8/7 cm, leading to the conclusion that surgery is necessary. Microscopic examination of the tumor showed great number of hypercellular areas with a high mitotic index, and focal necrosis with psammoma bodies. Using a panel of antibodies such as EMA, vimentin, CD34 GFAP, pancytokeratin and Ki67, we concluded that he final diagnosis was anaplastic meningioma, WHO grade III. Due to its morphological similarity with other tumors, the diagnosis of anaplastic meningioma may be challenging.

  14. Meningiomas, dicentric chromosomes, gliomas, and telomerase activity.

    Science.gov (United States)

    Carroll, T; Maltby, E; Brock, I; Royds, J; Timperley, W; Jellinek, D

    1999-08-01

    Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were telomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre-crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright 1999 John Wiley & Sons, Ltd.

  15. Influence of hyperthermia on the phosphorylation of ribosomal protein S6 from human skin fibroblasts and meningioma cells

    DEFF Research Database (Denmark)

    Richter, W W; Zang, K D; Issinger, O G

    1983-01-01

    Skin fibroblasts and meningioma cells, derived from primary cultures of the same patients have been used to study the influence of hyperthermia on (i) cell morphology and (ii) phosphorylation pattern of ribosomal and ribosome-associated proteins. Incubation of tumour cells and fibroblasts up to 7...

  16. Simultaneous meningioma and brain metastasis from renal cell carcinoma – a rare presentation. Case report

    Directory of Open Access Journals (Sweden)

    Aline Lariessy Campos Paiva

    2017-05-01

    Full Text Available ABSTRACT CONTEXT: Brain metastases are the most common tumors of the central nervous system. Because of their high frequency, they may be associated with rare situations. Among these are tumor-to-tumor metastasis and an even a rarer situation called simultaneous brain tumors, which are more related to primary tumors of the reproductive and endocrine systems. CASE REPORT: A 56-year-old male patient with a history of renal cell carcinoma (which had previously been resected presented with a ventricular lesion (suggestive of metastatic origin and simultaneous olfactory groove lesion (probably a meningioma. First, only the ventricular lesion was dealt with, but after a year, the meningothelial lesion increased and an occipital lesion appeared. Therefore, both of these were resected in a single operation. All the procedures were performed by the same neurosurgeon. The patient evolved without neurological deficits during the postoperative period. After these two interventions, the patient remained well and was referred for adjuvant treatment. CONCLUSIONS: This study provides the first description of an association between these two tumors. Brain metastases may be associated with several lesions, and rare presentations such as simultaneity with meningioma should alert neurosurgeons to provide the best oncological treatment.

  17. Integrin-based meningioma cell migration is promoted by photon but not by carbon-ion irradiation

    International Nuclear Information System (INIS)

    Simon, Florian; Dittmar, Jan-Oliver; Orschiedt, Lena; Weber, Klaus-Josef; Debus, Juergen; Rieken, Stefan; Brons, Stephan; Urbschat, Steffi; Combs, Stephanie E.

    2015-01-01

    Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms. Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-μm pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24 h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins ανβ 1 , ανβ 3 , and ανβ 5 were performed without IR and 6, 12 and 24 h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24 h. Cells and supernatants for FACS and ELISA were stored at - 18 C. The significance level was set at 5 % using both Student's t test and two-way ANOVA. Migration of meningioma cells was serum-inducible (p < 0.001). It could be increased by photon IR (p < 0.02). The integrins ανβ 1 and ανβ 5 showed a 21 and 11 % higher expression after serum stimulation (not significant), respectively, and ανβ 1 expression was raised by 14 % (p = 0.0057) after photon IR. Antibody blockage of the integrins ανβ 1 and ανβ 5 inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected. Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin receptor integrin ανβ 1 signaling

  18. Intraosseous meningioma

    International Nuclear Information System (INIS)

    Daffner, R.H.; Yakulis, R.; Maroon, J.C.

    1998-01-01

    A 71-year-old woman with a long history of slowly progressive proptosis was found to have an intraosseous meningioma of the right sphenoid bone. Radiologically, the lesion resembled fibrous dysplasia. The key to the diagnosis is irregularity of the inner table of the skull. The histologic appearance is characteristic. Intraosseous meningioma is one part of the spectrum of diseases known as primary extraneuraxial meningioma. In this paper we discuss the theories of cellular origin as well as the radiologic differential diagnosis. (orig.)

  19. B-Cell Hematologic Malignancy Vaccination Registry

    Science.gov (United States)

    2017-12-29

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  20. Peptide receptor radionuclide therapy with {sup 90}Y-DOTATOC in recurrent meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Bartolomei, Mirco; Bodei, Lisa; De Cicco, Concetta; Grana, Chiara Maria; Baio, Silvia Melania; Arico, Demetrio; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Botteri, Edoardo [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Radiometabolic Medicine Division, Meldola (Italy)

    2009-09-15

    Meningiomas are generally benign and in most cases surgery is curative. However, for high-grade histotypes or partially resected tumours, recurrence is fairly common. External beam radiation therapy (EBRT) is usually given in such cases but is not always effective. We assessed peptide receptor radionuclide therapy (PRRT) using {sup 90}Y-DOTATOC in a group of patients with meningioma recurring after standard treatments in all of whom somatostatin receptors were strongly expressed on meningioma cell surfaces. Twenty-nine patients with scintigraphically proven somatostatin subtype 2 receptor-positive meningiomas were enrolled: 14 had benign (grade I), 9 had atypical (grade II) and 6 had malignant (grade III) disease. Patients received intravenous {sup 90}Y-DOTATOC for 2-6 cycles for a cumulative dose in the range of 5-15 GBq. Clinical and neuroradiological evaluations were performed at baseline, during and after PRRT. The treatment was well tolerated in all patients. MRI 3 months after treatment completion showed disease stabilization in 19 of 29 patients (66%) and progressive disease in the remaining 10 (34%). Better results were obtained in patients with grade I meningioma than in those with grade II-III, with median time to progression (from beginning PRRT) of 61 months in the low-grade group and 13 months in the high-grade group. PRRT with {sup 90}Y-DOTATOC can interfere with the growth of meningiomas. The adjuvant role of this treatment, soon after surgery, especially in atypical and malignant histotypes, deserves further investigation. (orig.)

  1. Scalp meningioma

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    Singh Sunil

    2008-01-01

    Full Text Available Primary extracranial meningiomas occur very rarely. We present a rare case of extracranial meningioma of the transitional variant which was excised satisfactorily. There was no suggestion of any connection to the intracranial compartment or cranial nerves. The underlying galea was uninvolved, suggesting the true extracranial nature of this tumour. This rare diagnosis should nonetheless be kept in the differential diagnosis of scalp tumors.

  2. Is there an increased rate of additional malignancies in patients with mantle cell lymphoma?

    Science.gov (United States)

    Barista, I; Cabanillas, F; Romaguera, J E; Khouri, I F; Yang, Y; Smith, T L; Strom, S S; Medeiros, L J; Hagemeister, F B

    2002-02-01

    To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. These patients were followed for a median time of 26 months, and a total of 32 (21%) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 11 following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P <0.0001]. Of the 21 malignancies diagnosed prior to MCL, 16 were invasive and five non-invasive. There were a total of 10 urologic malignancies occurring before or after the diagnosis of MCL was established. Our findings suggest that there is an increased incidence of second malignancies in patients with MCL. In addition, the high number of cases with urinary tract cancer in our series may substantiate prior reports describing a possible association between lymphoma and urologic malignancies.

  3. Intracranial meningiomas after high-dose irradiation

    International Nuclear Information System (INIS)

    Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

    1989-01-01

    Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

  4. Quality assurance of radiotherapy in the ongoing EORTC 22042–26042 trial for atypical and malignant meningioma: results from the dummy runs and prospective individual case Reviews

    International Nuclear Information System (INIS)

    Coskun, Mehtap; Straube, William; Hurkmans, Coen W; Melidis, Christos; Haan, Patricia F de; Villà, Salvador; Collette, Sandra; Weber, Damien C

    2013-01-01

    The ongoing EORTC 22042–26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively. Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations

  5. Sporadic meningioangiomatosis-associated atypical meningioma mimicking parenchymal invasion of brain: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Luo Bo-ning

    2010-06-01

    Full Text Available Abstract Meningioangiomatosis is a rare hamartomatous lesion or meningiovascular malformation in brain. In extremely rare condition, meningioma may occur together with meningioangiomatosis, and only 19 cases have been described in English literature until now. We now report a case of meningioangiomatosis-associated meningioma with atypical and clear cell variant. A 34-year-old man presented a 3-month history of progressive numbness and weakness of his left lower extremity. He had no stigmata of neurofibromatosis type 2. Magnetic resonance imaging (MRI revealed multifocal lesions in the right frontoparietal lobe. The lesions were totally removed. Microscopically, parts of lesions were atypical and clear cell meningioma corresponding to WHO grade II. The adjacent brain parenchyma showed the histological features of meningioangiomatosis. Neoplastic cells in atypical meningioma area were immunoreactive to epithelial membrane antigen (EMA with high MIB-1 index of up to 20%. However, the spindle cells in meningioangiomatosis area were negative for EMA with low MIB-1 index of up to 1%. The diagnosis of atypical meningioma associated with sporadic meningioangiomatosis was made. To our knowledge, this is the first case of a meningioangiomatosis-associated meningioma with atypical and clear cell variant component to be described. The patient had been followed-up for 11 months without adjuvant radiotherapy or chemotherapy. No tumor recurrence was found during this period. Meningioangiomatosis-associated meningioma is more likely to occur in younger patients and histologically to mimic parenchymal invasion of brain. We suggest that postoperative radiotherapy or chemotherapy should be given careful consideration to avoid over-treatment due to erroneously interpret as malignant meningioma.

  6. The contribution of diffusion-weighted MR imaging to distinguishing typical from atypical meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, Bahattin [Uludag University School of Medicine, Department of Radiology, Gorukle, Bursa (Turkey); Bursa State Hospital, Department of Radiology, Bursa (Turkey); Yildirim, Nalan; Gokalp, Gokhan; Erdogan, Cuneyt; Parlak, Mufit [Uludag University School of Medicine, Department of Radiology, Gorukle, Bursa (Turkey)

    2006-08-15

    Atypical/malignant meningiomas recur more frequently then typical meningiomas. In this study, the contribution of diffusion-weighted MR imaging to the differentiation of atypical/malignant and typical meningiomas and to the determination of histological subtypes of typical meningiomas was investigated. The study was performed prospectively on 39 patients. The signal intensity of the lesions was evaluated on trace and apparent diffusion coefficient (ADC) images. ADC values were measured in the lesions and peritumoral edema. Student's t-test was used for statistical analysis. P<0.05 was considered statistically significant. Mean ADC values in atypical/malignant and typical meningiomas were 0.75{+-}0.21 and 1.17{+-}0.21, respectively. Mean ADC values for subtypes of typical meningiomas were as follows: meningothelial, 1.09{+-}0.20; transitional, 1.19{+-}0.07; fibroblastic, 1.29{+-}0.28; and angiomatous, 1.48{+-}0.10. Normal white matter was 0.91{+-}0.10. ADC values of typical meningiomas and atypical/malignant meningiomas significantly differed (P<0.001). However, the difference between peritumoral edema ADC values was not significant (P>0.05). Furthermore, the difference between the subtypes of typical meningiomas and atypical/malignant meningiomas was significant (P<0.001). Diffusion-weighted MR imaging findings of atypical/malignant meningiomas and typical meningiomas differ. Atypical/malignant meningiomas have lower intratumoral ADC values than typical meningiomas. Mean ADC values for peritumoral edema do not differ between typical and atypical meningiomas. (orig.)

  7. Extracellular vesicle-mediated phenotype switching in malignant and non-malignant colon cells

    International Nuclear Information System (INIS)

    Mulvey, Hillary E.; Chang, Audrey; Adler, Jason; Del Tatto, Michael; Perez, Kimberly; Quesenberry, Peter J.; Chatterjee, Devasis

    2015-01-01

    Extracellular vesicles (EVs) are secreted from many cells, carrying cargoes including proteins and nucleic acids. Research has shown that EVs play a role in a variety of biological processes including immunity, bone formation and recently they have been implicated in promotion of a metastatic phenotype. EVs were isolated from HCT116 colon cancer cells, 1459 non-malignant colon fibroblast cells, and tumor and normal colon tissue from a patient sample. Co-cultures were performed with 1459 cells and malignant vesicles, as well as HCT116 cells and non-malignant vesicles. Malignant phenotype was measured using soft agar colony formation assay. Co-cultures were also analyzed for protein levels using mass spectrometry. The importance of 14-3-3 zeta/delta in transfer of malignant phenotype was explored using siRNA. Additionally, luciferase reporter assay was used to measure the transcriptional activity of NF-κB. This study demonstrates the ability of EVs derived from malignant colon cancer cell line and malignant patient tissue to induce the malignant phenotype in non-malignant colon cells. Similarly, EVs derived from non-malignant colon cell lines and normal patient tissue reversed the malignant phenotype of HCT116 cells. Cells expressing an EV-induced malignant phenotype showed increased transcriptional activity of NF-κB which was inhibited by the NF--κB inhibitor, BAY117082. We also demonstrate that knock down of 14-3-3 zeta/delta reduced anchorage-independent growth of HCT116 cells and 1459 cells co-cultured with HCT derived EVs. Evidence of EV-mediated induction of malignant phenotype, and reversal of malignant phenotype, provides rational basis for further study of the role of EVs in tumorigenesis. Identification of 14-3-3 zeta/delta as up-regulated in malignancy suggests its potential as a putative drug target for the treatment of colorectal cancer

  8. A case of falx meningiomas showing an unusual extension on CT

    International Nuclear Information System (INIS)

    Tsuha, Mitsuru; Fudaba, Hiroyoshi; Orita, Tetsuji; Wakuta, Yukio; Aoki, Hideo

    1986-01-01

    It is well known that homogeneous high-density areas with well-defined borders and marked contrast enhancements on CT scans are characteristic features of meningiomas. However, there are a few cases of meningiomas which are more difficult to diagnose because of their unusual CT findings. We have, for example, recently experienced a case of falx meningioma with a small attachment to the flax and a large exophytic component in the brain parenchyma. This 53-year-old female had complained of dull headaches for several years. She had then suffered speech disturbance in June, 1983, followed by a weakness of her right arm. She was referred to our clinic on Oct. 31, 1983. The neurological findings on admission were dyscalculia, mild motor dysphasia, and right hemiparesis to a minor degree. CT revealed a left frontal iso- and high-density mass lesion and also central, partly visible, low-density areas. A postinfusion study showed a moderate contrast enhancement. Also noted were a partial attachment of these tumors to the falx and a more prominent contrast enhancement of these areas than those of other tumor sites. A left internal carotid angiogram revealed a frontal tumor stain, fed by the left ACA and MCAs; early venous drainage was also seen. Moreover, left external carotid angiography showed a small tumor stain adjacent to the falx. Left frontoparietal craniotomy, on Nov. 14, 1983, revealed a soft, well-defined tumor, partly attached to the tumor. Histology indicated a meningioma with partial anisocytosis and mitoses of tumor cells; this was consequently diagnosed as a malignant meningioma. Intracranial meningiomas with a small attachment to the falx and large areas of exophytic components are rare CT findings. In addition to the CT findings mentioned above, the heterogeneity of the absorption coefficients of meningiomas on CT and differential diagnosis were discussed. (author)

  9. Osteoclastome-like giant cell thyroid carcinoma controlled by intensive radiation and adriamycin, in a patient with meningioma and multiple myeloma treated by radiation and cytoxan

    International Nuclear Information System (INIS)

    Vizel-Schwartz, M.

    1981-01-01

    The eighth cases of osteoclastome-like giant cell carcinoma of the thyroid, and the first one to be treated with adriamycin in addition to surgery and radiation, is reported. This rare variant of anaplastic thyroid carcinoma appeared in a patient operated on for meningioma and treated for multiple myeloma with cranial radiation and chronic administration of cytoxan

  10. Multiple meningiomas CASE SERIES

    African Journals Online (AJOL)

    masses in the right parietal and parasagittal region (Figs 1a and b). Case 2: A ... scan showed hyperdense parasagittal and left cerebellopontine angle meningiomas (Figs ... Meningiomas are the most common primary non-glial brain tumours.

  11. Meningioma of the scapula

    Energy Technology Data Exchange (ETDEWEB)

    Llauger, Jaume; Aixut, Sonia; Canete, Noemi; Palmer, Jaume; Sola, Marta [Universitat Autonoma de Barcelona, Department of Radiology, Hospital de la Santa Creu I Sant Pau, Barcelona (Spain); Bague, Silvia [Universitat Autonoma de Barcelona, Department of Pathology, Hospital de la Santa Creu I Sant Pau, Barcelona (Spain)

    2008-02-15

    Meningiomas account for approximately 15% of all intracranial tumors and are the most common non-glial primary tumors of the central nervous system. Most meningiomas are benign neoplasms with characteristic imaging features. Primary extradural meningiomas account for only 1-2% of all meningiomas. They must be differentiated from intradural meningiomas with secondary extradural extension and/or metastases. The vast majority of extradural meningiomas are found in the skull or in the head and neck region. We report on an extremely rare case of primary extradural meningioma that was located in the scapula. The lesion was resected. Radiographic findings and pathologic features are discussed. To the best of our knowledge, this form of presentation of an extradural meningioma has not been previously described. (orig.)

  12. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  13. Integrin-based meningioma cell migration is promoted by photon but not by carbon-ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Florian; Dittmar, Jan-Oliver; Orschiedt, Lena; Weber, Klaus-Josef; Debus, Juergen; Rieken, Stefan [University Hospital of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Brons, Stephan [Heidelberg Ion Treatment Facility (HIT), Heidelberg (Germany); Urbschat, Steffi [University Hospital of Homburg/Saar, Department of Neurosurgery, Homburg-Saar (Germany); Combs, Stephanie E. [University Hospital Munich, Department of Radiation Oncology, Munich (Germany)

    2015-04-01

    Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms. Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-μm pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24 h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins ανβ{sub 1}, ανβ{sub 3}, and ανβ{sub 5} were performed without IR and 6, 12 and 24 h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24 h. Cells and supernatants for FACS and ELISA were stored at - 18 C. The significance level was set at 5 % using both Student's t test and two-way ANOVA. Migration of meningioma cells was serum-inducible (p < 0.001). It could be increased by photon IR (p < 0.02). The integrins ανβ{sub 1} and ανβ{sub 5} showed a 21 and 11 % higher expression after serum stimulation (not significant), respectively, and ανβ{sub 1} expression was raised by 14 % (p = 0.0057) after photon IR. Antibody blockage of the integrins ανβ{sub 1} and ανβ{sub 5} inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected. Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin

  14. Assessment of Epidermal Growth Factor Receptor (EGFR expression in human meningioma

    Directory of Open Access Journals (Sweden)

    Perry Arie

    2010-05-01

    Full Text Available Abstract Purpose This study explores whether meningioma expresses epidermal growth factor receptor (EGFR and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression. Methods Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI was scored on a scale 0-3 (from no staining to strong staining. Staining percentage of immunoreactive cells (SP was scored 1-5 (from the least to the maximum percent of the specimen staining. Immunohistochemical score (IHS was calculated as the product of SI and SP. Results Eighty-five samples of meningioma were classified in accordance with World Health Organization (WHO criteria: benign 57/85 (67%, atypical 23/85 (27%, and malignant 5/85 (6%. The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029. A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009. While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p Conclusions To our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors.

  15. Postoperative radiotherapy for intracranial meningioma

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2001-01-01

    To evaluate the effectiveness and tolerance of postoperative external radiotherapy for patients with intracranial meningiomas. The records of thirty three patients with intracranial meningiomas who were treated with postoperative external irradiation at our institution between Feb, 1988 and Nov, 1999 were retrospectively analyzed. Median age of patients at diagnosis was 53 years with range of 17 to 68 years. Sites of involvement were parasagital, cerebral convexity, sphenoid ridge, parasellar and tentorium cerebella. Of 33 evaluated patients, 15 transitional, 10 meningotheliomatous, 4 hemangiopericytic, 3 atypical and 1 malignant meningioma were identified. Four patients underwent biopsy alone and remaining 29 patients underwent total tumor resection. A dose of 50 to 60 Gy was delivered in 28-35 daily fractions over a period of 5 to 7 weeks. Follow-up period ranged from 12 months to 8 years. The actuarial survival rates at 5 and 7 years for entire group of patients were 78% and 67%, respectively. The corresponding disease free survival rates were 73% and 61 %, respectively. The overall local control rate at 5 years was 83%. One out of 25 patients in benign group developed local failure, while 4 out of 8 patients in malignant group did local failure (p <0.05), Of 4 patients who underwent biopsy alone, 2 developed local failure. There was no significant difference in 5 year actuarial survival between patients who underwent total tumor resection and those who did biopsy alone. Patients whose age is under 60 showed slightly better survival than those whose age is 60 or older, although this was not statistically significant. There was no documented late complications in any patients. Based on our study, we might conclude that postoperative external beam radiotherapy tends to improve survival of patients with intracranial meningiomas comparing with surgery alone

  16. Mast cells mediate malignant pleural effusion formation.

    Science.gov (United States)

    Giannou, Anastasios D; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M; Vreka, Malamati; Zazara, Dimitra E; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A; Patmanidi, Alexandra L; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S; Agalioti, Theodora; Stathopoulos, Georgios T

    2015-06-01

    Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.

  17. A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

    International Nuclear Information System (INIS)

    Matsuo, Yuki; Yano, Kenji

    2000-01-01

    We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

  18. A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Yuki; Yano, Kenji [Kure National Hospital, Hiroshima (Japan)

    2000-10-01

    We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

  19. Primary Intraorbital Ectopic Meningioma

    Science.gov (United States)

    Yokoyama, Tetsuo; Nishizawa, Shigeru; Sugiyama, Kenji; Yokota, Noki; Ohta, Seiji; Uemura, Kenichi; Hinokuma, Kaoru; Inenaga, Chikanori

    1999-01-01

    We report a case of intraorbital meningioma. Operative findings and histopathological examination revealed the tumoc to be meningothelial meningloma and to be located entirely outside the optic dura. This case demonstrates the occurrence of primary intraorbital ectopic meningioma, and the tumor was removed through a modified Dolenc approach. The primary intraorbital ectopic meningioma is discussed and the surgical approach to the orbital apex region is reviewed. ImagesFigure 1Figure 2Figure 4Figure 5 PMID:17171081

  20. Malignant Giant Cell Tumour of Bone with Axillary Metastasis

    African Journals Online (AJOL)

    2002-06-06

    Jun 6, 2002 ... SUMMARY. Giant Cell Tumour of bone is a typically benign and solitary tumour. However, multiple lesions have been described and 5-10% of lesions may be malignant. We present a case of a malignant giant cell tumour of the distal radius with metastasis to the ipsilateral axilla (an uncommon location).

  1. Congenital extracranial meningioma

    International Nuclear Information System (INIS)

    Wong, H.F.; Ng, S.H.; Wai, Y.Y.; Wan, Y.L.; Kong, M.S.

    1995-01-01

    The authors report a case of congenital meningioma in a newborn. This tumour is extremely rare and only six cases have been reported in the literature. Those reported cases were mainly intracranial. This is the first case of a neonatal extracranial meningioma that was evaluated preoperatively by computed tomography and magnetic resonance imaging. (orig.)

  2. MULTIPLE SPINAL CANAL MENINGIOMAS

    Directory of Open Access Journals (Sweden)

    Nandigama Pratap Kumar

    2016-10-01

    Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

  3. Synchronous pulmonary malignancies: atypical presentation of mantle cell lymphoma masking a lung malignancy

    Directory of Open Access Journals (Sweden)

    Luke Masha

    2015-09-01

    Full Text Available We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

  4. Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy.

    Science.gov (United States)

    Masha, Luke; Zinchuk, Andrey; Boosalis, Valia

    2015-09-07

    We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

  5. A case of clear cell sarcoma-A rare malignancy

    DEFF Research Database (Denmark)

    Juel, Jacob; Ibrahim, Rami Mossad

    2017-01-01

    INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour of the soft tissue often misdiagnosed, as it shares characteristics with malignant melanoma (MM). Previously, CCS has been characterised, as malignant melanoma of the soft tissue, contemporary immunohistochemical techniques, however, have made...

  6. Role of radiotherapy in the treatment of meningiomas

    International Nuclear Information System (INIS)

    Noel, G.; Renard, A.; Mazeron, J.J.; Valery, C.; Mokhtari, K.

    2001-01-01

    Role of radiotherapy in the treatment of meningiomas. Cerebral meningiomas account for 15-20% of all cerebral tumours. Although seldom malignant, they frequently recur in spite of complete surgery, which remains the cornerstone of the treatment. In order to decrease the probability of local recurrence, radiotherapy has often been recommended in atypical or malignant meningioma as well as in benign meningioma which was incompletely resected. However, this treatment never was the subject of prospective studies, randomized or not. The purpose of this review of the literature was to give a progress report on the results of different published series in the field of methodology as well as in the techniques of radiotherapy. Proposals for a therapeutic choice are made according to this analysis. For grade I or grade II-III meningiomas, limits of gross tumor volume (GTV) include the tumour in place or the residual tumour after surgery; clinical target volume (CTV) limits include gross tumour volume before surgery with a GTV-CTV distance of 1 and 2 cm respectively. Delivered doses are 55 Gy into CTV and 55-60 Gy and 70 Gy into GTV for grade I and grade II-III meningiomas respectively. (authors)

  7. Malignant atypical cell in urine cytology: a diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Kakkar Nandita

    2006-01-01

    Full Text Available Abstract Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i high nuclear and cytoplasmic (N/C ratio ii nuclear pleomorphism iii nuclear margin irregularity iv hyperchromasia and v chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

  8. Primary pleuro-pulmonary malignant germ cell tumours.

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2002-01-01

    Full Text Available Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

  9. Deregulation of Interferon Signaling in Malignant Cells

    Directory of Open Access Journals (Sweden)

    Leonidas C. Platanias

    2010-02-01

    Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

  10. Targeting the BCR signalosome in B cell malignancies

    NARCIS (Netherlands)

    de Rooij, M.F.M.

    2017-01-01

    Chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) are B-cell malignancies which are still incurable. In these lymphomas, the cells proliferate in specialized niches in lymph nodes and bone marrow, in which they are provided by stromal-derived

  11. The malignant niche: safe spaces for toxic stem cell marketing.

    Science.gov (United States)

    Sipp, Douglas

    2017-01-01

    Many tumors are sustained by microenvironments, or niches, that support and protect malignant cells, thus conferring a competitive advantage against both healthy cells and therapeutic interventions (for a brief review, see Yao and Link (Stem Cells 35: 3-8, 2017)). The global industry engaged in the commercial promotion of unproven and scientifically implausible cell-based "regenerative" therapies has developed a number of self-protective strategies that support its survival and growth in ways that are broadly analogous to the functions of the malignant niche.

  12. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  13. Primary intraosseous meningiomas

    International Nuclear Information System (INIS)

    Arana, E.; Diaz, C.; Latorre, F.F.; Menor, F.; Revert, A.; Beltran, A.; Navarro, M.

    1996-01-01

    Purpose: A retrospective study was performed to evaluate the clinical, radiological and histological findings of 14 intraosseous meningiomas. Material and Methods: 14 histologically proved intraosseous meningiomas were studied with plain skull film and CT. Pathological records were reviewed. Results: We found 9 calvarial cases and 5 spheno-orbital ones. The most common symptom in the calvarial cases was a lump in the scalp, and in the spheno-orbital lesions it was exophtalmos. Hyperostosis was present in all 5 spheno-orbital cases and in 3 out of the 9 calvarial ones; in the other 6 cases it had a mixed pattern. Enhanced dura was present in 3 calvarial cases and in 2 sphenoidal ones. Dura was involved in 5 cases: 2 with inflammatory changes, 2 with a minimal intradural tumour and one with a subdural tumour. Conclusion: CT better detected both the bony reaction and the intraosseous extension of the tumour. The dural changes were not specific of tumoural involvement. The differential diagnosis comprises: fibrous dysplasia, osteomas, blastic metastasis and mainly meningioma en plaque (MEP). Comparing our findings with other series, we noticed that in some cases the term MEP was used for similar cases. As the name MEP is merely descriptive and both entities share a larger number of similarities than differences, we believe that a differentiation between hyperostotic en plaque meningioma and intraosseous meningioma can hardly be made. (orig.)

  14. Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    G. Brás

    2017-01-01

    Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

  15. Role of Bruton's tyrosine kinase in B cells and malignancies

    NARCIS (Netherlands)

    Pal Singh, S. (Simar); F. Dammeijer (Floris); R.W. Hendriks (Rudi)

    2018-01-01

    textabstractBruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked

  16. Large mid-esophageal granular cell tumor: benign versus malignant

    Directory of Open Access Journals (Sweden)

    Prarthana Roselil Christopher

    2015-06-01

    Full Text Available Granular cell tumors are rare soft tissue neoplasms, among which only 2% are malignant, arising from nervous tissue. Here we present a case of a large esophageal granular cell tumor with benign histopathological features which metastasized to the liver, but showing on positron emission tomography-computerized tomography standardized uptake value suggestive of a benign lesion.

  17. Foramen Magnum Meningioma: a Case Report and Review of Literature.

    Science.gov (United States)

    Jurinovic, Pavao; Bulicic, Ana Repic; Marcic, Marino; Mise, Nikolina Ivica; Titlic, Marina; Suljic, Enra

    2016-02-01

    Meningiomas are slow-growing benign tumors that arise at any location where arachnoid cells reside. Although meningiomas account for a sizable proportion of all primary intracranial neoplasms (14.3-19%), only 1.8 to 3.2% arise at the foramen magnum. Their indolent development at the craniocervical junction makes clinical diagnosis complex and often leads to a long interval between onset of symptoms and diagnosis. We report a case of a 79-year-old male patient, presented with ataxia and sense of threatening fainting during verticalization. Magnetic resonance imaging revealed the presence of meningioma in the right side of craniospinal junction.

  18. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  19. Myeloid derived suppressor cells as therapeutic target in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Kim eDe Veirman

    2014-12-01

    Full Text Available Myeloid derived suppressor cells (MDSC are a heterogeneous population of immature myeloid cells that accumulate during pathological conditions such as cancer and are associated with a poor clinical outcome. MDSC expansion hampers the host anti-tumor immune response by inhibition of T cell proliferation, cytokine secretion and recruitment of regulatory T cells. In addition, MDSC exert non-immunological functions including the promotion of angiogenesis, tumor invasion and metastasis. Recent years, MDSC are considered as a potential target in solid tumors and hematological malignancies to enhance the effects of currently used immune modulating agents. This review focuses on the characteristics, distribution, functions, cell-cell interactions and targeting of MDSC in hematological malignancies including multiple myeloma, lymphoma and leukemia.

  20. Differentiation of purified malignant B cells induced by PMA or by activated normal T cells

    NARCIS (Netherlands)

    van Kooten, C.; Rensink, I.; Aarden, L.; van Oers, R.

    1993-01-01

    We studied the in vitro differentiation (immunoglobulin production) of purified malignant B cells of 21 patients with different B-cell malignancies, including chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) and non-Hodgkin lymphoma (NHL). Direct

  1. Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

    2016-01-01

    Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

  2. Correlation of DNA content and nucleomorphometric features with World Health Organization grading of meningiomas.

    Science.gov (United States)

    Grunewald, J P; Röhl, F W; Kirches, E; Dietzmann, K

    1998-02-01

    Many studies dealing with extracranial cancer showed a strong correlation of DNA ploidy to a poor clinical outcome, recurrence, or malignancy. In brain tumors, analysis of DNA content did not always provided significant diagnostic information. In this study, DNA density and karyometric parameters of 50 meningiomas (26 Grade I, 10 Grade II, 14 Grade III) were quantitatively evaluated by digital cell image analyses of Feulgen-stained nuclei. In particular, the densitometric parameter SEXT, which describes nuclear DNA content, as well as the morphometric values LENG (a computer-assisted measurement of nuclear circumference), AREA (a computer-assisted measurement of nuclear area), FCON (a parameter that describes nuclear roundness), and CONC (a describing nuclear contour), evaluated with the software IMAGE C, were correlated to World Health Organization (WHO) grading using univariate and multivariate methods. AREA and LENG values showed significant differences between tumors of Grades I and III. FCON values were unable to distinguish WHO Grade III from Grade I/II but were useful in clearly separating Grade II from Grade I tumors. CONC values detected differences between WHO Grades II and I/III tumors but not between the latter. SEXT values clearly distinguished Grade III from Grade I/II tumors. The 1c, 2c, 2.5c, and 5c exceeding rates showed no predictive values. Only the 6c exceeding rate showed a significant difference between Grades I and III. These results outline the characteristic features of the atypical (Grade II) meningiomas, which make them a recognizable tumor entity distinct from benign and anaplastic meningiomas. The combination of DNA densitometric and morphometric findings seems to be a powerful addition to the histopathologic classification of meningiomas, as suggested by the WHO.

  3. T. B-cell subpopulation in patients with malignant diseases

    International Nuclear Information System (INIS)

    Ogawa, Motoyoshi; Goto, Tatsuhiko; Naruto, Mamiko.

    1978-01-01

    T, B cells in the peripheural blood of patients with malignant diseases were investigated. The percentages of T cells in patients with malignant lymphomas correlated to the extent of disease determined by clinical stagings of Ann Arbor's classification, in stages III and IV T-cells decreased to compare with those in stages I and II, while B-cells did not show any changes. Absolute numbers of lymphocytes, blastogenesis induced by PHA or PWM decreased remarkably during combination chemotherapies and during radiotherapy whereas the percentages of T-cells measuring in the same patients did not influenced consistently by these treatments. The DNA pattern of lymphocytes during treatments was examined by Flow-Microphotometry and the result suggested that those lymphocytes were damaged by treatments and subsequently they were refractory to the action of mitogens. The results indicate that selective timing needs between chemotherapy and immunotherapy. (auth.)

  4. The results of radiation therapy for intracranial meningiomas. With special reference to the natural course of the tumor size after radiotherapy

    International Nuclear Information System (INIS)

    Kobayashi, Katsuhiro; Murakami, Masao; Kubo, Takeshi; Kono, Koichi; Okamoto, Yoshiaki; Kuroda, Yasumasa

    1998-01-01

    Twenty-four cases with intracranial meningioma received radiation therapy from 1967 to 1995 at Tenri Hospital. Two received preoperative radiotherapy and 22 post operative radiotherapy. Of all, 11 were benign, 9 were malignant and 4 were reported only as meningioma. The extent of surgery consisted of total resection in 4, subtotal resection in 10, partial resection in 6, biopsy in 2, exploration in 1 and unknown in 1. Twelve were initial treatments and another 12 were salvage treatments. In all cases, radiation therapy was given a mean dose of 53.6 Gy with 6 or 10 MV X-rays using conventional fractionation. The mean follow-up interval is 56.7 months. Total cause specific survival at 5 and 10 years were 79% and 69%, respectively. The 10-year recurrence-free survival was 100% in benign and 61% in malignant meningiomas. The clinical course of benign meningiomas suggested the value of postoperative radiation therapy, but that of malignant meningiomas were divided into 2 groups, in which some one had recurrence just after completion of radiotherapy or another had local control. It seemed that there were some radio-resistant varieties in malignant meningiomas. The result of the consecutive follow-up by enhanced CT or MRI revealed benign meningiomas had a tendency to decrease in size in a long interval and some malignant meningiomas changed their size soon after radiotherapy. From analysis of our study we conclude that radiation therapy is a useful post-surgical treatment for intracranial meningiomas. (author)

  5. Engaging the lysosomal compartment to combat B cell malignancies

    DEFF Research Database (Denmark)

    Gronbaek, K.; Jaattela, M.

    2009-01-01

    The combination of rituximab, a type I anti-CD20 mAb, with conventional chemotherapy has significantly improved the outcome of patients with B cell malignancies. Regardless of this success, many patients still relapse with therapy-resistant disease, highlighting the need for the development of m...

  6. Modulation of GLO1 Expression Affects Malignant Properties of Cells

    Directory of Open Access Journals (Sweden)

    Antje Hutschenreuther

    2016-12-01

    Full Text Available The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO. Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1 that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.

  7. Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review.

    Science.gov (United States)

    Farrag, Ashraf; Ansari, Jawaher; Ali, Muhammad; Sunbuli, Ghanem; Kassem, Hassan; Al Hamad, Abdul-Aziz

    2018-05-01

    Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity.

  8. Histological-subtypes and anatomical location correlated in meningeal brain tumors (meningiomas

    Directory of Open Access Journals (Sweden)

    Abdul Rashid Bhat

    2014-01-01

    Full Text Available Context: Not enough literature is available to suggest a link between the histological subtypes of intracranial meningeal brain tumors, called ′meningiomas′ and their location of origin. Aim: The evidence of correlation between the anatomical location of the intracranial meningiomas and the histopathological grades will facilitate specific diagnosis and accurate treatment. Materials and Methods: The retrospective study was conducted in a single high-patient-inflow Neurosurgical Center, under a standard and uniform medical protocol, over a period of 30 years from December 1982 to December 2012. The records of all the operated 729 meningiomas were analyzed from the patient files in the Medical Records Department. The biodata, x-rays, angiography, computed tomography (CT scans, imaging, histopathological reports, and mortality were evaluated and results drawn. Results: The uncommon histopathological types of meningiomas (16.88% had common locations of origin in the sphenoid ridge, posterior parafalcine, jugular foramen, peritorcular and intraventricular regions, cerebellopontine angle, and tentorial and petroclival areas. The histopathological World Health Organization (WHO Grade I (Benign Type meningiomas were noted in 89.30%, WHO Grade II (Atypical Type in 5.90%, and WHO Grade III (Malignant Type in 4.80% of all meningiomas. Meningiomas of 64.60% were found in females, 47.32% were in the age group of 41-50 years, and 3.43% meningiomas were found in children. An overall mortality of 6.04% was noted. WHO Grade III (malignant meningiomas carried a high mortality (25.71% and the most common sites of meningiomas with high mortality were: The cerebellopontine angles, intraventricular region, sphenoid ridge, tuberculum sellae, and the posterior parafalcine areas. Conclusion: The correlation between the histological subtypes and the anatomical location of intracranial meningeal brain tumors, called meningiomas, is evident, but further research is

  9. An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells

    OpenAIRE

    Castelnuovo Manuele; Massone Sara; Tasso Roberta; Fiorino Gloria; Gatti Monica; Robello Mauro; Gatta Elena; Berger Audrey; Strub Katharina; Florio Tullio; Dieci Giorgio; Cancedda Ranieri; Pagano Aldo

    2010-01-01

    Neuroblastoma (NB) is a pediatric cancer characterized by remarkable cell heterogeneity within the tumor nodules. Here, we demonstrate that the synthesis of a pol III-transcribed noncoding (nc) RNA (NDM29) strongly restricts NB development by promoting cell differentiation, a drop of malignancy processes, and a dramatic reduction of the tumor initiating cell (TIC) fraction in the NB cell population. Notably, the overexpression of NDM29 also confers to malignant NB cells an unpredicted suscept...

  10. Are All Highly Malignant Cancer Cells Identical?

    Science.gov (United States)

    1979-01-01

    embryo cells or even the original fertilized ovum. If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...whose activity leads to the suppression of the transcrip- tion of the genes responsible for the unique set of embryo -cancer proteins and whose mutation

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

    Energy Technology Data Exchange (ETDEWEB)

    Engenhart-Cabillic, R.; Henzel, M. [Philipps Univ., Marburg (Germany). Dept. of Radiotherapy and Radiooncology; Farhoud, A.; Sure, U.; Heinze, S.; Bertalanffy, H. [Philipps Univ., Marburg (Germany). Dept. of Neurosurgery; Mennel, H.D. [Philipps Univ., Marburg (Germany). Dept. of Neuropathology

    2006-11-15

    focal expression patterns of anaplastic meningioma in MIB-1 might be a marker of such malignant development. (orig.)

  12. Meningioma anaplásico Anaplastic meningioma

    Directory of Open Access Journals (Sweden)

    Arlines Alina Piña Tornés

    2013-03-01

    Full Text Available Se presenta el caso clínico de un paciente que comenzó a presentar cefalea, vértigos, trastornos visuales y pérdida del equilibrio. Mediante la resonancia magnética se visualizó una imagen tumoral parietal izquierda de 3 cm diámetro, de localización extraaxial y contornos lobulados bien definidos, con gran captación no homogénea de contraste, rodeada de extenso edema perilesional. Se realizó angiotomografía, previa a la cirugía, en busca de irrigación y daño vascular. Se logró la resección de 95% de la lesión (grado II de Simpson, que incluyó duramadre adyacente infiltrada y respetó el seno longitudinal superior. Los resultados anatomopatológicos confirmaron que se trataba de un meningioma anaplásico de grado III, con criterio de tratamiento coadyuvante.The case report of a patient who began presenting headache, vertigos, visual disorders and loss of balance is presented. By means of the magnetic resonance a left tumoral parietal image of 3 cm diameter was visualized, of extra-axial localization and well defined lobulated contours, with great non-homogeneous zones of contrast, surrounded by extensive perilesional edema. An angiotomography was carried out, previous to the surgery, looking for irrigation and vascular compromise. The resection of 95% of the lesion was achieved (grade II of Simpson which included adjacent infiltrated dura madre and preserving the superior longitudinal sinus. Pathological results confirmed that it was an anaplastic meningioma grade III, with criterium for adyuvant treatment.

  13. The Glycome of Normal and Malignant Plasma Cells

    Science.gov (United States)

    Hose, Dirk; Andrulis, Mindaugas; Moreaux, Jèrôme; Hielscher, Thomas; Willhauck-Fleckenstein, Martina; Merling, Anette; Bertsch, Uta; Jauch, Anna; Goldschmidt, Hartmut; Klein, Bernard; Schwartz-Albiez, Reinhard

    2013-01-01

    The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma. PMID:24386263

  14. The glycome of normal and malignant plasma cells.

    Directory of Open Access Journals (Sweden)

    Thomas M Moehler

    Full Text Available The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10 and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14, t(4;14, hyperdiploidy, 1q21-gain and deletion of 13q14. iv A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.

  15. MRI of meningioma

    International Nuclear Information System (INIS)

    Yamamoto, Yoshio; Hiraki, Yoshio; Kaji, Mitumasa

    1988-01-01

    MRI has gained a prominent position in the diagnosis of brain tumors. We examined 30 cases of meningiomas and distinguished their subtype according to the criteria of Rubinic histology. We discussed the MRI findings and compared then with X-CT findings so to their intensity, delination of tumors, whether accompanied by peripheral edema, and T 1 values. MRI delinated the tumors as well as CE-CT. No remarkable difference was found between the subtypes. (author)

  16. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  17. Bcl-2 antisense therapy in B-cell malignancies.

    Science.gov (United States)

    Chanan-Khan, Asher

    2005-07-01

    Bcl-2 is an apoptosis regulating protein, overexpression of which is associated with chemotherapy resistant disease, aggressive clinical course, and poor survival in patients with B-cell lymphoproliferative disorders. Overexpression of Bcl-2 protein results in an aberrant intrinsic apoptotic pathway that confers a protective effect on malignant cells against a death signal (e.g., chemotherapy or radiotherapy). Downregulation of this oncoprotein, thus, represents a possible new way to target clinically aggressive disease. Preclinical studies have shown that this oncoprotein can be effectively decreased by Bcl-2 antisense in malignant lymphoid cells and can reverse chemotherapy resistance, as well as enhance the anti-apoptotic potential of both chemotherapeutic and biologic agents. Ongoing clinical trials are exploring the role of Bcl-2 downregulation with oblimersen (Bcl-2 antisense) in patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia and multiple myeloma. Early results from these studies are promising and support the proof of the principle. As these studies are completed and mature data emerges, the role of Bcl-2 antisense therapy in the treatment of B-cell malignancies will become clearer.

  18. Primary extradural meningioma arising from the calvarium

    Directory of Open Access Journals (Sweden)

    N Ravi

    2013-06-01

    Full Text Available Meningiomas are the most common intracranial tumours. Meningiomas arising at other locations are termed primary extradural meningiomas (EDM and are rare. Here we report a case of EDM arising from the calvarium – a primary calvarial meningioma (PCM.

  19. Romidepsin targets multiple survival signaling pathways in malignant T cells

    International Nuclear Information System (INIS)

    Valdez, B C; Brammer, J E; Li, Y; Murray, D; Liu, Y; Hosing, C; Nieto, Y; Champlin, R E; Andersson, B S

    2015-01-01

    Romidepsin is a cyclic molecule that inhibits histone deacetylases. It is Food and Drug Administration-approved for treatment of cutaneous and peripheral T-cell lymphoma, but its precise mechanism of action against malignant T cells is unknown. To better understand the biological effects of romidepsin in these cells, we exposed PEER and SUPT1 T-cell lines, and a primary sample from T-cell lymphoma patient (Patient J) to romidepsin. We then examined the consequences in some key oncogenic signaling pathways. Romidepsin displayed IC 50 values of 10.8, 7.9 and 7.0 nm in PEER, SUPT1 and Patient J cells, respectively. Strong inhibition of histone deacetylases and demethylases, increased production of reactive oxygen species and decreased mitochondrial membrane potential were observed, which may contribute to the observed DNA-damage response and apoptosis. The stress-activated protein kinase/c-Jun N-terminal kinase signaling pathway and unfolded protein response in the endoplasmic reticulum were activated, whereas the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and β-catenin pro-survival pathways were inhibited. The decreased level of β-catenin correlated with the upregulation of its inhibitor SFRP1 through romidepsin-mediated hypomethylation of its gene promoter. Our results provide new insights into how romidepsin invokes malignant T-cell killing, show evidence of its associated DNA hypomethylating activity and offer a rationale for the development of romidepsin-containing combination therapies

  20. Effect of selenium on malignant tumor cells of brain.

    Science.gov (United States)

    Zhu, Z; Kimura, M; Itokawa, Y; Nakatsu, S; Oda, Y; Kikuchi, H

    1995-07-01

    Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

  1. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

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

    International Nuclear Information System (INIS)

    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

    2010-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yingbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); School of Life Science, Southwest University, Chongqing 400715 (China); Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Yang, Li [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); College of Pharmacy, Jinan University, Guangzhou 510632 (China); Yu, Shuhui [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Library of Southwest University, Chongqing 400715 (China); Jiang, Jiahuan; Yan, Xiaoqing [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Zhang, Haoxing [School of Life Science, Southwest University, Chongqing 400715 (China); Liu, Lan [Department of Laboratory of Medicine, Children' s Hospital of Chongqin Medical University, Chongqing 400014 (China); Liu, Qun [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Du, Jun [Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510080 (China); Cai, Shaohui [College of Pharmacy, Jinan University, Guangzhou 510632 (China); Sung, K.L. Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Departments of Orthopaedic Surgery and Bioengineering, University of California, SD 0412 (United States)

    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.

  4. Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

    Science.gov (United States)

    Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Gilioli, Andrea; Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Lewis, Russell E; Luppi, Mario

    2016-01-01

    Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

  5. Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

    Directory of Open Access Journals (Sweden)

    Leonardo Potenza

    Full Text Available Invasive mucormycosis (IM is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients.By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3% of 204 patients, accounting for 32 (5.3% of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD, showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD: 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD.Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

  6. Histological examination of the gadolinium-enhanced dura mater around meningiomas on magnetic resonance imaging

    International Nuclear Information System (INIS)

    Sakai, Keiichi; Tada, Tsuyoshi; Fukasaku, Kazuaki; Kyoshima, Kazuhiko; Kobayashi, Shigeaki

    1993-01-01

    Magnetic resonance imaging often demonstrates gadolinium (Gd) enhancement of the dura mater around meningiomas. The Gd-enhanced dura mater was histologically investigated to detect meningioma cells. Gd enhancement of the dura mater occurred in 11 (79%) of the 14 meningiomas studied, and extended as far as 35 mm from the tumor. Histological examination revealed generation of vascular-rich loose connective tissue at the surface of the dura in all five tumors examined. Some clusters of meningothelial cells were distributed in the loose connective tissue in three of the five specimens, and one cluster was obviously neoplastic. These observations suggest that clusters of meningioma cells occur in the Gd-enhanced dura mater around meningiomas. (author)

  7. Histological examination of the gadolinium-enhanced dura mater around meningiomas on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Keiichi; Tada, Tsuyoshi; Fukasaku, Kazuaki; Kyoshima, Kazuhiko; Kobayashi, Shigeaki [Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine

    1993-07-01

    Magnetic resonance imaging often demonstrates gadolinium (Gd) enhancement of the dura mater around meningiomas. The Gd-enhanced dura mater was histologically investigated to detect meningioma cells. Gd enhancement of the dura mater occurred in 11 (79%) of the 14 meningiomas studied, and extended as far as 35 mm from the tumor. Histological examination revealed generation of vascular-rich loose connective tissue at the surface of the dura in all five tumors examined. Some clusters of meningothelial cells were distributed in the loose connective tissue in three of the five specimens, and one cluster was obviously neoplastic. These observations suggest that clusters of meningioma cells occur in the Gd-enhanced dura mater around meningiomas. (author).

  8. Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Minnema-Luiting, Jorien; Vroman, Heleen; Aerts, Joachim; Cornelissen, Robin

    2018-03-30

    Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited therapy options and dismal prognosis. In recent years, the role of immune cells within the tumor microenvironment (TME) has become a major area of interest. In this review, we discuss the current knowledge of heterogeneity in immune cell content and checkpoint expression in MPM in relation to prognosis and prediction of treatment efficacy. Generally, immune-suppressive cells such as M2 macrophages, myeloid-derived suppressor cells and regulatory T cells are present within the TME, with extensive heterogeneity in cell numbers. Infiltration of effector cells such as cytotoxic T cells, natural killer cells and T helper cells is commonly found, also with substantial patient to patient heterogeneity. PD-L1 expression also varied greatly (16-65%). The infiltration of immune cells in tumor and associated stroma holds key prognostic and predictive implications. As such, there is a strong rationale for thoroughly mapping the TME to better target therapy in mesothelioma. Researchers should be aware of the extensive possibilities that exist for a tumor to evade the cytotoxic killing from the immune system. Therefore, no "one size fits all" treatment is likely to be found and focus should lie on the heterogeneity of the tumors and TME.

  9. Primary extradural meningioma arising from the calvarium | Ravi ...

    African Journals Online (AJOL)

    Meningiomas are the most common intracranial tumours. Meningiomas arising at other locations are termed primary extradural meningiomas (EDMs) and are rare. Here we report a case of EDM arising from the calvarium – a primary calvarial meningioma (PCM).

  10. Osteokalzinexpression and regulation in hematologic malignancies and in cultured cells

    International Nuclear Information System (INIS)

    Wihlidal, P.

    2010-01-01

    Main issue of this work was to gain further insight into the association of haematopoiesis and osteopoiesis. A crucial cue for that is the fact that haematopoietic stem cells of haematopoietic diseases, which are characterised by c-KIT (CD117) expression, express the osteoblast marker osteocalcin. Thus, attention was focussed on the expression and regulation of osteocalcin, on one hand in blood and bone marrow samples of haematological diseases and on the other hand in leukaemic and osteosarcoma cell lines, i.e., by 1. investigating the expression of osteocalcin (OCN) splicing variants in haematological malignancies. We analysed bone marrow obtained from two patients with chronic myeloid leukaemia (CML), seven patients with other myeloproliferative diseases (MPD) and four patients with acute myeloid leukaemia (AML). RT-PCR analyses were performed in order to assess and quantify spliced (OCNs) and unspliced (OCNu) mRNA, the associated transcription factors (AML1 and AML3) as well as c-KIT, which is a marker for activated stem cells. Our data indicate that OCNs mRNA and OCN protein are expressed in c-KIT positive neoplastic stem cells in haematological malignancies. 2. It has been suggested that the tyrosine kinase inhibitor imatinib mesylate (IM), which has proven anti-proliferative effect, influences osteogenesis and bone turnover in treated patients. Thus, we aimed to quantify OCN mRNA, its splicing variants, the associated Runt-domain transcription factors AML1 and AML3, c-KIT and several metabolic genes to gain evidence about the differentiation state in the HL-60 leukaemia cell line as well as MG63 and U2OS osteosarcoma cells and murine primary osteoblasts MC3T3-E1. Our data indicate that IM induces inhibition of proliferation and synthesis of total OCN-mRNA in all cell lines, but a relative increase of OCNs-mRNA was observed in the human cell lines. On the other hand, differentiation-associated genes appeared to be stimulated. This may also indicate an

  11. Olfactory groove meningiomas.

    Science.gov (United States)

    Hentschel, Stephen J; DeMonte, Franco

    2003-06-15

    Olfactory groove meningiomas (OGMs) arise over the cribriform plate and may reach very large sizes prior to presentation. They can be differentiated from tuberculum sellae meningiomas because OGMs arise more anterior in the skull base and displace the optic nerve and chiasm inferiorly rather than superiorly. The authors searched the neurosurgery database at the M. D. Anderson Cancer Center for cases of OGM treated between 1993 and 2003. The records of these patients were then reviewed retrospectively for details regarding clinical presentation, imaging findings, surgical results and complications, and follow-up status. Thirteen patients, (12 women and one man, mean age 56 years) harbored OGMs (mean size 5.7 cm). All patients underwent bifrontal craniotomies and biorbital osteotomies. There were 11 complete resections (including the hyperostotic bone and dura of the cribriform plate and any extension into the ethmoid sinuses) and two subtotal resections with minimal residual tumor left in patients with recurrent lesions. No complication directly due to the surgery occurred in any patient. There were no recurrences in a mean follow-up period of 2 years (range 0-5 years). With current microsurgical techniques, the results of OGM resection are excellent, with a high rate of total resection and a low incidence of complications. All hyperostotic bone should be removed with the dura of the anterior skull base to minimize the risk of recurrence.

  12. Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

    Science.gov (United States)

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-09-01

    The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells. DAPE-induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1. DAPE generated reactive oxygen species (ROS) followed by disruption of mitochondrial membrane potentials in NCI-H28 cells. DAPE-induced mitochondrial damage was attenuated by cyclosporin A, an inhibitor of cyclophilin D (CypD). DAPE did not affect expression and mitochondrial localization of p53 protein in NCI-H28 cells. DAPE significantly decreased intracellular ATP concentrations in NCI-H28 cells. Overall, the results of the present study indicate that DAPE induces necroptosis and necrosis of MPM cells; the former is mediated by RIP1 kinase and the latter is caused by generating ROS and opening CypD-dependent mitochondrial permeability transition pore, to reduce intracellular ATP concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Microvessel and mast cell densities in malignant laryngeal neoplasm

    Directory of Open Access Journals (Sweden)

    Balica Nicolae Constantin

    2014-01-01

    Full Text Available Laryngeal neoplasm contributes to 30-40% of carcinomas of the head and neck. Mast cells are normal connective tissue residents, well represented in the respiratory tract. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. The aim of this study was to evaluate the correlation between mast cell density, microvascular density, histopathological type and histological grade. Our study included 38 laryngeal carcinomas as follows: adenoid cystic carcinoma (2 cases, malignant papilloma (2 cases and squamous cell carcinoma (34 cases. The combined technique of CD 34-alcian blue safranin (ABS was used to identify microvessel and mast cell density, which was quantified by the hot spot method. A significant correlation was found between both mast cell and microvascular density, and G1/G2 histological grade (p=0.002 and p=0.004, respectively. Squamous cell carcinoma was significantly correlated with mast cell density (p=0.003, but not with microvascular density (p=0.454.

  14. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

  15. [A case of petrous ridge meningioma manifested as pneumocephalus followed by Eustachian tube insufflation].

    Science.gov (United States)

    Yamaguchi, Shinya; Gi, Hidefuku; Uno, Jyunji; Ikai, Yoshiaki; Inoha, Satoshi; Nagaoka, Shintarou; Nishio, Shunji

    2009-05-01

    A 50-year-old female, who had a headache after Eustachian tube insufflation for her ear congestion, came to our hospital. CT and MRI revealed pneumocephalus and petrous ridge meningioma which destroyed petrous bone and air cells. Eustachian tube insufflation was considered to make the air coming into the middle ear, mastoid air cell and then into the intracranial space destroying the tumor. At surgery, there was subdural hematoma around the tumor. Total removal of the tumor and the hematoma membrane was performed. Histologically, the tumor was transitional meningioma and the cluster of meningioma cells were noted in the subdural hematoma membrane.

  16. Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.

    Science.gov (United States)

    Takemura, Yukitoshi; Satoh, Motohiko; Hatanaka, Kenichi; Kubota, Shunichiro

    2018-04-24

    Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.

  17. Anaerobic glycolysis as a property of malignant cells and its application aspects

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Korogodin, V.I.

    1996-01-01

    Under hypoxia excess glucose causes fast death of malignant cells without affecting viability of benign tumor and normal tissue cells. Laws and mechanisms of this phenomenon are described. Relationship between glycolysis activation and malignant degeneration of normal cells, application of artificial hyperglycemia to cancer therapy are discussed. 21 refs., 5 figs., 2 tabs

  18. Posterior fossa meningioma (surgical experiences) | Moussa ...

    African Journals Online (AJOL)

    Symptoms included headache (75%), cerebellar manifestations (60%), cranial nerve affection (40%) and hearing disturbances (15%). Most of the cases (50%) were cerebellopontine angle meningioma while the least (5%) were foramen magnum meningioma. Surgical approaches used included retrosigmoid approach ...

  19. [Ibrutinib: A new drug of B-cell malignancies].

    Science.gov (United States)

    Thieblemont, Catherine

    2015-06-01

    Ibrutinib (Imbruvica®) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton's tyrosine kinase (BTK). Ibrutinib has been approved in USA in February 2014 and in France in October 2014 for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation. In clinical studies, ibrutinib induced an impressive overall response rate (68%) in patients with relapsed/refractory MCL (phase II study). In CLL, ibrutinib has shown to significantly improve progression-free survival, response rate and overall survival in patients with relapsed/refractory CLL, including in those with del 17p. Ibrutinib had an acceptable tolerability profile. Less than 10% of patients discontinued their treatment because of adverse events. Results are pending in other B-cell lymphomas subtypes such as in diffuse large B-cell lymphoma and in follicular lymphoma. An approval extension has already been enregistered for Waldenström disease in USA in January 2015. Given its efficacy and tolerability, ibrutinib is an emerging treatment option for patients with B-cell malignancies. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

  20. Management of primary malignant germ cell tumor of the mediastinum

    International Nuclear Information System (INIS)

    Sakurai, Hiroyuki; Asamura, Hisao; Suzuki, Kenji; Watanabe, Shun-ichi; Tsuchiya, Ryosuke

    2004-01-01

    Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear. Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile. Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had nonseminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%. Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine

  1. Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik

    2015-01-01

    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes...

  2. Monoclonal antibody studies in B(non-T)-cell malignancies.

    Science.gov (United States)

    Shimoyama, M; Minato, K; Tobinai, K; Nagai, M; Hirose, M

    1983-09-01

    Tumor cells suspensions prepared from 129 B- or non-T cell malignancies were investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin (sIg) and B1 antigen proved to be the most useful markers for B-cell lineage. Six major subtypes of acute lymphoblastic leukemia (ALL) of non-T cell nature are now recognized by these immunological techniques, including null-ALL, Ia-ALL, lymphoid stem cell ALL, pre-pre-B ALL, pre-B ALL and B-ALL. In cases of chronic leukemias and lymphomas of non-T cell nature, 80% of the tumor was defined by sIg and 88% by B1 antigen as definitely of B-cell lineage. The clonal character was also defined in 68% of the tumor on the basis of the detection of predominant single light chain in sIg. Ia-like antigen was detected in almost all cases (96%). Leukemic cells from all cases of chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (CLsCL) and hairy cell leukemia (HCL) reacted with OKIa1 and anti-B1, and leukemic cells from most of them with anti-pan T monoclonal antibody (10.2). In more than half of CLL and CLsCL, leukemic cells were reactive with J5, OKM1, 9.6 and OKT8, but not with OKT3, OKT4 and OKT6. HCL cells had almost the same reactivity with these monoclonal antibodies as CLL and CLsCL cells except that J5 remained unreactive. These results indicated that Japanese CLL, CLsCL and HCL were different from Western ones at least with respect to surface marker characteristics. In cases of lymphomas, heavy chains of sIg were expressed in polyclonal fashion, especially in follicular lymphoma and diffuse lymphomas of medium sized cell type and large cell type, indicating that lymphomas of these types may originate from follicular center cells of the heavy chain switching stage. Anti-T monoclonals were also reactive with lymphoma cells. In about half of follicular lymphomas and diffuse lymphomas of the medium sized cell type, lymphoma cells reacted with 10.2, and less

  3. Expression and clinical value of EGFR in human meningiomas

    Directory of Open Access Journals (Sweden)

    Magnus B. Arnli

    2017-03-01

    Full Text Available 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

  4. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  5. Intracranial meningiomas in the present era of modern neuroimaging

    African Journals Online (AJOL)

    Background: Intracranial meningioma is the most common primary, intracranial, extra-axial neoplasm. It is mesenchymal in origin and arises from meningothelial cells of arachnoid villi of meninges. Objectives: To re-emphasize the regional anatomic localisation and diagnostic radiological features of intracranial ...

  6. Cytogenetic studies of 11 meningiomas and their clinical significance. II

    DEFF Research Database (Denmark)

    Poulsgård, L; Schrøder, H D; Rønne, M

    1990-01-01

    Cytogenetic analyses of 11 consecutive cases of meningiomas from 7 female and 4 male patients are reported. Chromosomal abnormalities were found in all cases. Only two of the cases showed cells with normal karyotype in addition to the abnormal stemline. Two of the cases displayed a more aggressive...

  7. An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells.

    Science.gov (United States)

    Castelnuovo, Manuele; Massone, Sara; Tasso, Roberta; Fiorino, Gloria; Gatti, Monica; Robello, Mauro; Gatta, Elena; Berger, Audrey; Strub, Katharina; Florio, Tullio; Dieci, Giorgio; Cancedda, Ranieri; Pagano, Aldo

    2010-10-01

    Neuroblastoma (NB) is a pediatric cancer characterized by remarkable cell heterogeneity within the tumor nodules. Here, we demonstrate that the synthesis of a pol III-transcribed noncoding (nc) RNA (NDM29) strongly restricts NB development by promoting cell differentiation, a drop of malignancy processes, and a dramatic reduction of the tumor initiating cell (TIC) fraction in the NB cell population. Notably, the overexpression of NDM29 also confers to malignant NB cells an unpredicted susceptibility to the effects of antiblastic drugs used in NB therapy. Altogether, these results suggest the induction of NDM29 expression as possible treatment to increase cancer cells vulnerability to therapeutics and the measure of its synthesis in NB explants as prognostic factor of this cancer type.

  8. Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.

    Directory of Open Access Journals (Sweden)

    Jiangxin Wang

    Full Text Available Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single-cell level. We present a study on changes in cellular heterogeneity in the context of pre-malignant progression in response to hypoxic stress. Utilizing pre-malignant progression of Barrett's esophagus (BE as a disease model system we studied molecular mechanisms underlying the progression from metaplastic to dysplastic (pre-cancerous stage. We used newly developed methods enabling measurements of cell-to-cell differences in copy numbers of mitochondrial DNA, expression levels of a set of mitochondrial and nuclear genes involved in hypoxia response pathways, and mitochondrial membrane potential. In contrast to bulk cell studies reported earlier, our study shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes. Based on single-cell data analysis, we propose that mitochondria may be one of the key factors in pre-malignant progression in BE.

  9. MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

    OpenAIRE

    Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

    2009-01-01

    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

  10. Primary intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

    1988-01-01

    Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found. (author)

  11. Ki-67 immunoreactivity in meningiomas--determination of the proliferative potential of meningiomas using the monoclonal antibody Ki-67

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1997-01-01

    The proliferative potential of 66 human intracranial meningiomas (15 benign, 15 atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This antibody recognizes a nuclear antigen present in human cells...

  12. Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells

    Directory of Open Access Journals (Sweden)

    Tzuu-Yuan Huang

    2012-01-01

    Full Text Available Demethoxycurcumin (DMC; a curcumin-related demethoxy compound has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC50 values at 22.71 μM and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP, DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

  13. Role of MR imaging in the differentiation of benign and nonbenign intracranial meningiomas. The utility of contrast-enhanced T1-weighted images

    International Nuclear Information System (INIS)

    Tanaka, Yasunori; Matsuo, Michimasa

    1996-01-01

    The purpose of this study was to develop useful criteria for distinguishing nonbenign (atypical and malignant) primary intracranial meningiomas from their benign counterparts by using magnetic resonance imaging (MRI). To determine useful MRI findings for this purpose, 12 benign and five nonbenign meningiomas were retrospectively evaluated according to the following items: tumor signal intensity on plain T1-, T2- and proton density-weighted images, degree of perifocal edema on T2-weighted images, morphology of the tumor margin on contrast-enhanced T1-weighted images, presence of irregular nodule and/or mushrooming pattern on contrast-enhanced T1-weighted images, homogeneity of the tumor on contrast-enhanced T1-weighted images, and presence of marked skull destruction. Markedly irregular tumor margin, presence of irregular nodule and/or mushrooming pattern and markedly inhomogeneous enhancing pattern were significantly more frequent in nonbenign meningiomas. We defined these three MRI findings as nonbenign findings, and tried to categorize meningiomas by the number of nonbenign findings. It was found that 10 meningiomas with no or one nonbenign finding were benign lesions, of four meningiomas with two nonbenign findings two were benign lesions and two were nonbenign lesions, and three meningiomas with three nonbenign findings were nonbenign lesions. The two benign meningiomas with two nonbenign findings were accompanied by increased mitotic activity or brain invasion. Contrast-enhanced T1-weighted images were considered very useful in distinguishing benign and nonbenign meningiomas. (author)

  14. Identification of a third protein 4.1 tumor suppressor, protein 4.1R, in meningioma pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Robb, Victoria A.; Li, Wen; Gascard, Philippe; Perry, Arie; Mohandas, Narla; Gutmann, David H.

    2003-06-11

    Meningiomas are common tumors of the central nervous system, however, the mechanisms under lying their pathogenesis are largely undefined. Two members of the Protein 4.1 super family, the neuro fibromatosis 2 (NF2) gene product (merlin/schwannomin) and Protein 4.1B have been implicated as meningioma tumor suppressors. In this report, we demonstrate that another Protein 4.1 family member, Protein 4.1R, also functions as a meningioma tumor suppressor. Based on the assignment of the Protein 4.1R gene to chromosome 1p32-36, a common region of deletion observed in meningiomas, we analyzed Protein 4.1R expression in meningioma cell lines and surgical tumor specimens. We observed loss of Protein 4.1R protein expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningioma as by immuno histo chemistry (IHC). Analysis of a subset of these sporadic meningiomas by fluorescent in situ hybridization (FISH) with a Protein 4.1R specific probe demonstrated 100 percent concordance with the IHC results. In support of a meningioma tumor suppressor function, over expression of Protein 4.1R resulted in suppression of IOMM-Lee and CH157MN cell proliferation. Similar to the Protein 4.1B and merlin meningioma tumor suppressors, Protein 4.1R localization in the membrane fraction increased significantly under conditions of growth arrest in vitro. Lastly, Protein 4.1R interacted with some known merlin/Protein 4.1B interactors such as CD44 and bII-spectrin, but did not associate with the Protein 4.1B interactors 14-3-3 and PRMT3 or the merlin binding proteins SCHIP-1 and HRS. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor important in the molecular pathogenesis of meningioma.

  15. Cell Fusion in the War on Cancer: A Perspective on the Inception of Malignancy

    Directory of Open Access Journals (Sweden)

    Jeffrey L. Platt

    2016-07-01

    Full Text Available Cell fusion occurs in development and in physiology and rarely in those settings is it associated with malignancy. However, deliberate fusion of cells and possibly untoward fusion of cells not suitably poised can eventuate in aneuploidy, DNA damage and malignant transformation. How often cell fusion may initiate malignancy is unknown. However, cell fusion could explain the high frequency of cancers in tissues with low underlying rates of cell proliferation and mutation. On the other hand, cell fusion might also engage innate and adaptive immune surveillance, thus helping to eliminate or retard malignancies. Here we consider whether and how cell fusion might weigh on the overall burden of cancer in modern societies.

  16. A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening

    NARCIS (Netherlands)

    Gerkes, Erica H.; Fock, J. M.; den Dunnen, W. F. A.; van Belzen, M. J.; van der Lans, C. A.; Hoving, Eelco W.; Fakkert, I. E.; Smith, M.J.; Evans, D. G.; Olderode-Berends, M. J. W.

    Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young patients. Heterozygous loss-of-function germline mutations in the SMARCE1 gene are

  17. Cystic meningiomas in 2 dogs

    International Nuclear Information System (INIS)

    Bagley, R.S.; Kornegay, J.N.; Lane, S.B.; Thrall, D.L.; Page, R.L.

    1996-01-01

    Two dogs with signs of forebrain disease had hypodense lesions on computed tomography evaluation. Magnetic resonance imaging of the first dog showed a hypointense lesion on the T1-weighted scan and a hyperintense lesion on T2-weighted scanning. At surgery, both dogs had a primary cystic intracranial lesion, and the abnormal tissue adjacent to the cyst had histological features of meningioma. Each dog underwent whole brain irradiation after surgery, and 1 dog lived for 3 years after treatment. While uncommon, meningioma should be considered as a differential diagnosis in dogs with cystic intracranial lesions

  18. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis.

    Science.gov (United States)

    Savage, Philip

    2016-11-21

    Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies. In this review we will examine the cancer stem cell/cancer cell relationship of each of the chemotherapy curable malignancies and how this relationship impacts on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell types. In contrast to the common epithelial cancers, in each of the chemotherapy curable malignancies there are no conventional hierarchical cancer stem cells. However cells with cancer stem like qualities can arise stochastically from within the general tumour cell population. These stochastic stem cells acquire a degree of resistance to DNA damaging agents but also retain much of the key characteristics of the cancer cells from which they develop. We would argue that the balance between the acquired resistance of the stochastic cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell determines the overall chemotherapy curability of each diagnosis. The cancer stem cells in the chemotherapy curable malignancies appear to have two key biological differences from those of the more common chemotherapy incurable malignancies. The first difference is that the conventional hierarchical pattern of cancer stem cells is absent in each of the chemotherapy curable malignancies. The other key difference, we suggest, is that the stochastic stem cells in the chemotherapy curable malignancies

  19. Biology and clinical application of CAR T cells for B cell malignancies.

    Science.gov (United States)

    Davila, Marco L; Sadelain, Michel

    2016-07-01

    Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

  20. Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

    Science.gov (United States)

    Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

    2018-06-01

    Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

  1. Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma

    Directory of Open Access Journals (Sweden)

    Hong Wei Yang

    2012-01-01

    Full Text Available Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

  2. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    International Nuclear Information System (INIS)

    Uziel, Orit; Kanfer, Gil; Beery, Einat; Yelin, Dana; Shepshelovich, Daniel; Bakhanashvili, Mary; Nordenberg, Jardena; Lahav, Meir

    2014-01-01

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway

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

    International Nuclear Information System (INIS)

    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.

    2006-01-01

    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

  4. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Uziel, Orit, E-mail: Oritu@clalit.org.il [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Kanfer, Gil [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Beery, Einat [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Yelin, Dana; Shepshelovich, Daniel [Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Bakhanashvili, Mary [Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel); Nordenberg, Jardena [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva (Israel); Lahav, Meir [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)

    2014-07-18

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

  5. Identification of cancer stem cell markers in human malignant mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Ghani, Farhana Ishrat; Yamazaki, Hiroto; Iwata, Satoshi; Okamoto, Toshihiro [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Aoe, Keisuke; Okabe, Kazunori; Mimura, Yusuke [Departments of Medical Oncology, Yamaguchi-Ube Medical Center, Yamaguchi (Japan); Fujimoto, Nobukazu; Kishimoto, Takumi [Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama (Japan); Yamada, Taketo [Department of Pathology, Keio University School of Medicine, Tokyo (Japan); Xu, C. Wilson [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-01-14

    Research highlights: {yields} We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. {yields} SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. {yields} SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony. {yields} The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. In addition, CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

  6. Tenascin in meningioma: expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape.

    Science.gov (United States)

    Kiliç, Türker; Bayri, Yaşar; Ozduman, Koray; Acar, Melih; Diren, Semin; Kurtkaya, Ozlem; Ekinci, Gazanfer; Buğra, Kuyaş; Sav, Aydin; Ozek, M Memet; Pamir, M Necmettin

    2002-07-01

    Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transcriptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression but not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two specimens. In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

  7. Malignant transformation of lichen planus hypertrophicus into squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Aniket Bhagwat Bhole

    2016-01-01

    Full Text Available Neoplastic transformation of lichen planus (LP is reported, but it's a rare event. Squamous cell carcinoma (SCC complicating cutaneous LP has an incidence of 0.4%. Average age at the time of diagnosis of SCC in patients of LP is 58 years with a range of 29–78 years. We report an extremely rare case of 17-year-old female patient who developed SCC from lichen planus hypertrophicus (LPH, a variant of LP. Patient presented with LPH over the anterior aspect of both legs since the age of 7 years which is again a pediatric rarity. SCC developed over an anteromedial aspect of left ankle after 10 years when she came to us. Both the diagnoses were histopathologically confirmed. The patient was treated with complete excision of tumor and defect was closed with rotation flap. This report emphasizes that the long-standing hypertrophic form of LP seems to have a considerable propensity for malignant transformation, even in the juvenile age group. Hence, careful vigilance of a longstanding LPH is necessary to allow early detection of a developing SCC.

  8. Current treatment options for meningioma.

    Science.gov (United States)

    Apra, Caroline; Peyre, Matthieu; Kalamarides, Michel

    2018-03-01

    With an annual incidence of 5/100,000, meningioma is the most frequent primary tumor of the central nervous system. Risk factors are radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Areas covered: This review details the current standard therapy based on international guidelines and recent literature, and describes new approaches developed to treat refractory cases. First-line treatments are observation and surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and indicated for anaplastic meningiomas. The most problematic cases include skull base meningiomas that enclose vasculo-nervous structures and surgery- and radiation-refractory tumors that present with significant morbidity and mortality. The treatment of recurrent tumors is based on radiotherapy and repeated surgery. Systematic therapies are not effective in general but several clinical trials are ongoing. Expert commentary: Molecular characterization of the tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the methylation profile are developing, completing the histological classification and giving new insights into prognosis and treatment options.

  9. Canine Intracranial Meningioma: Case report

    Directory of Open Access Journals (Sweden)

    José Ricardo Gomes de Carvalho

    2016-11-01

    Full Text Available ABSTRACT. Carvalho J.R.G., Vasconcellos C.H.C., Bastos I. P.B., Trajano F.L.C., Costa T.S. & Fernandes J.I [Canine Intracranial Meningioma: Case report.] Meningioma intracraniano canino: Relato de caso. Revista Brasileira de Medicina Veterinária, 38(supl. 3:1- 7, 2016. Programa de Pós-Graduação em Ciências Veterinária, Universidade Federal Rural do Rio de Janeiro, BR 465 Km 7, Seropédica, RJ 23.897-000, Brasil, E-mail: vetjulio@yahoo.com.br Intracranial neoplasms usually show their signals in a moderate way, revealing a long background of nonspecific signs, making the diagnosis more difficult. The meningioma is the most common intracranial neoplasm in dogs and cats. Along the years, the Veterinary Medicine has experienced important technological improvements, making it possible the diagnosis of a lot of diseases. Therefore, diseases considered not common in the past, started being diagnosed more frequently, for instance, brain lesions. The objective of this research is to report a case of intracranial meningioma in a Boxer dog that arrived at the Veterinary Hospital of the Federal Rural University of Rio de Janeiro, highlighting its clinical improvement, diagnosis and treatment.

  10. Orbital meningioma, the Utrecht experience

    NARCIS (Netherlands)

    Mourits, Maarten Ph.; Berkelbach van der Sprenkel, Jan Willem

    2001-01-01

    AIMS. 1) To evaluate epidemiological data (age, gender, initial complaints, and ophthalmic findings) of a patient cohort with a primary or secondary orbital meningioma. 2) To evaluate the clinical course of these patients. 3) To evaluate the outcome of treatment. PATIENTS AND METHODS. All

  11. Preoperative embolization of gigantic meningioma

    International Nuclear Information System (INIS)

    Wang Hongsheng; Chen Huaqun; Dong Congsong; Li Wenhui; Dai Zhenyu; Chen Guozhi

    2006-01-01

    Objective: To evaluate the clinical efficacy of preoperative embolization in treatment of patients with gigantic meningioma. Methods: Fourteen cases of gigantic meningioma diameter from 6 to 11 cm were measured by CT and MRI scan. DSA manifested that they are vascularizd meningioma and showed the mainly feeding arteries. We used getation sponge to superselectively embilized the feeding arteries. All tumors were performed surgical excision 3-7 days after the embolization. Results: DSA showed the blood supplies in the tumors in 9 cases were completely blocked, and that in 5 cases were dramatically eliminated. All patients were operated 3-7 days after the embolization. During the operations the bleeding were dramatically decreased and the operation time was shortened compared with those in unembolized cases. It helps us remove the tumors easy and quickly from the attachments. No complication occurred during and after the operations. Conclusion: Preoperative embolization of gigantic meningioma is a useful and relatively safe method in helping surgicaly and completely excised of tumor with significant reduction of blood loss and operation time. (authors)

  12. The Role of Postoperative Radiotherapy in the Management of Intracranial Meningiomas

    International Nuclear Information System (INIS)

    Chang, Sei Kyung; Suh, Chang Ok; Shin, Hyun Soo; Kim, Gwi Eon

    1994-01-01

    Purpose: To evaluate the role of postoperative radiotherapy in the management of primary or recurrent intracranial meningiomas. Methods and Materials: A retrospective review of 34 intracranial meningioma patients referred to the Yonsei Cancer Center for postoperative radiotherapy between 1981 and 1990 was undertaken. Of the 34 patients, 24 patients received elective postoperative radiotherapy after total or subtotal resection(Group 1), and 10 patients received postoperative radiotherapy as a salvage treatment for recurrent tumors(Group 2). Ten patients received postoperative radiotherapy after total resection, and twenty-four after subtotal resection. Ten patients who had total tumor resection were referred for radiotherapy either because of angioblastic or malignant histologic type (4 patients in Group 1) or because of recurrent disease after initial surgery(6 patients in Group 2). Radiation dose of 50-56Gy was delivered over a period of 5-5.5 weeks using 4MV LINAC or Co-60 teletherapy unit. Results: Overall actuarial progression free survival (PFS) at 5 years was 80%. Survival was most likely affected by histologic subtypes. Five year PFS rate was 52% for benign angioblastic histology, as compared with 100% for classic benign histology. For malignant meningiomas, 5 year PFS rate was 44%. The recurrence rates of classic, angioblastic, and malignant type were 5%(1/21), 80%(4/5), and 50%(4/8), respectively. The duration between salvage post-operative radiotherapy and recurrence was longer than the duration between initial surgery and recurrence in the patients of group 2 with angioblastic or malignant histology. Conclusion: Postoperative radiotherapy of primary or recurrent intracranial meningiomas appears to be effective modality, especially in the patients with classic meningiomas. In angioblastic or malignant histologies, a more effective approach seems to be needed for decreasing recurrence rate

  13. Fine needle aspiration cytology diagnosis of metastatic malignant diffuse type tenosynovial giant cell tumor

    Directory of Open Access Journals (Sweden)

    Prashant Ramteke

    2017-01-01

    Full Text Available Tenosynovial giant cell tumors (TGCTs arise from the synovium of joint, bursa, and tendon sheath, and are classified into localized and diffuse types. Diffused type often affects the large joint, and has more recurrence, metastasis, and malignant transformation potential compared to the localized type. Malignant diffused TGCT (D-TGCT usually occurs as a large tumor (>5 cm, in older patients, and its histopathologic features include necrosis, cellular anaplasia, prominent nucleoli, high nuclear cytoplasmic ratio, brisk mitosis, discohesion of tumor cells, paucity of giant cells, and a diffuse growth pattern. At least five of these criteria are required for the histopathologic diagnosis of malignant TGCT because the benign TGCT also shares many of these morphological features. We describe the cytomorphologic features of a malignant D-TGCT from an unusual case of pulmonary metastasis in an adult patient. Fine needle aspiration cytologic features of malignant D-TGCT have not been described earlier in the English literature.

  14. Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

    OpenAIRE

    Choi, Goda; van den Broek, Esther C; Stam, Olga CG; van Noesel, C.J.M.; Tonino, Sanne H.; Kater, Armon P.

    2015-01-01

    We present a patient with chemotherapy-refractory Chronic Lymphocytic Leukemia (CLL) in whom postmortem examination showed hepatosplenomegaly, with both multiple small-cellular CLL lesions and large-cellular, monoclonal T-cell infiltrates. Following this case, the co-incidence of T-cell malignancies and CLL was studied using Dutch and American cancer registry databases. Analysis showed an excess risk for T-cell malignancies in CLL patients, with increased standardized incidence ratios compare...

  15. Role of radiotherapy in the treatment of meningiomas; Role de la radiotherapie dans le traitement des meningiomes cerebraux

    Energy Technology Data Exchange (ETDEWEB)

    Noel, G. [Centre de protontherapie, 91 - Orsay (France); Renard, A.; Mazeron, J.J. [Groupe Hospitalier la Pitie-Salpetriere, Service de Radiotherapie, AP-HP, 75 - Paris (France); Valery, C. [Groupe Hospitalier la Pitie-Salpetriere, Service de Neurochirurgie, AP-HP, 75 - Paris (France); Mokhtari, K. [Groupe Hospitalier la Pitie-Salpetriere, Lab. de Neuropathologie Raymond-Escourolle, AP-HP, 75 - Paris (France)

    2001-06-01

    Role of radiotherapy in the treatment of meningiomas. Cerebral meningiomas account for 15-20% of all cerebral tumours. Although seldom malignant, they frequently recur in spite of complete surgery, which remains the cornerstone of the treatment. In order to decrease the probability of local recurrence, radiotherapy has often been recommended in atypical or malignant meningioma as well as in benign meningioma which was incompletely resected. However, this treatment never was the subject of prospective studies, randomized or not. The purpose of this review of the literature was to give a progress report on the results of different published series in the field of methodology as well as in the techniques of radiotherapy. Proposals for a therapeutic choice are made according to this analysis. For grade I or grade II-III meningiomas, limits of gross tumor volume (GTV) include the tumour in place or the residual tumour after surgery; clinical target volume (CTV) limits include gross tumour volume before surgery with a GTV-CTV distance of 1 and 2 cm respectively. Delivered doses are 55 Gy into CTV and 55-60 Gy and 70 Gy into GTV for grade I and grade II-III meningiomas respectively. (authors)

  16. Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases.

    Science.gov (United States)

    Slavin, S; Nagler, A; Shapira, M; Panigrahi, S; Samuel, S; Or, A

    2001-01-01

    Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) following BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. The latter working hypothesis suggested that effective BMT procedures may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell transplantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality.

  17. An analysis of the magnetic resonance imaging and pathology of intracal lymphoplasmacyte-rich meningioma

    International Nuclear Information System (INIS)

    Liu Jianli; Zhou Junlin; Ma Yongheng; Dong Chi

    2012-01-01

    Objective: To discuss the MRI features of the intracranial lymphoplasmacyte-rich meningioma and the correlation between the MRI features and pathology. Methods: Review retrospectively the MRI and pathologic data of seven patients with lymphoplasmacyte-rich meningioma which were confirmed by surgery and pathology. Results: The seven cases of lymphoplasmacyte-rich meningioma were solitary, six cases demonstrated flat growth along the meninges, five cases had not yet formed specific nodules, and two cases exhibited irregular lobulation. Seven cases had no clear boundary, peritumoral brain edema was obvious and adjacent brain tissues were invaded to varying degrees. After plain MRI scans, the focuses of seven cases exhibited lower-isointense signal in T1WI, five cases revealed higher-isointense signal and two cases showed lower-isointense signal in T2WI. Enhancement scans demonstrated marked enhancement in seven cases, and the meninges in six cases thicken irregularly and extensively. Pathology showed the richness and diversity of cells, an infiltration containing plasma cells and lymphocytes, as well as the unequal areas of neoplastic spindle cells and meninge epithelial cells. Conclusion: Lymphoplasmacyte-rich meningioma is a subtype meningioma of WHO I-grade, which is seldom seen and whose imaging appearances are varied from ordinary meningioma. Its features include growing flat along the meninges, irregular forms, unclear boundary, obvious edema, notable strengthening effect, usual invasion of adjacent brain tissues, and similar inflammation.

  18. Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.

    Science.gov (United States)

    Johnsen, Hans Erik; Bergkvist, Kim Steve; Schmitz, Alexander; Kjeldsen, Malene Krag; Hansen, Steen Møller; Gaihede, Michael; Nørgaard, Martin Agge; Bæch, John; Grønholdt, Marie-Louise; Jensen, Frank Svendsen; Johansen, Preben; Bødker, Julie Støve; Bøgsted, Martin; Dybkær, Karen

    2014-06-01

    Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

  19. Congenital intracranial meningioma. A case report and literature review

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1993-01-01

    A case report of congenital intracranial meningioma is presented. We describe what appears to be the first fetal meningioma of the fibroblastic subtype. The literature is reviewed, and the subtype and sex distribution of fetal meningiomas is discussed.......A case report of congenital intracranial meningioma is presented. We describe what appears to be the first fetal meningioma of the fibroblastic subtype. The literature is reviewed, and the subtype and sex distribution of fetal meningiomas is discussed....

  20. Radiation-induced meningiomas in pediatric patients

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  1. Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Kopp, Katharina; Krejsgaard, Thorbjørn

    2010-01-01

    is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal-regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood......, whereas an activator of Jak3 and NF-¿B, interleukin-2 (IL-2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10...

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

    Science.gov (United States)

    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.

  3. Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma.

    Science.gov (United States)

    Drexler, H G; Matsuo, Y

    2000-05-01

    Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.

  4. The role of postoperative external irradiation for the incompletely resected meningiomas

    International Nuclear Information System (INIS)

    Kim, Tae Hyun; Yang, Dae Sik; Kim, Chul Young; Choi, Myung Sun

    2000-01-01

    The aim of this study is to look for the possible efficacy of postoperative external irradiation for incompletely resected meningiomas. From August 1981 to January 1997, forty-four patients with intracranial meningioma were treated by postoperative external irradiation. Of the 44 meningiomas, 18 transitional, 13 meningotheliomatous, 6 hemangiopericytic, 4 atypical, 2 fibroblastic and 1 malignant meningioma were identified. We classified all patients into two groups by the histology. The benign group was consisted of the meningotheliomatous, transitional and fibroblastic types. The malignant group was consisted of the atypical, hemangiopericytic and malignant types.In the means of surgery, 37 patients were resected incompletely and 7 patients were managed by biopsy only. After surgery, all patients were received postoperative external irradiation. Radiotherapy was delivered using Co-60 or 4 MV photon beam to a total dose of 50 to 66 Gy (mean dose:57.4 Gy) with a 1.8 to 2 Gy per fraction. The median follow-up was 48 months (range:21-101 months). Multivariate analysis of the influence by age, sex, location, histology and radiation dose on local control has been done using Cox's proportional hazard model. 5-year local control rate was 93.8% for the benign histology and 51.8% for the malignant histology (p=0.0110) and overall local control rate at 5 years was 87.4%. The analysis of the prognostic factors, such as age, sex, location, and radiation dose were not significant except for the histology. Adjuvant postoperative external irradiation appears to be significantly improved local control in the patients with incompletely resected meningiomas

  5. Induction of malignant transformation in CHL-1 cells by exposure to tritiated water

    International Nuclear Information System (INIS)

    Zou Shu'ai; Wang Hui

    1992-01-01

    The induction of neoplastic transformation in CHL-1 cells by low-dose-rate exposure to tritiated water was reported. CHL-1 cells were exposed to tritiated water (9.25 x 10 5 - 3.7 x 10 6 Bq/mL) for 24-96 hours and the accumulated doses were estimated to be 0.055-0.88 Gy, respectively. Neoplastic transformation was found in all exposed cell groups. The morphological study and transplantation test was carried out for demonstration malignancy of the transformed cells and the results show that they are with the morphology and behaviour for malignant tumour cells. For CHL-1 cells exposed to various doses of tritiated water, transformation rates were found to be from 3.28% to 13.0% at dose of 0.055-0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to 137 Cs gamma-rays was carried out at dose rates of 0.359 Gy/24 hr and transformation rates for irradiated CHL-1 cells were found to be from 2.59% to 13.4%. Based on these data, RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6

  6. Nephrotic syndrome associated with meningioma

    Directory of Open Access Journals (Sweden)

    P P Zachariah

    2013-01-01

    Full Text Available A 58-year-old man presented with recurrent frontal meningioma and nephrotic syndrome. Renal biopsy could not be done in view of the rapid neurological deterioration. The patient underwent surgical resection of the tumor. Within 4 weeks, the edema decreased, serum albumin improved, and proteinuria decreased spontaneously. At three months of followup, the patient had attained complete remission of nephrotic state.

  7. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells.

    Directory of Open Access Journals (Sweden)

    Ayako Nakano

    Full Text Available Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2, KG-1 (ABCB1 and HepG2 cells (ABCB1 and ABCG2. Interestingly, although side population (SP cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.

  8. A case of hypervascular meningioma

    International Nuclear Information System (INIS)

    Takahashi, Jun; Makita, Yasumasa; Nabeshima, Sachio; Tei, Taikyoku; Keyaki, Atsushi; Miyamoto, Yoshihisa

    1988-01-01

    A 30-year-old, right handed male was admitted with headache and mild right-sided motor weakness of one year's duration. A CT scan revealed a mass over the left frontal convexity. A cerebral angiogram showed a huge, hypervascular tumor which was fed by bilateral external carotid and left internal carotid arteries. Because of its size and location, a surgical intervention was considered contraindicated at that time. Instead he was initially irradiated 52 Gy in total dose with 10 MV x-rays (Lineac). A CT scan 4 month thereafter revealed remarkable decrease in the size of tumor and reduction of its mass effect. A CT scan 12 months later, however, revealed increase in low density area around mass, although the size of the tumor was much smaller than before. He was readmitted for surgery 14 months after irradiation. An angiogram visualized more reduction of tumor stain and the caliber of feeding arteries. The tumor was totally removed without resultant neurological deficits. A histological diagnosis of the tumor was meningotheliomatous meningioma with well developed vascular networks. Meningioma is usually not a radiosensitive tumor, but there are some reports of cases with hypervascular meningiomas which have been effectively treated with irradiation preoperatively. In the present case, because of a huge vascular tumor in the dominant hemisphere, irradiation was given initial and 14 months thereafter the tumor was totally removed without neurological deficits. (author)

  9. Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.

    Science.gov (United States)

    Narbonne-Reveau, Karine; Lanet, Elodie; Dillard, Caroline; Foppolo, Sophie; Chen, Ching-Huan; Parrinello, Hugues; Rialle, Stéphanie; Sokol, Nicholas S; Maurange, Cédric

    2016-06-14

    Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation. However, the molecular basis of this early malignant susceptibility remains unknown. During Drosophila development, neural stem cells (NSCs) divide asymmetrically and generate intermediate progenitors that rapidly differentiate in neurons. Upon gene inactivation, these progeny can dedifferentiate and generate malignant tumors. Here, we find that intermediate progenitors are prone to malignancy only when born during an early window of development while expressing the transcription factor Chinmo, and the mRNA-binding proteins Imp/IGF2BP and Lin-28. These genes compose an oncogenic module that is coopted upon dedifferentiation of early-born intermediate progenitors to drive unlimited tumor growth. In late larvae, temporal transcription factor progression in NSCs silences the module, thereby limiting mitotic potential and terminating the window of malignant susceptibility. Thus, this study identifies the gene regulatory network that confers malignant potential to neural tumors with early developmental origins.

  10. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    International Nuclear Information System (INIS)

    Gross, Emilie; Quillet-Mary, Anne; Ysebaert, Loic; Laurent, Guy; Fournie, Jean-Jacques

    2011-01-01

    The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity

  11. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Fournie

    2011-03-01

    Full Text Available The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

  12. Scintigraphy with In-111 labeled lymphokine-activated killer cells of malignant brain tumor

    International Nuclear Information System (INIS)

    Itoh, Kazuo; Sawamura, Yutaka; Hosokawa, Masuo; Kobayashi, Hiroshi

    1988-01-01

    This study was undertaken to assess the in vivo distribution and migration of lymphokine-activated killer (LAK) cells to the target malignant foci in four patients with advanced malignant brain tumor. All four patients had failed to respond to prior adoptive immunotherapy. After the intravenous administration of radiolabeled LAK cells, most of the radiolabeled cells were distributed in the liver and spleen, with lesser radioactivity in the lung and bone marrow. Scintigraphy revealed the target malignant foci in all four patients to be areas of increased radioactivity. The number of radiolabeled LAK cells that accumulated in the intracranial malignant lesions, however, seemed to be insufficient to mediate regression of the solid tumor mass by direct cell-to-cell interaction. We conclude that the failure of adoptive immunotherapy could be accounted for by the poor migration of infused LAK cells to the target malignant foci. We also conclude that radionuclide study with radiolabeled lymphokine-activated culture cells against tumors is likely to be helpful as a means to investigate effective possibilities for subsequent adoptive immunotherapy. (author)

  13. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.

    Science.gov (United States)

    Liu, Jun; Zhong, Jiang F; Zhang, Xi; Zhang, Cheng

    2017-01-31

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells) can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable. In this review, we first discuss the use of CAR-T cells for relapsed cases after allo-HSCT. We then review the toxicities and the occurrence of graft-versus-host disease in relapsed patients who received CAR-T cells post allo-HSCT. Finally, we review clinical trial registrations and the therapeutic time window for infusion of CAR-T cells post allo-HSCT. The treatment of allogeneic CAR-T cells is beneficial for patients with relapsed B cell malignancies after allo-HSCT with low toxicities and complications. However, multicenter clinical trials with larger sample sizes should be performed to select the optimal therapeutic window and confirm its efficacy.

  14. T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

    Science.gov (United States)

    2017-11-29

    Hematologic Malignancy; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia in Blast Crisis; Anemia, Refractory, With Excess of Blasts; Chronic Myeloproliferative Disease; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Lymphoma; Large Cell Non-Hodgkin's Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Non-Hodgkin's Lymphoma

  15. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  16. Solitary, multiple, benign, atypical, or malignant: the "Granular Cell Tumor" puzzle.

    Science.gov (United States)

    Machado, Isidro; Cruz, Julia; Lavernia, Javier; Llombart-Bosch, Antonio

    2016-05-01

    The clinical evolution and biology of granular cell tumors (GCT) are poorly understood and treatment remains an issue of discussion. The majority of GCT are benign, although some display malignant behavior. The distinction between benign, atypical, and malignant GCT is controversial due to morphological and immunohistochemical overlap and lack of consistent histological and phenotypic criteria that predict behavior. Although histological criteria may indicate increased risk of malignant evolution, some GCT with evident benign appearance exceptionally progress towards metastatic disease. In this review, we discuss current knowledge on GCT, including histologic, immunophenotypic, and molecular characteristics and differential diagnosis. We focus on the following problematic items in GCT: (1) evolution of classification, (2) neural versus non-neural GCT, (3) neoplastic versus reactive disease, (4) malignant transformation of benign GCT, and (5) multiple versus metastatic GCT. We conclude that although a Ki-67 index >10 % and the presence of mitoses and/or of necrosis are frequently associated with malignant behavior, metastasis remains the only unequivocal sign of malignancy in GCT. An infiltrative growth pattern and vascular and/or perineural invasion are not indicative of malignancy. GCT with atypical/uncertain features almost never metastasize, and many of these tumors either behave in a benign fashion or only recur locally (similar to incompletely excised benign tumors). We therefore propose that classical and atypical histological variants form a single group of GCT. GCT with various unfavorable histological features might be labeled as "GCT with increased risk of metastasis" rather than malignant GCT.

  17. Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression.

    Science.gov (United States)

    Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A; Zhou, Yunli; Cheunsuchon, Pornsuk; Louis, David N; Klibanski, Anne

    2010-03-15

    Meningiomas are common tumors, representing 15% to 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. The 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. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes a noncoding RNA with an antiproliferative 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 bromodeoxyuridine 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 noncoding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism.

  18. Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

    International Nuclear Information System (INIS)

    Chromik, Ansgar M; Weyhe, Dirk; Mittelkötter, Ulrich; Uhl, Waldemar; Hahn, Stephan A; Daigeler, Adrien; Flier, Annegret; Bulut, Daniel; May, Christina; Harati, Kamran; Roschinsky, Jan; Sülberg, Dominique

    2010-01-01

    The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1). This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis

  19. Pure intrasellar meningioma located under the pituitary gland: Case report

    International Nuclear Information System (INIS)

    Cha, Seung Woo; Park, Dong Woo; Park, Choong Ki; Pyo, Ju Yeon; Lee, Young Jun; Lee, SAeung Ro

    2013-01-01

    Most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae. Subglandular meningiomas located under the pituitary gland are extremely rare. Intrasellar meningiomas in the subdiaphragmatic and subglandular region probably originate from the dura in the sellar floor. We report a case of a subglandular meningioma along with a review of the literature.

  20. Pure intrasellar meningioma located under the pituitary gland: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seung Woo; Park, Dong Woo; Park, Choong Ki; Pyo, Ju Yeon [College of Medicine, Hanyang University, Guri Hospital, Guri (Korea, Republic of); Lee, Young Jun; Lee, SAeung Ro [Dept. of Radiology, College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2013-04-15

    Most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae. Subglandular meningiomas located under the pituitary gland are extremely rare. Intrasellar meningiomas in the subdiaphragmatic and subglandular region probably originate from the dura in the sellar floor. We report a case of a subglandular meningioma along with a review of the literature.

  1. Magnetic resonance imaging of xanthomatous meningioma

    International Nuclear Information System (INIS)

    Katayama, Y.; Tsubokawa, T.; Tanaka, A.; Koshinaga, M.; Nemoto, N.

    1993-01-01

    A case of meningioma with extensive xanthomatous metaplasia occurring in the left frontal convexity of a 37-year-old woman is reported. The tumour was demonstrated as a hypodense mass with minimal enhancement on CT. Our findings suggest that magnetic resonance imaging may provide a clue to the diagnosis of meningiomas with extensive xanthomatous metaplasia when CT is less specific. (orig.)

  2. Peritumoral brain edema in angiomatous supratentorial meningiomas

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Sørensen, Lars Peter; Dyrbye, Henrik

    2013-01-01

    The aim of this work was to study the vascular endothelial growth factor A (VEGF-A) pathway and peritumoral brain edema (PTBE) through comparison of non-angiomatous and angiomatous meningiomas. Meningiomas are common intracranial tumors, which often have PTBE. VEGF-A is an integral part of PTBE...

  3. Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

    Science.gov (United States)

    Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

    2017-11-01

    Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

  4. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

    Science.gov (United States)

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  5. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

    Directory of Open Access Journals (Sweden)

    Gianfranco ePittari

    2015-05-01

    Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  6. Relationship between regulatory and type 1 T cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Horiuchi, Yutaka; Tominaga, Makiko; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Nakajima, Yuko; Kuwabara, Masato; Yukawa, Masayoshi

    2010-03-01

    Recent data suggest a decreased prevalence of IFN-gamma-producing T lymphocytes (Type 1 T cells) in tumor-bearing hosts. Moreover, it has been reported that Treg have a strong impact on the activation and proliferation of CD4 (+) and CD8 (+) lymphocytes; however, no previous reports have described the relationship between Treg and the progression of tumor, or Type 1 T cell populations in dogs with malignant tumor. In this study, the percentage of Treg, Th1, and Tc1 in the peripheral blood of dogs with oral malignant melanoma and healthy dogs was measured and compared. Although the percentages of Th1 and Tc1 in dogs with oral malignant melanoma were less than those in healthy dogs (Th1: P dogs with oral malignant melanoma. In dogs, Treg appears to suppress Type 1 immunity, which may be responsible for anti-tumor responses.

  7. Sentinel lymphoscintigraphy in malignant melanoma and Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Dekova, M.; Kirov, V.; Donchev, M.; Slavova, M.; Tsarovska, T.

    2013-01-01

    Full text:Introduction: The concept of a biopsy of the sentinel lymph node (SLN) was developed by Mortan in 1992, using blue dye. In 1993. Alex and Krag identified SLN with radiocolloid and gamma probe in case of malignant melanoma. Today, both methods are applied separately or together with a success rate above 90% and false negative rate of 5 %. Materials and Methods: The study includes 10 patients, 9 of whom have been diagnosed with malignant melanoma and 1 – with Merkel cancer. All patients were of a higher risk of lymphatic metastases without distinct clinical symptoms. Lymphoscintigraphy was performed with double-headed SPECT gamma camera Toshiba CGA 7200 UI. The visualized lymph nodes were projected and marked on the skin by a point radioactive source under monitoring. The marked lymph nodes were verified during the operation by staining and patent Blau then removed and studies histopathologically. Results: In all patients the Lymphoscintigraphy visualized SLN, which were surgically found just below the skin markers and removed. In the SLN of one patient a diffuse metastasis was found. In the SLN of nine patients no evidence for metastatic process was found. Conclusion: The technique of marking the SLN with subsequent biopsy is a minimally invasive method for the detection of lymph node metastases in patients with malignant melanoma and Merkel carcinoma with a high degree of reliability of the results

  8. Parapharyngeal meningioma extending from the intracranial space

    International Nuclear Information System (INIS)

    Uchibori, M.; Odake, G.; Ueda, S.; Yasuda, N.; Hisa, I.

    1990-01-01

    A 50-year old woman with a giant parapharyngeal meningioma extending from the intracranial cavity was admitted to our hospital. The parapharyngeal tumor was biopsied using the transoral approach, and a histological section diagnosis suggested meningioma. Thereafter, further examination by magnetic resonance images (MRI) and contrast enhanced CT scans revealed a diffuse meningioma en plaque in the posterior fossa. Invasion extended from the clival dura to the right sigmoid sinus. The extracranial extension of a meningioma is very rare but a few cases have been reported. In almost all of the reported cases, a large intracranial meningioma was simultaneously or previously verified by CT scans. Our case was special in that the intracranial mass was not voluminous but showed en plaque extension, and also because the pathway of the extracranial extension through the jugular foramen was clearly visualized by CT and MRI. Obliteration and invasion of the right sigmoid sinus and the internal jugular vein by tumor were also demonstrated. (orig.)

  9. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    International Nuclear Information System (INIS)

    Yamagishi, Naoko; Teshima-Kondo, Shigetada; Masuda, Kiyoshi; Nishida, Kensei; Kuwano, Yuki; Dang, Duyen T; Dang, Long H; Nikawa, Takeshi; Rokutan, Kazuhito

    2013-01-01

    Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF

  10. The split personality of NKT cells in malignancy, autoimmune and allergic disorders

    Science.gov (United States)

    Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H

    2011-01-01

    NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy. PMID:21995570

  11. The split personality of NKT cells in malignancy, autoimmune and allergic disorders.

    Science.gov (United States)

    Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H

    2011-10-01

    NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy.

  12. Malignant granular cell tumour on the thoracic wall: a case report and literature review

    International Nuclear Information System (INIS)

    Perez, E.; Esteban, R.; Alcalaya, R.; Albors, L.; Jimenez, C.; Ovelar, Y.; Cantera, M.G.

    1993-01-01

    A case is presented of a malignant granular cell tumour in a 52-year-old patient the initial location of which was the thoracic wall. After the tumour's removal there was recurrence in the lymph nodes, retroperitoneum, bone, lung and orbits. The important features of this case are its extraordinary rarity, the unusual location in the thoracic wall, and the tumour's infrequent malignancy. The radiological and histological findings are discussed, and the literature on the subject is reviewed. (orig.)

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

    International Nuclear Information System (INIS)

    Ferraro, Daniel J; Zoberi, Imran; Simpson, Joseph R; Jaboin, Jerry J; Funk, Ryan K; Blackett, John William; Ju, Michelle R; DeWees, Todd A; Chicoine, Michael R; Dowling, Joshua L; Rich, Keith M; Drzymala, Robert E

    2014-01-01

    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. 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. 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. Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly

  14. Metastatic meningioma presenting as cancer of unknown primary

    Directory of Open Access Journals (Sweden)

    Vinay Gupta

    2013-12-01

    Full Text Available We describe a case of anaplastic meningioma presenting in an extracranial osseous location, initially diagnosed as cancer of unknown primary. Although anaplastic meningioma comprise 3% of all meningiomas, this subtype is more likely to be associated with metastases. The increased degree of dedifferentiation in anaplastic meningioma makes diagnosis difficult, especially if characteristic imaging findings of meningioma are not identified. Adequate tissue for diagnostic purposes and appropriate imaging studies may help in establishing a definitive diagnosis.

  15. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    Science.gov (United States)

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  16. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin

    Directory of Open Access Journals (Sweden)

    Yiwen Jiang

    2017-01-01

    Full Text Available The identity of the glioblastoma (GBM cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES or 2,′3′-cyclic nucleotide 3′-phosphodiesterase (mGC3CNP-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

  18. A role for Lin28 in primordial germ cell development and germ cell malignancy

    Science.gov (United States)

    West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Sero, Julia E.; Zhu, Hao; Perez-Atayde, Antonio; Frazier, A. Lindsay; Surani, M. Azim; Daley, George Q.

    2009-01-01

    The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwarts efforts to investigate molecular mechanisms of germ cell specification. Stella marks the minute founder population of the germ lineage1,2. Here we differentiate mouse embryonic stem cells (ESCs) carrying a Stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3-6, is essential for proper PGC development. We further show that Blimp1, a let-7 target and a master regulator of PGC specification7-9, can rescue the effect of Lin28-deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Over-expression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimeric embryos, and is associated with human germ cell tumours. The differentiation of putative PGCs from ESCs in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ cell development and malignancy. PMID:19578360

  19. Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Baixin Ye

    2017-01-01

    Full Text Available A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR T-cell therapy and engineered T-cell receptor (TCR T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells. In clinic trials, CAR-T-cell- and TCR-T-cell-based adoptive immunotherapy have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. The purpose of the present review is to (1 provide a detailed overview of the multiple mechanisms for immune evasion related with T-cell-based therapies; (2 provide a current summary of the applications of CAR-T-cell- as well as neoantigen-specific TCR-T-cell-based adoptive immunotherapy and routes taken to overcome immune evasion; and (3 evaluate alternative approaches targeting immune evasion via optimization of CAR-T and TCR-T-cell immunotherapies.

  20. Receptores de progesterona en meningioma.

    Directory of Open Access Journals (Sweden)

    Herminio Ojeda Di Ninno

    1995-04-01

    Full Text Available Objetivo: Determinar la presencia de los receptores de progesterona en meningiomas y su frecuencia mediante la inmunohistoquímica. Material y Métodos: Se analizaron 24 muestras provenientes de pacientes intervenidos quirúrgicamente en el Instituto Nacional de Enfermedades Neoplásicas entre los años 1990 y 1992 con diagnóstico anatomopatológico de meningioma. La determinación de los receptores se hizo mediante una técnica de inmunohistoquímica rápida que permite el estudio de tejidos fijados previamente en parafina. Resultados: De los 24 casos estudiados, nueve resultaron ser positivos en la determinación de receptores de progesterona (37%. Se pudo observar un marcado predominio dentro del grupo femenino quienes constituyeron 8/9 casos positivos. Conclusiones: El empleo de esta reciente técnica de inmunohistoquímica aplicada a tejido de fijado en parafina, nos ha permitido confirmar la presencia de receptores de progesterona en meningiomas con una frecuencia elevada que creemos amerita un estudio más amplio de manera sistemática que incluya la intervención terapéutica mediante el uso de antiprogestágenos, como el Mifepristone o RU 486. De este estudio podrían beneficiarse no sólo pacientes operados recientemente sino aquellos que, intervenidos en el pasado sean detectados como portadores de receptores de progesterona mediante la aplicación de esta novedosa técnica (Rev Med Hered 1995; 6: 121-130.

  1. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Adachi, Nanao; Nimura, Yoshinori

    2004-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  2. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Nimura, Yoshinori; Kato, Masaki; Seki, Naohiko; Miyahara, Nobuyuki; Aoki, Mizuho; Shino, Yayoi; Furusawa, Yoshiya; Mizota, Atsushi

    2005-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  3. Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells.

    Science.gov (United States)

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L; Park, John K

    2008-07-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 micromol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects.

  4. Nitrosoureas Inhibit the Stathmin Mediated Migration and Invasion of Malignant Glioma Cells

    Science.gov (United States)

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L.; Park, John K.

    2008-01-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement related processes. Scratch-wound healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down regulation of cellular stathmin levels and in the absence and presence of sub-lethal nitrosourea (CCNU; [1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]) concentrations. We demonstrate that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 μM, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain and that nitrosoureas may have therapeutic benefits in addition to their anti-proliferative effects. PMID:18593927

  5. Higher positive identification of malignant CSF cells using the cytocentrifuge than the Suta chamber

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    Full Text Available ABSTRACT Objective To define how to best handle cerebrospinal fluid (CSF specimens to obtain the highest positivity rate for the diagnosis of malignancy, comparing two different methods of cell concentration, sedimentation and cytocentrifugation. Methods A retrospective analysis of 411 CSF reports. Results This is a descriptive comparative study. The positive identification of malignant CSF cells was higher using the centrifuge than that using the Suta chamber (27.8% vs. 19.0%, respectively; p = 0.038. Centrifuge positively identified higher numbers of malignant cells in samples with a normal concentration of white blood cells (WBCs (< 5 cells/mm3 and with more than 200 cells/mm3, although this was not statistically significant. There was no lymphocyte loss using either method. Conclusions Cytocentrifugation positively identified a greater number of malignant cells in the CSF than cytosedimentation with the Suta chamber. However, there was no difference between the methods when the WBC counts were within the normal range.

  6. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    Holte, H.; Kvaloey, S.O.; Engan, T.

    1996-01-01

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

  7. MRI findings of intracranial cystic meningiomas

    International Nuclear Information System (INIS)

    Zhang, D.; Hu, L.-B.; Zhen, J.W.; Zou, L.-G.; Feng, X.-Y.; Wang, W.-X.; Wen, L.

    2009-01-01

    Aim: To report the magnetic resonance imaging (MRI) features of intracranial cystic meningiomas and compare these features in intra- and peritumoural cyst groups. Materials and methods: Fourteen cases of peritumoural cystic meningiomas were compared with 18 cases of intratumoural cystic meningiomas. All patients were examined using non-enhanced and contrast-enhanced MRI. Tumour location, tumour size, signal intensity, enhancement characteristics, and cystic changes were assessed. The MRI features were compared between the intra- and peritumoural cyst groups. Results: Most cystic meningiomas comprised two or more cysts. The solid parts of the tumours showed moderate or marked enhancement after the injection of contrast material. An enhanced cyst wall was found in six out of 14 cases in the peritumoural cyst group, but not in the intratumoural cyst group. Peritumoural cystic meningiomas were predominately located in the cerebral falx, whereas the intratumoural cystic meningiomas were predominantly found in frontal convexity (X 2 = 7.434, p = 0.024). The cysts were larger in the peritumoural cyst group than in the intratumoural cyst group (t = 5.274, p = 0.0258). Peritumoural oedema was more commonly found in the intratumoural cyst group (X 2 = 6.863, p = 0.008). Cystic meningiomas with solid parts located inside the cyst are reported for the first time. Conclusion: Cystic meningiomas, although uncommon, should be differentiated from other cystic intracranial lesions. Peri- and intratumoural cystic meningiomas have distinct MRI features. The present study provides the first report of two lesions with solid parts located inside the cyst, as well as one lesion with a calcified solid nodule and haemorrhage within the cyst.

  8. Differentiation of Human Malignant Melanoma Cells that Escape Apoptosis After Treatment with 9-Nitrocamptothecin In Vitro

    Directory of Open Access Journals (Sweden)

    Panayotis Pantazis

    1999-08-01

    Full Text Available After in-vitro exposure to 0.05 μmol/L 9-nitrocamptothecin (9NC for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1 B cells die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G2 exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G1-arrested, but downregulated in density G1-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells.

  9. ATM suppresses SATB1-induced malignant progression in breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ellen Ordinario

    Full Text Available SATB1 drives metastasis when expressed in breast tumor cells by radically reprogramming gene expression. Here, we show that SATB1 also has an oncogenic activity to transform certain non-malignant breast epithelial cell lines. We studied the non-malignant MCF10A cell line, which is used widely in the literature. We obtained aliquots from two different sources (here we refer to them as MCF10A-1 and MCF10A-2, but found them to be surprisingly dissimilar in their responses to oncogenic activity of SATB1. Ectopic expression of SATB1 in MCF10A-1 induced tumor-like morphology in three-dimensional cultures, led to tumor formation in immunocompromised mice, and when injected into tail veins, led to lung metastasis. The number of metastases correlated positively with the level of SATB1 expression. In contrast, SATB1 expression in MCF10A-2 did not lead to any of these outcomes. Yet DNA copy-number analysis revealed that MCF10A-1 is indistinguishable genetically from MCF10A-2. However, gene expression profiling analysis revealed that these cell lines have significantly divergent signatures for the expression of genes involved in oncogenesis, including cell cycle regulation and signal transduction. Above all, the early DNA damage-response kinase, ATM, was greatly reduced in MCF10A-1 cells compared to MCF10A-2 cells. We found the reason for reduction to be phenotypic drift due to long-term cultivation of MCF10A. ATM knockdown in MCF10A-2 and two other non-malignant breast epithelial cell lines, 184A1 and 184B4, enabled SATB1 to induce malignant phenotypes similar to that observed for MCF10A-1. These data indicate a novel role for ATM as a suppressor of SATB1-induced malignancy in breast epithelial cells, but also raise a cautionary note that phenotypic drift could lead to dramatically different functional outcomes.

  10. Clinical diagnosis and treatment of olfactory meningioma

    International Nuclear Information System (INIS)

    Li Xiangdong; Wang Zhong; Zhang Shiming; Zhu Fengqing; Zhou Dai; Hui Guozhen

    2005-01-01

    Objective: To analyze the clinical diagnosis and treatment of olfactory meningioma. Methods: In this group 17 olfactory meningiomas were operated, and the clinical presentations and the surgery results were obtained. Results: The symptoms of psychiatrical disorder, visual disturbances and eclipse at presentation was higher. In 16 cases the grade of resection was Simpson II, 1 case Simpson III, most of the cases had a good recovery. Conclusion: Attention should be paid to the early symptom at presentation such as psychiatrical disorder to obtain an early diagnosis. Microsurgery is useful in the treatment of olfactory meningioma. (authors)

  11. THE STUDY OF MECHANISMS OF PHOTOINDUCED APOPTOSIS IN THE SKIN MALIGNANT MELANOMA CELL MODEL

    Directory of Open Access Journals (Sweden)

    M. L. Gelfond

    2016-01-01

    Full Text Available The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2 induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

  12. Malignant mesothelioma

    OpenAIRE

    Parker Robert J; Moore Alastair J; Wiggins John

    2008-01-01

    Abstract 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 featu...

  13. Characterization of membrane lipid fluidity in human embryo cells malignantly transfer med post 238Pu α irradiation

    International Nuclear Information System (INIS)

    Qi Zirong; Sun Ling; Liu Guolian; Shen Zhiyuan

    1992-01-01

    The membrane lipid fluidity of malignantly transformed human embryo cells following 238 Pu α particlce irradiation in vitro has been studied. The results indicate that the ontogenesis depends on irradiation dose (Gy) and the membrane lipid fluidity in malignantly transformed cells is higher than that in normal embryo cells. With the microviscosity (η) of cells plotted against the cell counts, the correlation coefficient (γ) is calculated to be between 0.9936 and 0.9999. Since the malignant transformation of irradiated embryo cells is manifested early on cell membrane lipid, the fluidity of membrane lipid can be used as an oncologic marker

  14. Ewing's sarcoma mimicking a meningioma in radiological findings: a case report

    International Nuclear Information System (INIS)

    Kwon, Hee Jin; Choi, Sun Seob

    2007-01-01

    Ewing's sarcoma is an uncommon primary bone tumor. Primary Ewing's sarcoma of the cranium is extremely rare and constitutes only 1% of all Ewing's sarcoma cases. Usually, primary Ewing's sarcoma of the carnium manifests as an expansile osteolytic malignant bone tumor with or without intracranial extension. We report here the radiological findings of a case of Ewing's sarcoma mimicking a meningioma in an 18-year-old man

  15. Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Kunio; Kamezaki, Takao; Shibata, Yasushi; Tsunoda, Takashi; Meguro, Kotoo; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    1995-01-01

    The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors. (author).

  16. Lymphocyte interactions with the extracellular matrix of malignant cells in vítro: A morphological and immunocytochemical study

    OpenAIRE

    Logothetou-Rella, H.

    1993-01-01

    The interactions of lymphocytes with the glycosaminoglycans-protease-membrane extracellular matrix, produced by mixed cell cultures of normal with malignant cell clones, were examined. Pre-activated and activated heterologous peripheral lymphocytes were used. Co-cultures of activated lymphocytes with al1 cell types used, formed identical cell nodules. Histology of cell nodules showed that activated lymphocytes were cytolytic to pure normal or malignant cell clo...

  17. Downregulation of the expression of HDGF attenuates malignant biological behaviors of hilar cholangiocarcinoma cells.

    Science.gov (United States)

    Liu, Yanfeng; Sun, Jingxian; Yang, Guangyun; Liu, Zhaojian; Guo, Sen; Zhao, Rui; Xu, Kesen; Wu, Xiaopeng; Zhang, Zhaoyang

    2015-09-01

    Hepatoma-derived growth factor (HDGF) has been reported to be a potential predictive and prognostic marker for several types of cancer and important in malignant biological behaviors. However, its role in human hilar cholangiocarcinoma remains to be elucidated. Our previous study demonstrated that high expression levels of HDGF in hilar cholangiocarcinoma tissues correlates with tumor progression and patient outcome. The present study aimed to elucidate the detailed functions of the HDGF protein. This was performed by downregulating the protein expression of HDGF in the FRH0201 hilar cholangiocarcinoma cell line by RNA interference (RNAi) in vitro, and revealed that downregulation of the HDGF protein significantly inhibited the malignant biological behavior of the FRH0201 cells. In addition, further investigation revealed that downregulation of the protein expression of HDGF significantly decreased the secretion of vascular endothelial growth factor, which may be the mechanism partially responsible for the inhibition of malignant biological behaviors. These findings demonstrated that HDGF is important in promoting malignant biological behaviors, including proliferation, migration and invasion of hilar cholangiocarcinoma FRH0201 cells. Inhibition of the expression of HDGF downregulated the malignant biological behaviors, suggesting that downregulation of the protein expression of HDGF by RNAi may be a novel therapeutic approach to inhibit the progression of hilar cholangiocarcinoma.

  18. TCR Translocations at the Normal-malignant T Cell Interface

    NARCIS (Netherlands)

    N.S.D. Larmonie (Nicole)

    2013-01-01

    textabstractHematopoiesis is the process leading to production and maturation of peripheral blood cells. All blood cells are derived from hematopoietic stem cells (HSCs) which reside in hematopoietic organs. In mammals, the site of hematopoiesis changes during development, which is sequentially

  19. Tumor initiating cells in malignant gliomas: biology and implications for therapy.

    Science.gov (United States)

    Hadjipanayis, Costas G; Van Meir, Erwin G

    2009-04-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

  20. Studies of the endothelial origin of cells in systemic angioendotheliomatosis and other vascular lesions of the brain and meninges using ulex europaeus lectin stains.

    Science.gov (United States)

    Schelper, R L; Olson, S P; Carroll, T J; Hart, M N; Witters, E

    1986-01-01

    Ulex europaeus agglutinin I (UEA-I) is a plant lectin which binds specifically to alpha-L-fucose moieties on the surface glycoproteins of human endothelial cells. The binding is completely inhibited by preincubation of the lectin with fucose. UEA-I can be conjugated directly to fluorescein or peroxidase and can be used to stain endothelium of paraffin embedded tissues. UEA-I staining was evaluated on normal and infarcted brain, systemic angioendotheliomatosis, metastatic epidural angiosarcoma, hemangioendothelioma, hemangioblastoma, angioblastic meningioma of both the hemangioblastic and hemangiopericytic types, and vascular meningioma. The endothelium, but not neuropil of normal and infarcted brain was positive for UEA-I. The tumor cells of hemangioendothelioma and angiosarcoma also stained. However, no staining was seen in malignant intravascular cells of angioendotheliomatosis, the stromal cells of hemangioblastoma, or pericytes of angioblastic meningioma. It is concluded that the malignant cells in angioendotheliomatosis, the stromal cells of hemangioblastoma and the pericytes of angioblastic meningioma do not produce surface glycoproteins characteristic of endothelial cells.

  1. Nitrosoureas Inhibit the Stathmin Mediated Migration and Invasion of Malignant Glioma Cells

    OpenAIRE

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L.; Park, John K.

    2008-01-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify...

  2. Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells

    International Nuclear Information System (INIS)

    Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon; Lim, Eun-Jung; An, Sungkwan; Park, Myung-Jin; Hyun, Jin-Won; Suh, Yongjoon; Kim, Min-Jung; Lee, Su-Jae

    2011-01-01

    A subpopulation of cancer cells with stem cell properties is responsible for tumor maintenance and progression, and may contribute to resistance to anticancer treatments. Thus, compounds that target cancer stem-like cells could be usefully applied to destroy cancer. In this study, we investigated the effect of Eckol, a phlorotannin compound, on stemness and malignancies in glioma stem-like cells. To determine whether Eckol targets glioma stem-like cells, we examined whether Eckol treatment could change the expression levels of glioma stem-like cell markers and self-renewal-related proteins as well as the sphere forming ability, and the sensitivity to anticancer treatments. Alterations in the malignant properties of sphere-derived cells by Eckol were also investigated by soft-agar colony forming assay, by xenograft assay in nude mice, and by cell invasion assay. Treatment of sphere-forming glioma cells with Eckol effectively decreased the sphere formation as well as the CD133 + cell population. Eckol treatment suppressed expression of the glioma stem-like cell markers and the self-renewal-related proteins without cell death. Moreover, treatment of glioma stem-like cells with Eckol significantly attenuated anchorage-independent growth on soft agar and tumor formation in xenograft mice. Importantly, Eckol treatment effectively reduced the resistance of glioma stem-like cells to ionizing radiation and temozolomide. Treatment of glioma stem-like cells with Eckol markedly blocked both phosphoinositide 3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. These results indicate that the natural phlorotannin Eckol suppresses stemness and malignancies in glioma stem-like cells, and thereby makes glioma stem-like cells more sensitive to anticancer treatments, providing novel therapeutic strategies targeting specifically cancer stem-like cells.

  3. Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma.

    Science.gov (United States)

    A G, Deepa; Janardanan-Nair, Bindu; B R, Varun

    2017-12-01

    Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation. Key words: Immunohistochemistry, Oral leukoplakia, Oral submucous fibrosis, Podoplanin, Squamous cell carcinoma.

  4. Mucorales-Specific T Cells in Patients with Hematologic Malignancies

    OpenAIRE

    Potenza, L; Vallerini, D; Barozzi, P; Riva, G; Gilioli, A; Forghieri, F; Candoni, A; Cesaro, S; Quadrelli, C; Maertens, J; Rossi, G; Morselli, M; Codeluppi, M; Mussini, C; Colaci, E

    2016-01-01

    Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Method...

  5. Meningiomas in 2009: controversies and future challenges.

    Science.gov (United States)

    Campbell, Belinda A; Jhamb, Ashu; Maguire, John A; Toyota, Brian; Ma, Roy

    2009-02-01

    Meningiomas are the most common intracranial primary neoplasm in adults. Over recent years, interest in this clinically diverse group of tumors has intensified, bringing new questions and challenges to the fore, particularly in the fields of epidemiology, radiology, pathology, genetics, and treatment. Interest in modern meningioma research has been stimulated by the high tumor prevalence and the advances in technology. The incidence of meningiomas is climbing, and may indicate increased exposure to environmental risk factors or more sensitive diagnostic modalities. Technological advances have dramatically improved radiologic imaging and radiotherapy treatments, and further refinements are under investigation. Furthermore, the current era of tumor genetics and molecular biology is challenging translational researchers to discover new, targeted, therapeutic agents. This review is an update on the recent advances in the understanding of meningiomas and their management, and highlights pertinent research questions to be addressed in the future.

  6. Prostate carcinoma mimicking a sphenoid wing meningioma

    Directory of Open Access Journals (Sweden)

    Lucas H. Bradley

    2015-01-01

    Conclusion: We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead.

  7. Atypical imaging appearances of intracranial meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    O' Leary, S. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Adams, W.M. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Parrish, R.W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Mukonoweshuro, W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom)]. E-mail: William.mukonoweshuro@phnt.swest.nhs.uk

    2007-01-15

    Meningiomas are the commonest primary, non-glial intracranial tumours. The diagnosis is often correctly predicted from characteristic imaging appearances. This paper presents some examples of atypical imaging appearances that may cause diagnostic confusion.

  8. A case of primary extracranial meningioma of the forearm with bone invasion

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Hideki [Self-Defense Force Fuji Hospital, Division of Orthopaedic Surgery, Oyama-cho, Sunto-gun, Shizuoka (Japan); Takahashi, Mitsuru; Takagi, Tatsuya; Katagiri, Hirohisa [Shizuoka Cancer Center Hospital, Division of Orthopaedic Oncology, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Ito, Ichiro [Shizuoka Cancer Center Hospital, Division of Pathology, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Ishida, Tsuyoshi [Kohnodai Hospital, Department of Pathology and Laboratory Medicine, National Center of Neurology and Psychiatry, Ichikawa, Chiba (Japan)

    2007-06-15

    We report here a rare case of primary extracranial meningioma in a 73-year-old woman with an asymptomatic mass located in the left distal-dorsal forearm. MRI revealed the lesion to be poorly circumscribed and unclear, with iso-signal intensity to muscle on T1 and with a relatively high signal intensity on T2-weighted imaging. The histopathology of the specimen from incision biopsy was typical of meningioma, showing bland spindle cell proliferation with a whorling pattern. Immunohistochemically, the tumor cells were positive for epithelial membrane antigen and vimentin, and negative for S-100 expression. (orig.)

  9. Introduction: surgical management of skull base meningiomas.

    Science.gov (United States)

    Zada, Gabriel; Başkaya, Mustafa K; Shah, Mitesh V

    2017-10-01

    Meningiomas represent the most common primary intracranial neoplasm treated by neurosurgeons. Although multimodal treatment of meningiomas includes surgery, radiation-based treatments, and occasionally medical therapy, surgery remains the mainstay of treatment for most symptomatic meningiomas. Because of the intricate relationship of the dura mater and arachnoid mater with the central nervous system and cranial nerves, meningiomas can arise anywhere along the skull base or convexities, and occasionally even within the ventricular system, thereby mandating a catalog of surgical approaches that neurosurgeons may employ to individualize treatment for patients. Skull base meningiomas represent some of the most challenging pathology encountered by neurosurgeons, on account of their depth, invasion, vascularity, texture/consistency, and their relationship to bony anatomy, cranial nerves, and blood vessels. Resection of complex skull base meningiomas often mandates adequate bony removal to achieve sufficient exposure of the tumor and surrounding region, in order to minimize brain retraction and optimally identify, protect, control, and manipulate sensitive neurovascular structures. A variety of traditional skull base approaches has evolved to address complex skull base tumors, of which meningiomas are considered the paragon in terms of both complexity and frequency. In this supplemental video issue of Neurosurgical Focus, contributing authors from around the world provide instructional narratives demonstrating resection of a variety of skull base meningiomas arising from traditionally challenging origins, including the clinoid processes, tuberculum sellae, dorsum sellae, petroclival region, falco-tentorial region, cerebellopontine angle, and foramen magnum. In addition, two cases of extended endoscopic endonasal approaches for tuberculum sellae and dorsum sellae meningiomas are presented, representing the latest evolution in accessing the skull base for selected tumors

  10. Lethal effect of glucose load on malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Kozubek, S.

    1987-01-01

    Ehrlich ascites tumor (EAT) cells were treated with glucose load under anoxic conditions (for 15 or 60 min) and/or with γ radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells using glucose load in anoxia and γ radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. (author). 5 figs., 2 tabs., 12 refs

  11. Intraventricular trigonal meningioma: Neuronavigation? No, thanks!

    OpenAIRE

    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...

  12. Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

    Science.gov (United States)

    Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

    2016-09-01

    According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

  13. Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms.

    Science.gov (United States)

    Wang, J; Ishii, T; Zhang, W; Sozer, S; Dai, Y; Mascarenhas, J; Najfeld, V; Zhao, Z J; Hoffman, R; Wisch, N; Xu, M

    2009-09-01

    The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F). Peripheral blood (PB) CD34(+) cells from patients with polycythemia vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer mast cells (MCs) than normal PB CD34(+) cells. The numbers of MC progenitors assayed from MPN CD34(+) cells were, however, similar to that assayed from normal CD34(+) cells. A higher percentage of the cultured MPN MCs expressed FcvarepsilonRIalpha, CD63 and CD69 than normal MCs, suggesting that cultured MPN MCs are associated with an increased state of MC activation. Further analysis showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality markers, we showed that the malignant process involved MPN MCs. JAK2V617F-positive MC colonies were assayable from the PB CD34(+) cells of each of the 17 JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2 inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells, indicating that malignant MC progenitor cells are a potential cellular target for such JAK2 inhibitor-directed therapy.

  14. An Epidemiologic study of Oral and Pharyngeal Nonsquamous Cell Malignant Tumors in Kerman province, Iran

    Directory of Open Access Journals (Sweden)

    MR. Zarei

    2007-03-01

    Full Text Available Objective: The aim of the present study was to estimate crude and age-standardized incidence rates for oral and pharyngeal nonsquamous cell malignant tumors in Kerman province over a period of 11 years.Materials and Methods: The data used in this retrospective population-based study were extracted from the records registered in all pathology centers of Kerman province from 1991 to 2001. All confirmed cases of oral and pharyngeal nonsquamous cell malignant tumors were included in the study. The crude and age-standardized incidence rates per 1 million populations were calculated based on the 1996 census data and the population growth rate.Results: The total number of new nonsquamous cell cancers was 61, representing 18.2% of all oral and pharyngeal cancers in Kerman province. The average annual ageadjusted incidence rate per 1,000,000 population was 3.45 for both oral and pharyngeal tumors. The temporal variations in the annual incidence of oral and pharyngeal nonsquamous cell cancers was statistically significant (p=0.015. The most common types of nonsquamous cell malignant tumors in the oral cavity and pharynx were minor salivary tumors and lymphomas, respectively. The age-adjusted incidence was 0.74 formalignant salivary gland tumors, 0.66 for malignant melanomas, 0.4 for different types of sarcomas, and 1.65 for lymphomas.Conclusion: It can be concluded that the incidence rate and other features of nonsquamous cell malignant tumors of the oral cavity and pharynx in residents of Kerman province are similar to those reported by other investigators.

  15. miR-155 as a Biomarker in B-Cell Malignancies

    Directory of Open Access Journals (Sweden)

    Hanne Due

    2016-01-01

    Full Text Available MicroRNAs have the potential to be useful biomarkers in the development of individualized treatment since they are easy to detect, are relatively stable during sample handling, and are important determinants of cellular processes controlling pathogenesis, progression, and response to treatment of several types of cancers including B-cell malignancies. miR-155 is an oncomiR with a crucial role in tumor initiation and development of several B-cell malignancies. The present review elucidates the potential of miR-155 as a diagnostic, prognostic, or predictive biomarker in B-cell malignancies using a systematic search strategy to identify relevant literature. miR-155 was upregulated in several malignancies compared to nonmalignant controls and overexpression of miR-155 was further associated with poor prognosis. Elevated expression of miR-155 shows potential as a diagnostic and prognostic biomarker in diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Additionally, in vitro and in vivo studies suggest miR-155 as an efficient therapeutic target, supporting its oncogenic function. The use of inhibiting anti-miR structures indicates promising potential as novel anticancer therapeutics. Reports from 53 studies prove that miR-155 has the potential to be a molecular tool in personalized medicine.

  16. [Malignant T-cell lymphoma with osteomyelitis-like bone infiltration].

    Science.gov (United States)

    Mittelmeier, H; Schmitt, O

    1980-01-01

    After a short review on the late literature, existing about various forms of acute lymphoblastic leucemias, it is reported on a rare case of malignant T-cell-Lymphoma with ostemyelitis-like, painfull bone infiltration. The clinical symptoms, as well as differential-diagnostic criterias to other leucemias are described.

  17. Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation

    International Nuclear Information System (INIS)

    Khalil, A.A.; Jameson, M.J.; Broaddus, W.C.; Lin, P.S.; Chung, T.D.

    2013-01-01

    It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, extracellular regulated kinase (ERK), and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR tyr992 , AKT ser473 , and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways. (author)

  18. Malignant Granular Cell Tumor of the Back: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Laura Stone McGuire

    2014-01-01

    Full Text Available Malignant granular cell tumors are rare, intensely aggressive entities. This paper presents a case of a large rapidly recurrent malignant granular cell tumor with regional and distal metastases on the back of a 54-year-old Cuban man. The primary tumor recurred within six months of the original wide local excision and with satellite lesions apparent at twelve months, and the mass was diagnosed using the histological criteria established by Fanburg-Smith et al. for malignant granular cell tumors. By fifteen months, right axillary lymphadenopathy, multiple satellite lesions, pulmonary nodules, and distant metastasis in the right thigh were present. At sixteen months, wide local excision of recurrent mass and local satellite masses along with right axillary dissection and placement of Integra with subsequent split-thickness skin graft were performed by surgical oncology and plastic surgery teams. The surgical specimen measured 32.0 × 13.5 × 5.5 cm, containing multiple homogeneous masses with the largest mass 22.0 × 9.0 × 4.6 cm. Following surgery, patient was started on Pazopanib 800 mg/day based on phase III randomized trial data in the treatment of soft tissue sarcomas showing this as a potential novel therapy for malignant granular cell tumors.

  19. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome pr...

  20. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques

    2013-01-01

    Ovarian tissue cryopreservation and transplantation is a real option to preserve and restore fertility in young cancer patients. However, there is a concern regarding the possible presence of malignant cells in the ovarian tissue, which could lead to recurrence of the primary disease after reimpl...

  1. Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

    Science.gov (United States)

    Kolson Kokohaare, Eva; Riva, Francesco M G; Bernstein, Jonathan M; Miah, Aisha B; Thway, Khin

    2018-04-01

    We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

  2. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.......A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  3. Aldehyde dehydrogenase (ALDH activity does not select for cells with enhanced aggressive properties in malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Lina Prasmickaite

    Full Text Available BACKGROUND: Malignant melanoma is an exceptionally aggressive, drug-resistant and heterogeneous cancer. Recently it has been shown that melanoma cells with high clonogenic and tumourigenic abilities are common, but markers distinguishing such cells from cells lacking these abilities have not been identified. There is therefore no definite evidence that an exclusive cell subpopulation, i.e. cancer stem cells (CSC, exists in malignant melanoma. Rather, it is suggested that multiple cell populations are implicated in initiation and progression of the disease, making it of importance to identify subpopulations with elevated aggressive properties. METHODS AND FINDINGS: In several other cancer forms, Aldehyde Dehydrogenase (ALDH, which plays a role in stem cell biology and resistance, is a valuable functional marker for identification of cells that show enhanced aggressiveness and drug-resistance. Furthermore, the presence of ALDH(+ cells is linked to poor clinical prognosis in these cancers. By analyzing cell cultures, xenografts and patient biopsies, we showed that aggressive melanoma harboured a large, distinguishable ALDH(+ subpopulation. In vivo, ALDH(+ cells gave rise to ALDH(- cells, while the opposite conversion was rare, indicating a higher abilities of ALDH(+ cells to reestablish tumour heterogeneity with respect to the ALDH phenotype. However, both ALDH(+ and ALDH(- cells demonstrated similarly high abilities for clone formation in vitro and tumour initiation in vivo. Furthermore, both subpopulations showed similar sensitivity to the anti-melanoma drugs, dacarbazine and lexatumumab. CONCLUSIONS: These findings suggest that ALDH does not distinguish tumour-initiating and/or therapy-resistant cells, implying that the ALDH phenotype is not associated with more-aggressive subpopulations in malignant melanoma, and arguing against ALDH as a "universal" marker. Besides, it was shown that the ability to reestablish tumour heterogeneity is not

  4. Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies

    National Research Council Canada - National Science Library

    Huang, Shuang

    2004-01-01

    .... Our proposal is designed to develop an endothelial cell-targeted adenoviral vector and to use the targeted vector to express high levels of anticancer therapeutic genes in the sites of angiogenenic...

  5. Magnetic resonance imaging of intramedullary meningioma of the spinal cord: case report and review of the literature

    International Nuclear Information System (INIS)

    Covert, S.; Gandhi, D.; Goyal, M.; Woulfe, J.; Belanger, E.; Miller, W.; Modha, A.

    2003-01-01

    Intramedullary meningioma of the spinal cord is an extremely rare tumour. To the best of our knowledge, only 4 cases have been reported in the English literature, and limited information on imaging features is available. We present a further case and review the literature on this entity. Meningiomas are among the most common tumours that occur in the spinal canal, representing about 25% of all adult intraspinal tumours. They are commonly found in the thoracic segment of the spine and are most often intradural-extramedullary. Their location is explained by the way in which they develop. Meningiomas are derived from persistent arachnoid cell remnants in the spinal coverings, most commonly from arachnoid. They are usually adherent to, but do not arise from, dura. We present a case of intramedullary meningioma, a rare clinical entity, discuss the magnetic resonance imaging (MRI) findings and review the 4 cases that have been previously reported. (author)

  6. Type I collagen gene suppresses tumor growth and invasion of malignant human glioma cells

    Directory of Open Access Journals (Sweden)

    Miyata Teruo

    2007-06-01

    Full Text Available Abstract Background Invasion is a hallmark of a malignant tumor, such as a glioma, and the progression is followed by the interaction of tumor cells with an extracellular matrix (ECM. This study examined the role of type I collagen in the invasion of the malignant human glioma cell line T98G by the introduction of the human collagen type I α1 (HCOL1A1 gene. Results The cells overexpressing HCOL1A1 were in a cluster, whereas the control cells were scattered. Overexpression of HCOL1A1 significantly suppressed the motility and invasion of the tumor cells. The glioma cell growth was markedly inhibited in vitro and in vivo by the overexpression of HCOL1A1; in particular, tumorigenicity completely regressed in nude mice. Furthermore, the HCOL1A1 gene induced apoptosis in glioma cells. Conclusion These results indicate that HCOL1A1 have a suppressive biological function in glioma progression and that the introduction of HCOL1A1 provides the basis of a novel therapeutic approach for the treatment of malignant human glioma.

  7. Primary optic nerve sheath meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Jeremic, Branislav [International Atomic Energy Agency, Vienna (Austria); Pitz, Susanne (eds.) [University Eye Hospital, Mainz (Germany)

    2008-07-01

    Optic nerve sheath meningioma (ONSM) is a rare tumour. Cases are usually separated into primary ONSM, which arises either intraorbitally or, less commonly, intracanalicularly, and secondary ONSM, which arises intracranially and subsequently invades the optic canal and orbit. This is the first book to cover all important aspects of the diagnosis and treatment of primary ONSM. After a general introduction, individual chapters discuss the clinical presentation, clinical examination and diagnosis, imaging, and histology. Treatment options are then addressed in detail, with special emphasis on external beam radiation therapy, and in particular stereotactic fractionated radiation therapy. The latter has recently produced consistently good results and is now considered the emerging treatment of choice for the vast majority of patients with primary ONSM. This well-illustrated book will prove invaluable to all practitioners who encounter primary ONSM in their clinical work. (orig.)

  8. Second-harmonic generation as a DNA malignancy indicator of prostate glandular epithelial cells

    International Nuclear Information System (INIS)

    Zheng-Fei, Zhuang; Han-Ping, Liu; Zhou-Yi, Guo; Xiao-Yuan, Deng; Shuang-Mu, Zhuo; Bi-Ying, Yu

    2010-01-01

    This paper first demonstrates second-harmonic generation (SHG) in the intact cell nucleus, which acts as an optical indicator of DNA malignancy in prostate glandular epithelial cells. Within a scanning region of 2.7 μm×2.7 μm in cell nuclei, SHG signals produced from benign prostatic hyperplasia (BPH) and prostate carcinoma (PC) tissues (mouse model C57BL/6) have been investigated. Statistical analyses (t test) of a total of 405 measurements (204 nuclei from BPH and 201 nuclei from PC) show that SHG signals from BPH and PC have a distinct difference (p < 0.05), suggesting a potential optical method of revealing very early malignancy in prostate glandular epithelial cells based upon induced biochemical and/or biophysical modifications in DNA. (geophysics, astronomy and astrophysics)

  9. Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells

    Science.gov (United States)

    Vetro, Calogero; Romano, Alessandra; Ancora, Flavia; Coppolino, Francesco; Brundo, Maria V.; Raccuia, Salvatore A.; Puglisi, Fabrizio; Tibullo, Daniele; La Cava, Piera; Giallongo, Cesarina; Parrinello, Nunziatina L.

    2015-01-01

    The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells (MDSCs) have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of MDSCs in the settings of lymphoid malignancies. PMID:26052505

  10. PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling

    International Nuclear Information System (INIS)

    Yamada, Tamaki; Tsuda, Masumi; Ohba, Yusuke; Kawaguchi, Hideaki; Totsuka, Yasunori; Shindoh, Masanobu

    2008-01-01

    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

  11. Polycomb group proteins in hematopoietic stem cell aging and malignancies

    NARCIS (Netherlands)

    Klauke, Karin; de Haan, Gerald

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many

  12. Chimeric Antigen Receptor Therapy for B-cell Malignancies

    Directory of Open Access Journals (Sweden)

    David L Porter, Michael Kalos, Zhaohui Zheng, Bruce Levine, Carl June

    2011-01-01

    Full Text Available We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce rapid and potent anti-tumor activity in chemotherapy refractory CLL patients.

  13. Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies.

    Science.gov (United States)

    Gayko, Urte; Fung, Mann; Clow, Fong; Sun, Steven; Faust, Elizabeth; Price, Samiyeh; James, Danelle; Doyle, Margaret; Bari, Samina; Zhuang, Sen Hong

    2015-11-01

    Ibrutinib is a first-in-class oral covalent inhibitor of Bruton's tyrosine kinase that has demonstrated clinical benefit for many patients with B cell malignancies. Positive results in initial trials led the U.S. Food and Drug Administration to grant ibrutinib three breakthrough therapy designations for mantle cell lymphoma (MCL), del17p chronic lymphocytic leukemia (CLL), and Waldenström's macroglobulinemia (WM). Ibrutinib was approved for these three cancers within 14 months of the original U.S. approval. Additionally, ibrutinib is approved for patient subsets with MCL and/or CLL in >45 other countries. Via a unique mechanism of action, ibrutinib inhibits B cell signaling pathways that regulate the survival, proliferation, adhesion, and homing of cancerous cells. This marks a paradigm shift from the conventional cytotoxic chemotherapy approach to treating B cell malignancies. Ibrutinib continues to be evaluated across a range of B cell malignancies, either as single-agent therapy or in combination with other therapies, and continues to transform the lives of these patients. © 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  14. Dose-effect relationships for malignancy in cells with different genetic characteristics

    International Nuclear Information System (INIS)

    Chadwick, K.H.; Leenhouts, H.P.

    1978-01-01

    By combining the proposals that malignancy behaves as a recessive genetic character, that a somatic mutation is an important step in the development of cancer, and that radiation-induced DNA double-strand breaks are the critical lesions which may lead to cell death, mutation and chromosomal aberrations, considerations can be made and equations derived for the incidence of malignancy in cells having different genotypes. Equations are derived for diploid carrier cells and tetraploid carrier cells, and are compared with data in literature on cell transformation. It is shown that some differences in experimental results could be due to the different genetic character of the cells used. The theoretical considerations are extended to the population which is considered to be constituted of 'carriers' and 'non-carriers' of the recessive malignant genotype. The possible influence of radiation on 'non-carriers' is discussed as are the implications of the presence of two groups within the population for the estimation of risk to low doses of radiation. (author)

  15. Surgical Management of Olfactory Groove Meningiomas | El-Naggar ...

    African Journals Online (AJOL)

    Objective: To study the bifrontal approach to olfactory groove meningiomas ... in all patients was Grade I meningiomas (World Health Organization grading). ... Bifrontal approach offers excellent exposure, and when combined with modern ...

  16. Predictors of severe complications in intracranial meningioma surgery

    DEFF Research Database (Denmark)

    Bartek, Jiri; Sjåvik, Kristin; Förander, Petter

    2015-01-01

    OBJECTIVE: To investigate predictors of complications after intracranial meningioma resection using a standardized reporting system for adverse events. METHODS: A retrospective review was conducted in a Scandinavian population-based cohort of 979 adult operations for intracranial meningioma perfo...

  17. Effect of human cell malignancy on activity of DNA polymerase iota.

    Science.gov (United States)

    Kazakov, A A; Grishina, E E; Tarantul, V Z; Gening, L V

    2010-07-01

    An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase iota (Pol iota) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that activates homogeneous Pol iota preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn2+ the activity of Pol iota was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol iota activity was observed in the presence of either Mn2+ or Mg2+. Manganese ions activated Pol iota in both cases, though to a different extent. In the presence of Mn2+ the Pol iota activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol iota. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by

  18. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    Directory of Open Access Journals (Sweden)

    Sharma Kamal

    2008-12-01

    Full Text Available Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

  19. Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity.

    Directory of Open Access Journals (Sweden)

    King Yiu Lee

    Full Text Available Makorin-2 (MKRN2 is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively. Our results provided the first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels of MKRN2 were generally higher in primary leukemia samples compared with those in age-matched normal BM cells. In all leukemia subtypes, there was no significant correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+ cells had a significantly lower proliferation capacity and decreased levels of the early stem/progenitor subpopulation (CFU-GEMM compared with control cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis.

  20. Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

    International Nuclear Information System (INIS)

    Isom, H.C.; Mummaw, J.; Kreider, J.W.

    1983-01-01

    Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

  1. Management of pregnant female with meningioma for craniotomy

    Directory of Open Access Journals (Sweden)

    Sandeep Sahu

    2010-01-01

    Full Text Available Intracranial meningioma during pregnancy challenges the skill of obstetricians, neurosurgeons and neuroanesthesiologists in resection of the tumor and to secure delivery of the baby. Advances in fetal and maternal monitoring, neuroanesthesia, and microsurgical techniques allow safe neurosurgical management of these patients. Urgent neurosurgical intervention is reserved for the management of malignancies, active hydrocephalus, and benign brain tumors associated with signs of impending herniation or progressive neurological deficit. Particular attention is given to maintain stable maternal hemodynamics to avoid uterine hypo perfusion and fetal hypoxia intraoperatively. Therefore, the major challenge of neuroanesthesia during pregnancy is to provide an appropriate balance between competing, and even contradictory, clinical goals of neuroanesthesiology and obstetric practice.

  2. Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells

    International Nuclear Information System (INIS)

    Nakabayashi, Hiromichi; Yawata, Toshio; Shimizu, Keiji

    2010-01-01

    The constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumours. In particular, MMP-2 and MMP-9 have been reported to be closely associated with invasion and angiogenesis in malignant gliomas. Our study aimed to evaluate the antitumour effects of MMI-166 (Nalpha-[4-(2-Phenyl-2H- tetrazole-5-yl) phenyl sulfonyl]-D-tryptophan), a third generation MMP inhibitor, on three human glioma cell lines (T98G, U87MG, and ONS12) in vitro and in vivo. The effects of MMI-166 on the gelatinolytic activity was analysed by gelatine zymography. The anti-invasive effect of MMI-166 was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by MMI-166 was determined by the MTT assay. The effect of MMI-166 on an orthotropic implantation model using athymic mice was also evaluated. Gelatine zymography revealed that MMP-2 and MMP-9 activities were suppressed by MMI-166. The invasion of glioma cells was suppressed by MMI-166. The angiogenesis assay showed that MMI-166 had a suppressive effect on glioma cell-induced angiogenesis. However, MMI-166 did not suppress glioma cell proliferation in the MTT assay. In vivo, MMI-166 suppressed tumour growth in athymic mice implanted orthotropically with T98G cells and showed an inhibitory effect on tumour-induced angiogenesis and tumour growth. This is the first report of the effect of a third generation MMP inhibitor on malignant glioma cells. These results suggest that MMI-166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas

  3. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...... in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p

  4. Gaucher disease and comorbidities: B-cell malignancy and parkinsonism.

    Science.gov (United States)

    Cox, Timothy M; Rosenbloom, Barry E; Barker, Roger A

    2015-07-01

    Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non-Hodgkin's B-cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B-cell proliferation and neoplasia in Gaucher disease have been proposed, including the possible influence of sphingosine (derived from the extra lysosomal metabolism of glucosylceramide), gene modifiers, splenectomy and immune system deregulation induced by cytokines, chemokines, and hydrolases released from Gaucher cells. Parkinson's disease is frequently seen in the otherwise-healthy relatives of Gaucher disease patients leading to the finding that GBA mutations represent a genetic risk factor for Parkinson's disease. The mechanism of the association between GBA mutations and Parkinson's disease has yet to be elucidated but the pathogenesis appears distinct from that of Gaucher disease. Several pathogenic pathways have been proposed including lysosomal and/or mitochondrial dysfunction. The effect of Gaucher disease specific therapies on the incidence of cancer or Parkinson's disease are not clear and will likely be evaluated in future ICGG Gaucher Registry studies. © 2015 Wiley Periodicals, Inc.

  5. Subcellular localization of YKL-40 in normal and malignant epithelial cells of the breast

    DEFF Research Database (Denmark)

    Roslind, A.; Balslev, E.; Kruse, H.

    2008-01-01

    . YKL-40 protein expression was redistributed in carcinoma versus normal glandular tissue of the breast. A reduced expression of YKL-40 in relation to intermediate filaments and desmosomes was found in tumor cells. Changes in YKL-40 expression suggest that the function of YKL-40 in cells of epithelial......YKL-40 is a new prognostic biomarker in cancer. The biological function is only poorly understood. This study aimed at determining the subcellular localization of YKL-40, using immunogold labeling, in normal epithelial cells and in malignant tumor cells of the breast by immunoelectron microscopy...

  6. Skull base chordoid meningioma: Imaging features and pathology

    International Nuclear Information System (INIS)

    Soo, Mark Y.S.; Gomes, Lavier; Ng, Thomas; Cruz, Malville Da; Dexter, Mark

    2004-01-01

    The clinical, imaging and pathological features of a skull base chordoid meningioma (CM) are described. The huge tumour resulted in obstructive hydrocephalus and partial erosion of the clivus such that a chordoma was suspected. The lesion's MRI findings were similar to those of a meningioma. Light microscopic, immunohistochemistry and ultrastructural features were diagnostic of CM. Chordoid meningioma is a rare subtype of meningioma and has a great tendency to recur should surgical resection be incomplete Copyright (2004) Blackwell Publishing Asia Pty Ltd

  7. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    Energy Technology Data Exchange (ETDEWEB)

    Hoshiba, Takashi [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tanaka, Masaru, E-mail: tanaka@yz.yamagata-u.ac.jp [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan)

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  8. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    International Nuclear Information System (INIS)

    Hoshiba, Takashi; Tanaka, Masaru

    2013-01-01

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression

  9. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy

    DEFF Research Database (Denmark)

    Litvinov, Ivan V.; Shtreis, Anna; Kobayashi, Kenneth

    2016-01-01

    -Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S....... aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells...

  10. Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn; Lindahl, Lise M; Mongan, Nigel P

    2017-01-01

    Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage......, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early...... of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We...

  11. Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

    International Nuclear Information System (INIS)

    Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

    2007-01-01

    Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependent and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy

  12. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    International Nuclear Information System (INIS)

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-01-01

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy

  13. Extraosseous extension of Gaucher cell deposits mimicking malignancy

    International Nuclear Information System (INIS)

    Hermann, G.; Shapiro, R.; Abdelwahab, I.F.; Klein, M.J.; Pastores, G.; Grabowski, G.

    1994-01-01

    Two cases are described in which patients with type I Gaucher disease developed extraosseous soft tissue masses consisting of Gaucher cell deposits. In one instance the mass destroyed the posterior cortex of the left distal femur and protruded into the soft tissues. In the second case the lesion involved the proximal tibia and gradually extended into the soft tissues. While the incidence of neoplastic disorder such as lymphoproliferative disease appears to be more common in Gaucher disease patients than in the general population, lesions of benign etiology that mimic these aggressive processes should be considered in the differential diagnosis when cortical destruction with coexisting soft tissue most is found in these patients. (orig.)

  14. Extraosseous extension of Gaucher cell deposits mimicking malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Hermann, G. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Shapiro, R. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Abdelwahab, I.F. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Klein, M.J. (Dept. of Pathology, Mount Sinai Center of the City Univ. of New York, NY (United States)); Pastores, G. (Dept. of Human Genetics, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Grabowski, G. (Cincinnati Children' s Hospital, Cincinnati Univ., Coll. of Medicine, OH (United States))

    1994-05-01

    Two cases are described in which patients with type I Gaucher disease developed extraosseous soft tissue masses consisting of Gaucher cell deposits. In one instance the mass destroyed the posterior cortex of the left distal femur and protruded into the soft tissues. In the second case the lesion involved the proximal tibia and gradually extended into the soft tissues. While the incidence of neoplastic disorder such as lymphoproliferative disease appears to be more common in Gaucher disease patients than in the general population, lesions of benign etiology that mimic these aggressive processes should be considered in the differential diagnosis when cortical destruction with coexisting soft tissue most is found in these patients. (orig.)

  15. CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

    Science.gov (United States)

    Al Sayed, Mohamad F; Ruckstuhl, Carla A; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F

    2017-07-20

    The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia. © 2017 by The American Society of Hematology.

  16. Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn Frej; Ralfkiær, Ulrik; Clasen-Linde, Erik

    2011-01-01

    IL-17 is a proinflammatory cytokine that is crucial for the host's protection against a range of extracellular pathogens. However, inappropriately regulated expression of IL-17 is associated with the development of inflammatory diseases and cancer. In cutaneous T-cell lymphoma (CTCL), malignant T...

  17. The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

    Science.gov (United States)

    Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

    2008-12-01

    Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

  18. Maternally Expressed Gene 3, an imprinted non-coding RNA gene, is associated with meningioma pathogenesis and progression

    Science.gov (United States)

    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

  19. Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies

    Directory of Open Access Journals (Sweden)

    J. Kimble Frazer

    2012-01-01

    Full Text Available Genomic instability plays a crucial role in oncogenesis. Somatically acquired mutations can disable some genes and inappropriately activate others. In addition, chromosomal rearrangements can amplify, delete, or even fuse genes, altering their functions and contributing to malignant phenotypes. Using array comparative genomic hybridization (aCGH, a technique to detect numeric variations between different DNA samples, we examined genomes from zebrafish (Danio rerio T-cell leukemias of three cancer-prone lines. In all malignancies tested, we identified recurring amplifications of a zebrafish endogenous retrovirus. This retrovirus, ZFERV, was first identified due to high expression of proviral transcripts in thymic tissue from larval and adult fish. We confirmed ZFERV amplifications by quantitative PCR analyses of DNA from wild-type fish tissue and normal and malignant D. rerio T cells. We also quantified ZFERV RNA expression and found that normal and neoplastic T cells both produce retrovirally encoded transcripts, but most cancers show dramatically increased transcription. In aggregate, these data imply that ZFERV amplification and transcription may be related to T-cell leukemogenesis. Based on these data and ZFERV’s phylogenetic relation to viruses of the murine-leukemia-related virus class of gammaretroviridae, we posit that ZFERV may be oncogenic via an insertional mutagenesis mechanism.

  20. Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

    Science.gov (United States)

    Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

    2010-03-01

    Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

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

    Science.gov (United States)

    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.

  2. Clinical impact of the immunome in lymphoid malignancies: the role of Myeloid-Derived Suppressor Cells

    Directory of Open Access Journals (Sweden)

    Calogero eVetro

    2015-05-01

    Full Text Available The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of myeloid-derived suppressor cells in the settings of lymphoid malignancies.

  3. Special AT rich-binding1 protein (SATB1) in malignant T cells

    DEFF Research Database (Denmark)

    Fredholm, Simon; Willerslev-Olsen, Andreas; Met, Özcan

    2018-01-01

    Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL......) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression...

  4. Use of Monoclonal Antibodies for the Diagnosis of T-cell Malignancies: Applications and Limitations.

    Science.gov (United States)

    Hastrup, N; Pallesen, G; Ralfikiaer, E

    1990-01-01

    Biopsy samples from 136 peripheral T-cell lymphomas have been examined and compared with benign inflammatory T-cell infiltrates in an attempt to establish whether immunohistological methods may help to improve the distinction between these conditions. The results confirm and extend previous reports and indicate that the aberrant T-cell phenotypes constitute the single most reliable criterion for the distinction between benign and malignant T-cell infiltrates. These phenotypes are expressed frequently in T-cell malignancies in. lymphoid organs and are also seen in a substantial number of biopsy samples from advanced cutaneous T-cell lymphomas (CTCL). In contrast, early CTCL do not express aberrant T-cell phenotypes and are indistinguishable from benign cutaneous conditions in terms of their immunophenotypic properties. It is concluded that immunophenotypic techniques form a valuable supplement to routine histological methods for the diagnosis of T-cell lymphomas in lymphoid organs. The methods may also help to improve the diagnosis of advanced CTCL, but are of no or only limited help for the recognition of the early stages.

  5. [Clinical Value of Cell Block in the Diagnosis of Malignant Pleural Effusion].

    Science.gov (United States)

    Wang, Xintong; Cheng, Fangyuan; Zhong, Diansheng; Zhang, Lisha; Meng, Fanlu; Shao, Yi; Yu, Tao

    2017-06-20

    Malignant pleural effusion (MPE) is due tumor which arises from the mesothelium or metastases from tumor origniating other sites. Generally, the prognosis of MPE is poor, in the premise of reducing the pain of patients, as soon as possible make clear the property of pleural effusion and cause of the disesease, rightly and quickly, providing effective information for subsequent treatment. The cell block of 103 patients by using natural sedimentation or plasma coagulation method combined with HE staining and immunohistochemical staining method maked clear diagnosis and compared with other methods. 90 patients were diagnosed by cell block section from 103 patients who had MPE (diagnostic rate 87.4%); 32 cases were diagnosed by cell block section only, 74 cases pointed out that the pathological type , 23 cases even pointed out the primary lesions; 71 cases examined other invasive methods at the same time, the diagnostic rate was 87.3% and 81.7%; the detection rate of cell block section and cytological smear in detecting malignant tumor cells was 86.7%and 44.0% respectively. Cell block can not only increase the diagnosis, in contrast to cytological smear, and own the same diagnostic rate compared with other invasive methods, but also can confirm pathological type and primary lesion; especially, for other invasive methods, cell block method is a preferable complementary method, and that cell block method maybe the only way for some patients.

  6. Anti-ATLA (antibody to adult T-cell leukemia virus-associated antigen), highly positive in OKT4-positive mature T-cell malignancies.

    Science.gov (United States)

    Tobinai, K; Nagai, M; Setoya, T; Shibata, T; Minato, K; Shimoyama, M

    1983-01-01

    Serum or plasma specimens from 252 patients with lymphoid malignancies were screened for reactivity with adult T-cell leukemia virus-associated antigen (ATLA), and the relationship between the immunologic phenotype of the tumor cells and ATLA reactivity was determined. Anti-ATLA antibodies were found in 24 (29.3%) of 82 patients with T-cell malignancy. In contrast, the antibodies were found in none of the 106 patients with B-cell malignancy and only rarely in patients with other lymphoid malignancies without blood transfusions. Among the patients with T-cell malignancy, anti-ATLA antibodies were found in 23 (45.1%) of the 51 patients with OKT4-positive mature T-cell (inducer/helper T-cell) malignancy, but in none of the patients with T-cell malignancy of pre-T, thymic T-cell or OKT8-positive mature T-cell (suppressor/cytotoxic T-cell) phenotype. Furthermore, among the OKT4-positive mature T-cell malignancies, the antibodies were found in 16 (84.2%) of 19 patients with ATL and in 5 (27.8%) of 18 patients with mature (peripheral) T-cell lymphoma, in none of four with typical T-chronic lymphocytic leukemia, in one of nine with mycosis fungoides and in the one patient with small-cell variant of Sézary's syndrome. These results suggest that anti-ATLA positive T-cell malignancies with OKT4-positive mature T-cell phenotype must be the same disease, because it is highly possible that they have the same etiology and the same cellular origin. In the atypical cases, it seems necessary to demonstrate monoclonal integration of proviral DNA of ATLV or HTLV into the tumor cells in order to establish the final diagnosis of ATL.

  7. Multi-modality treatment in males with advanced malignant germ cell tumours

    International Nuclear Information System (INIS)

    Fossaa, S.D.; Klepp, O.; Ous, S.; Lien, H.; Stenwig, J.T.; Abeler, V.; Eliasson, G.; Hoest, H.

    1984-01-01

    After chemotherapy with cis-platinum, vinblastine and bleomycin, 33 surgical prosedures were performed in 29 patients with advanced malignant germ-cell tumours. The tumour masses could be completely resected macroscopially in 26 patients. Patients with fibros/necrosis or completely resected mature teratoma had an excellent prognosis, whereas only 5 of the 11 patients with vital malignant tumour survived in spite of second-line treatment with chemotherapy/radiotherapy. Preoperatively elevated serum levels of AFP, β-HCG and/or LDH indicated the presence of residual germ cell tumour. Eight of 14 patients were rendered tumour-free by radiotherapy given as second- or third-line treatment. In general, tumour masses, remaining after cis-platinum-based induction chemotherapy should be resected as completely as possible even in the case of mature teratoma or fibrosis/necrosis. Radiotherapy should be considered as second -and thirdline treatment

  8. Does Histologic Subtype Influence the Post-Operative Outcome in Spinal Meningioma?

    Science.gov (United States)

    Zham, Hanieh; Moradi, Afshin; Rakhshan, Azadeh; Zali, Alireza; Rahbari, Ali; Raee, Mohammadreza; Ashrafi, Farzad; Ahadi, Mahsa; Larijani, Leila; Baikpour, Masoud; Khayamzadeh, Maryam

    2016-04-01

    Postoperative outcome of spinal meningiomas is an important issue in surgery decision-making. There are limited and conflicting data in the literature about the prognostic factors influencing recovery, especially about the histopathologic subtypes. This study was carried out to evaluate the effect of some of these factors on postoperative outcome. This study was performed on 39 patients operated for spinal meningioma between October 1998 and January 2012; their histopathologic subtype was determined according to WHO criteria. The follow up period ranged between 8 - 120 months. The influence of histopathologic subtype, grade, age, sex, surgical approach, local adhesion and anatomical location was assessed according to Frankel classification of neurologic deficit. From a total number of 39 spinal meningiomas, 34 cases were WHO grade I, from which 15 cases were psammomatous, 7 cases were meningothelial, 9 cases were transitional and 3 cases were fibroblastic. Five cases were grade II, 3 of which had clear cell appearance and the remaining 2 had chordoid appearance. The mean age was 51.6 (22 to 76) years; 25 cases were female and 14 cases were male. This study revealed that grade II meningioma cases had poor prognosis in all 5 cases and psammomatous subtype had poor postoperative outcome in 40% of cases while the other subtypes had good outcome in all cases (P = 0.026). Cervical location of the tumor was also related with poor outcome in 37.5% of the cases, while 22.5% had poor outcome in other locations (P = 0.029). Age below and above 45 years and sex had no significant influence on the outcome. Spinal meningiomas of psammomatous type and grade II spinal meningiomas are associated with less favorable postoperative neurologic outcome. Cervical location has also a negative correlation with a good outcome.

  9. Instability of the Null Steady State: The Fundamental Problem of Inhibiting Malignant Cell Growth

    Science.gov (United States)

    Varfolomeev, S. D.; Lukovenkov, A. V.

    2018-07-01

    Mathematical modeling of the process of inhibiting malignant growth by common chemotherapeutic agents and biological therapeutics is used to investigate the effect kinetic parameters of the model have on the outcome of treatment. It is shown that the ultimate suppression of growth, i.e., the formation of a stable steady-state with no cancer cells, cannot be attained if only the means of classical chemotherapy are used.

  10. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

    OpenAIRE

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A.

    2011-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therape...

  11. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  12. Percutaneous Biliary Drainage Using Open Cell Stents for Malignant Biliary Hilar Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sun Jun; Bae, Jae Ik; Han, Tae Sun; Won, Je Hwan; Kim, Ji Dae; Kwack, Kyu Sung; Lee, Jae Hee; Kim, Young Chul [Dept. of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of)

    2012-11-15

    To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.

  13. Percutaneous Biliary Drainage Using Open Cell Stents for Malignant Biliary Hilar Obstruction

    International Nuclear Information System (INIS)

    Ahn, Sun Jun; Bae, Jae Ik; Han, Tae Sun; Won, Je Hwan; Kim, Ji Dae; Kwack, Kyu Sung; Lee, Jae Hee; Kim, Young Chul

    2012-01-01

    To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.

  14. Cell-surface associated with transformation of human hepatocytes to the malignant phenotype

    International Nuclear Information System (INIS)

    Wilson, B.; Ozturk, M.; Takahashi, H.; Motte, P.; Kew, M.; Isselbacher, K.J.; Wands, J.R.

    1988-01-01

    Hepatocellular carcinoma is one of the leading causes of cancer death in the world. To understand the cellular changes associated with transformation of hepatocytes to the malignant state, the authors have made several libraries of monoclonal antibodies against the hepatocellular carcinoma cell line FOCUS and have found six antibodies (AF-20, SF-25, SF-31, SF-90, XF-4, and XF-8) that recognize antigens expressed at consistently higher levels on hepatoma cells. They have studied malignant and nontransformed liver tissue from the same individual by using direct 125 I-labeled antibody binding and immunoperoxidase staining techniques. For each of these antibodies, they found striking increases in antigen expression on the transformed tissues. These antigens were found to be expressed throughout the tumor and on distant metastases, with little, if any, expression on the nontransformed adjacent liver. These antibodies demonstrate that hepatic transformation may be accompanied by stereotyped and predictable antigenic changes. The uniformity of such antigenic changes suggests an association between these cell-surface alterations and the malignant transformation process

  15. Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells.

    Science.gov (United States)

    Inaba, Nobuharu; Ishizawa, Sho; Kimura, Masaki; Fujioka, Kouki; Watanabe, Michiko; Shibasaki, Toshiaki; Manome, Yoshinobu

    2010-09-01

    Malignant glioma is one of the most intractable diseases in the human body. Rho-kinase (ROCK) is overexpressed and has been proposed as the main cause for the refractoriness of the disease. Since efficacious treatment is required, this study investigated the effect of inhibition of ROCK isoforms. The short hairpin RNA transcription vector was transfected into the RT2 rat glioma cell line and the characteristics of the cells were investigated. The effect of nimustine hydrochloride (ACNU) anti-neoplastic agent on cells was also measured. Inhibition of ROCK isoforms did not alter cell growth. Cell cycle analysis revealed that ROCK1 down-regulation reduced the G(0) phase population and ROCK2 down-regulation reduced the G(2)/M phase population. When ROCK1-down-regulated cells were exposed to ACNU, they demonstrated susceptibility to the agent. The roles of ROCK1 and ROCK2 may be different in glioma cells. Furthermore, the combination of ROCK1 down-regulation and an anti-neoplastic agent may be useful for the therapy of malignant glioma.

  16. Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

    Directory of Open Access Journals (Sweden)

    Carla Marchetti

    2015-01-01

    Full Text Available Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L., is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca2+ and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca2+ dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca2+ concentration (Ca2+i. Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca2+ channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca2+ channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca2+ channels and thereby dysregulating intracellular Ca2+ dynamics.

  17. Accumulation and biological effects of gallium in malignant cell lines in vitro

    International Nuclear Information System (INIS)

    Awano, Takayuki; Matsuzawa, Taiju

    1977-01-01

    Accumulation and biological effects of gallium (Ga) in malignant cells in vitro were studied. Biological effects were investigated cytokinetically and morphologically. The malignant cultured FM3A cells (originated from mammary carcinoma of C3H mice) accumulated 67 Ga actively. This accumulation was more intensive in proliferating cells than in non-proliferating cells. 6.5 percent of 67 Ga accumulated in the cultured FM3A cells was bound loosely at the cell surface. The colony forming capacity of C2W cells (originated from amelanotic melanoma of C57 Black mice ) was studied. The capacity decreased markedly when stable Ga was added to the medium in low concentration, but it decreased very little more in the range of rather high concentration. The growth response of FM3A cells to various concentrations of stable Ga was studied. The saturation density decreased and the doubling time became prolonged with increased Ga concentration. When 0.5 mM of stable Ga was added to the medium, the speed of proliferation changed markedly. The doubling time increased 1.7 times as compared to that before addition of Ga. The shape of the FM3A cells was usually spheroid in the medium. Swelling of the cells was observed when stable Ga was added to the culture medium. In particular, several per cent of these cells showed remarkable changes; that is, the cells were flattened and adhered to the dish and showed remarkable locomotion. It may be that these results are related to cell differentiation rather than to the cytotoxicity of stable Ga. (auth.)

  18. Accumulation and biological effects of gallium in malignant cell lines in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Awano, T; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1977-02-01

    Accumulation and biological effects of gallium (Ga) in malignant cells in vitro were studied. Biological effects were investigated cytokinetically and morphologically. The malignant cultured FM3A cells (originated from mammary carcinoma of C3H mice) accumulated /sup 67/Ga actively. This accumulation was more intensive in proliferating cells than in non-proliferating cells. 6.5 percent of /sup 67/Ga accumulated in the cultured FM3A cells was bound loosely at the cell surface. The colony forming capacity of C2W cells (originated from amelanotic melanoma of C57 Black mice ) was studied. The capacity decreased markedly when stable Ga was added to the medium in low concentration, but it decreased very little more in the range of rather high concentration. The growth response of FM3A cells to various concentrations of stable Ga was studied. The saturation density decreased and the doubling time became prolonged with increased Ga concentration. When 0.5 mM of stable Ga was added to the medium, the speed of proliferation changed markedly. The doubling time increased 1.7 times as compared to that before addition of Ga. The shape of the FM3A cells was usually spheroid in the medium. Swelling of the cells was observed when stable Ga was added to the culture medium. In particular, several per cent of these cells showed remarkable changes; that is, the cells were flattened and adhered to the dish and showed remarkable locomotion. It may be that these results are related to cell differentiation rather than to the cytotoxicity of stable Ga.

  19. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

    2009-02-15

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  20. Malignant mast cell tumor of the thymus in an Royal College of Surgeons (RCS) rat.

    Science.gov (United States)

    Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2017-01-01

    A 152-week-old male Royal College of Surgeons (RCS) rat kept as a non-treated animal in a long-term animal study presented with a soft mass in the anterior mediastinum, which adhered to the pleura of the lung. Histopathologically, the mass mainly consisted of round to short spindle-shaped tumor cells that had infiltrated through the hyperplastic thymic tissue. The tumor cells were arranged in loose to dense sheets. Nuclei were moderate in size and round to spindle-shaped, with small nucleoli. Almost all tumor cells exhibited abundant eosinophilic cytoplasm, including eosinophilic granules of a range of sizes. The granules of tumor cells exhibited metachromasia with toluidine blue stain and were positive for c-kit and mast cell protease II. These findings indicate that the tumor described here represents a rare case of spontaneous malignant mast cell tumor with thymic epithelial hyperplasia.

  1. Dumbbell meningioma of the cervico-clavicular region.

    Science.gov (United States)

    Hlavka, V; Miklić, P; Besenski, N; Miklić, D; Franz, G

    1991-01-01

    The authors are reporting on a case of a 55-year-old man with an epidural meningioma in the region from the C VII. to the Th I. segment. The tumor encircled this region, and to the front and right involved the channels through which pass the C VI, C VII. and C VIII. roots. Subdurally, no tumoral mass was found. Another part of this tumor, of the same histological architecture as the epidural cervicospinal part was found in the supraclavicular region to the right, closely connected to the arteries and nerves of this region. The authors discuss the possibility of the tumoral occurrence at this site, primarily taking into account the origin of this tumor from the cells of the outer surface of the arachnoidea, i.e. cap cells which can invade the dura, with later separation from the main arachnoidal layer. The other possibility of such dumbbell meningioma occurring at the outgoing openings of the neural paths from the spinal channel should be looked for in the remnants of the arachnoidal cells in the region of the outgoing openings. In the paper are also discussed and correlated clinico-pathological, CT and angiographic findings.

  2. Stereological estimation of nuclear mean volume in invasive meningiomas

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1996-01-01

    A stereological estimation of nuclear mean volume in bone and brain invasive meningiomas was made. For comparison the nuclear mean volume of benign meningiomas was estimated. The aim was to investigate whether this method could discriminate between these groups. We found that the nuclear mean...... volume in the bone and brain invasive meningiomas was larger than in the benign tumors. The difference was significant and moreover it was seen that there was no overlap between the two groups. In the bone invasive meningiomas the nuclear mean volume appeared to be larger inside than outside the bone....... No significant difference in nuclear mean volume was found between brain and bone invasive meningiomas. The results demonstrate that invasive meningiomas differ from benign meningiomas by an objective stereological estimation of nuclear mean volume (p

  3. Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma.

    Science.gov (United States)

    Bhattacharya, A; Schmitz, U; Wolkenhauer, O; Schönherr, M; Raatz, Y; Kunz, M

    2013-06-27

    WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1 expression was significantly downregulated in patient samples of metastatic origin as compared with primary melanomas and in melanoma cell lines of high aggressiveness as compared with cell lines of low aggressiveness. Moreover, there was an inverse correlation between the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1 mRNA and protein expression in these cells. Reporter gene analysis confirmed direct targeting of the WEE1 3' untranslated region (3'UTR) by miR-195. Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1 reduction and significantly reduced stress-induced G2-M cell cycle arrest, which could be restored by stable overexpression of WEE1. Moreover, miR-195 overexpression and WEE1 knockdown, respectively, increased melanoma cell proliferation. miR-195 overexpression also enhanced migration and invasiveness of melanoma cells. Taken together, the present study shows that WEE1 expression in malignant melanoma is directly regulated by miR-195. miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells.

  4. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    Science.gov (United States)

    Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

    2011-01-01

    Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. Conclusion: In conclusion, kefir is

  5. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    Directory of Open Access Journals (Sweden)

    Katia Maalouf

    2011-02-01

    Full Text Available Katia Maalouf1, Elias Baydoun2, Sandra Rizk11Department of Natural Sciences, Lebanese American University, Beirut, Lebanon; 2Department of Biology, American University of Beirut, Beirut, LebanonBackground: Adult lymphoblastic leukemia (ALL is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer.Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1-negative malignant T-lymphocytes.Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α, transforming growth factor- beta1 (TGF-β1, matrix metalloproteinase-2 (MMP-2, and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR. Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA and flow cytometry.Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 µg/µL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF- β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was

  6. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    International Nuclear Information System (INIS)

    Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

    2011-01-01

    Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG 1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. In conclusion, kefir is effective in inhibiting proliferation and inducing

  7. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies.

    Science.gov (United States)

    Hay, Kevin A; Turtle, Cameron J

    2017-03-01

    Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy. Reviewing the lessons learned thus far in CD19 CAR-T cell trials and how some of these challenges may be overcome will help guide the development of CAR-T cell therapy for malignancies of B-cell origin, as well as for other hematopoietic and non-hematopoietic cancers.

  8. Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Feng-Yuan [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Nuclear Medicine, Chiayi (China); Liao, Chun-Ta [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Otorhinolaryngology, Head and Neck Surgery, Taoyuan (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan County (China)

    2011-06-15

    Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity (OCSCC) are occasionally encountered. In the current study we tried to evaluate their frequency, detectability by {sup 18}F-fluorodeoxyglucose (FDG) studies, and prognostic factors. A retrospective analysis of patients with primary OCSCC enrolled for {sup 18}F-FDG studies from 2002 to 2008 was performed. The detectability of synchronous second cancers by {sup 18}F-FDG studies was defined by the scoring of two interpreters. Prognostic factors for overall survival in patients receiving curative-intent treatment were assessed using the univariate Kaplan-Mayer analysis and the multivariate Cox regression model. Of 764 patients, 40 (5.2%) had synchronous malignancies. {sup 18}F-FDG studies detected 22 (48%) of 46 synchronous second cancers. For synchronous cancers at the hypopharynx, esophagus, or liver, the median survival of patients was no longer than 1 year, and the detection rates by {sup 18}F-FDG studies were 100, 86, and 25%, respectively. In the 33 patients receiving curative-intent treatment, the site of second cancer, complete surgical resection of all known tumors, and the oral habit of betel quid/areca nut chewing are significant prognostic factors in the univariate analysis, while the site of second cancer is the only significant prognostic factor in the multivariate analysis (p = 0.041). The site of second cancer is the most significant prognostic factor in OCSCC patients with synchronous malignancies receiving curative-intent treatment. {sup 18}F-FDG studies detect synchronous malignancies with poor prognosis in OCSCC patients except for hepatic cancers. In OCSCC patients with synchronous malignancies with poor prognosis, prospective studies comparing different treatment options should be further conducted. (orig.)

  9. Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity

    International Nuclear Information System (INIS)

    Liu, Feng-Yuan; Liao, Chun-Ta; Yen, Tzu-Chen

    2011-01-01

    Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity (OCSCC) are occasionally encountered. In the current study we tried to evaluate their frequency, detectability by 18 F-fluorodeoxyglucose (FDG) studies, and prognostic factors. A retrospective analysis of patients with primary OCSCC enrolled for 18 F-FDG studies from 2002 to 2008 was performed. The detectability of synchronous second cancers by 18 F-FDG studies was defined by the scoring of two interpreters. Prognostic factors for overall survival in patients receiving curative-intent treatment were assessed using the univariate Kaplan-Mayer analysis and the multivariate Cox regression model. Of 764 patients, 40 (5.2%) had synchronous malignancies. 18 F-FDG studies detected 22 (48%) of 46 synchronous second cancers. For synchronous cancers at the hypopharynx, esophagus, or liver, the median survival of patients was no longer than 1 year, and the detection rates by 18 F-FDG studies were 100, 86, and 25%, respectively. In the 33 patients receiving curative-intent treatment, the site of second cancer, complete surgical resection of all known tumors, and the oral habit of betel quid/areca nut chewing are significant prognostic factors in the univariate analysis, while the site of second cancer is the only significant prognostic factor in the multivariate analysis (p = 0.041). The site of second cancer is the most significant prognostic factor in OCSCC patients with synchronous malignancies receiving curative-intent treatment. 18 F-FDG studies detect synchronous malignancies with poor prognosis in OCSCC patients except for hepatic cancers. In OCSCC patients with synchronous malignancies with poor prognosis, prospective studies comparing different treatment options should be further conducted. (orig.)

  10. Adoptive cell transfer using autologous tumor infiltrating lymphocytes in gynecologic malignancies.

    Science.gov (United States)

    Mayor, Paul; Starbuck, Kristen; Zsiros, Emese

    2018-05-23

    During the last decade, the field of cancer immunotherapy has been entirely transformed by the development of new and more effective treatment modalities with impressive response rates and the prospect of long survival. One of the major breakthroughs is adoptive cell transfer (ACT) based on autologous T cells derived from tumor-infiltrating lymphocytes (TILs). TIL-based ACT is a highly personalized cancer treatment. T cells are harvested from autologous fresh tumor tissues, and after ex vivo activation and extensive expansion, are reinfused to patients. TIL-based therapies have only been offered in small phase I/II studies in a few centers given the highly specialized care required, the complexity of TIL production and the very intensive nature of the three-step treatment protocol. The treatment includes high-dose lymphodepleting chemotherapy, the infusion of the expanded and activated T cells and interleukin-2 (IL-2) injections to increase survival of the T cells. Despite the limited data on ACT, the small published studies consistently confirm an impressive clinical response rate of up to 50% in metastatic melanoma patients, including a significant proportion of patients with durable complete response. These remarkable results justify the need for larger clinical trials in other solid tumors, including gynecologic malignancies. In this review we provide an overview of the current clinical results, future applications of TIL-based ACT in gynecologic malignancies, and on risks and challenges associated with modern T cell therapy. Copyright © 2018. Published by Elsevier Inc.

  11. Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy.

    Science.gov (United States)

    Grzes, K M; Swamy, M; Hukelmann, J L; Emslie, E; Sinclair, L V; Cantrell, D A

    2017-12-01

    This study explores the regulation and importance of System L amino acid transport in a murine model of T-cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1α or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN -/- T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T-cell malignancies, highlighting how a single amino acid transporter can have a key role.

  12. Balloon Cell Malignant Melanoma in a Young Female: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yui Hattori

    2016-04-01

    Full Text Available Balloon cell malignant melanoma (BCMM is a very rare malignant melanoma subtype. The clinical appearance of BCMM varies; it may be nodular, ulcerated, polypoid, papillomatous and often non-pigmented. The tumor cells histologically appear large, polygonal or round and contain abundant granular or vacuolated cytoplasm. We herein report the case of a 32-year-old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years. She underwent tumor excision. The histopathological analysis showed epithelioid melanocytes with clear cytoplasm. An immunohistochemical analysis revealed that the cells were positive for HMB-45 and S-100 protein and negative for cytokeratin. The balloon cell component stained negative for Fontana-Masson. A month later, the patient underwent excision of the bilateral inguinal lymph nodes and metastatic BCMM was revealed. The lymph node metastases showed the complete replacement of lymph nodes by balloon cells. A diagnosis of BCMM (Breslow depth 10 mm, Clark level V without ulcer was rendered. Staining with Ki-67 was positive in almost 44% of the balloon cells.

  13. Monstrous cell in malignant gliomas. In relation to radiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ogashiwa, M; Takeuchi, K; Akai, K [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1981-06-01

    The pathological effects of irradiation and chemotherapy have been studied in 9 autopsy cases of malignant and low grade gliomas. The brains have been examined by means of the complete study technique. Many histological features have been related to surgery, grading of histological classification of gliomas, irradiation and chemotherapy. Following irradiation and chemotherapy, in addition to increased necrosis and vascular response, a variety of characteristic changes were observed in cell and nuclear morphology with prominent formation of monstrous cells in all of 5 malignant gliomas treated with nitrosourea. These monstrous cells had irregular and hyperchromatic multinuclei and showed cytoplasmic degeneration. These cells which had no direct relationship to vessels distributed both in the periphery of tumor or necrosis and in the white matter remote from the main tumor. These changes were more pronounced in autopsy than in biopsy. The features showed here indicate that the monstrous cells may appear due to the result of inhibition of tumor cell division at the late mitotic phase after irradiation and chemotherapy.

  14. Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies

    Science.gov (United States)

    Sadek, Jouliana; Hernandez-Hopkins, Denise; Akar, Gunkut; Barelli, Peter J.; Sahai, Michelle A.; Zhou, Hufeng; Totonchy, Jennifer; Jayabalan, David; Niesvizky, Ruben; Guasparri, Ilaria; Liu, Yifang; Sei, Shizuko; Shoemaker, Robert H.; Elemento, Olivier; Kaye, Kenneth M.

    2017-01-01

    Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI–sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers. PMID:28504647

  15. Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies.

    Science.gov (United States)

    Nayar, Utthara; Sadek, Jouliana; Reichel, Jonathan; Hernandez-Hopkins, Denise; Akar, Gunkut; Barelli, Peter J; Sahai, Michelle A; Zhou, Hufeng; Totonchy, Jennifer; Jayabalan, David; Niesvizky, Ruben; Guasparri, Ilaria; Hassane, Duane; Liu, Yifang; Sei, Shizuko; Shoemaker, Robert H; Warren, J David; Elemento, Olivier; Kaye, Kenneth M; Cesarman, Ethel

    2017-06-01

    Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

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

    Directory of Open Access Journals (Sweden)

    Hisataka Ogawa

    Full Text Available 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.

  17. Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

    International Nuclear Information System (INIS)

    Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo

    2013-01-01

    A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

  18. Microrna-31 mediates radiation induced apoptosis selectively in malignant tumour cells with dysfunctional P53

    International Nuclear Information System (INIS)

    Kumar, Ashish; Mukherjee, Prabuddho; Babu, Bincy; Chandna, Sudhir

    2016-01-01

    The protein p53 has been recognized as an important radio-responsive protein which functions mainly through transcriptional control of its target genes and microRNAs that target multiple response pathways. In this study, we investigate a putative link between p53 functionality and microRNA-31 expression that largely contributes to cellular transformation/malignancy and also establishes the role of miR-31 in radiation-induced cell death. The expression of miR-31 is found to be attenuated in cells in successive stages of cancer progression

  19. Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-08-15

    A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

  20. Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Vakil, Erik; Evans, Scott E

    2017-03-01

    Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies

    Science.gov (United States)

    Gonsalves, Wilson I.; Hitosugi, Taro; Ghosh, Toshi; Jevremovic, Dragan; Petterson, Xuan-Mai; Wellik, Linda; Kumar, Shaji K.; Nair, K. Sreekumaran

    2018-01-01

    The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle. Furthermore, the 13C SIRM studies in HMCLs also demonstrate that glutamine is preferentially utilized by the TCA cycle compared with glucose. Finally, measuring the levels of 2-HG in the BM supernatant and peripheral blood plasma from patients with precursor PC malignancies such as smoldering MM (SMM) demonstrates that relatively elevated levels of 2-HG are associated with higher levels of c-MYC expression in the BM clonal PCs and with a subsequent shorter time to progression (TTP) to MM. Thus, measuring 2-HG levels in BM supernatant or peripheral blood plasma of SMM patients offers potential early identification of those patients at high risk of progression to MM, who could benefit from early therapeutic intervention. PMID:29321378

  2. Clinical use of PI3K inhibitors in B-cell lymphoid malignancies: today and tomorrow.

    Science.gov (United States)

    Greenwell, I B; Flowers, C R; Blum, K A; Cohen, J B

    2017-03-01

    PI3K inhibitors are an important new therapeutic option for the treatment of relapsed and refractory B-cell lymphoid malignancies. Idelalisib is a PI3Kδ inhibitor that has been approved for the treatment of lymphoma and chronic lymphocytic leukemia in the relapsed/refractory setting, and several other PI3K inhibitors are being developed targeting other isoforms of the PI3K enzyme, which results in distinct toxicities and variable efficacy in the clinical setting. Areas covered: We provide a general overview of PI3K inhibitors, recommended applications, and the mechanism and management of toxicities. We further review trials, ongoing and completed, leading to the approval of idelalisib as well other PI3K inhibitors currently in development. Articles were obtained from PubMed, and abstracts were searched for the past 5 years from the websites for ASCO, ASH, EHA, and ICML/Lugano. Expert commentary: PI3K inhibitors provide an important and powerful pharmacologic tool in the armamentarium against hematologic malignancies, especially for relapsed/refractory B-cell lymphoid malignancies. Unique toxicities are associated with inhibition of different isoforms of the PI3K enzyme, as demonstrated with the infectious and autoimmune toxicities associated with the PI3Kδ inhibitor, idelalisib. Due to these unique toxicities, PI3K inhibitors should only be used in formally approved combinations and settings.

  3. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.

    Science.gov (United States)

    Quoc Trung, Ly; Espinoza, J Luis; Takami, Akiyoshi; Nakao, Shinji

    2013-01-01

    Natural killer (NK) cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.

  4. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.

    Directory of Open Access Journals (Sweden)

    Ly Quoc Trung

    Full Text Available Natural killer (NK cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.

  5. Chimeric Antigen Receptor (CAR) T cells: Lessons Learned from Targeting of CD19 in B cell malignancies

    Science.gov (United States)

    Hay, Kevin A; Turtle, Cameron J

    2017-01-01

    Adoptive immunotherapy with chimeric antigen receptor-modified T (CAR-T) cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy. Reviewing the lessons learned thus far in CD19 CAR-T cell trials and how some of these challenges may be overcome will help guide the development of CAR-T cell therapy for malignancies of B-cell origin, as well as for other hematopoietic and non-hematopoietic cancers. PMID:28110394

  6. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

    DEFF Research Database (Denmark)

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received...... an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97......%, respectively; Pblood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28...

  7. Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

    Directory of Open Access Journals (Sweden)

    Nadine Gelbrich

    2017-01-01

    Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

  8. Comparison of photocytotoxicyty of PDT with hypericin by model of healthy versus malignant colon epithelium cells

    International Nuclear Information System (INIS)

    Mikes, J.; Kleban, J.; Jendzelovsky, R.; Solar, P.; Fedorocko, P.; Hyzdalova, M.

    2006-01-01

    Photodynamic therapy (PDT) is becoming a rapidly developing method in cancer therapy, recently. PDT is based on administration of nontoxic/weakly toxic photosensitive compound and its activation with light. The phototoxicity of PDT depends on generation of superoxide radicals (Type-I reaction), which in turn might form peroxide and hydroxyl radicals, and production of singlet oxygen ( 1 O 2 ) (Type-II reaction) after irradiation with light of appropriate wavelength which properly overlaps the photosensitizer's absorbing spectra. Oxidative damage in the cell induced by reactive oxygen species depends on the intracellular localisation and affects different cell organelles. Although PDT is of use in clinical practise, new promising photosensitive compounds with advantageous attributes are discovered continuously. Hypericin, one of these compounds, is known to affect cell cycle and proliferation, to alter gene expression and to induce cell death. Due to its spectral characteristics, hypericin is applicable for treatment of superficial malignancies and therefore also for treatment of colon adenocarcinomas. We compared two cell lines of identical histological origin, one as a model of colon adenocarcinoma (HT29) and second as a model of healthy colon epithelium, to evaluate photo-cytotoxicity of PDT with hypericin to healthy tissue and determine applicability of this therapy in treatment of colon malignancies. (authors)

  9. IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma.

    Science.gov (United States)

    Coquet, Jonathan M; Skak, Kresten; Davis, Ian D; Smyth, Mark J; Godfrey, Dale I

    2013-10-01

    Interleukin-21 (IL-21) is a common γ-chain cytokine produced by T helper and natural killer T (NKT) cells. It has been shown to regulate the response of various lymphocyte subsets including NK, NKT, T and B cells. Owing to its potent anti-tumor function in preclinical studies and its ability to induce cytotoxicity and interferon-γ (IFN-γ) production in NK and CD8 T cells, recombinant IL-21 (rIL-21) was fast-tracked into early-phase clinical trials of patients with various malignancies. In a phase 2a trial of patients with metastatic melanoma, we analyzed the frequency and function of NKT cells in patients receiving rIL-21. NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. Unlike our observations in NK and CD8 T cells, rIL-21 appeared to reduce IFN-γ and TNF production by NKT cells, whereas it enhanced IL-4 production. It also modulated the expression of cell surface markers, specifically on CD4(-) NKT cells. In addition, an increase in CD3(+)CD56(+) NKT-like cells was observed over the course of rIL-21 administration. These results highlight that IL-21 is a potent regulator of NKT cell function in vivo.

  10. Meningioma of Foramen Magnum Causing Drop Attacks

    Directory of Open Access Journals (Sweden)

    Amit Mahore

    2015-01-01

    Full Text Available A 52-year-old female presented with frequent episodes of falls without loss of consciousness. These episodes lasted for brief period followed by full neurological recovery. Magnetic resonance imaging (MRI of the brain showed foramen magnum meningioma encasing left vertebral artery. The patient had dramatic improvement after excision of the tumor.

  11. Analysis of peritumoral cerebral edema of meningiomas

    International Nuclear Information System (INIS)

    Okada, Masaaki; Tanaka, Katsuyuki; Abe, Juzo; Sekino, Hiroaki; Ogawa, Takei; Hayashi, Tatsuo.

    1992-01-01

    Peritumoral edema associated with 28 meningiomas was studied. The results of radiological investigation, using MRI, CT, and angiography, and histological studies were described and correlated with each other in order to clarify the mechanism of peritumoral cerebral edema production. Extensive peritumoral edema was recognized when the venous sinus or cortical veins, especially the superficial and deep Sylvian veins, were invaded and/or compressed markedly by the tumor. Therefore, large tumors (more than 5 cm in diameter) which were located in the parasagittal area and the middle cranial fossa had a tendency to be associated with extensive peritumoral edema. The posterior fossa meningiomas were associated with small edema because there were rich venous channels in the posterior fossa. Although there have been several reports that the peritumoral edema of meningioma would be produced by the vessels of the tumor itself and would migrate through the tumor capsule into the surrounding brain tissue, and although mechanical factors alone are not sufficient to explain peritumoral edema production, we would like to postulate that the longstanding mechanical compression of venous circulation by the meningioma might be an important factor in the production of the peritumoral cerebral edema. (author)

  12. Intraventricular trigonal meningioma: Neuronavigation? No, thanks!

    Science.gov (United States)

    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

    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. 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. 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. 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.

  13. Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Ellegaard, J

    1981-01-01

    This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunolog...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

  14. Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Annelisa M. Cornel

    2018-05-01

    Full Text Available Dendritic cell (DC vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines. Generation of DC from CD34+ hematopoietic stem and progenitor cells (HSPCs may provide potential in patients undergoing allogeneic HSPC transplantations for hematologic malignancies. CD34+ HSPC from the graft can be genetically modified to optimize antigen presentation and to provide sufficient T cell stimulatory signals. We here describe beneficial (gene-modifications that can be implemented in various processes in T cell activation by DC, among which major histocompatibility complex (MHC class I and MHC class II presentation, DC maturation and migration, cross-presentation, co-stimulation, and immunosuppression to improve anti-tumor responses.

  15. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    Science.gov (United States)

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

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    Julia Pollak

    Full Text Available Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

  17. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

    Science.gov (United States)

    Pollak, Julia; Rai, Karan G; Funk, Cory C; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D; Paddison, Patrick J; Ramirez, Jan-Marino; Rostomily, Robert C

    2017-01-01

    Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

  18. Malignant perivascular epithelioid cell tumor of the orbit: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Md Shahid Alam

    2017-01-01

    Full Text Available Perivascular epithelioid cell tumor (PEComa is a rare neoplasm considered to arise from myomelanocytic cell lineage. The uterus is reportedly the most common site to be involved. Orbital PEComa is extremely rare with only two cases reported till date. A 5-year-old male presented with a right medial orbital mass for the last 6 months. The patient was diagnosed with alveolar soft part sarcoma elsewhere. Magnetic resonance imaging features were suggestive of lymphangioma with bleeding. The excision biopsy revealed multiple tumor cells comprising epithelioid cells with clear cytoplasm, along with nuclear atypia and mitosis. Immunohistochemistry was positive for HMB-45, smooth muscle actin, vimentin, and CD-34. It was negative for cytokeratin, S-100, and synaptophysin, which clinched the diagnosis of malignant orbital PEComa. Neoadjuvant chemotherapy was administered. There was no recurrence at 24 months of follow-up. At present, there is no consensus on management protocol for malignant PEComa. Complete surgical excision with chemotherapy appears to offer the best prognosis.

  19. Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

    International Nuclear Information System (INIS)

    Kodama, S.; Okumura, Y.; Komatsu, K.; Sasaki, M.S.

    1991-01-01

    Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state

  20. Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies.

    Science.gov (United States)

    Png, Yi Tian; Vinanica, Natasha; Kamiya, Takahiro; Shimasaki, Noriko; Coustan-Smith, Elaine; Campana, Dario

    2017-11-28

    Effective immunotherapies for T-cell malignancies are lacking. We devised a novel approach based on chimeric antigen receptor (CAR)-redirected T lymphocytes. We selected CD7 as a target because of its consistent expression in T-cell acute lymphoblastic leukemia (T-ALL), including the most aggressive subtype, early T-cell precursor (ETP)-ALL. In 49 diagnostic T-ALL samples (including 14 ETP-ALL samples), median CD7 expression was >99%; CD7 expression remained high at relapse (n = 14), and during chemotherapy (n = 54). We targeted CD7 with a second-generation CAR (anti-CD7-41BB-CD3ζ), but CAR expression in T lymphocytes caused fratricide due to the presence of CD7 in the T cells themselves. To downregulate CD7 and control fratricide, we applied a new method (protein expression blocker [PEBL]), based on an anti-CD7 single-chain variable fragment coupled with an intracellular retention domain. Transduction of anti-CD7 PEBL resulted in virtually instantaneous abrogation of surface CD7 expression in all transduced T cells; 2.0% ± 1.7% were CD7 + vs 98.1% ± 1.5% of mock-transduced T cells (n = 5; P < .0001). PEBL expression did not impair T-cell proliferation, interferon-γ and tumor necrosis factor-α secretion, or cytotoxicity, and eliminated CAR-mediated fratricide. PEBL-CAR T cells were highly cytotoxic against CD7 + leukemic cells in vitro and were consistently more potent than CD7 + T cells spared by fratricide. They also showed strong anti-leukemic activity in cell line- and patient-derived T-ALL xenografts. The strategy described in this study fits well with existing clinical-grade cell manufacturing processes and can be rapidly implemented for the treatment of patients with high-risk T-cell malignancies.

  1. Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

    International Nuclear Information System (INIS)

    Gomez, Daniel R.; Komaki, Ritsuko

    2012-01-01

    For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

  2. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

    Directory of Open Access Journals (Sweden)

    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  3. Natural history of intracranial meningioma after radiotherapy

    International Nuclear Information System (INIS)

    Monzen, Yoshio

    1999-01-01

    The author examined the natural history of intracranial meningioma after radiotherapy using CT or MR imaging. Twenty patients with intracranial meningioma received radiotherapy from a high-energy linear accelerator (4-10 MV X rays) from 1980 to 1996. The total doses were 50 Gy to the tumor bed in single doses of 2 Gy in 5 weekly fractions. Meningiomas in 10 of 20 patients were reduced within 1 to 38 months after radiotherapy, the average being 11 months. The tumors were controlled for a median of 60 months after radiotherapy (range 19-126 months). Four other patients have shown no change in tumor size after radiotherapy. The tumors were controlled for a median of 70 months after radiotherapy (range 37-127 months). The other six patients have shown tumor growth within 3 to 25 months after radiotherapy, after which the tumors stopped growing for a median of 71 months (range 2-181 months). Neither tumor size nor histological type was related to response. The growth of tumors was controlled by radiotherapy for a median duration of 43 months in the meningothelial type, 52 months in the fibroblastic type, and 61 months in the transitional type. The median duration for all benign tumors was 52 months. A moderate correlation was noted between tumor response and functional outcome after radiotherapy in 9 patients with neurological deficits. The natural histories of intracranial meningiomas after radiotherapy were grouped into three categories. Some tumors showed no change in size over a long period. This was a characteristic response after radiotherapy that differed from that of other brain tumors. The results of this study provide important information for the follow-up of intracranial meningiomas after radiotherapy. (author)

  4. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    International Nuclear Information System (INIS)

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-01-01

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

  5. Pregnant woman with an intracranial meningioma – case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Dumitrescu Bogdan Constantin

    2014-12-01

    Full Text Available It is about a 33-year-old female, with a 36 weeks uncomplicated pregnancy and with signs of increased intracranial pressure. Hours after admission and an obstetric evaluation, uterine contraction started and the patient was taken to the delivery room, where she presented a partial motor seizure on the left side with secondary generalization and urine emission. A caesarean section was performed without fetal or maternal complications. The urgent MRI gadolinium-enhanced brain scan revealed a 39/50/54 mm tumoral mass having an aspect of an anterior third falx cerebri meningioma. The patient was transferred to our neurosurgical department and afterwards surgery was performed with gross total removal of the tumoral mass. Histological examination revealed atypical meningioma with direct invasion into the adjacent brain parenchyma. A week later she was discharged from the hospital in good condition. One month after surgery, a contrastenhanced magnetic resonance imaging of the brain did not reveal any signs of tumor recurrence or residual tumor. Our recommendation is for postpartum surgery when is possible. Urgent neurosurgical interventions should be made in case of patients with malignant tumors, active hydrocephalus or benign intracranial tumor such as meningioma associated with signs of impending herniation, progress

  6. EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Cho, Min Chul; Cho, Sung Yong; Yoon, Cheol Yong; Lee, Seung Bae; Kwak, Cheol; Kim, Hyeon Hoe; Jeong, Hyeon

    2015-01-01

    To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells. Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively. In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation. Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of

  7. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  8. Parakeratotic-like cells in effusions - A clue to diagnosis of malignant mesothelioma

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    Ling Gao

    2012-01-01

    Full Text Available Background : Malignant mesothelioma (MM is an aggressive neoplasm with a poor prognosis. Its incidence has been increasing worldwide. Cytological examination of an effusion is often the first opportunity to diagnose MM. However, the cytological diagnosis of MM can be difficult. We have noticed that parakeratotic-like cells, with orange cytoplasm and pyknotic nuclei, are present in many cases of mesothelioma on Papanicolaou-stained cytology slides. Although this cytological finding has been described previously, to our knowledge, there has been no systematic study of this finding. Our study is to determine whether the presence of small parakeratotic / orangeophilic cells (PK-like cells is specific for the cytodiagnosis of mesothelioma. Materials and Methods: A total of 90 body fluid cases were selected from our archived specimens in the Cytology Section at the University of Chicago Hospital accessioned between January 2000 to November 2011. They included 30 cases of mesothelioma, 30 cases of adenocarcinoma, and 30 cases of reactive mesothelial cells. Results: PK-like cells were present in 83% of the mesothelioma cases, 13% of the adenocarcinoma cases, and 7% of the reactive cases. Our data showed that the presence of PK-like cells has a specificity of 90%, sensitivity of 83%, positive predictive value of 81%, and negative predictive value of 84% for the diagnosis of malignant mesothelioma in body cavity fluids. Conclusion: The presence of PK-like cells in the effusion specimen, especially in pleural effusions, is a highly specific and moderately sensitive cytological feature for diagnosis of mesothelioma.

  9. Understanding Drug Resistance to Targeted Therapeutics in Malignant B-Cell Lymphoproliferative Disorders (B-LPDs)

    Science.gov (United States)

    2014-10-01

    1063-70. PMC2783430. 2. Zhang J, Jima DD, Jacobs C, Fischer R, Gottwein E, Huang G, Lugar PL, Lagoo AS, Rizzieri DA, Friedman DR, Weinberg JB...Khoury, Thomas R Klumpp, Hillard M Lazarus, Victor A Lewis, Philip L McCarthy, David A Rizzieri, Mitchell Sabloff, Jeff Szer, Martin S Tallman, and...malignant human B cells identifies hundreds of novel microRNAs. Blood. 2010;116(23):e118-27 5. Zhang J, Jima DD, Jacobs C, Fischer R, Gottwein E, Huang G

  10. Clear cell hidradenocarcinoma--a case report with unusual in situ malignant changes.

    Science.gov (United States)

    Al-Irhayim, B

    1984-05-01

    Clear cell hidradenocarcinoma is a rare tumour, the histogenesis of which has been much debated in the past. However, it is now considered a tumour of sweat gland origin. Presented herewith is a report of a case with unusual histological features of in situ malignant changes within sweat glands. These changes very closely simulate lobular cancerisation of the breast. On reviewing the English literature on the histopathology of sweat gland tumours, we have not found similar histological findings. These histological findings provide supportive evidence of the sweat gland origin of these tumours.

  11. Intrapleural cisplatin for management of malignant pleural effusion in a patient with plasma cell leucaemia.

    Science.gov (United States)

    Agarwal, Abhishek; Klair, Jagpal; Patolia, Setu; Meena, Nikhil K

    2015-06-29

    Plasma cell leucaemia (PCL) is a rare aggressive form of multiple myeloma. It occasionally involves the pleura, causing malignant pleural effusion (MPE). MPE presents a management dilemma for physicians, given the different treatment options available with varying efficacy and side effects. We report a case of a 64-year-old man with MPE due to PCL, successfully managed with intrapleural cisplatin and a tunnelled pleural catheter. We believe this to be the first report of management of PCL-associated MPE with intrapleural cisplatin. 2015 BMJ Publishing Group Ltd.

  12. Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

    Science.gov (United States)

    Horton, Sarah J; Giotopoulos, George; Yun, Haiyang; Vohra, Shabana; Sheppard, Olivia; Bashford-Rogers, Rachael; Rashid, Mamunur; Clipson, Alexandra; Chan, Wai-In; Sasca, Daniel; Yiangou, Loukia; Osaki, Hikari; Basheer, Faisal; Gallipoli, Paolo; Burrows, Natalie; Erdem, Ayşegül; Sybirna, Anastasiya; Foerster, Sarah; Zhao, Wanfeng; Sustic, Tonci; Petrunkina Harrison, Anna; Laurenti, Elisa; Okosun, Jessica; Hodson, Daniel; Wright, Penny; Smith, Ken G; Maxwell, Patrick; Fitzgibbon, Jude; Du, Ming Q; Adams, David J; Huntly, Brian J P

    2017-09-01

    Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies.

  13. T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Aileen G Rowan

    2016-11-01

    Full Text Available There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL, human T lymphotropic virus type-1 (HTLV-1, contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1 to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we quantified the rate of CD8+-mediated killing of the putative malignant clone in ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable to lyse autologous ATL clones when tested directly ex vivo. However, short in vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which expressed the viral sense strand gene products was significantly enhanced after in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene were most likely to make a detectable lytic CD8+ response to the ATL cells. We conclude that some patients with ATL possess functional tumour-specific CTLs which could be exploited to contribute to control of the disease.

  14. 17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis.

    Science.gov (United States)

    Siegelin, Markus David; Habel, Antje; Gaiser, Timo

    2009-02-01

    17-AAG is a selective HSP90-inhibitor that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, LN229 and U251) were treated with 17-AAG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of 17-AAG in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. 17-AAG treatment down-regulated survivin through proteasomal degradation. In addition, over-expression of survivin attenuated cytotoxicity induced by the combination of 17-AAG and TRAIL. In summary, survivin is a key regulator of TRAIL-17-AAG mediated cell death in malignant glioma.

  15. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  16. Atypical olfactory groove meningioma associated with uterine fibromatosis; case report

    Directory of Open Access Journals (Sweden)

    Toma I. Papacocea

    2016-11-01

    Full Text Available The concomitant presence of the olfactory groove meningioma with uterine fibrosis is very rare. Our report presents the case of a giant olfactory groove meningioma revealed after a uterine fibroma resection in a 44 years-old female, due to a generalized seizure 10 days after operation. Cranial CT-scan identified the tumor as an olfactory groove meningioma. The tumor was operated with a macroscopically complete resection; the endothermal coagulation of the dura attachment was performed (Simpson II with a good postoperative evolution. Laboratory results showed the presence of receptors for steroid hormones both in meningioma and uterine tumor, and the histopathological examination revealed an atypical meningioma with 17% proliferation markers. Our findings suggest that even though meningiomas are benign tumors and a complete resection usually indicates a good prognosis, the association with uterine fibromatosis and the presence of high percentage of steroid receptors creates a higher risk to relapse, imposing therefore a good monitoring.

  17. LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.

    Science.gov (United States)

    Tanaka, I; Osada, H; Fujii, M; Fukatsu, A; Hida, T; Horio, Y; Kondo, Y; Sato, A; Hasegawa, Y; Tsujimura, T; Sekido, Y

    2015-01-02

    Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.

  18. Effect of flupirtine on the growth and viability of U373 malignant glioma cells

    International Nuclear Information System (INIS)

    Panchanathan, Elango; Ramanathan, Gnanasambandan; Lakkakula, Bhaskar Venkata Kameswara Subrahmanya

    2013-01-01

    Flupirtine is a non-opioid analgesic without antipyretic or antiphlogistic properties but with favorable tolerability in humans. This analgesic also exhibits neuroprotective activities. Furthermore, flupirtine antagonizes glutamate- and NMDA-induced intracellular levels of Ca 2+ and counteracts the effects of focal cerebral ischemia. Although flupirtine has been used to relieve pain caused by different diseases and clinical procedures, information on the safety and efficacy of flupirtine is limited. The present study was conducted to investigate the neuroprotective effects of flupirtine on U373 malignant glioma (MG) cell lines. Cell viability and cell cycle analysis was performed by MTT assay and flow cytometry, respectively. Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines. The variation in the percentage of gated cell population in different cell cycle phases showed significant variations after 48 h of treatment. Flupirtine has neuroprotective effect of on U373 MG cells, which limits its use in the pain management of brain tumors. This property warrants further studies using animal models and large-scale clinical trials

  19. An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells.

    Science.gov (United States)

    Tone, Kiyoshi; Kojima, Keiko; Hoshiai, Keita; Kumagai, Naoya; Kijima, Hiroshi; Kurose, Akira

    2016-06-01

    The essential of urine cytology for the diagnosis and the follow-up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination. Using Papanicolaou-stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4',6-diamidino-2-phenylindole for detection of the nuclei and the nucleoli. Z-stack method was performed to analyze. When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483-491. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

    Science.gov (United States)

    Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

    2016-12-01

    The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. CT bronchus sign in malignant solitary pulmonary lesions: value in the prediction of cell type

    International Nuclear Information System (INIS)

    Choi, J.A.; Kim, J.H.; Hong, K.T.; Kim, H.S.; Oh, Y.W.; Kang, E.Y.

    2000-01-01

    The aim of this study was to evaluate differences in the prevalence of patterns of CT bronchus sign in malignant solitary pulmonary lesions (SPLs), according to their histologic cell types and with respect to size, location, and degree of cell differentiation. Computed tomography scans of 78 patients, in whom pathologically confirmed malignant SPLs with CT bronchus sign were present, were randomly selected and reviewed by two radiologists under consensus. All 78 were CT scans done using spiral technique with 10-mm collimation and 10-mm reconstruction intervals with enhancement, and 75 included additional high-resolution CT scans. Lesions were classified into four cell types as squamous cell carcinoma (n=24), small cell carcinoma (n=12), adenocarcinoma (n=23), bronchioloalveolar carcinoma (BAC; n=9), and others (n=12), into three degrees of differentiation, into three size groups, and according to location (central or peripheral). Patterns of CT bronchus sign were classified into abruptly obstructing (I), patent (II), displacing (III), or tapered narrowing (IV) types. The relationships between the patterns of CT bronchus sign and cell type and degree of cell differentiation were evaluated. Eighty patterns of CT bronchus sign were observed in 78 patients. According to cell type, squamous cell carcinoma showed most often type-I pattern (45.8%) but no type-II pattern, which was the most common pattern observed in BAC (77.8%) and adenocarcinoma (34.8%; p<0.01). Small cell carcinoma showed a varied distribution among the four patterns of CT bronchus sign. According to location, in central squamous cell carcinomas, type-I pattern was more common(55%; p<0.01). Bronchioloalveolar carcinoma showed more peripheral lesions and in both central and peripheral lesions, type-II pattern was significantly more common (100 and 66.7%; p<0.01). In SPLs with CT bronchus sign of obstructing pattern, especially if central location, squamous cell carcinoma should be suspected, whereas in

  2. Stereological estimation of nuclear volume in benign and atypical meningiomas

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1993-01-01

    A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups....... The results demonstrate that atypical meningiomas can be distinguished from benign meningiomas by an objective stereological estimation of nuclear volume....

  3. Epilepsy and adverse quality of life in surgically resected meningioma.

    Science.gov (United States)

    Tanti, M J; Marson, A G; Jenkinson, M D

    2017-09-01

    Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64). QoL was measured with the Short Form 36 version 2 (SF-36), the Functional Assessment of Cancer Therapy (FACT-BR), and the Liverpool Adverse Events Profile (LAEP). Regression analyses identified significant determinants of QoL. Patients with meningioma and epilepsy had poorer QoL scores than meningioma patients without epilepsy in all measures. In FACT-BR, this difference was significant. Multiple regression analyses demonstrated that current AED use had a greater impact on QoL scores than recent seizures. Other variables associated with impaired QoL included depression, unemployment, and meningioma attributed symptoms. Epilepsy has a negative impact on quality of life in patients with benign meningioma. AED use is correlated with impaired QoL and raised LAEP scores, suggesting that AEDs and adverse effects may have led to impaired QoL in our meningioma patients with epilepsy. The severity of epilepsy in our meningioma population was comparatively mild; therefore, a more conservative approach to AED therapy may be indicated in an attempt to minimize adverse effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

    International Nuclear Information System (INIS)

    Li Hongzhen; Zhou Jianjun; Miki, Jun; Furusato, Bungo; Gu Yongpeng; Srivastava, Shiv; McLeod, David G.; Vogel, Jonathan C.; Rhim, Johng S.

    2008-01-01

    Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1 hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

  5. Surgery for convexity/parasagittal/falx meningiomas

    International Nuclear Information System (INIS)

    Ochi, Takashi; Saito, Nobuhito

    2013-01-01

    Incidence of the complication related with the surgical treatment of meningiomas in the title was reviewed together with consideration of data about progress observation and stereotactic radiosurgery. MEDLINE papers in English were on line searched with keywords contained in above using PubMed System. For the convexity meningioma, 50-141 cases (mean age, 48-58.9 y) with 1.9-3.6 cm or 146.3 mL of the tumor size or volume were reported in 6 literatures (2006-2011), presenting 0% of surgery related death, 1-5.9% of internal medical or 5.5-37.4% of surgical complication, 0-2% of postoperative hemorrhage, 0-15.4% of neurological and 0-15.4% of prolonged/permanent deficits. For the parasagittal/falx meningioma, 46-108 cases (age, 55-58 y) with 1.9-4 cm tumor were reported in 8 literatures (2004-2011), presenting 0-5.7% death, 2-7.4% medical or 5.4-31% surgical complication, 0-3% hemorrhage, 0-15.4 neurologic and 0-15.4% prolonged deficits. For complications after the radiosurgery of the all 3 meningiomas, 41-832 cases (50-60 y) with tumors of 24.7-28 mm or 4.7-7.4 mL were reported in 8 literatures (2003-2012), presenting the incidence of 6.8-26.8% of radiation-related complications like headache, seizures and paralysis necessary for steroid treatment, and 1.20 or 4.80% of permanent morbidity. For the natural history of incidental meningiomas involving tentorium one, 16-144 cases in 6 literatures (2000-2012) revealed the growth rate/y of 1.9-3.9 mm or 0.54-1.15 mL. The outcome of surgical treatment of the meningiomas, a representative benign tumor, was concluded to be rather good as surgery was generally needed only when the disease became symptomatic due to the tumor growth. (T.T.)

  6. Stereotactic radiotherapy of meningiomas compressing optical pathways

    International Nuclear Information System (INIS)

    Hamm, Klaus-Detlef; Henzel, Martin; Gross, Markus W.; Surber, Gunnar; Kleinert, Gabriele; Engenhart-Cabillic, Rita

    2006-01-01

    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

  7. Preoperative subtyping of meningiomas by perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao [University Medical Center Groningen, University of Groningen (Netherlands); Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China); Department of Radiology, University of Groningen (Netherlands); Roediger, Lars A.; Oudkerk, Matthijs [University Medical Center Groningen, University of Groningen (Netherlands); Department of Radiology, University of Groningen (Netherlands); Shen, Tianzhen [Fudan University Huashan Hospital, Department of Radiology, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China)

    2008-10-15

    This paper aims to evaluate the value of perfusion magnetic resonance (MR) imaging in the preoperative subtyping of meningiomas by analyzing the relative cerebral blood volume (rCBV) of three benign subtypes and anaplastic meningiomas separately. Thirty-seven meningiomas with peritumoral edema (15 meningothelial, ten fibrous, four angiomatous, and eight anaplastic) underwent perfusion MR imaging by using a gradient echo echo-planar sequence. The maximal rCBV (compared with contralateral normal white matter) in both tumoral parenchyma and peritumoral edema of each tumor was measured. The mean rCBVs of each two histological subtypes were compared using one-way analysis of variance and least significant difference tests. A p value less than 0.05 indicated a statistically significant difference. The mean rCBV of meningothelial, fibrous, angiomatous, and anaplastic meningiomas in tumoral parenchyma were 6.93{+-}3.75, 5.61{+-}4.03, 11.86{+-}1.93, and 5.89{+-}3.85, respectively, and in the peritumoral edema 0.87{+-}0.62, 1.38{+-}1.44, 0.87{+-}0.30, and 3.28{+-}1.39, respectively. The mean rCBV in tumoral parenchyma of angiomatous meningiomas and in the peritumoral edema of anaplastic meningiomas were statistically different (p<0.05) from the other types of meningiomas. Perfusion MR imaging can provide useful functional information on meningiomas and help in the preoperative diagnosis of some subtypes of meningiomas. (orig.)

  8. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

    Science.gov (United States)

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-02-16

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

  9. Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?

    Science.gov (United States)

    Haeryfar, S M Mansour; Shaler, Christopher R; Rudak, Patrick T

    2018-02-22

    Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression. On the other hand, they can express a potent arsenal of cytotoxic effector molecules, NKG2D and IFN-γ, all of which have established roles in cancer immune surveillance. In this review, we highlight MAIT cells' characteristics as they might pertain to cancer initiation, progression, or control. We discuss recent findings, including our own, that link MAIT cells to cancer, with a focus on colorectal carcinoma, as well as some of the outstanding questions in this active area of research. Finally, we provide a hypothetical picture in which MAIT cells constitute attractive targets in cancer immunotherapy.

  10. MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis.

    Science.gov (United States)

    Roden, Christine; Lu, Jun

    2016-09-01

    Studies on hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have helped to establish the paradigms of normal and cancer stem cell concepts. For both HSCs and LSCs, specific gene expression programs endowed by their epigenome functionally distinguish them from their differentiated progenies. MicroRNAs (miRNAs), as a class of small non-coding RNAs, act to control post-transcriptional gene expression. Research in the past decade has yielded exciting findings elucidating the roles of miRNAs in control of multiple facets of HSC and LSC biology. Here we review recent progresses on the functions of miRNAs in HSC emergence during development, HSC switch from a fetal/neonatal program to an adult program, HSC self-renewal and quiescence, HSC aging, HSC niche, and malignant stem cells. While multiple different miRNAs regulate a diverse array of targets, two common themes emerge in HSC and LSC biology: miRNA mediated regulation of epigenetic machinery and cell signaling pathways. In addition, we propose that miRNAs themselves behave like epigenetic regulators, as they possess key biochemical and biological properties that can provide both stability and alterability to the epigenetic program. Overall, the studies of miRNAs in stem cells in the hematologic contexts not only provide key understandings to post-transcriptional gene regulation mechanisms in HSCs and LSCs, but also will lend key insights for other stem cell fields.

  11. Modulation of photochemical damage in normal and malignant cells by naturally occurring compounds.

    Science.gov (United States)

    Lee, Yuan-Hao; Kumar, Neeru C; Glickman, Randolph D

    2012-01-01

    Certain phytochemicals, such as the stilbene, resveratrol (RES, found in red grapes and berries), and the triterpenoid, ursolic acid (UA, found in waxy berries and herbs such as rosemary and oregano), have antioxidant, anti-inflammatory and antiproliferative effects. Two human-derived cell lines, hTERT-RPE with a nonmalignant phenotype derived from retinal pigment epithelium, and ATCC CRL-11147 derived from a malignant skin melanoma, were used as in vitro models of photooxidative stress produced by exposure to the broadband output of a 150 W Hg vapor arc lamp at an irradiance of 19-26 mW cm(-2). In untreated cells, UV-VIS broadband light exposure produced a loss of proliferative ability, an activation of NF-κB and an increase in protein carbonyl adducts at 24 h postexposure. Pretreatment of the cells with RES or UA at 1-2 μmsignificantly reduced the amount of phosphorylated NF-κB at 24 h postexposure. RES pretreatment reduced the burden of light-induced protein carbonyl adducts by up to 25% in exposed cells. UA treatment markedly increased the sensitivity of melanoma cells to UV radiation, while conferring some photoprotection to RPE cells. These observations indicate that phytochemicals modulate the cellular response to photochemical stress by interacting with specific cell-signaling pathways. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  12. Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Serena Meraviglia

    2011-12-01

    Full Text Available The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.

  13. Frequency of tuberculosis in haematological malignancies and stem cell transplant recipients

    International Nuclear Information System (INIS)

    Khan, Badsha; Raza, S.; Ahmed, P.; Ullah, K.; Hussain, C.A.; Hussain, I.

    2005-01-01

    Objective: To assess magnitude of tuberculosis (TB) in patients suffering from various haematological malignancies and stem cell transplant (SCT) recipients. Patients and Methods: Patients suffering from various haematological malignancies treated between July 2001 and December 2002 were included in the study. The hospital records and out-patient follow-up charts were reviewed for demographic information, diagnosis, clinical presentation, laboratory investigations, radiological and pathological examinations, sites involved in TB, methods of diagnosis, number and type of anti-tuberculosis drugs given and response to treatment. Results: During the study period a total of 213 (including 25 allogeneic stem cell transplant (SCT) recipients) patients with different haematological disorders were treated. Out of these, 34, including 4 SCT recipients developed tuberculosis. Overall frequency of TB was 16 %. Median age of TB patients was 33.5 years (range 8-80 years). Median time between diagnosis of haematological disorders and tuberculosis was 21 weeks. Sites of involvement by TB were lung (18), disseminated (6), lymph node (5), pleura (2), spine (2) and pericardium (1). Three of the patients died of TB; one undiagnosed, second with multi-drug resistant TB and the third soon after the start of anti-tuberculosis treatment while remaining 31 cases responded to anti-tuberculosis treatment. Conclusion: Tuberculosis is a major problem in immunocompromised patients and there is need to establish guidelines for TB chemoprophylaxis in our setup. (author)

  14. Neuroradiological findings and clinical features of fourth-ventricular meningioma: A study of 10 cases

    International Nuclear Information System (INIS)

    Zhang, B.-Y.; Yin, B.; Li, Y.-X.; Wu, J.-S.; Chen, H.; Wang, X.-Q.; Geng Daoyng

    2012-01-01

    Aim: To present the neuroradiological and clinical findings of fourth-ventricular meningiomas to increase awareness of this entity. Materials and methods: The computed tomography (CT; n = 5), magnetic resonance imaging (MRI; n = 9) features and clinical presentations of 10 patients with pathologically documented fourth-ventricular meningiomas were retrospectively analysed. Results: All tumours appeared as well-demarcated masses in the fourth ventricle at CT and MRI. The tumour shape was round in eight cases (80%) and irregular in two cases (20%). The CT images of five cases showed predominantly isoattenuation in three cases and high attenuation in two cases, with a mean attenuation value of 52 HU. In addition, calcifications were seen in three cases. At MRI, nine masses were isointense (n = 6) or hypointense (n = 3) to grey matter on T1-weighted images and mildly hyperintense (n = 4), isointense (n = 3), hypointense (n = 1), and of mixed signal intensity (n = 1) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Signal voids were visible in two cases. Enhancement after injection of contrast material was marked homogeneous (n = 5) or heterogeneous (n = 5) on CT or T1-weighted images. Three tumours had mild peritumoural oedema. Three tumours were associated with obstructive hydrocephalus. The pathological subtype of the 10 meningiomas was fibromatous (n = 5), atypical (n = 2), and one each of transitional, psammomatous, and clear-cell type. Conclusion: Although fourth-ventricular meningioma is quite rare, it should be considered in differential diagnosis of neoplasms within the fourth ventricle. The relatively typical radiological appearance, combined the age and sex of patients, can suggest the diagnosis of fourth-ventricular meningioma.

  15. Neuroradiological findings and clinical features of fourth-ventricular meningioma: A study of 10 cases

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, B.-Y.; Yin, B.; Li, Y.-X. [Department of Radiology, Huashan Hospital, Fudan University, Shanghai (China); Wu, J.-S. [Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai (China); Chen, H. [Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai (China); Wang, X.-Q., E-mail: wangxq10@126.com [Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai (China); Geng Daoyng, E-mail: fdhsgdy@126.com [Department of Radiology, Huashan Hospital, Fudan University, Shanghai (China)

    2012-05-15

    Aim: To present the neuroradiological and clinical findings of fourth-ventricular meningiomas to increase awareness of this entity. Materials and methods: The computed tomography (CT; n = 5), magnetic resonance imaging (MRI; n = 9) features and clinical presentations of 10 patients with pathologically documented fourth-ventricular meningiomas were retrospectively analysed. Results: All tumours appeared as well-demarcated masses in the fourth ventricle at CT and MRI. The tumour shape was round in eight cases (80%) and irregular in two cases (20%). The CT images of five cases showed predominantly isoattenuation in three cases and high attenuation in two cases, with a mean attenuation value of 52 HU. In addition, calcifications were seen in three cases. At MRI, nine masses were isointense (n = 6) or hypointense (n = 3) to grey matter on T1-weighted images and mildly hyperintense (n = 4), isointense (n = 3), hypointense (n = 1), and of mixed signal intensity (n = 1) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Signal voids were visible in two cases. Enhancement after injection of contrast material was marked homogeneous (n = 5) or heterogeneous (n = 5) on CT or T1-weighted images. Three tumours had mild peritumoural oedema. Three tumours were associated with obstructive hydrocephalus. The pathological subtype of the 10 meningiomas was fibromatous (n = 5), atypical (n = 2), and one each of transitional, psammomatous, and clear-cell type. Conclusion: Although fourth-ventricular meningioma is quite rare, it should be considered in differential diagnosis of neoplasms within the fourth ventricle. The relatively typical radiological appearance, combined the age and sex of patients, can suggest the diagnosis of fourth-ventricular meningioma.

  16. Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

    OpenAIRE

    Ayako Tsuchiya; Yoshiko Kaku; Takashi Nakano; Tomoyuki Nishizaki

    2015-01-01

    1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species ...

  17. Bone marrow-derived CD13+ cells sustain tumor progression: A potential non-malignant target for anticancer therapy.

    Science.gov (United States)

    Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2014-01-01

    Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b + CD13 + myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b + CD13 + myeloid cells could become a non-malignant target for the development of novel anticancer regimens.

  18. Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model

    International Nuclear Information System (INIS)

    Ke, Xi-song; Li, Wen-cheng; Hovland, Randi; Qu, Yi; Liu, Run-hui; McCormack, Emmet; Thorsen, Frits; Olsen, Jan Roger; Molven, Anders; Kogan-Sakin, Ira; Rotter, Varda; Akslen, Lars A.; Oyan, Anne Margrete; Kalland, Karl-Henning

    2011-01-01

    Epithelial to mesenchymal transition (EMT) is pivotal in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to cells with mesenchymal phenotype (EPT1) without malignant transformation. To promote prostate cell transformation, cells were maintained in saturation density cultures to select for cells overriding quiescence. Foci formed repeatedly following around 8 weeks in confluent EPT1 monolayers. Only later passage EPT1, but not EP156T cells of any passage, could form foci. Cells isolated from the foci were named EPT2 and formed robust colonies in soft agar, a malignant feature present neither in EP156T nor in EPT1 cells. EPT2 cells showed additional malignant traits in vitro, including higher ability to proliferate following confluence, higher resistance to apoptosis and lower dependence on exogenous growth factors than EP156T and EPT1 cells. Microarray profiling identified gene sets, many of which belong to cell junction modules, that changed expression from EP156T to EPT1 cells and continued to change from EPT1 to EPT2 cells. Our findings provide a novel stepwise cell culture model in which EMT emerges independently of transformation and is associated with subsequent accumulation of malignant features in prostate cells. Reprogramming of cell junction modules is involved in both steps.

  19. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Falzon, G; Pearson, S; Murison, R; Hall, C; Siu, K; Round, A; Schueltke, E; Kaye, A H; Lewis, R

    2007-01-01

    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

  20. Shape-dependent regulation of proliferation in normal and malignant human cells and its alteration by interferon

    International Nuclear Information System (INIS)

    Kulesh, D.A.; Greene, J.J.

    1986-01-01

    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

  1. Malignant human cell transformation of Marcellus Shale gas drilling flow back water

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yixin [Department of Epidemiology, Shanghai Jiaotong University School of Public Health (China); Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987 (United States); Chen, Tingting [School of Material Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Shen, Steven S. [Biochemistry and Molecular Pharmaceutical, New York University School of Medicine (United States); Niu, Yingmei; DesMarais, Thomas L.; Linn, Reka; Saunders, Eric; Fan, Zhihua [Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987 (United States); Lioy, Paul [Robert Wood Johnson Medical School Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); Kluz, Thomas; Chen, Lung-Chi [Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987 (United States); Wu, Zhuangchun, E-mail: wuzhuangchun@mail.njust.edu.cn [College of Science, Donghua University, Shanghai 201620 (China); Costa, Max, E-mail: max.costa@nyumc.org [Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987 (United States)

    2015-10-01

    The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity and potential carcinogenic effects of these wastewaters, flow back waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed. The physicochemical nature of these samples was analyzed by inductively coupled plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray spectroscopy. A cytotoxicity study using colony formation as the endpoint was carried out to define the LC{sub 50} values of test samples using human bronchial epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to assess the carcinogenic potential of the samples. Barium and strontium were among the most abundant metals in these samples and the same metals were found to be elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for 6 weeks with flow back waters produced colony formation in soft agar that was concentration dependent. In addition, flow back water-transformed BEAS-2B cells show better migration capability when compared to control cells. This study provides information needed to assess the potential health impact of post-hydraulic fracturing flow back waters from Marcellus Shale natural gas mining. - Highlights: • This is the first report of potential cytotoxicity and transforming activity of Marcellus shale gas mining flow back to mammalian cells. • Barium and Strontium were elevated in flow back water exposed cells. • Flow back water malignantly transformed cells and formed tumor in athymic nude mice. • Flow back transformed cells exhibited altered transcriptome with dysregulated cell migration pathway and adherent junction pathway.

  2. Malignant human cell transformation of Marcellus Shale gas drilling flow back water

    International Nuclear Information System (INIS)

    Yao, Yixin; Chen, Tingting; Shen, Steven S.; Niu, Yingmei; DesMarais, Thomas L.; Linn, Reka; Saunders, Eric; Fan, Zhihua; Lioy, Paul; Kluz, Thomas; Chen, Lung-Chi; Wu, Zhuangchun; Costa, Max

    2015-01-01

    The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity and potential carcinogenic effects of these wastewaters, flow back waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed. The physicochemical nature of these samples was analyzed by inductively coupled plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray spectroscopy. A cytotoxicity study using colony formation as the endpoint was carried out to define the LC 50 values of test samples using human bronchial epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to assess the carcinogenic potential of the samples. Barium and strontium were among the most abundant metals in these samples and the same metals were found to be elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for 6 weeks with flow back waters produced colony formation in soft agar that was concentration dependent. In addition, flow back water-transformed BEAS-2B cells show better migration capability when compared to control cells. This study provides information needed to assess the potential health impact of post-hydraulic fracturing flow back waters from Marcellus Shale natural gas mining. - Highlights: • This is the first report of potential cytotoxicity and transforming activity of Marcellus shale gas mining flow back to mammalian cells. • Barium and Strontium were elevated in flow back water exposed cells. • Flow back water malignantly transformed cells and formed tumor in athymic nude mice. • Flow back transformed cells exhibited altered transcriptome with dysregulated cell migration pathway and adherent junction pathway.

  3. Physiological oxygen concentration alters glioma cell malignancy and responsiveness to photodynamic therapy in vitro.

    Science.gov (United States)

    Albert, Ina; Hefti, Martin; Luginbuehl, Vera

    2014-11-01

    The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to 15%. Nevertheless, the majority of in vitro experiments with glioblastoma multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to 21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy. GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX accumulation and localization were investigated, and cell survival and cell death were observed following in vitro PDT. A physiological pO2 of 9% stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha levels, and elevated resistance to camptothecin in U-87 MG cells compared to cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced intracellular PpIX accumulation. However, physiological pO2 changed the responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20% more irradiation light was required to kill U-87 MG cells at physiological pO2, resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and inhibition of caspase 3 activation. Reduction of oxygen concentration from atmospheric to a more physiological level can influence the malignant behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise oxygen concentration control should be considered when designing and performing experiments with GBM cells.

  4. Bcl-2 antisense therapy in B-cell malignant proliferative disorders.

    Science.gov (United States)

    Chanan-Khan, Asher; Czuczman, Myron S

    2004-08-01

    Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms.

  5. Stem Cell Factor-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells

    Directory of Open Access Journals (Sweden)

    Walter Blum

    2017-04-01

    Full Text Available Summary: Malignant mesothelioma (MM is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1 increased resistance to cisplatin, (2 increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3 a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. Overexpression of NF2 (neurofibromatosis 2, merlin, a tumor suppressor often mutated or lost in MM, did not affect proliferation and viability of CSC-enriched MM populations but robustly decreased the viability of reporter-negative cells. In contrast, downregulation of calretinin strongly decreased proliferation and viability of both populations. In summary, we have enriched and characterized a small MM cell subpopulation that bears the expected CSC characteristics. : A cancer stem cell (CSC-enriched malignant mesothelioma (MM cell subpopulation was identified by an OCT4/SOX2 reporter approach. These EGFP-expressing cells showed an altered sensitivity toward chemotherapeutic drugs and a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. While NF2 overexpression had no effect on proliferation/viability of CSC-enriched MM populations, they were susceptible to downregulation of calretinin. Keywords: mesothelioma, cancer stem cells, SOX2, OCT4, NF2, merlin, calretinin, defactinib

  6. Differential effects of malignant mesothelioma cells on THP-1 monocytes and macrophages.

    Science.gov (United States)

    Izzi, Valerio; Chiurchiù, Valerio; D'Aquilio, Fabiola; Palumbo, Camilla; Tresoldi, Ilaria; Modesti, Andrea; Baldini, Patrizia M

    2009-02-01

    Malignant mesothelioma (MM) is a highly fatal tumor arising from inner body membranes, whose extensive growth is facilitated by its week immunogenicity and by its ability to blunt the immune response which should arise from the huge mass of leukocytes typically infiltrating this tumor. It has been reported that the inflammatory infiltrate found in MM tissues is characterized by a high prevalence of macrophages. Thus, in this work we evaluated the ability of human MM cells to modulate the inflammatory phenotype of human THP-1 monocytes and macrophages, a widely used in vitro model of monocyte/macrophage differentiation. Furthermore, we tested the hypothesis that the exposure to MM cells could alter the differentiation of THP-1 monocytes favoring the development of alternatively activated, tumor-supporting macrophages. Our data prove for the first time that MM cells can polarize monocytes towards an altered inflammatory phenotype and macrophages towards an immunosuppressive phenotype. Moreover, we demonstrate that monocytes cocultivated with MM cells 'keep a memory' of their encounter with the tumor which influences their differentiation to macrophages. On the whole, we provide evidence that MM cells exert distinct, cell-specific effects on monocytes and macrophages. The thorough characterization of such effects may be of a crucial importance for the rational design of new immunotherapeutic protocols.

  7. A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells.

    Directory of Open Access Journals (Sweden)

    Ke-Jia Wu

    Full Text Available The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.

  8. Mapping the HLA ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

    Science.gov (United States)

    Löffler, Markus W; Kowalewski, Daniel J; Backert, Linus; Bernhardt, Jörg; Adam, Patrick; Schuster, Heiko; Dengler, Florian; Backes, Daniel; Kopp, Hans-Georg; Beckert, Stefan; Wagner, Silvia; Königsrainer, Ingmar; Kohlbacher, Oliver; Kanz, Lothar; Königsrainer, Alfred; Rammensee, Hans-Georg; Stevanovic, Stefan; Haen, Sebastian P

    2018-05-22

    Immune cell infiltrates have proven highly relevant for colorectal carcinoma (CRC) prognosis, making CRC a promising candidate for immunotherapy. Since tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here we comprehensively describe the naturally presented HLA-ligandome of CRC and corresponding non-malignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA-class I ligands on CRC and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic CRC-associated pathways including Wnt, TGF-β, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired CRC and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be over-represented merely within the CRC ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T cell repertoire. Overall, these data show that the HLA-ligandome reflects cancer-associated pathways implicated in CRC oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived tumor-antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells might comprise promising candidates for immunotherapeutic applications. Copyright ©2018, American Association for Cancer Research.

  9. Primary atypical sacral meningioma- not always benign

    International Nuclear Information System (INIS)

    Bhadra, A.K.; Casey, A.T.H.; Saifuddin, A.; Briggs, T.W.

    2007-01-01

    We present a case of an atypical recurrent meningioma of the sacrum with pulmonary metastasis in a 31-year-old man. He presented with deep-seated buttock pain and urinary hesitancy for 3 months. MRI revealed a lesion occupying the central and left side of the sacral canal at the S1-S2 level. Surgical excision of the lesion via a posterior approach was undertaken, and the patient became symptom-free post-operatively. Histology confirmed atypical meningioma. Eight months later he re-presented with similar symptoms, and MRI confirmed local recurrence. The patient underwent left hemisacrectomy. Six months later he again presented with low back pain and MRI confirmed a second local recurrence. A CT scan of the chest showed multiple lung metastases. The patient died of a severe chest infection 18 months later. (orig.)

  10. Brain edema associated with intracranial meningiomas

    International Nuclear Information System (INIS)

    Asahi, Minoru; Kikuchi, Haruhiko; Hirai, Osamu

    1992-01-01

    Brain edema associated with intracranial meningiomas was investigated on 80 patients, excluding recurrent cases. Statistically significant positive correlations with the degree of edema were found with large tumors, the convexity or parasagittal locations, the venous outflow disturbance, and the evidence of cortical disruption or peritumoral enhancement visualized on computed tomography or magnetic resonance imagings. Patients with a short clinical history and with angiographic evidence of hypervascularity tended to have edema, but there was no statistical significance. It is concluded that various factors are responsible for the edema associated with meningiomas and that it would be hard to determine the most important cause, since each factor plays a part edema production, spread, and resolution. (author)

  11. Olfactory groove meningiomas: approaches and complications.

    Science.gov (United States)

    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.

  12. Primary atypical sacral meningioma- not always benign

    Energy Technology Data Exchange (ETDEWEB)

    Bhadra, A.K.; Casey, A.T.H.; Saifuddin, A.; Briggs, T.W. [Royal National Orthopaedic Hospital, Stanmore, London (United Kingdom)

    2007-06-15

    We present a case of an atypical recurrent meningioma of the sacrum with pulmonary metastasis in a 31-year-old man. He presented with deep-seated buttock pain and urinary hesitancy for 3 months. MRI revealed a lesion occupying the central and left side of the sacral canal at the S1-S2 level. Surgical excision of the lesion via a posterior approach was undertaken, and the patient became symptom-free post-operatively. Histology confirmed atypical meningioma. Eight months later he re-presented with similar symptoms, and MRI confirmed local recurrence. The patient underwent left hemisacrectomy. Six months later he again presented with low back pain and MRI confirmed a second local recurrence. A CT scan of the chest showed multiple lung metastases. The patient died of a severe chest infection 18 months later. (orig.)

  13. Modulation of B-cell receptor and microenvironment signaling by a guanine exchange factor in B-cell malignancies

    International Nuclear Information System (INIS)

    Liao, Wei; Sharma, Sanjai

    2016-01-01

    Objective: Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cells over-express a guanine exchange factor (GEF), Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods: N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor (BCR) and chemokine signaling pathways were compared in the Rasgrf-1 over-expressing and a control transfected cell line. Results: Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions: This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells

  14. Pericytes and endothelial precursor cells: cellular interactions and contributions to malignancy.

    Science.gov (United States)

    Bagley, Rebecca G; Weber, William; Rouleau, Cecile; Teicher, Beverly A

    2005-11-01

    Tumor vasculature is irregular, abnormal, and essential for tumor growth. Pericytes and endothelial precursor cells (EPC) contribute to the formation of blood vessels under angiogenic conditions. As primary cells in culture, pericytes and EPC share many properties such as tube/network formation and response to kinase inhibitors selective for angiogenic pathways. Expression of cell surface proteins including platelet-derived growth factor receptor, vascular cell adhesion molecule, intercellular adhesion molecule, CD105, desmin, and neural growth proteoglycan 2 was similar between pericytes and EPC, whereas expression of P1H12 and lymphocyte function-associated antigen-1 clearly differentiates the cell types. Further distinction was observed in the molecular profiles for expression of angiogenic genes. Pericytes or EPC enhanced the invasion of MDA-MB-231 breast cancer cells in a coculture assay system. The s.c. coinjection of live pericytes or EPC along with MDA-MB-231 cells resulted in an increased rate of tumor growth compared with coinjection of irradiated pericytes or EPC. Microvessel density analysis indicated there was no difference in MDA-MB-231 tumors with or without EPC or pericytes. However, immunohistochemical staining of vasculature suggested that EPC and pericytes may stabilize or normalize vasculature rather than initiate vasculogenesis. In addition, tumors arising from the coinjection of EPC and cancer cells were more likely to develop lymphatic vessels. These results support the notion that pericytes and EPC contribute to malignancy and that these cell types can be useful as cell-based models for tumor vascular development and selection of agents that may provide therapeutic benefit.

  15. Evaluation of preoperative embolization of meningioma

    International Nuclear Information System (INIS)

    Park, Sung Tae; Suh, Dae Chul; Lee, Ho Kyu; Choi, Choong Gon; Lee, Myung Jun; Ji, Eun Kyung; Shin, Byung Suck; Kim, Chang Jin; Kim, Jong Uk; Whang, C. Jin

    1998-01-01

    To evaluate the efficacy and safety of preoperative embolization of intrancranial meningioma.Materials and Methods : We retrospectively reviewed intrancranial meningioma patients (n=37) who underwent preoperative embolization. They were categorized into two groups, skull base lesions (n=22) and non-skull base lesions (n=15), according to tumor location. In addition, embolization results were classified by comparison between pre- and post-embolization angiography as complete (residual tumor staining 10 or 30%). In each group, estimated blood loss (EBL) was estimated by amount of intraoperative transfusion with pre- and post-operative hemoglobin level. Tumor resectability was evaluated by follow-up computed tomography. New symptoms occurring within 24 hours of embolization were considered to be those associated with embolization ; symptoms improved by conservative treatment were regarded as mild, while those resulting in new deficits were considered severe. Results : In the group with skull base lesions (n=22), complete embolization with the criteria of residual tumor staining of less than 30% was performed in 14 patients(EBL=1770ml;complete surgical removal in nine patients and incomplete removal four). Incomplete embolization was performed in eight patients (EBL=3210ml; complete and incomplete removal each in four patients). In the group with non-skull base lesions, complete embolization with the criteria of residual tumor staining of less than 10% was performed in five patients (EBL=970ml) and incomplete embolization in ten (EBL=2260ml). Complete tumor removal was possible in this group regardless of the completeness of preoperative tumor embolization. In a case of intraventricular meningioma (3%), intratumoral hemorrhage occurred on the day following embolization. Other mild post-embolization complications occurred in three cases (8%). Conclusion : Preoperative embolization can be an effective and safe procedure for meningioma and may reduce intraoperative blood

  16. Prostate carcinoma mimicking a sphenoid wing meningioma.

    Science.gov (United States)

    Bradley, Lucas H; Burton, Matthew; Gokden, Murat; Serletis, Demitre

    2015-01-01

    We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. New malignancies after squamous cell carcinoma and melanomas: a population-based study from Norway

    International Nuclear Information System (INIS)

    Robsahm, Trude E; Karagas, Margaret R; Rees, Judy R; Syse, Astri

    2014-01-01

    Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers. All invasive cutaneous malignant melanomas (CMM, N = 28 069) and squamous cell carcinomas (SCC, N = 24 620) diagnosed in Norway during 1955–2008 were included. Rates of new primary cancers in skin cancer survivors were compared to rates of primary malignancies in the general population using standardized incidence ratios (SIR). Discrete-time logistic regression models were applied to individual-level data to estimate cancer risk among those with and without a prior skin cancer, accounting for residential region, education, income, parenthood, marital status and parental cancer status, using a 20% random sample of the entire Norwegian population as reference. Further analyses of the skin cancer cohort were undertaken to determine risk factors related to subsequent cancers. During follow-up, 9608 new primary cancers occurred after an initial skin cancer. SIR analyses showed 50% and 90% increased risks for any cancer after CMM and SCC, respectively (p < 0.01). The logistic regression model suggested even stronger increase after SCC (130%). The highest risk was seen for subsequent skin cancers, but several non-skin cancers were also diagnosed in excess: oral, lung, colon, breast, prostate, thyroid, leukemia, lymphoma and central nervous system. Factors that were associated with increased risk of subsequent cancers include male sex, older age, lower residential latitude, being married and low education and income. Parental cancer did not increase the risk of a subsequent cancer after SCC, but was a significant predictor among younger CMM survivors. Our results provide information on shared environmental and genetic risk factors for first and later cancers and may help to identify

  18. Imaging diagnosis of meningiomas of ethmoid sinuses

    International Nuclear Information System (INIS)

    Lu Bingfeng; Liang Shuming; Li Mao

    2001-01-01

    Objective: To study the imaging features of meningiomas of ethmoid sinuses. Methods: Six cases of meningiomas of ethmoid sinuses verified pathologically were analyzed retrospectively. Results: CT scans of 6 cases exhibited huge cystic masses (n = 3), huge cystic-solid masses (n = 2), huge solid mass (n = 1). The cystic walls were remarkable osteosclerosis. The density of solid masses were homogeneous, or heterogeneous with calcifications and cystic changes, and prominent contrast-enhancement. MR images of 1 case (1/6) showed a cystic-solid mass, the cystic portion was high signal intensity on T 2 WI and low signal intensity on T 1 WI, while the solid mass was iso-signal intensity on T 1 WI and T 2 WI. The solid portion was enhanced. X-ray plain films of 3 cases (3/6) displayed ethmoid sinuses enlargement and high density. Conclusion: For the meningiomas of ethmoid sinuses, CT finding was specific, MRI was helpful in differential diagnosis, and X-ray plain films was of no qualitative value

  19. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Guang Zhang

    2013-01-01

    Full Text Available Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC remains disastrous. Cancer stem cells (CSCs may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2 is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

  20. NATURAL KILLER T CELLS IN HEPATIC LEUCOCYTE INFILTRATES IN PATIENTS WITH MALIGNANT PROCESS AND VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    O. V. Lebedinskaya

    2010-01-01

    Full Text Available Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.

  1. Biological effects of radiation: The induction of malignant transformation and programmed cell death

    International Nuclear Information System (INIS)

    Servomaa, K.

    1991-04-01

    In the Chernobyl explosions and fire, powderized nuclear fuel was released from the reactor core, causing an unexpected fallout. X-ray analysis and scanning electron microscopy showed that the isolated single particles were essentially pure uranium. These uranium aerosols contained all of the nonvolatile fission products, including the b-emitters, 95 Zr, 103 Ru, 106 Ru, 141 Ce, and 144 Ce. The hot particles are extremely effective in inducing malignant transformation in mouse fibroblast cells in vitro. The major factor responsible for this effect is focus promotion caused by a wound-mediated permanent increase in cell proliferation (mitogenesis associated with mutagenesis). Transformed foci were analysed for the activation of c-abl, c-erb-A, c-erb-B, c-fms, c-fos, c-myb, c-myc, c-Ha-ras, c-Ki-ras, c-sis, and c-raf oncogenes at the transcriptional level. The pattern of oncogene activation was found to vary from focus to focus. Long interspersed repeated DNA (L1 or LINE makes up a class of mobile genetic elements which can amplify in the cell genome by retroposition. This element is spontaneously transcriptionally activated at a critical population density and later amplified in rat chloroleukaemia cells. UV light and ionizing radiation induce this activation prematurely, and the activation is followed by programmed cell death (apoptosis) in a sequence of events identical to that seen in LIRn activation occurring spontaneously

  2. Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.

    Science.gov (United States)

    Bobek, Vladimir; Kacprzak, Grzegorz; Rzechonek, Adam; Kolostova, Katarina

    2014-05-01

    Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients. Patients with diagnosed MPM were enrolled into this study. A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope. The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

  3. Incomplete ovariosalpingectomy and subsequent malignant granulosa cell tumor in a female green iguana (Iguana iguana).

    Science.gov (United States)

    Cruz Cardona, Janice A; Conley, Kenneth J; Wellehan, James F X; Farina, Lisa L; Origgi, Francesco C; Wamsley, Heather L

    2011-07-15

    A 9-year-old spayed female green iguana (Iguana iguana) was evaluated because of a distended coelom and weight loss. History included a single episode of egg binding and subsequent bilateral ovariosalpingectomy. Physical examination revealed a mass within the coelomic cavity. Ultrasonography revealed a large, irregular mass with hypoechoic regions and coelomic effusion. Clinicopathologic derangements included heterophilia, monocytosis, lymphopenia, basophilia, hypocholesterolemia, hypoproteinemia, and hypercalcemia. Results of cytologic evaluation of the mass were suggestive of malignant epithelial neoplasia, but neoplastic cells were not found in the effusion. An ovarian tumor was suspected on the basis of clinical signs, clinicopathologic findings, and results of cytologic evaluation of the mass. Surgical exploration revealed a large left ovary, a normal-appearing contralateral ovary, and a mass in the fat body, all of which were removed and submitted for histologic examination. The histologic diagnosis was granulosa cell tumor with metastasis to the fat body. The patient died 11 months after evaluation, and disseminated granulosa cell tumor was confirmed at necropsy; histologic examination at that time also identified systemic mastocytosis. Granulosa cell tumors are uncommon in reptiles, and this was the first granulosa cell tumor described antemortem cytologically, histologically, and ultrastructurally in an iguana. Findings in this iguana underscored concerns associated with incomplete oophorectomy of iguanas; cytologic and histopathologic findings were similar to those observed in other domestic animals. Oophorectomy should be considered as an alternative to standard ovariosalpingectomy to avoid potential complications in pet reptiles, and use of microsurgical instruments and vascular clips is advised.

  4. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

    2014-01-01

    Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

  5. Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies.

    Science.gov (United States)

    Ferry, C; Gemayel, G; Rocha, V; Labopin, M; Esperou, H; Robin, M; de Latour, R P; Ribaud, P; Devergie, A; Leblanc, T; Gluckman, E; Baruchel, A; Socié, G

    2007-08-01

    We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.

  6. Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas

    International Nuclear Information System (INIS)

    Tedeschi, E.; Soricelli, A.; Brunetti, A.; Romano, M.; Bucciero, A.; Iaconetta, G.; Alfieri, A.; Postiglione, A.; Salvatore, M.

    1996-01-01

    To evaluate the possibility of preoperatively obtaining an index of aggressiveness for intracranial meningiomas, we prospectively studied 22 patients with computed tomographic or magnetic resonance imaging evidence of meningeal tumour, using single-photon emission tomography (SPET) of the brain and thallium-201 ( 201 Tl). On a brain-dedicated SPET scanner, a rapid acquisition protocol with early, short scans was started simultaneously with the intravenous administration of 111 MBq 201 Tl, covering the initial intratumoral distribution of the tracer. Twenty minutes post injection, a delayed SPET scan was also obtained. On the reconstructed and attenuation-corrected images we calculated the 201 Tl concentration in tumour and normal contralateral brain tissue, and compared intratumoral tracer concentration in the initial and the final part of the rapid acquisition protocol. Benign and malignant meningiomas were classified as such based on histological examination. In malignant lesions, the ratio of the 201 Tl concentration at 2-4 min post injection to that at 14-16 min was found to be significantly higher than in non-aggressive neoplasms (mean±1 SD: 1.14±0.31 and 0.56±0.13, respectively, P 201 Tl concentration values at 2-4 and at 14-16 min. Our findings suggest that the comparative assessment of intratumoral 201 Tl concentration at 2-4 and at 14-16 min post injection could provide a fast, simple method to differentiate preoperatively intracranial meningiomas with different biological behaviour. (orig.). With 3 figs., 1 tab

  7. Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto; Naito, Motohiko; Ghani, Farhana Ishrat [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Dang, Nam H. [Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610 (United States); Iwata, Satoshi [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer We focused on CD24 and CD26 for further analysis of CSC properties in MM. Black-Right-Pointing-Pointer Their expressions were correlated with chemoresistance, cell growth, and invasion. Black-Right-Pointing-Pointer Their expressions were also correlated with several cancer related genes. Black-Right-Pointing-Pointer The expression of each marker was correlated with different CSC property in Meso1. Black-Right-Pointing-Pointer Phosphorylation of ERK by EGF was regulated by expression of CD26, but not CD24. -- Abstract: Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.

  8. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

    Science.gov (United States)

    Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

    2018-04-05

    B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.

    Science.gov (United States)

    Enomoto, Y; Kitaura, J; Hatakeyama, K; Watanuki, J; Akasaka, T; Kato, N; Shimanuki, M; Nishimura, K; Takahashi, M; Taniwaki, M; Haferlach, C; Siebert, R; Dyer, M J S; Asou, N; Aburatani, H; Nakakuma, H; Kitamura, T; Sonoki, T

    2011-12-01

    MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eμ/miR-125b-TG mice). Eμ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eμ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.

  10. Hepcidin as a possible marker in determination of malignancy degree and sensitivity of breast cancer cells to cytostatic drugs.

    Science.gov (United States)

    Yalovenko, T M; Todor, I M; Lukianova, N Y; Chekhun, V F

    2016-06-01

    To investigate the role of hepcidin (Hepc) in the formation of cells malignant phenotype in vitro and its expression in the dyna-mics of growth of Walker-256 carcinosarcoma with different sensitivity to doxorubicin (Dox). The cell lines used in the analysis included T47D, MCF-7, MDA-MB-231, MDA-MB-468, MCF/CP, and MCF/Dox. Hepc expression was studied by immunocytochemical method. "Free" iron content was determined by EPR spectroscopy. Determination of Hepc expression in homogenates of tumor tissue and in blood serum of rats with Dox-sensitive and -resistant Walker-256 carcinosarcoma was performed. It was found that Hepc levels in breast cancer (BC) cells with high degree of malignancy (MDA-MB-231, MDA-MB-468) and drug-resistant phenotype (MCF/CP, MCF/Dox) were by 1.5-2 times higher (p < 0.05) in comparison with sensitive and less malignant BC cells. The development of drug-resistant phenotype in Walker-256 carcinosarcoma cells was accompanied by increasing of Hepc and "free" iron content (by 2.4 and 1.2 times, respectively). The data of in vitro and in vivo research evidenced on involvement of Hepc in formation of BC cells malignant phenotype and their resistance to Dox.

  11. Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); Guo Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); West China Eye Center of Huaxi Hospital, Sichuan University, Chengdu 610064 (China); Fan Hongsong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)], E-mail: leewave@126.com; Zhang Xingdong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)

    2008-11-15

    To investigate the effects of nano-hydroxyapatite (HA) particles with different morphology on highly malignant melanoma cells, three kinds of HA particles with different morphology were synthesized and co-cultured with highly malignant melanoma cells using phosphate-buffered saline (PBS) as control. A precipitation method with or without citric acid addition as surfactant was used to produce rod-like hydroxyapatite (HA) particles with nano- and micron size, respectively, and a novel oil-in-water emulsion method was employed to prepare ellipse-like nano-HA particles. Particle morphology and size distribution of the as prepared HA powders were characterized by transmission electron microscope (TEM) and dynamic light scattering technique. The nano- and micron HA particles with different morphology were co-cultured with highly malignant melanoma cells. Immunofluorescence analysis and MTT assay were employed to evaluate morphological change of nucleolus and proliferation of tumour cells, respectively. To compare the effects of HA particles on cell response, the PBS without HA particles was used as control. The experiment results indicated that particle nanoscale effect rather than particle morphology of HA was more effective for the inhibition on highly malignant melanoma cells proliferation.

  12. Hormone replacement therapy increases the risk of cranial meningioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....

  13. Suprasellar Anaplastic Meningioma Masquerading As Craniopharyngioma: A Case Report

    Directory of Open Access Journals (Sweden)

    Eman Abdelzaher

    2014-06-01

    Full Text Available Anaplastic meningiomas are uncommon. We report the clinical, radiological and pathological features of an anaplastic meningioma in a young male Egyptian patient presenting as a suprasellar solid/cystic enhancing mass resembling a craniopharyngioma. [J Interdiscipl Histopathol 2014; 2(3.000: 154-157

  14. Lipomatous secretory meningioma: case report and review of the literature

    International Nuclear Information System (INIS)

    Liebig, T.; Hoffmann, T.; Hosten, N.; Sander, B.; Lanksch, W.R.

    1998-01-01

    Secretory meningioma is a rare entity which may be characterised by imaging features unusual for other subtypes of meningoma, such as low attenuation on CT, high (fat-tissue equivalent) signal intensity on T1-weighted MRI, marked surrounding oedema, and irregular contrast enhancement. We report a case of secretory meningioma and review the literature. (orig.) (orig.)

  15. Rare suprasellar chordoid meningioma with INI1 gene mutation ...

    African Journals Online (AJOL)

    Background: Chordoid Meningioma is a rare brain tumour characterized genetically by loss of genetic material from chromosome 22q at cytogenetic level resulting in mutation of NF2 gene. Objectives and case report: In the present report, we described a rare case of suprasellar chordoid meningioma, which presented in a ...

  16. An "off-the-shelf" fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies.

    Science.gov (United States)

    Cooper, Matthew L; Choi, Jaebok; Staser, Karl; Ritchey, Julie K; Devenport, Jessica M; Eckardt, Kayla; Rettig, Michael P; Wang, Bing; Eissenberg, Linda G; Ghobadi, Armin; Gehrs, Leah N; Prior, Julie L; Achilefu, Samuel; Miller, Christopher A; Fronick, Catrina C; O'Neal, Julie; Gao, Feng; Weinstock, David M; Gutierrez, Alejandro; Fulton, Robert S; DiPersio, John F

    2018-02-20

    T cell malignancies represent a group of hematologic cancers with high rates of relapse and mortality in patients for whom no effective targeted therapies exist. The shared expression of target antigens between chimeric antigen receptor (CAR) T cells and malignant T cells has limited the development of CAR-T because of unintended CAR-T fratricide and an inability to harvest sufficient autologous T cells. Here, we describe a fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7+ T cell malignancies and, through CRISPR/Cas9 gene editing, lacks both CD7 and T cell receptor alpha chain (TRAC) expression. UCART7 demonstrates efficacy against human T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary T-ALL in vitro and in vivo without the induction of xenogeneic GvHD. Fratricide-resistant, allo-tolerant "off-the-shelf" CAR-T represents a strategy for treatment of relapsed and refractory T-ALL and non-Hodgkin's T cell lymphoma without a requirement for autologous T cells.

  17. Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

    International Nuclear Information System (INIS)

    Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W.

    1991-01-01

    Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma

  18. Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists

    Science.gov (United States)

    Urso, Loredana; Biasini, Lorena; Zago, Giulia; Calabrese, Fiorella; Conte, Pier Franco; Ciminale, Vincenzo; Pasello, Giulia

    2017-01-01

    Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL. In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs. In vivo studies were conducted on a sarcomatoid MPM mouse model. In all the cell lines tested (with the exception of ZL55, which carries a biallelic loss-of-function mutation of p53), Nutlin 3a enhanced p21, MDM2 and DR5 expression, and decreased survivin expression. These changes were associated to cell cycle arrest but not to a significant induction of apoptosis. A synergistic pro-apoptotic effect was obtained through the association of rhTRAIL in all the cell lines harboring functional p53. This synergistic interaction of MDM2 inhibitor and TRAIL agonist was confirmed using a mouse preclinical model. Our results suggest that the combined targeting of MDM2 and TRAIL might provide a novel therapeutic option for treatment of MPM patients, particularly in the case of sarcomatoid MPM with MDM2 overexpression and functional inactivation of wild-type p53. PMID:28562336

  19. IMMUNE STATE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AT LATE TERMS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    N. V. Minaeva

    2012-01-01

    Full Text Available Abstract. Autologous hematopoietic stem cell transplantation (auto-HSCT is one of the most effective methods for treatment of patients with various forms of hemoblastoses, both in adults and children. However, high-dose chemotherapy protocols used in this procedure are characterized by pronounced myeloand immunotoxicity. Appropriate data concerning immune state at long terms after high-dose chemotherapy and auto-HSCT are sparse and controversial, and there is no consensus on time dynamics of immune system reconstitution. The aim of this study was a comprehensive evaluation of immunity in recipients of auto-HSCT at longer terms. Clinical and immunological testing was performed in ninety-eight patients with hematological malignancies before starting a high-dose chemotherapy, and at late post-transplant period. The state of cellular immunity was assessed as expression of surface CD3+, CD4+, CD8+, CD16+, CD19+ lymphocyte antigens. Humoral immunity was evaluated by serum IgG, IgA, and IgM levels. The studies have revealed disorders of cellular and humoral immunity, as well as nonspecific immune resistance factors in recipients of autologous hematopoietic stem cells at late terms post-transplant. Immune reconstitution in patients receiving highdose consolidation treatment followed by auto-HSCT takes longer time than in patients who did not receive autologous hematopoietic stem cells. Severity of these disturbances and immune reconstitution rates depend on the type of conditioning regimen, and the source of haematopoietic stem cells used for transplantation.

  20. Clinical, ultrasonographic, and laboratory findings in 12 llamas and 12 alpacas with malignant round cell tumors

    Science.gov (United States)

    Martin, Jeanne M.; Valentine, Beth A.; Cebra, Christopher K.

    2010-01-01

    Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings were evaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or was euthanized. Common clinical findings were anorexia, recumbency or weakness, and weight loss or poor growth. Peripheral lymphadenomegaly occurred in only 7 animals and was detected more often at necropsy than during physical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia, hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluid or tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or less prior to death or euthanasia was more common in animals ≤ 2 y of age (9/11) than in older animals (6/13). Regular examination of camelids to include clinical pathology and evaluation of peripheral lymph nodes may result in early detection of MCRT. PMID:21358931

  1. Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer

    DEFF Research Database (Denmark)

    Kier, Maria G; Hansen, Merete K; Lauritsen, Jakob

    2016-01-01

    radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL). Main Outcomes and Measures: Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls. Results: The study......Importance: Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options....... Objective: To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens. Design, Setting, and Participants: This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular...

  2. Early and late endocrinologic complications of the hematopoetic stem cell transplantation performed for hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Murat Albayrak

    2012-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is usedfor various hematologic malignancies seen in childrenand adults. There may be several complications before,during, and after the HSCT. Just one of them is endocrinologiccomplications, since endocrine system (particularlythe pituitary gland, thyroid gland, adrenal glands, andgonads is highly sensitive against various stress. Chemotherapyand/or total body irradiation used as preparativeregimens and immunosuppressive agents (especiallycorticosteroids used for the graft-versus-host diseasecan cause hormonal disorders. Time elapsed after theHSCT, transplantation type (autologous or allogeneic,preparative regimen choice, age, and gender determinesthe complications. A multidisciplinary management containinga specialist of endocrinology for these patients ispreferred. In this report, we reviewed the endocrinologiccomplications that observed after the HSCT in childrenand adults referring to the recent literatures. J Clin ExpInvest 2012; 3(1: 149-156

  3. Improved photochemotherapy of malignant cells with daunomycin and the KTP laser.

    Science.gov (United States)

    Paiva, M B; Saxton, R E; Graeber, I P; Jongewaard, N; Eshraghi, A A; Suh, M J; Paek, W H; Castro, D J

    1998-01-01

    Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 microg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose.

  4. Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

    DEFF Research Database (Denmark)

    Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

    2016-01-01

    . We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

  5. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Science.gov (United States)

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  6. The incidence rate and mortality of malignant brain tumors after 10 years of intensive cell phone use in Taiwan.

    Science.gov (United States)

    Hsu, Min-Huei; Syed-Abdul, Shabbir; Scholl, Jeremiah; Jian, Wen-Shan; Lee, Peisan; Iqbal, Usman; Li, Yu-Chuan

    2013-11-01

    The issue of whether cell phone usage can contribute toward the development of brain tumors has recently been reignited with the International Agency for Research on Cancer classifying radiofrequency electromagnetic fields as 'possibly' carcinogenic to humans in a WHO report. To our knowledge, this is the largest study reporting on the incidence and mortality of malignant brain tumors after long-term use of the cell phone by more than 23 million users. A population-based study was carried out the numbers of cell phone users were collected from the official statistics provided by the National Communication Commission. According to National Cancer Registry, there were 4 incidences and 4 deaths due to malignant neoplasms in Taiwan during the period 2000-2009. The 10 years of observational data show that the intensive user rate of cell phones has had no significant effect on the incidence rate or on the mortality of malignant brain tumors in Taiwan. In conclusion, we do not detect any correlation between the morbidity/mortality of malignant brain tumors and cell phone use in Taiwan. We thus urge international agencies to publish only confirmatory reports with more applicable conclusions in public. This will help spare the public from unnecessary worries.

  7. The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yu-Ling Lin

    2013-01-01

    Full Text Available Glioblastoma multiforme (GBM is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

  8. Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies

    International Nuclear Information System (INIS)

    Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Farzana, T.; Kahlid, M.Z.; Panwani, V.K.; Baig, M.I.; Shakoor, N.

    2004-01-01

    Objective: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematogical malignancies in Pakistan. Patients and Methods: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. Results: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10/sup 9/I was 10 days (range 8 -12 days) and platelet count of > 20 x 10/sup 9/1 was 14 days (12-17 days). Acute graft versus host disease (aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Conclusion: Haematopoietic stem cell transplant

  9. Radiation-induced malignant melanoma following radiation treatment for squamous cell carcinoma of the oral cavity - a case report and review of literature -

    International Nuclear Information System (INIS)

    Shin, Young Ju; Yang, Koang Mo; Suh, Hyun Suk

    1998-01-01

    Malignant melanoma of the oral cavity is rare, accounting for 1 to 8% of all malignant melanomas. The overall prognosis remains poor despite the available treatments such as radical surgery, adjuvant radiotherapy, chemotherapy and immunotherapy due to failure in early detection and tendency in early metastasis. The etiology of mucosal malignant melanoma remains unkown. However, there are few cases of malignant melanoma of the oral cavity reported in the literature, which might be related to preexisting melanosis and radiation treatment. A case with malignant melanoma developed on the same site after 6 years following irradiation for squamous cell carcinoma of the oral cavity is reported in this article

  10. Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

    International Nuclear Information System (INIS)

    Fox, Simon A.; Richards, Alex K.; Kusumah, Ivonne; Perumal, Vanathi; Bolitho, Erin M.; Mutsaers, Steven E.; Dharmarajan, Arun M.

    2013-01-01

    Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer

  11. Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Simon A., E-mail: s.fox@curtin.edu.au [Molecular Pharmacology Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia); Richards, Alex K.; Kusumah, Ivonne; Perumal, Vanathi [Molecular Pharmacology Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia); Bolitho, Erin M. [Western Australian Institute for Medical Research, The University of Western Australia Centre for Medical Research, Perth, WA (Australia); Mutsaers, Steven E. [Lung Institute of Western Australia, Centre for Asthma Allergy and Respiratory Research, University of Western Australia, Nedlands (Australia); Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia and Western Australian Institute for Medical Research, Nedlands (Australia); Dharmarajan, Arun M. [School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia)

    2013-10-11

    Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.

  12. Effects of concomitant temozolomide and radiation therapies on WT1-specific T-cells in malignant glioma

    International Nuclear Information System (INIS)

    Chiba, Yasuyoshi; Hashimoto, Naoya; Tsuboi, Akihiro

    2010-01-01

    Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1-specific T-cells in patients with malignant gliomas. Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8 + T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests. Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, natural killer (NK) cells and natural killer T (NKT) cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count. Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted. (author)

  13. CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

    Science.gov (United States)

    2017-07-13

    Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

  14. Malignant primary germ-cell tumor of the brain: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh (Kobe Municipal Central Hospital (Japan))

    1983-04-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported. The first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe. Total removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule. Histological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma. Primary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma. In this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy.

  15. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

    Directory of Open Access Journals (Sweden)

    Kota Washimi

    Full Text Available 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. [Merkel cell carcinoma: cutaneous manifestation of a highly malignant pre-/pro-B cell neoplasia? : Novel concept about the cellular origin of Merkel cell carcinoma].

    Science.gov (United States)

    Sauer, C M; Chteinberg, E; Rennspiess, D; Kurz, A K; Zur Hausen, A

    2017-03-01

    Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure. Based on histomorphology, gene expression profiling, and molecular analyses, we have recently hypothesized that MCC originates from pre‑/pro-B cells. Here we review putative cells of MCC, including Merkel cells, (epi‑)dermal stem cells, and pro‑/pre-B cells. In the present work, the focus is on the concept of pre‑/pro-B cells as the cellular origin of MCC, which might also impact the understanding of other human small cell malignancies of unknown cellular origin, such as small cell carcinomas of the lung and other anatomical locations. In addition, this concept might pave the way for novel treatment options, especially for advanced MCC.

  17. Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction.

    Directory of Open Access Journals (Sweden)

    Qiuling Tang

    Full Text Available 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.

  18. Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

    Science.gov (United States)

    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

  19. Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors

    NARCIS (Netherlands)

    Agesen, Trude Holmeide; Florenes, Viva Ann; Molenaar, Willemina M.; Lind, Guro E.; Berner, Jeane-Marie; Plaat, Boudewijn E.C.; Komdeur, Rudy; Myklebost, Ola; van den Berg, Eva; Lothe, Ragnhild A.

    The molecular biology underlying the development of highly malignant peripheral nerve sheath tumors (MPNSTs) remains mostly unknown. In the present study, the expression pattern of 10 selected cell cycle components is investigated in a series of 15 MPNSTs from patients with (n = 9) or without (n =

  20. 68Ga DOTATATE PET/CT of Synchronous Meningioma and Prolactinoma.

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Hazarika, Suman

    2016-03-01

    Ga DOTATATE PET/CT in noninvasive characterization of synchronous pituitary neoplasm and meningioma in a 38-year-old man is illustrated. The patient presented with an MRI-detected lobulated enhancing sellar-suprasellar mass with erosion of bony sella measuring 4.5 × 3.5 × 3.4 cm (with differential diagnosis with germ cell tumor) and a right parafalcine mass (2.7 × 2.6 cm) suggesting meningioma. Ga DOTATATE PET/CT demonstrated intense uptake in both lesions, suggesting the sellar mass to be pituitary macroadenoma. The finding of high serum prolactin and normal LH, FSH, cortisol, and testosterone levels suggested diagnosis of prolactinoma, and the patient was started on cabergoline.

  1. Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions

    Directory of Open Access Journals (Sweden)

    Joanna Budna

    2018-01-01

    Full Text Available Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs, indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF-β and IL-10 concentrations and measured expression of FOXP3, CTLA-4, CD28, and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system. TGF-β and IL-10 concentrations were measured using human TGF-β1 and IL-10 ELISA kit. Relative mRNA expression of studied genes was analyzed by real-time PCR. The frequency of Tregs was significantly higher in MPEs compared to benign effusions; however, the level of TGF-β and IL-10 in analyzed groups was comparable, and no correlation between concentrations of TGF-β and IL-10 and percentage of Tregs was observed. Relative mRNA expression of all the genes was higher in CD4+CD25+ compared to CD4+CD25− cells. In CD4+CD25+ cells from MPEs, relative mRNA expression of FOXP3, CTLA-4, and CD28 genes was significantly higher than in benign effusions; however, the level of CD4+CD25+CTLA-4+ cells in analyzed groups showed no significant differences. We found numerous genes correlations in an entire CD4+CD25+ cell subset and CD4+CD25+ cells from MPEs. Enhanced suppressive activity of Tregs is observed in the microenvironment of MPEs. Understanding of relations between cellular and cytokine immunosuppressive factors in tumor microenvironment may determine success of anticancer response.

  2. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    Science.gov (United States)

    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.

  3. Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20-year experience

    International Nuclear Information System (INIS)

    Pourel, Nicolas; Auque, Jean; Bracard, Serge; Hoffstetter, Sylvette; Luporsi, Elisabeth; Vignaud, Jean-Michek; Bey, Pierre

    2001-01-01

    Background: This is a retrospective analysis of a series of meningiomas treated by radiotherapy. Materials and methods: From 1978 to 1997, 45 patients with intracranial meningiomas were referred for external fractionated radiotherapy at Centre Alexis Vautrin. All patients were given 50-70 Gy to the tumor bed (median: 56 Gy), 1.8-2 Gy per fraction. Results: Evaluation was performed in June 1999 using the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1-166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years; overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5 and 8 years. One major radiation-induced complication occurred in this series (decline of cognitive function). According to the indication of radiotherapy, we divided the series into four groups: postoperative irradiation after a first subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (±salvage surgery, 14 patients), 73%; after further recurrence (±salvage surgery, 11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients but one died before 42 months. Age at the time of irradiation (≥60 vs. <60 years) and radiotherapy dose (≥60 vs. <60 Gy) did not influence local control or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a worse outcome than benign lesions (WHO grade I, P<0.01). Conclusions: These results compare favorably with previously published data. External fractionated radiotherapy is well tolerated and effective. There is still a debate about the place of radiotherapy in the treatment of meningiomas: after subtotal resection, should radiotherapy be given postoperatively or at the time of progression? Should radiotherapy replace surgery when the risk of postoperative sequellae is high

  4. Feasibility of Helical Tomotherapy for Debulking Irradiation Before Stem Cell Transplantation in Malignant Lymphoma

    International Nuclear Information System (INIS)

    Chargari, Cyrus; Vernant, Jean-Paul; Tamburini, Jerome; Zefkili, Sofia; Fayolle, Maryse; Campana, Francois; Fourquet, Alain; Kirova, Youlia M.

    2011-01-01

    Purpose: Preliminary clinical experience has suggested that radiation therapy (RT) may be effectively incorporated into conditioning therapy before transplant for patients with refractory/relapsed malignant lymphoma. We investigated the feasibility of debulking selective lymph node irradiation before autologous and/or allogeneic stem cell transplantation (SCT) using helical tomotherapy (HT). Methods and Materials: Six consecutive patients with refractory malignant lymphoma were referred to our institution for salvage HT before SCT. All patients had been previously heavily treated but had bulky residual tumor despite chemotherapy (CT) intensification. Two patients had received previous radiation therapy. HT delivered 30-40 Gy in the involved fields (IF), using 6 MV photons, 2 Gy per daily fraction. Total duration of treatment was 28 to 35 days. Results: Using HT, doses to critical organs (heart, lungs, esophagu, and parotids) were significantly decreased and highly conformational irradiation could be delivered to all clinical target volumes. HT delivery was technically possible, even in patients with lesions extremely difficult to irradiate in other conditions or in patients with previous radiation therapy. No Grade 2 or higher toxicity occurred. Four months after the end of HT, 5 patients experienced complete clinical, radiologic, and metabolic response and were subsequently referred for SCT. Conclusions: By more effectively sparing critical organs, HT may contribute to improving the tolerance of debulking irradiation before allograft. Quality of life may be preserved, and doses to the heart may be decreased. This is particularly relevant in heavily treated patients who are at risk for subsequent heart disease. These preliminary results require further prospective assessment.

  5. PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non-Small Cell Lung Cancer Patients with Malignant Pleural Effusion.

    Science.gov (United States)

    Tseng, Yen-Han; Ho, Hsiang-Ling; Lai, Chiung-Ru; Luo, Yung-Hung; Tseng, Yen-Chiang; Whang-Peng, Jacqueline; Lin, Yi-Hsuan; Chou, Teh-Ying; Chen, Yuh-Min

    2018-03-01

    Whether immunohistochemical staining of programmed death ligand 1 (PD-L1) on cells of pleural effusion could be used to predict response to immunotherapy treatment has not been reported. We retrospectively enrolled patients who had undergone malignant pleural effusion drainage and had effusion cell block specimens from 2014 to 2016. Immunohistochemical staining for PD-L1 was performed with tumor cells, immune cells, and macrophages of all cell block specimens. Immunoactivity was scored as 0 for absence of staining and 1+ for faint, 2+ for moderate, and 3+ for intense membranous staining. Patients' clinicopathological characteristics were also collected. PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of macrophages (p = 0.003) and immune cells (p pleural effusion tumor cells and macrophages. The low intensity of PD-L1 expression in immune cells is associated with the poor survival of patients with lung cancer with malignant pleural effusion. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Kasprzycka, Monika; Zhang, Qian; Witkiewicz, Agnieszka

    2008-01-01

    In this study, we demonstrate that malignant mature CD4(+) T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed...... that FOXP3-expressing cells were common among the CD7-negative enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate...

  7. Posterior fossa meningioma (surgical experiences)

    African Journals Online (AJOL)

    Wael M. Moussa

    2012-08-27

    Aug 27, 2012 ... of the CNS, representing about a third of brain tumors. They arise from the ... subtypes based on cell structure.1–4 In 1979, the World Health. Organization .... anterior or posterior to the internal auditory meatus), petrocli-.

  8. Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Fatima, Zareen; Motosugi, Utaroh; Ishigame, Keiichi; Araki, Tsutomu [University of Yamanashi, Department of Radiology, Chuo-shi, Yamanashi (Japan); Waqar, Ahmed Bilal [University of Yamanashi, Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, Chuo-shi, Yamanashi (Japan); Hori, Masaaki [Juntendo University, Department of Radiology, School of Medicine, Tokyo (Japan); Oishi, Naoki; Katoh, Ryohei [University of Yamanashi, Department of Pathology, Chuo-shi, Yamanashi (Japan); Onodera, Toshiyuki; Yagi, Kazuo [Tokyo Metropolitan University, Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo (Japan)

    2013-08-15

    The purposes of this MR-based study were to calculate q-space imaging (QSI)-derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI). MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI in 17 patients who underwent subsequent surgery. ADC and MDP values were found to have a strong correlation: r = 0.78 (P = <0.0001). Both ADC and MDP values had a significant negative association with TCC: r = -0.53 (p = 0.02) and -0.48 (P = 0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters. In meningiomas, both ADC and MDP may be representative of cell density. (orig.)

  9. Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas

    International Nuclear Information System (INIS)

    Fatima, Zareen; Motosugi, Utaroh; Ishigame, Keiichi; Araki, Tsutomu; Waqar, Ahmed Bilal; Hori, Masaaki; Oishi, Naoki; Katoh, Ryohei; Onodera, Toshiyuki; Yagi, Kazuo

    2013-01-01

    The purposes of this MR-based study were to calculate q-space imaging (QSI)-derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI). MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI in 17 patients who underwent subsequent surgery. ADC and MDP values were found to have a strong correlation: r = 0.78 (P = <0.0001). Both ADC and MDP values had a significant negative association with TCC: r = -0.53 (p = 0.02) and -0.48 (P = 0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters. In meningiomas, both ADC and MDP may be representative of cell density. (orig.)

  10. [Microsurgical removal of olfactory groove meningiomas].

    Science.gov (United States)

    Liang, Ri-Sheng; Zhou, Liang-Fu; Mao, Ying; Zhang, Rong; Yang, Wei-Zhong

    2011-01-01

    To explore an effective method for further improving the surgical results of treatment of olfactory groove meningiomas. Sixty seven cases of olfactory groove meningiomas were treated by microneurosurgery, among which fifty seven were de novo cases, eight were recurrent tumors and the other two re-recurrent cases. Modified Derome approach was used in 12 cases, bilateral subfrontal approach in 28 cases, modified pterional approach in 21 cases and unilateral subfrontal approach in six cases. Tumors were resected microsurgically with radical removal of invaded dura, bone, and paranasal sinus mucosa. Reconstruction was performed in patients with skull base defect. Simpson grade I removal was accomplished in 59 cases, grade II in seven cases and grade IV in one case. Among 57 patients with de novo tumor, Simpson I resection was accomplished in 54 cases. Postoperative rhinorrhea and intracranial infection occurred in one case and was cured after temporal lumbar CSF drainage and antibiotic therapy. Two patients (2.9%) died within one month after operation, i.e.one aged patient of heart failure and the other of severe hypothalamus complication. Forty seven patients (72.3%) were followed up from one to ten years with an average of five years and four months. With the exception of two cases died, among the alive 45 patients, there were only three patients with tumor recurrence, which had undergone Simpson II or IV tumor resection. No recurrence was found in cases with Simpson I tumor removal. Previous blurred vision was not improved in three patients, hemiparalysis in two patients, and the other patients recovered well, resuming previous jobs or being able to take care themselves. Total tumor removal (Simpson I) should be the surgical goal for treatment of olfactory groove meningiomas, especially for de novo cases. An appropriate approach is fundamental in the effort to remove an OGM totally. Appropriate anterior skull base reconstruction with vascularized material is

  11. A case of primary osseous malignant immunoblastic B-cell lymphoma with intracytoplasmic mu lambda immunoglobulin inclusions.

    Science.gov (United States)

    Fiche, M; Le Tourneau, A; Audouin, J; Touzard, R C; Diebold, J

    1990-02-01

    Primary malignant lymphoma of bone, so-called Parker-Jackson reticulosarcoma, is a rare form of extranodal lymphoma with a relatively good prognosis. It often corresponds to B-cell lymphoma of high-grade malignancy. We report a case of mu lambda immunoblastic lymphoma showing two distinctive features: an abundant reactive T-lymphocytic population and unusual intra-cytoplasmic inclusions. These inclusions were PAS positive and consisted of monotypic mu lambda immunoglobulin localized in peculiar aggregates of rough endoplasmic reticulum. Their morphological appearances resembled the well-documented inclusions described in some varieties of non-Hodgkin's lymphoma.

  12. Embolisation of intracranial meningiomas without subsequent surgery

    International Nuclear Information System (INIS)

    Bendszus, M.; Solymosi, L.; Martin-Schrader, I.; Schlake, H.P.

    2003-01-01

    In an open, prospective study, we embolised intracranial meningiomas in seven patients, without subsequent surgery. Follow-up over a mean of 20 months included serial neurological examination, MRI and MR spectroscopy. Clinically, embolisation had no adverse effects. Symptomatic patients showed clinical improvement. On MRI marked tumour shrinkage occurred after embolisation in six patients, and was most pronounced during the first 6 months. In a young boy the tumour was unchanged despite complete angiographic devascularisation. Embolisation without subsequent surgery may cause substantial tumour shrinkage and thus be used in selected in patients. However, thorough follow-up is mandatory to ascertain the effects of embolisation. (orig.)

  13. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

  14. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma.

    Science.gov (United States)

    Sato, Yusuke; Shimizu, Kanako; Shinga, Jun; Hidaka, Michihiro; Kawano, Fumio; Kakimi, Kazuhiro; Yamasaki, Satoru; Asakura, Miki; Fujii, Shin-Ichiro

    2015-03-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1 + CD11b + Ly6G med Ly6C med MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27 + CD11b + NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14 + HLA-DR - and CD14 - HLA-DR - MDSC) in NHL patients and found that higher IL-10-producing CD14 + HLA-DR - MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.

  15. LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

    Science.gov (United States)

    Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

    2013-01-01

    Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

  16. Malignant T Cells Secrete Galectins and Induce Epidermal Hyperproliferation and Disorganized Stratification in a Skin Model of Cutaneous T Cell Lymphoma

    DEFF Research Database (Denmark)

    Thode, Christenze; Andersen, Anders Woetmann; Wandall, Hans H

    2015-01-01

    Cutaneous T cell lymphomas (CTCL) are the most common primary skin lymphomas; which are characterized by an accumulation of malignant T cells in the skin. The early lesion resembles both clinically and histologically benign inflammatory disorders, which also presents with hyperproliferative epide...... in CTCL.Journal of Investigative Dermatology accepted article preview online, 09 July 2014; doi:10.1038/jid.2014.284....

  17. Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues.

    Science.gov (United States)

    Thomas, Mini; Kularatne, Sumith A; Qi, Longwu; Kleindl, Paul; Leamon, Christopher P; Hansen, Michael J; Low, Philip S

    2009-09-01

    Potential clinical applications of small interfering RNA (siRNA) are hampered primarily by delivery issues. We have successfully addressed the delivery problems associated with off-site targeting of highly toxic chemotherapeutic agents by attaching the drugs to tumor-specific ligands that will carry the attached cargo into the desired cancer cell. Indeed, several such tumor-targeted drugs are currently undergoing human clinical trials. We now show that efficient targeting of siRNA to malignant cells and tissues can be achieved by covalent conjugation of small-molecular-weight, high-affinity ligands, such as folic acid and DUPA (2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid), to siRNA. The former ligand binds a folate receptor that is overexpressed on a variety of cancers, whereas the latter ligand binds to prostate-specific membrane antigen that is overexpressed specifically on prostate cancers and the neovasculature of all solid tumors. Using these ligands, we show remarkable receptor-mediated targeting of siRNA to cancer tissues in vitro and in vivo.

  18. Detection of circulating tumour cells in peripheral blood of patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Raphael, Jacques; Massard, Christophe; Gong, Inna Y; Farace, Françoise; Margery, Jacques; Billiot, Fanny; Hollebecque, Antoine; Besse, Benjamin; Soria, Jean-Charles; Planchard, David

    2015-01-01

    The independent prognostic value of Circulating Tumour Cells (CTC) level has been demonstrated in several solid tumours. There is currently few data on Malignant Pleural Mesothelioma (MPM) and CTC. We investigated whether the presence of CTC was correlated with prognosis factors and treatment efficacy. MPM patients (pts) were enrolled in a prospective monocentric study. CTC detection was made using the "CellSearch" assay. The correlation between the presence of CTC and worse prognosis factors was assessed using the X(2) test. Comparison of Overall Survival (OS) and Progression Free Survival (PFS) according to CTC detection was performed using the log-rank test. Twenty-seven MPM pts with a median follow-up of 4.2 months were included. CTC were detected in 44% of pts with a median level of 1.5. No significant correlation was observed between the presence of CTC and worse prognosis factors. Moreover, CTC detection was not a significant predictor of OS or PFS (p=0.155 and p=0.32 respectively). CTC were detected in a small cohort of MPM patients. We couldn't demonstrate a significant prognostic value or a difference in OS/PFS between CTC levels. Further analyses, validation studies and detection techniques are needed to establish their real clinical value in MPM.

  19. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  20. N-Myc knockdown and apigenin treatment controlled growth of malignant neuroblastoma cells having N-Myc amplification.

    Science.gov (United States)

    Hossain, Md Motarab; Banik, Naren L; Ray, Swapan K

    2013-10-15

    Malignant neuroblastomas mostly occur in children and are frequently associated with N-Myc amplification. Oncogene amplification, which is selective increase in copy number of the oncogene, provides survival advantages in solid tumors including malignant neuroblastoma. We have decreased expression of N-Myc oncogene using short hairpin RNA (shRNA) plasmid to increase anti-tumor efficacy of the isoflavonoid apigenin (APG) in human malignant neuroblastoma SK-N-DZ and SK-N-BE2 cell lines that harbor N-Myc amplification. N-Myc knockdown induced morphological and biochemical features of neuronal differentiation. Combination of N-Myc knockdown and APG most effectively induced morphological and biochemical features of apoptotic death. This combination therapy also prevented cell migration and decreased N-Myc driven survival, angiogenic, and invasive factors. Collectively, N-Myc knockdown and APG treatment is a promising strategy for controlling the growth of human malignant neuroblastoma cell lines that harbor N-Myc amplification. © 2013 Elsevier B.V. All rights reserved.

  1. Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

    Directory of Open Access Journals (Sweden)

    Louise J. Smith

    2012-04-01

    Full Text Available Although malignant melanoma (MM and both basal cell carcinoma (BCC and actinic keratosis (AK are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS. In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV.

  2. Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma

    Directory of Open Access Journals (Sweden)

    Gagliardi Franco

    2004-01-01

    Full Text Available Abstract Background The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the early passages in vitro of 17 primary cell lines grown from 3 grade III and from 14 grade IV malignant astrocytoma explants. The explanted tumors were genetically characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing EGR-1 was tested in the primary cell lines. Results Low levels of EGR-1 protein were found in all primary cultures examined, with lower values present in grade IV tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1 protein were significantly correlated to the amount of intracellular fibronectin, but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p = 0.0082. Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the p53 mutated tumor cultures compared to those carrying wild-type p53. Growth arrest was achieved in both types of tumor within 1–2 weeks following infection with a recombinant adenovirus overexpressing EGR-1 but not with the control adenovirus. Conclusions Suppression of EGR-1 is a common event in gliomas and in most cases this is achieved through down-regulation of gene expression. Expression of EGR-1 by recombinant adenovirus infection almost completely abolishes the growth of tumor cells in vitro, regardless of the mutational status of the p53 gene.

  3. CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies.

    Science.gov (United States)

    Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

    2017-01-01

    CD20 is a surface antigen, which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/ relapsed disease. In this regard, new generations of MAbs with enhanced affinity or improved anti-tumor properties have been developed. CD20 directed therapeutics have heterogeneous features and mechanisms of action. Hence, having sufficient knowledge on the immunological and molecular aspects of CD20 based cancer therapy is necessary for predicting the clinical outcomes and taking the necessary measures. An extensive search was performed in PubMed and similar databases for peer-reviewed articles concerning the biology, function and characteristics of CD20 molecule as well as the mechanisms of action and evolutionary process of CD20 targeting agents. This review provides information about the current situation of CD20 targeting immunotherapeutics including MAbs, bispecific antibodies (which exert multiple functions or involve Tcells in tumor elimination) and CAR T-cells (engineered T-cells armed with chimeric antigen receptors). Moreover, limitations, challenges and available solutions regarding the application of CD20 targeting treatments are addressed. Utilization of CD20-targeted therapeutics, due to their diverse properties, requires special considerations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ji Hyun [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Hwang, Yeo Hyun; Lee, David J.; Kim, Dan Hyo; Park, Ji Min [Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, In Ah, E-mail: inah228@snu.ac.kr [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2016-02-01

    Purpose: We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved. Methods and Materials: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed. Results: Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1. Conclusions: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.

  5. MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells

    International Nuclear Information System (INIS)

    Chang, Ji Hyun; Hwang, Yeo Hyun; Lee, David J.; Kim, Dan Hyo; Park, Ji Min; Wu, Hong-Gyun; Kim, In Ah

    2016-01-01

    Purpose: We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved. Methods and Materials: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed. Results: Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1. Conclusions: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.

  6. Population heterogeneity in the surface expression of Ulex europaeus I-lectin (UEA I)-binding sites in cultured malignant and transformed cells

    Energy Technology Data Exchange (ETDEWEB)

    Virtanen, I.; Lehtonen, E.; Naervaenen, O.; Leivo, I.; Lehto, V.P.

    1985-11-01

    We studied the binding of fluorochrome-coupled Ulex europaeus I-lectin (UEA-I) to cultured malignant cells: all human malignant and transformed cells and also mouse teratocarcinoma cells examined gave a homogeneous cell membrane-type of surface staining only in some of the cells. Such a population heterogeneity appeared to be independent of the cell cycle. Instead, other lectin conjugates used bound homogeneously to all cell. In permeabilized cells, a juxtanuclear reticular staining of the Golgi apparatus was seen in the UEA-I-positive cells. No staining of the pericellular matrix components, produced by malignant cells grown in serum-free culture medium, could be obtained with TRITC-UEA-I. UEA-I-lectin recognized most polypeptides from A8387 fibrosarcoma cells and HeLa cells, metabolically labelled with (/sup 3/H)fucose. Furthermore, surface labelling of these cells with the neuraminidase-galactose oxidase/sodium borohydride method disclosed that both UEA-I and Ricinus communis agglutinin I revealed the same major surface glycoproteins. Results with metabolically labelled cells showed, in addition, that UEA-I-lectin did not bind to secreted glycoproteins produced by A8387 cells and recognized by other lectins. The results indicate that transformed and malignant cells show a distinct population heterogeneity in their expression of some cell surface-associated fucosyl glycoconjugates. The results also suggest that malignant cells can glycosylate their membrane and secreted glycoproteins in a different manner.

  7. High incidence of meningioma among Hiroshima atomic bomb survivors

    International Nuclear Information System (INIS)

    Shintani, Takahiro; Hayakawa, Norihiko; Hoshi, Masaharu

    1999-01-01

    Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10 5 persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima. (author)

  8. Stereological analysis of nuclear volume in recurrent meningiomas

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1994-01-01

    A stereological estimation of nuclear volume in recurrent and non-recurrent meningiomas was made. The aim was to investigate whether this method could discriminate between these two groups. We fou