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Sample records for adult anaplastic ependymoma

  1. Anaplastic ependymoma simulating glioblastoma in the cerebrum of an adult.

    PubMed

    Shintaku, Masayuki; Hashimoto, Kenji

    2012-01-01

    A case of anaplastic ependymoma of the cerebral hemisphere in which the histopathological features closely simulated those of glioblastoma is reported. The patient was a 72-year-old woman with a large, well-demarcated tumor in the left temporal lobe. The tumor was totally extirpated, but recurred 18 months later, and the patient died after 4 months. The extirpated tumor was well circumscribed from the surrounding brain tissue and consisted of a sheet-like, dense proliferation of atypical, short spindle or polygonal cells. Extensive geographic necrosis with nuclear pseudopalisading was seen. Although perivascular pseudorosettes were observed in many areas, true ependymal rosettes were absent. Immunohistochemistry for glial fibrillary acidic protein and epithelial membrane antigen and ultrastructural study confirmed the ependymal nature of tumor cells. The histopathological spectrum of anaplastic ependymoma is very wide and reflects the basically dual characteristics of ependymal cells: epithelial and glial phenotypes. The present case indicates that some anaplastic ependymomas strongly express the glial phenotype and also show remarkable anaplastic cytological features, thus closely simulating glioblastoma. The diagnostic criteria for anaplastic ependymoma, and the nosological position of highly anaplastic ependymoma and its possible clinical implications, are briefly discussed.

  2. Anaplastic extramedullary cervical ependymoma with leptomeningeal metastasis.

    PubMed

    Pomeraniec, I J; Dallapiazza, R F; Sumner, H M; Lopes, M B; Shaffrey, C I; Smith, J S

    2015-12-01

    We present a rare extramedullary ependymoma with diffuse spinal metastatic disease, and review the previous reports of extramedullary spinal ependymomas. Ependymomas are the most common intramedullary spinal cord tumor in adults. These tumors rarely present as extramedullary masses. We treated a 23-year-old man with a history of progressive neck, shoulder and arm pain, with sensory and motor symptoms in the C7 dermatome. MRI of the cervical spine demonstrated a ventral contrast-enhancing lesion with evidence of enhancement along the dura and spinal cord of the upper cervical spine, thoracic spine, and cauda equina. He underwent a tumor debulking procedure without complications. Following surgery, he received craniospinal radiation to treat the remaining tumor and diffuse leptomeningeal disease. The final pathology of the tumor revealed that is was a World Health Organization Grade III anaplastic ependymoma. At the 1 year follow-up, the patient had stable imaging and had returned to his preoperative functional status. Of the 19 reported patients with primary intradural, extramedullary spinal ependymomas, two had extradural components and seven had anaplastic grades. Only one tumor with an anaplastic grade resulted in metastatic disease, but without spinal recurrence. To our knowledge, this is the first report of an intradural, extramedullary spinal ependymoma with an anaplastic grade, presenting with concomitant diffuse, nodular leptomeningeal metastasis involving the upper cervical spine, thoracic spine, conus medullaris, and cauda equina. Similar to the treatment of intramedullary ependymomas with metastasis, this patient underwent an aggressive debulking procedure followed by radiation therapy to the entire neuroaxis.

  3. Supratentorial extraventricular anaplastic ependymoma with extracranial metastasis.

    PubMed

    Pachella, Laura A; Kamiya-Matsuoka, Carlos; Lee, Eva Lu T; Olar, Adriana; Yung, W K Alfred

    2015-03-01

    Ependymoma is a relatively rare malignancy accounting for 2.0% of all primary central nervous system tumors in adults. Extracranial metastasis is a very uncommon complication of gliomas, especially of anaplastic ependymomas. The objective of this paper is to show that ependymomas can metastasize to soft tissue and lymph nodes as well as to share our approach to this challenge. We report a male patient with anaplastic ependymoma that recurred, metastasizing to the neck and lymph nodes. Metastatic disease was diagnosed based on clinical presentation of a palpable nodule on the right neck and diffuse cervical lymphadenopathies. A biopsy was obtained and pathology revealed anaplastic ependymoma. Whole-body fluorodeoxyglucose positron emission tomography scan showed metastatic disease in the right mastoid region with diffuse uptake in the cervical lymph nodes. Clinical and radiologic response was achieved after three chemotherapy cycles of etoposide, cisplatin, vincristine, and cyclophosphamide. This case highlights extracranial metastasis to the soft tissue as an atypical presentation of recurrent anaplastic ependymoma. Other reported instances of extracranial metastatic ependymoma with this presentation are discussed. The possible metastatic pathways of intracranial disease are discussed. It also illustrates how extracranial disease remains stable with systemic chemotherapy.

  4. Supratentorial extraventricular anaplastic ependymoma in an adult with repeated intratumoral hemorrhage.

    PubMed

    Iwamoto, Naotaka; Murai, Yasuo; Yamamoto, Yoichiro; Adachi, Koji; Teramoto, Akira

    2014-04-01

    We report the case of a 61-year-old man with supratentorial extraventricular anaplastic ependymoma who presented with repeated intratumoral hemorrhage. The patient was admitted with headache. Computed tomography and magnetic resonance imaging showed an enhancing mass with intratumoral hemorrhage in the right temporal lobe. Gross total resection was performed. The tumor was well demarcated from the brain tissue, and showed no continuity with the ventricular system. Histopathological examination revealed the features of anaplastic ependymoma. Therefore, additional radiation therapy and adjuvant chemotherapy were administered. Ten months later, the tumor recurred with hemorrhage in the spinal canal. This case showed rapid malignant progression and repeated intratumoral hemorrhage within a short period of time, both of which are characteristics of anaplastic ependymomas. Close observation of the central nervous system and adjuvant radiotherapy are mandatory, even if the ependymoma presents with repeated intratumoral hemorrhage.

  5. [Surgical seeding of an anaplastic ependymoma].

    PubMed

    Yamada, Masayuki; Sato, Taku; Kuromi, Yosuke; Matsumoto, Yuka; Oda, Keiko; Kishida, Yugo; Tamura, Takamitsu; Ichikawa, Masahiro; Sakuma, Jun; Saito, Kiyoshi

    2013-12-01

    Ependymomas can relapse at the primary site and disseminate to the spinal cord. Furthermore, extraneural metastases are rare. We present a case of anaplastic ependymoma with extraneural metastasis, possibly caused by surgical seeding. An 18-year-old female was referred to us after experiencing frequent convulsive attacks. At age 9 years, she underwent partial resection of a left frontal anaplastic ependymoma, followed by 45 Gy radiation. At age 15 years, a recurrent tumor was totally removed. Three years later, magnetic resonance images revealed a left frontal recurrent tumor and a new parietal lesion. Our preoperative diagnosis of the parietal tumor was a radiation-induced meningioma. However, intraoperative pathological examinations revealed the lesion to be an anaplastic ependymoma. The tumor, which was located in the epidural space and had invaded extensively into the cranial bone, was gross totally removed. Although extremely rare, surgical seeding of anaplastic ependymomas should be considered as a differential diagnosis for recurrent tumors in the surgical field.

  6. Anaplastic ependymoma with ependymoblastic multilayered rosettes.

    PubMed

    Nobusawa, Sumihito; Suzuki, Aya; Nagaishi, Masaya; Isoda, Koji; Ikota, Hayato; Yokoo, Hideaki; Hirato, Junko; Nakazato, Yoichi

    2013-11-01

    Anaplastic ependymoma, World Health Organization grade III, is a malignant glioma with ependymal differentiation characterized by high mitotic activity often accompanied by microvascular proliferation and necrosis, where, generally, much fewer ependymal rosettes are found than in ependymoma, World Health Organization grade II. Ependymal rosettes, forming a single layer of tumor cells, differ from ependymoblastic multilayered rosettes, which are characteristic histologic features of ependymoblastoma, a variant of central nervous system primitive neuroectodermal tumor. Here, we report an autopsy case involving a 24-year-old woman with a frontal lobe tumor, which showed the aggregation of true rosettes with multilayering of tumor cells resembling the ependymoblastoma histology. Molecular and cytogenetic analyses revealed the absence of 19q13.42 amplification, a specific molecular hallmark of ependymoblastoma and embryonal tumor with abundant neuropil and true rosettes, supporting the diagnosis of anaplastic ependymoma.

  7. Ependymoma

    MedlinePlus

    ... Information > Types of Tumors Ependymomas arise from the ependymal cells that line the ventricles of the brain and ... Ependymomas (grade II): The most common of the ependymal tumors. This type can be ... and tancytic ependymomas. Anaplastic ependymomas (grade III): ...

  8. Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

    PubMed

    Komori, Kazutoshi; Yanagisawa, Ryu; Miyairi, Yosuke; Sakashita, Kazuo; Shiohara, Masaaki; Fujihara, Ikuko; Morita, Daisuke; Nakamura, Tomohiko; Ogiso, Yoshifumi; Sano, Kenji; Shirahata, Mitsuaki; Fukuoka, Kohei; Ichimura, Koichi; Shigeta, Hiroaki

    2016-01-01

    The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

  9. Supratentorial extraventricular WHO grade III (anaplastic) ependymoma 17 years after total removal of WHO grade II ependymoma of the fourth ventricle.

    PubMed

    Takeda, Naoya; Nishihara, Masamitsu; Harada, Tomoaki; Kidoguchi, Keiji; Hashimoto, Kimio

    2017-04-01

    We report a WHO grade III ependymoma of the supratentorial interhemispheric fissure and grew to form a large mass with anaplastic transformation without local recurrence 17 years after the total removal of a fourth ventricular WHO grade II ependymoma. We emphasize the necessity of long-term follow-up, even in benign ependymomas.

  10. Magnetic resonance imaging findings of extraventricular anaplastic ependymoma: A report of 11 cases

    PubMed Central

    Leng, Xi; Tan, Xin; Zhang, Chi; Lin, Huan; Qiu, Shijun

    2016-01-01

    Anaplastic ependymomas are rare malignant tumors of the central nervous system. Few studies are available regarding their neuroradiological characteristics. The present study aimed to retrospectively review a series of patients with extraventricular anaplastic ependymoma and to analyze the magnetic resonance imaging (MRI) characteristics to distinguish anaplastic ependymoma from other intracranial tumors. The clinical and pathological images of 11 patients who presented with histologically proven anaplastic ependymoma at Nanfang Hospital (Southern Medical University, Guangzhou, Guangdong, China) between September 2004 and March 2015 were retrospectively reviewed. MRI scans were obtained in all 11 cases. Computed tomography scans were obtained in only 3 cases. In total, 8 tumors were located at the supratentorial parenchyma, and 3 tumors were derived from the cerebellar hemisphere. Images displayed quasi-circular (4/11), irregularly-lobulated (7/11) variable-intensity masses. The masses presented with cysts or necrosis (8/11), hemorrhage (7/11), marked (9/11) or mild (2/11) enhancement, and moderate (4/11), mild (3/11) or absent (4/11) peritumoral edema. The tumors were also frequently closely associated with the lateral ventricle (6/11). Tumors appeared isointense to hypointense on T1-weighted imaging (T1WI) and heterogeneously hyperintense or hypointense on T2WI, demonstrating wreath-like and ring-like characteristics, with intratumoral nodules (3/11) or marked flake-like inhomogeneous (6/11) enhancement on post-contrast MRI. Only 2 solid lesions showed mild enhancement (2/11). Although the MRI features of the extraventricular anaplastic ependymomas varied and were non-specific, these characteristic MRI findings, combined with the locations of the lesions, the age of onset and the short disease course, could be useful in differentiating anaplastic ependymomas from other intracranial neoplasms in the future. PMID:27602137

  11. Ectopic cortical anaplastic ependymoma: an unusual case report and literature review.

    PubMed

    Zhang, Ji; Sai, Ke; Wang, Jian; Chen, Yin Shen; Yan, Shu-Mei; Chen, Zhong-Ping

    2014-09-01

    Ependymona occasionally occurs outside the ventricular structures, which is called ectopic ependymona (EE), while pure cortex location is uncommon. However, cortical anaplastic ependymoma (CE) is rare, especially in children. There were only four primary CEs, which is located in the superficial cortex, were reported the age of the patient under 12 years old. The present case is a 20-month-old boy presenting with simple partial seizure was treated in our department. Cranial magnetic resonance imaging (MRI) revealed a fronto-parietal lobe mass of more than 50mm in diameter with mixed signal intensity. Total removal of the mass lesion was performed without any neurological deficit. Pathological examination of the excised tumor were consistent with anaplastic ependymoma (AE). The patient had a good recovery after his surgical resection. Radiotherapy and chemotherapy were not taken into account in view of his age, the favorable site and the complete resection. The management of this unusual tumor is summarized in this paper.

  12. Predictors of survival among older adults with ependymoma.

    PubMed

    Amirian, E Susan; Armstrong, Terri S; Gilbert, Mark R; Scheurer, Michael E

    2012-03-01

    The biological process of aging encompasses a multitude of complex physiological and lifestyle changes that may alter the way typical prognostic factors affect survival among older ependymoma patients. Because very little is known about the clinical significance of traditional prognostic factors and the magnitude of their effects among older individuals, the purpose of this study was to evaluate the associations between survival and demographic and tumor characteristics among patients with ependymoma who were 60 years of age or older. Using the 1973-2007 dataset from the Surveillance, Epidemiology and End Results (SEER) program, we evaluated the impact of several factors on both overall and ependymoma-specific survival, utilizing multivariable Cox proportional hazards regression. We identified 367 ependymoma cases who were 60 years of age or older at diagnosis and had complete data from SEER. Of these, 19 (5.2%) had anaplastic tumors; all others were low-grade tumors. Age, tumor site, extent of surgery, and tumor histology were found to be significant predictors of ependymoma prognosis. The strongest predictor of poor outcome was supratentorial tumor location (adjusted HR: 6.94, 95% CI: 3.19-15.08, compared to spinal cord tumors). Our study suggests that tumor location, tumor histology, and surgical margin may be key predictors of survival among older ependymoma patients. We believe our study is one of the first to assess the prognostic value of these factors for ependymoma survival exclusively in an older patient population.

  13. Radiation-induced anaplastic ependymoma mimicking a skull base meningioma: A case report

    PubMed Central

    SPALLONE, ALDO; MARCHIONE, PASQUALE; DI CAPUA, MARIO; BELVISI, DANIELE

    2016-01-01

    The present study describes the case of a 63-year-old woman presenting with headache, dizziness and vomiting due to a an ovoid mass in the left pre-bulbar cistern, apparently arising from the lower clivus and the foramen magnum. The clinical history revealed the subtotal removal of a right cerebellar low-grade glioma 15 years previously and subsequent conventional 60-Gy radiotherapy. Notably, following gross total resection, histopathological examination showed microscopic features that resulted in a diagnosis of anaplastic ependymoma. The patient underwent surgery to remove the mass and post-operative chemotherapy with temozolomide. A progressive improvement of neurological signs and symptoms was observed during the postoperative course. At the 6-month follow-up, the patient was free from clinical and radiological recurrence. The unusual features of this rare secondary brain tumor were the extrassial location in the posterior fossa, the unusual age-associated location of the histological subtype and the fact that it closely mimicked a skull-base meningioma. PMID:26893630

  14. Anaplastic Ependymoma in a Child With Sickle Cell Anemia: A Case Report Highlighting Treatment Challenges for Young Children With Central Nervous System Tumors and Underlying Vasculopathy.

    PubMed

    Crotty, Erin E; Meier, Emily R; Wells, Elizabeth M; Hwang, Eugene I; Packer, Roger J

    2016-03-01

    A 3-year-old boy with sickle cell anemia (SCA) presented with progressive daily emesis and was found to have an anaplastic ependymoma. Radiation therapy and chemotherapy are usually employed after subtotal resections of anaplastic ependymomas, although the benefits from chemotherapy are unclear. To mitigate the risks of adjuvant treatment in this patient at risk for SCA-associated vasculopathy, renal impairment, and other end-organ damage, proton beam irradiation without chemotherapy was chosen. Scheduled packed red blood cell transfusions were instituted to maintain sickle hemoglobin levels less than 30%. This case highlights treatment complexities for malignant brain tumors in patients predisposed to treatment-related adverse effects.

  15. [Early magnetic resonance imaging detection of a cavernous angioma after cranial radiotherapy for an anaplastic ependymoma in a boy].

    PubMed

    Martínez León, M I

    2013-01-01

    Radiotherapy forms part of most therapeutic, preventive, and conditioning regimens in pediatric oncology. Numerous late secondary effects of cranial radiation are well known. However, radiation-induced cavernous angiomas (RICA) have been reported only sporadically and even fewer cases of earlier presentation of RICA have been reported. In this brief report, we describe a RICA that appeared in a boy treated for a CNS tumor (an infratentorial anaplastic ependymoma) after a short latency period between the end of radiotherapy and the development of the RICA. We comment on the different variables proposed to explain the formation of these lesions, as well as on their imaging features, treatment, prognosis, and follow-up.

  16. Ependymoma in adults: Local experience with an uncommon tumour.

    PubMed

    Asaid, Mina; Preece, Patrick D; Rosenthal, Mark A; Drummond, Katharine J

    2015-09-01

    This study reviews our tertiary hospital experience in an adult population of ependymoma patients. Ependymomas are uncommon tumours of the central nervous system (CNS) and the literature provides little information to guide management and predict prognosis. The prospectively maintained Australian Comprehensive Cancer Outcomes and Research Database of CNS tumours was searched for patients diagnosed with ependymomas at the Royal Melbourne Hospital between January 2008 and December 2013. A total of 39 adult patients with ependymoma were identified, including 13 with spinal myxopapillary ependymoma. The mean age at diagnosis was 44 years. All patients underwent surgical resection, 67% of whom had a gross macroscopic resection. Postoperative adjuvant radiotherapy was administered to 11 patients (30%), two (5%) died from progressive disease and seven (18%) developed recurrent disease. Our findings are consistent with the existing literature for patient demographics and the approach to treatment, whilst our clinical outcomes appear more favourable. This study provides the basis for further and necessary research, including determination of the molecular characterisation of these tumours and the identification of prognostic and predictive biomarkers and treatment targets.

  17. Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma

    ClinicalTrials.gov

    2015-08-18

    Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma

  18. Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2.

    PubMed

    Walbert, Tobias; Mendoza, Tito R; Vera-Bolaños, Elizabeth; Acquaye, Alvina; Gilbert, Mark R; Armstrong, Terri S

    2015-01-01

    Ependymoma is a rare central nervous system tumor of adults. Reports of patient symptoms, interference patterns and costs encountered by patients and families are limited. Adult ependymoma patients completed the online Ependymoma Outcomes Questionnaire II. The survey assesses disease and functional status as well as socio-economic factors. Descriptive statistics were used to report disease characteristics as well as economic and social impact. Independent samples t test was used to test if differences exist between high- and low-income groups in terms of symptom severity. Correlations were calculated between symptoms and cost estimates. 86 international patients participated (male = 50 %). The economic analysis focused on 78 respondents from the US. 48 % were employed and 55 % earned ≥$60,000. Tumors were located in the brain (44 %), spine (44 %) or both (12 %). Spine patients compared to brain patients reported significantly worse pain (4.4 versus 2.2, p < .003), numbness (5.3 versus 2.2, p < .001), fatigue (5.1 versus 3.6, p < .03), changes in bowel patterns (3.8 versus 1.4, p < .003) and weakness (4.2 versus 2.1, p < .006). Brain patients compared with spine patients had increased lack of appetite (.4 versus 2, p < .014). Patients with lower income (≤$59,999) had more problems concentrating (p < .024) and worse cognitive module severity scores (p < .024). Estimated average monthly out-of-pocket spending was $168 for medical co-pays and $59 for prescription medication. Patients with ependymoma are highly affected by their symptoms. Spinal patients report higher severity of symptoms. Patients in the lower income group report significantly higher severity of cognitive symptoms independent of disease site.

  19. “Drop” Metastases from an Operated Case of Intracranial Anaplastic Ependymoma Identified on Fluoro-2-deoxyglucose Positron Emission Tomography/Computed Tomography

    PubMed Central

    Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

    2017-01-01

    The seeding of tumor through cerebrospinal fluid (CSF) from primary intracranial tumors is very rare, often goes undetected, and is usually identified only on autopsy. CSF cytology along with magnetic resonance imaging constitutes the standard approach of diagnosing this grave condition. Use of fluoro-2-deoxyglucose positron emission tomography/computed tomography (PET/CT) in indentifying spinal metastases from primary intracranial malignancies is very limited and has been reported in patients with metastatic glioblastoma multiforme and medulloblastomas. We present a rare case of metastatic anaplastic ependymoma to show the potentially clinically utility of PET/CT in diagnosing leptomeningeal or the so-called “drop” metastases. PMID:28242994

  20. Prognosis of ependymoma.

    PubMed

    Schiffer, D; Giordana, M T

    1998-08-01

    Ependymoma is a rare tumor entity. It affects children and adults and has four preferential locations: supra- and infra-tentorial, spinal, and conus-cauda-filum. For statistical reasons, therefore, it is difficult to identify prognostic factors in series from single institutions because of the limited number of cases. The problem is complicated by the existence of some variants and by the difficulty in recognizing the anaplastic variant, because the common criteria used for recognizing malignancy in gliomas are not completely reliable in ependymomas. Apart from age and location, many parameters have been considered for prognostic purposes, including extension of surgical removal and radiotherapy. Among histological factors, the number of mitoses, labelling indices of proliferation markers, and cell density turned out to be good parameters for prognostic purposes. An overview is given of the contributions in the literature, including our own, on this problem.

  1. Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors.

    PubMed

    Hollon, Todd; Nguyen, Vincent; Smith, Brandon W; Lewis, Spencer; Junck, Larry; Orringer, Daniel A

    2016-08-01

    OBJECTIVE Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall survival (OS), and prognostic factors for hemispheric ependymomas. METHODS The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors. RESULTS Anaplastic histology/WHO Grade III tumors were identified in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identified on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS. CONCLUSIONS A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients

  2. Disseminated spinal myxopapillary ependymoma in an adult at initial presentation: a case report and review of the literature.

    PubMed

    Straus, David; Tan, Lee A; Takagi, Ippei; O'Toole, John E

    2014-10-01

    Disseminated spinal myxopapillary ependymoma (MPE) is extremely rare in adults. We report a 63-year-old man with chronic low-back pain found to have multiple MPEs in the thoracic, lumbar and sacral spine. Diagnostic and management strategies of disseminated MPE are discussed with a review of pertinent literature.

  3. Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: a multifactorial analysis of 176 patients.

    PubMed

    Chen, Chunjui; Chen, Lingchao; Yao, Yu; Qin, Zhiyong; Chen, Hong

    2016-03-01

    Ependymoma typically has a better overall survival rate than most gliomas. Only a few comprehensive clinical studies have been published, but these are mostly from Western countries and use small sample sizes. Histopathological classification is not sufficient to show variable outcomes, and fails to show prognostic markers of the diverse outcomes; hence, it is essential to understand biological mechanisms. In this study, 176 ependymoma samples (World Health Organization grade II and III) were reviewed at Huashan Hospital. Both children and adults were included. We performed multifactorial analyses of clinical prognostic factors and the biomolecular marker expressions of nucleolin, epidermal growth factor receptor (EGFR) and caveolae-associated protein caveolin-1 by immunohistochemistry. We identified the probabilities of progression-free survival and overall survival using univariate and multivariate statistical methods. The participants were diagnosed with ependymomas between 2002 and 2010, including distributions of tumor locations in intracranial and extracranial regions. Nucleolin was overexpressed in 67 % of our samples, demonstrating a subgroup with poor outcome; particularly infratentorial and anaplastic ependymomas. There was no significant correlation between the expression of EGFR and caveolin-1 and clinical outcomes. Clinically, inferior prognosis was observed with regard to age (<18 years), intracranial location, high grade ependymomas, and incomplete resection. We found that nucleolin was an unfavorable prognostic predictor for ependymomas. Moreover, our findings show a subset of aggravating outcomes in high-grade and posterior fossa tumors.

  4. Radiation combined with temozolomide contraindicated for young adults diagnosed with anaplastic glioma

    PubMed Central

    Cai, Jinquan; You, Gan; Wang, Yinyan; Qiu, Xiaoguang; Li, Shouwei; Wu, Chenxing; Yao, Kun; Li, Wenbin; Peng, Xiaoxia; Zhang, Wei; Jiang, Tao

    2016-01-01

    Purpose Age is a major prognostic factor for malignant gliomas. However, few studies have investigated the management of gliomas in young adults. We determined the role of survival and treatment in young adults with advanced gliomas in a large population from the Chinese Glioma Genome Atlas (CGGA). Methods This study included 726 adults (age ≥ 18) with histologically proven anaplastic glioma or glioblastoma multiforme (GBM). The overall and progression-free survival was determined in young (age < 50) and older groups (age ≥ 50). Results The study included an older group (OP) of 264 patients and a younger group (YP) of 462patients. In the OP group with GBM and anaplastic glioma, patients treated with RT combined with temozolomide (TMZ) manifested significantly longer OS and PFS compared with patients assigned to RT alone (P < 0.05). In contrast, the YP group diagnosed with anaplastic glioma failed to show any survival advantage with RT plus TMZ compared with RT alone. Conclusions We observed no survival benefit in young adults (age < 50) with anaplastic glioma when treated with TMZ combined with RT. Our findings warrant further investigation of younger patients diagnosed with anaplastic glioma treated with radiotherapy plus TMZ chemotherapy. PMID:27590514

  5. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    ClinicalTrials.gov

    2016-12-07

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  6. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  7. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  8. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    PubMed

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

  9. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features

    PubMed Central

    Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-01-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution. PMID:25882650

  10. Supratentorial cortical ependymoma: case series and review of the literature.

    PubMed

    Liu, Zhiguo; Li, Jing; Liu, Zhiyan; Wang, Qian; Famer, Peter; Mehta, Ashesh; Chalif, David; Wang, Yunyan; Li, Jian Yi

    2014-06-01

    Supratentorial cortical ependymoma (CE), a rare type of ependymoma, is located in the superficial cortex. We reported 11 patients (six female and five male) with CE. The age of the patients ranged from 2 to 63 years old with a median age of 47 years at the time of diagnosis. On MRI, enhancement was noted in all cases with solid appearance in six cases, and solid and cystic appearance in five cases. The frontal and parietal regions were the most common locations for CE. On histology, two were low-grade (WHO grade II) and nine were WHO grade III anaplastic ependymomas. Some tumors exhibited clear cell, spindle (tanycytic) and giant cell morphologies, as well as the classic ependymoma morphology. Dura-based tumor nodules and even tumor dissemination along the dura can be seen in CEs. Low grade CEs have a higher likelihood to present with seizures, a lower likelihood to cause brain edema, tumor recurrence and lower mortality than anaplastic ependymomas. While difficult, anaplastic CEs may be distinguished from glioblastoma by a clear interface between tumor and adjacent brain tissue, relative uniformity of tumor cell nuclei and immunopositivity for epithelial membrane antigen and/or CD99. As is the case for ependymomas in general, gross total resection is still the treatment of choice for CEs.

  11. Concomitant Double Tumors of Myxopapillary Ependymoma Presented at Cauda Equina-Filum Terminale in Adult Patient

    PubMed Central

    Güdük, Mustafa; Ekşi, Murat Şakir; Aytar, Murat Hamit; Sav, Aydın; Özgen, Serdar

    2016-01-01

    A 32-year-old man presented with gradually increasing bilateral buttock pain. He had intermittent claudication. Multiple, homogenously enhanced intradural extramedullary lesions at L2-L3 and L5-S1 levels were observed on magnetic resonance imaging. The tumors were debulked and were removed in piecemeal pattern until they had completely been resected. Histopathological examination of the surgical specimens confirmed that both tumors were myxopapillary ependymomas (MPE). MPE presenting as concomitant double tumor at conus-cauda-filum level are very rare. This kind of presentation could not be directly considered as dissemination, since both tumors were in the site of classical origin of MPE. Ten cases of double spinal MPEs have been reported to date. Including the present case, analysis of the 11 patients revealed some facts. There is a male predominance, which is opposite to the ependymomas that are commonly observed in females. Median age at presentation is 15 years. Most pronounced symptom is low back pain that sometimes radiates to lower extremities. Surgical approach was aimed in all tumors, which could be succeeded in all tumors except one. Adjuvant radiation therapy was applied in 5 patients. No recurrences have been reported after surgery or surgery + radiotherapy regimens. PMID:27123029

  12. Cytologic diagnosis of spinal cord ependymoma in cerebrospinal fluid.

    PubMed

    Kalogeraki, A; Tamiolakis, D; Sinatkas, V; Xekalou, A; Papadakis, M; Stathopoulos, E N

    2012-12-01

    Ependymoma cells are known to rarely exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the author's knowledge the cytomorphologic features of tumour cells have not been well described to date. In this study, the CSF findings in a patient with ependymoma and the cytopathological features of this tumor are reported. The patient presented at the University Hospital of Heraklion, Crete, suffering from a chest to back pain. Computed tomography, scanning and magnetic resonance imaging (MRI) were performed and a mass of 3x2 cm in the thoracic aspect of the spinal cord was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic examination and a diagnosis of ependymoma was made. A biopsy was performed and histology confirmed the cytologic diagnosis of ependymoma grade II (WHO). Exfoliated cells from ependymomas of spinal cord are rarely recognizable in CSF samples. Except in patients with myxopapillary tumours and anaplastic tumours, cytomorphologic features of ependymoma have been described only in case reports of intraoperative imprinting or fine needle aspiration biopsies (FNABs) and not in CSF cytology.

  13. CDKN2A/p16 in ependymomas.

    PubMed

    Bortolotto, S; Chiadò-Piat, L; Cavalla, P; Bosone, I; Mauro, A; Schiffer, D

    2001-08-01

    Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.

  14. Extraneural metastasis of an ependymoma: a rare occurrence.

    PubMed

    Alzahrani, Ahmed; Alassiri, Ali; Kashgari, Amna; Alrehaili, Jihad; Alshaalan, Hesham; Zakzouk, Reem

    2014-04-01

    Extraneural metastases of ependymoma are very rare, and have been reported in the lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone. We describe the radiological findings of pathologically proven lung metastases from an anaplastic ependymoma. The tumor which arose in the posterior fossa was first diagnosed in 2007 when first surgical resection was performed outside our institute. Multiple operations were performed after that due to tumor relapse. Multiple lung nodules were discovered incidentally during a VP shunt survey. Biopsy from the lung nodules displayed identical histomorphology to the primary brain tumor.

  15. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors.

    PubMed

    Lassman, Andrew B; Iwamoto, Fabio M; Cloughesy, Timothy F; Aldape, Kenneth D; Rivera, Andreana L; Eichler, April F; Louis, David N; Paleologos, Nina A; Fisher, Barbara J; Ashby, Lynn S; Cairncross, J Gregory; Roldán, Gloria B; Wen, Patrick Y; Ligon, Keith L; Schiff, David; Robins, H Ian; Rocque, Brandon G; Chamberlain, Marc C; Mason, Warren P; Weaver, Susan A; Green, Richard M; Kamar, Francois G; Abrey, Lauren E; DeAngelis, Lisa M; Jhanwar, Suresh C; Rosenblum, Marc K; Panageas, Katherine S

    2011-06-01

    Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed from 1981-2007 treated initially with RT alone (n = 200), CT + RT (n = 528), CT alone (n = 201), or other strategies (n = 84). Median overall survival (OS) was 6.3 years and time to progression (TTP) was 3.1 years. 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion. In codeleted cases, median TTP was longer following CT + RT (7.2 y) than following CT (3.9 y, P = .003) or RT (2.5 y, P < .001) alone but without improved OS; median TTP was longer following treatment with PCV alone than temozolomide alone (7.6 vs. 3.3 y, P = .019). In cases with no deletion, median TTP was longer following CT + RT (3.1 y) than CT (0.9 y, P = .0124) or RT (1.1 y, P < .0001) alone; OS also favored CT + RT (median 5.0 y) over CT (2.2 y, P = .02) or RT (1.9 y, P < .0001) alone. In codeleted cases, CT alone did not appear to shorten OS in comparison with CT + RT, and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage. Combined CT + RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion. Ongoing trials will address these issues prospectively.

  16. Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult.

    PubMed

    Benjamin, Carolina; Faustin, Arline; Snuderl, Matija; Pacione, Donato

    2015-08-01

    We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process.

  17. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  18. Tanycytic ependymoma in a 76-year-old Puerto Rican male.

    PubMed

    Ortiz, Yvis del Mar; Pérez Berenguer, Juan L; Mercado Acosta, Juan; Polo, Mario; de Jesús-Garces, Orlando; Vega, Irving E

    2014-01-01

    Ependymoma is a slowly growing tumor in children and young adults originating from the wall of the ventricles or from the spinal canal that is composed of neoplastic ependymal cells. Tanycytic ependymoma is a rare variant of ependymoma usually arising in the intra medullary spine. The World Health Organization classifies the tanycytic ependymoma as a grade II tumor. The diagnosis of tanycytic ependymoma is challenging since the morphology of the lesions resemble those found in schwannoma and astrocytomas. In the present study, we show a case of a 76 years old male with a progressive paraparesis for 8 years, due to a spinal tumor. Radiological and histological studies were used to classify the tumor as tanycytic ependymoma. Therefore, it is important to be aware of tanycytic ependymoma and its immunohistochemistry profile in older patients, especially within the Caribbean Hispanic population. To our knowledge this is the oldest patient known to have this rare tumor and the first case reported in Puerto Rico.

  19. Primary central nervous system ALK-positive anaplastic large cell lymphoma in an adult

    PubMed Central

    Dong, Xiaoqin; Li, Jun; Huo, Na; Wang, Yan; Wu, Zhao; Lin, Xiaohong; Zhao, Hong

    2016-01-01

    Abstract Rationale: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma. It mostly invades lymph nodes with extranodal involvement observed in the soft tissue, bone, and skin. Patient concerns: We report a 34-year-old Chinese male patient who presented with headache, diplopia, and vomit. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed elevated CSF pressure, elevated CSF protein concentrations, decreased CSF glucose and chloride concentration significantly, and pleocytosis of 68 to 350 × 106/L, in which lymphocytes and monocytes were predominant. These changes could be suggestive of tuberculous (TB) meningitis. Enhanced magnetic resonance imaging of spinal cord delineated multiple enhancing nodules in spinal cord, cauda equina, and cristae membrane, and multiple abnormal enhancing lesions in bilateral lumbar intervertebral foramen. Diagnoses: Spinal dura mater biopsy and paraffin pathology examination revealed anaplastic lymphoma kinase positive ALCL. Interventions: High-dose methotrexate, cytosine arabinoside craniospinal, and radiotherapy. Outcomes: Last follow-up on September 22, 2015 showed no evidence of tumor recurrence and the lower extremity muscle strength recovered to 4/5. Lessons: ALCL of primary central nervous system is an exceedingly rare tumor, which is usually misdiagnosed as meningitis (especially TB meningitis) according to clinical manifestation and laboratory examination. Thus closely monitoring patient's conditions and timely adjusting therapeutic regimen during treatment are necessary. PMID:27930548

  20. Adult Systemic Anaplastic Large Cell Lymphoma: Recommendations for Diagnosis and Management

    PubMed Central

    Bennani-Baiti, Nabila; Ansell, Stephen

    2016-01-01

    Summary Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas characterized by CD30 expression and other unifying pathologic features. ALK fusions are present in about 50% of cases. Pathological diagnosis can be challenging, particularly in ALK-negative cases. Though ALK-positive and ALK-negative sALCL are similar morphologically and immunophenotypically, they are separate entities with different genetics, clinical behavior, and outcomes. Evidence-based data evaluating treatment regimens are limited as randomized controlled trials are lacking and most prospective studies are too small to draw definitive conclusions. However, recent advances in molecular biology are bringing forth much needed knowledge in this field, and are likely to guide further targeted therapeutic development. PMID:26581318

  1. Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

    ClinicalTrials.gov

    2016-10-10

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

  2. Influence of Radiotherapy Treatment Concept on the Outcome of Patients With Localized Ependymomas

    SciTech Connect

    Combs, Stephanie E. Kelter, Verena; Welzel, Thomas; Behnisch, Wolfgang; Kulozik, Andreas E.; Bischof, Marc; Hof, Holger; Debus, Juergen; Schulz-Ertner, Daniela

    2008-07-15

    Purpose: To assess the outcome of 57 patients with localized ependymomas treated with radiotherapy (RT). Methods and Materials: Fifty-seven patients with localized ependymomas were treated with RT. Histology was myxopapillary ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In 16 patients, irradiation of the craniospinal axis (CSI) was performed with a median dose of 20 Gy. Forty-one patients were treated with local RT, with a local dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy. In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy. Results: Overall survival after primary diagnosis was 83% and 71% at 3 and 5 years. Five-year overall survival was 80% in low-grade and 79% in high-grade tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a significant difference in overall survival between CSI and local RT only. Freedom of local failure was 67% at 5 years in patients treated with CSI and 60% at 5 years after local RT. A rate of 83% for distant failure-free survival could be observed in the CSI group as opposed to 93% in the group receiving local RT only. Conclusion: Local RT in patients with localized tumors is equieffective to CSI. The radiation oncologist must keep in mind that patients with localized ependymomas benefit from local doses {>=}45 Gy.

  3. Posttransplant Lymphoproliferative Disorder Manifesting as Intestinal Epstein-Barr Virus-Positive Anaplastic Large-Cell Lymphoma in an Adult Renal Transplant Recipient.

    PubMed

    Börcek, Pelin; Özdemir, B Handan; Özgün, Gonca; Haberal, Mehmet

    2016-11-01

    Posttransplant lymphoproliferative disorder is a relatively common posttransplant malignancy affecting as many as 10% of all solid-organ recipients. Most cases of posttransplant lymphoproliferative disorder are of B-cell origin, with common Epstein-Barr virus association. Posttransplant lymphoproliferative disorders of T-cell origin are much rarer and less frequently associated with Epstein-Barr virus. Here, we report an unusual case of Epstein-Barr virus-positive anaplastic large-cell lymphoma causing an intestinal perforation in an adult renal transplant recipient. A 52-year-old male patient with renal allograft developed cryptogenic end-stage liver failure and was accepted as a candidate for liver transplant. Before transplant, he was admitted with severe abdominal pain, which turned out to result from ileal perforation. Pathologic evaluation of the intestinal resection showed diffuse malignant lymphoid infiltration of the ileum, consistent with anaplastic large-cell lymphoma. The tumor was positive for Epstein-Barr virus genome. Anaplastic large-cell lymphoma is a rare form of T-cell posttransplant lymphoproliferative disorder that is infrequently associated with Epstein-Barr virus. The occurrence of this extraordinary form of post transplant lymphoproliferative disorder, its late onset, intestinal localization, and Epstein-Barr virus as sociation represent a unique clinical rarity.

  4. Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

    PubMed

    Decaestecker, C; Salmon, I; Camby, I; Dewitte, O; Pasteels, J L; Brotchi, J; Van Ham, P; Kiss, R

    1995-05-01

    The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.

  5. An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

    PubMed

    DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

    2015-05-01

    Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

  6. Rearranged Anaplastic Lymphoma Kinase (ALK) Gene in Adult-Onset Papillary Thyroid Cancer Amongst Atomic Bomb Survivors

    PubMed Central

    Mukai, Mayumi; Takahashi, Keiko; Hayashi, Yuzo; Nakachi, Kei; Kusunoki, Yoichiro

    2012-01-01

    Background We previously noted that among atomic bomb survivors (ABS), the relative frequency of cases of adult papillary thyroid cancer (PTC) with chromosomal rearrangements (mainly RET/PTC) was significantly greater in those with relatively higher radiation exposure than those with lower radiation exposure. In contrast, the frequency of PTC cases with point mutations (mainly BRAFV600E) was significantly lower in patients with relatively higher radiation exposure than those with lower radiation exposure. We also found that among ABS, the frequency of PTC cases with no detectable gene alterations in RET, neurotrophic tyrosine kinase receptor 1 (NTRK1), BRAF, or RAS was significantly higher in patients with relatively higher radiation exposure than those with lower radiation exposure. However, in ABS with PTC, the relationship between the presence of the anaplastic lymphoma kinase (ALK) gene fused with other gene partners and radiation exposure has received little study. In this study, we tested the hypothesis that the relative frequency of rearranged ALK in ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, would be greater in those having relatively higher radiation exposures. Methods The 105 subjects in the study were drawn from the Life Span Study cohort of ABS of Hiroshima and Nagasaki who were diagnosed with PTC between 1956 and 1993. Seventy-nine were exposed (>0 mGy), and 26 were not exposed to A-bomb radiation. In the 25 ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, we examined archival, formalin-fixed, paraffin-embedded PTC specimens for rearrangement of ALK using reverse transcription–polymerase chain reaction and 5′ rapid amplification of cDNA ends (5′ RACE). Results We found rearranged ALK in 10 of 19 radiation-exposed PTC cases, but none among 6 patients with PTC with no radiation exposure. In addition, solid/trabecular-like architecture in PTC was closely associated with ALK

  7. Anaplastic thyroid cancer

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

  8. Supratentorial Ependymoma: Disease Control, Complications, and Functional Outcomes After Irradiation

    SciTech Connect

    Landau, Efrat; Boop, Frederick A.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-03-15

    Purpose: Ependymoma is less commonly found in the supratentorial brain and has known clinical and molecular features that are unique. Our single-institution series provides valuable information about disease control for supratentorial ependymoma and the complications of supratentorial irradiation in children. Methods and Materials: A total of 50 children with newly diagnosed supratentorial ependymoma were treated with adjuvant radiation therapy (RT); conformal methods were used in 36 after 1996. The median age at RT was 6.5 years (range, 1-18.9 years). The entire group was characterized according to sex (girls 27), race (white 43), extent of resection (gross-total 46), and tumor grade (anaplastic 28). The conformal RT group was prospectively evaluated for neurologic, endocrine, and cognitive effects. Results: With a median follow-up time of 9.1 years from the start of RT for survivors (range, 0.2-23.2 years), the 10-year progression-free and overall survival were 73% + 7% and 76% + 6%, respectively. None of the evaluated factors was prognostic for disease control. Local and distant failures were evenly divided among the 16 patients who experienced progression. Eleven patients died of disease, and 1 of central nervous system necrosis. Seizure disorders were present in 17 patients, and 4 were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult-to-control seizures. The average values for intelligence quotient and academic achievement (reading, spelling, and math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy. Conclusion: RT may be administered with acceptable risks for complications in children with supratentorial ependymoma. These results suggest that outcomes for these children are improving and that complications may be limited by use of focal irradiation methods.

  9. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  10. Spinal tanycytic ependymoma with diffusion restriction on MRI.

    PubMed

    Tosun, O; Turkoglu, O F; Ozmen, E K; Onursever, A; Arslan, H

    2012-03-01

    Tanycytic ependymoma is a rare spindle-cell variant of ependymoma derived from tanycytes. Primitive neuroectodermal tumors usually have diffusion restriction, whereas ependymomas do not. Here, we present a case of tanycytic ependymoma with diffusion restriction. As far we are aware, this is the first case of tanycytic ependymoma in the English literature with diffusion restriction.

  11. Supratentorial ependymoma with glial component of two different histologies and neuropil-like islands: a case report.

    PubMed

    Ahn, Soomin; Kang, So Young; Suh, Yeon-Lim

    2014-01-01

    Glioneuronal tumors with neuropil-like islands (GTNIs) are a basically infiltrating astrocytoma or mixed oligoastrocytoma, containing large neuropil-like islands (NIs). Recently, we experienced a peculiar case of supratentorial ependymoma with NIs. A 29-month-old girl presented with seizure and a brain magnetic resonance image revealed a huge heterogeneous mass in the left lateral ventricle. Histologically, glial components of the tumor showed two different histologies: anaplastic ependymoma and myxopapillary ependymomatous features. The latter was admixed with numerous NIs. Immunohistochemically, the glial components expressed GFAP and a paranuclear dot pattern of EMA and CD99, whereas the NIs were positive for synaptophysin and MAP2. KI-67 was high in the anaplastic ependymoma, but very low in the fascicles of spindle cells and NIs. Quantitative PCR confirmed mRNA expression of five genes related to neuronal differentiation in both the glial and neuronal components of this tumor. Our case suggests that ependymoma with NIs may be in a spectrum of GTNIs.

  12. Intensity-Modulated Radiation Therapy in Childhood Ependymoma

    SciTech Connect

    Schroeder, Thomas M.; Chintagumpala, Murali; Okcu, M. Fatih; Chiu, J. Kam; Teh, Bin S.; Woo, Shiao Y.; Paulino, Arnold C.

    2008-07-15

    Purpose: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. Methods and Materials: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. Results: The 3-year overall survival rate was 87% {+-} 9%. The 3-year local control rate was 68% {+-} 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. Conclusions: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.

  13. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2017-01-17

    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

  14. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    ClinicalTrials.gov

    2017-03-22

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  15. Computed tomography of intracranial ependymomas

    SciTech Connect

    Swartz, J.D.; Zimmerman, R.A.; Bilaniuk, L.T.

    1982-04-01

    Twenty-six patients with ependymoma were evaluated by computed tomography (CT) over a period of 5 1/2 years. The usual CT appearance was an isodense, partially calcified mass, capable of contrast enhancement, occurring in the posterior fossa (73%) in an infant or child (77%). Outcome remains poor despite modern diagnostic and therapeutic methods.

  16. Pediatric Ependymoma: A Proteomics Perspective

    PubMed Central

    TSANGARIS, GEORGE TH; PAPATHANASIOU, CHRISSA; ADAMOPOULOS, PANAGIOTIS G; SCORILAS, ANDREAS; VORGIAS, CONSTANTINOS E; PRODROMOU, NEOFYTOS; TZORTZATOU-STATHOPOULOU, FOTEINI; STRAVOPODIS, DIMITRIOS J; ANAGNOSTOPOULOS, ATHANASIOS K

    2017-01-01

    Background/Aim: Proteomics based on high-resolution mass spectrometry (MS) is the tool of choice for the analysis of protein presence, modifications and interactions, with increasing emphasis on the examination of tumor tissues. Application of MS-based proteomics offers a detailed picture of tumor tissue characteristics, facilitating the appreciation of different tumor entities, whilst providing reliable and fast results for therapeutic marker targeting and prognostic factor assessment. Through use of the high analytical resolution of nano-high-pressure liquid chromatography (nanoHPLC) and the high resolution of an Orbitrap Elite mass spectrometer, the present study aimed to provide knowledge on the proteome of the generally unknown entity of pediatric ependymal tumors. Materials and Methods: Ten resected specimens of childhood ependymoma were analyzed through a one-dimensional (1D) nanoLC-MS/MS approach. Method optimization steps were undertaken for both the sample preparation/protein extraction procedure and LC parameters, aiming to achieve the highest possible identification rates. Results: Following method optimization, each nanoLC-MS/MS run resulted in identification of more than 5,000 proteins and more than 25,000 peptides for every analyzed sample, thus detailing the greater part of the ependymoma proteome. Identified proteins were found to spread throughout all known tumor categories regarding their molecular function and subcellular localization. Conclusion: Through the proposed nanoLC-MS/MS method herein we report, for the firs time, the ependymoma proteome database. A large number of similarities regarding proteome content are revealed compared to other two pediatric brain tumor entities; astrocytomas and medulloblastomas. Furthermore, through our approach, the majority of currently proposed markers for ependymoma (e.g. nucleolin, nestin, Ki67 and laminin subunit A2 ) as well as all major key players of the phosphoinositide 3-kinase pathway (seemingly

  17. Imaging features of spinal tanycytic ependymoma.

    PubMed

    Tomek, Michal; Jayajothi, Anandapadmanabhan; Brandner, Sebastian; Jaunmuktane, Zane; Lee, Cheong Hung; Davagnanam, Indran

    2016-02-01

    Tanycytic ependymoma is an unusual morphological variant of WHO grade II ependymoma, typically arising from the cervical or thoracic spinal cord. Although the literature deals extensively with pathological features of this tumour entity, imaging features have not been well characterised. The purpose of this study was to review magnetic resonance imaging (MRI) features of spinal tanycytic ependymomas reported in the literature to date, exemplified by a case of a patient with tanycytic ependymoma of the conus medullaris presenting to our hospital. A Medline search of the English literature for all previously published cases of spinal tanycytic ependymoma was carried out and the reported MRI features reviewed. The tumours were found to be typically well-demarcated masses, predominantly showing isointensity on T1-weighted signal, and T2-weighted hyperintensity, with variable patterns of contrast enhancement. A cystic component was seen in half of the cases, and in a minority a mural nodule was present within the cyst wall. Associated syrinx formation was observed in one-third of the cases and haemorrhage was rare, which may be helpful pointers in differentiating the lesion from other ependymoma subtypes. In conclusion, MRI characteristics of spinal tanycytic ependymoma are variable and non-specific, and radiological diagnosis thus remains challenging, although certain predominant features are identified in this report. Knowledge of these is important in the diagnostic differentiation from other intramedullary and extramedullary spinal tumours in order to guide appropriate surgical management.

  18. Treatment implications of posterior fossa ependymoma subgroups.

    PubMed

    Ramaswamy, Vijay; Taylor, Michael D

    2016-11-15

    Posterior fossa ependymoma comprises two distinct molecular entities, ependymoma_posterior fossa A (EPN_PFA) and ependymoma_posterior fossa B (EPN_PFB), with differentiable gene expression profiles. As yet, the response of the two entities to treatment is unclear. To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment, we studied a cohort of 820 patients with molecularly profiled, clinically annotated posterior fossa ependymomas. We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA, which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis" in the Journal of Clinical Oncology. Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy, whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

  19. Clinicopathological features of myxopapillary ependymoma.

    PubMed

    Wang, Hai; Zhang, Shu; Rehman, Sumaiyah K; Zhang, Zhiyuan; Li, Wanchun; Makki, Mohammad Shahidul; Zhou, Xiaojun

    2014-04-01

    Myxopapillary ependymoma (MPE) is a rare and distinct variant of ependymoma with a tendency for local recurrence and metastasis. Its clinicopathological spectrum is heterogenous, underscoring the need to understand and characterize MPE for better diagnosis and treatment. The purpose of this study was to explore the tumor biology and assess the management of patients with MPE. Tumors from a cohort of 19 patients were analyzed by light microscopy, electron microscopy, immunohistochemistry and fluorescence in situ hybridization (FISH). Clinical characteristics, therapeutic options and clinical follow-up data were also analyzed. Back pain was the most common presenting symptom. The main pathological morphology observed was papillae embedded in a myxoid background, but other rare morphologies were also present. Immunostaining revealed epidermal growth factor receptor (EGFR) expression in four MPE, while FISH for EGFR was negative. No correlation between tumor recurrence and EGFR overexpression was found. Ultrastructural examination revealed adherens junctions and intracytoplasmic lumina with microvilli. Patients with gross-total resection (GTR) had no tumor recurrence (p=0.021). Also, patients with subtotal resection (STR) followed by radiotherapy showed a higher local control rate than patients with STR alone (p=0.043). The diagnosis of MPE should be made considering the histology, immunohistochemistry, imaging studies and anatomical site. GTR of the tumor or STR followed by radiotherapy are more likely to avoid tumor recurrence than STR alone. Based on our findings, there is no correlation between tumor recurrence and EGFR expression.

  20. Ependymoma in children: molecular considerations and therapeutic insights.

    PubMed

    Kim, J-H; Huang, Y; Griffin, A S; Rajappa, P; Greenfield, J P

    2013-10-01

    A multi-modality approach that encompasses maximal surgical resection in combination with adjuvant therapy is critical for achieving optimal disease control in children with ependymoma. In view of its complex biology and variable response to therapy, ependymoma remains a challenge for clinicians involved in the care of these patients. Meanwhile, translation of molecular findings can characterize unique features of childhood ependymoma and their natural history. Furthermore, understanding the biology of pediatric ependymoma serves as a platform for development of future targeted therapies. In line with these goals, we review the molecular basis of pediatric ependymoma and its prognostic implications, as well as novel therapeutic advances in the management of ependymoma in children.

  1. Minimally invasive management of ependymoma of the aqueduct of Sylvius: therapeutic considerations and management.

    PubMed

    Terasaki, M; Uchikado, H; Takeuchi, Y; Shigemori, M

    2005-12-01

    A major concern in the neuroendoscopic approach to an intraventricular tumor is the histological confirmation from a limited biopsy. However, the effort to excise the whole bulk of the tumor should be made for the minimally invasive management of selected intraventricular tumors. The case of an adult male with focal aqueductal ependymoma who presented with the clinical syndrome of hydrocephalus is reported. This may be of particular interest because it represents the first case of aqueductal ependymoma that has been successfully treated with endoscopic surgery.

  2. Ependymomas: results of radiation treatment

    SciTech Connect

    Garrett, P.G.; Simpson, W.J.K.

    1983-08-01

    Between 1958 and 1980, 102 patients with the diagnosis of ependymoma were seen at the Princess Margaret Hospital. Eleven patients had recurrent disease or were treated elsewhere and 91 patients received radiation therapy following their primary surgical procedure. Fifty patients had cranial tumors and 41 had spinal tumors. The overall survival at five years was 60% and at 10 years was 54%. Those patients with spinal tumors did significantly better with a five year survival of 83% versus 43% for the group with cranial tumors. The other prognostic factors included tumor grade, functional status, age of the patient and interval from surgery to radiation. The most common site of relapse was at the original tumor location, but five patients did show spread through the craniospinal axis. An analysis of dose and the volume treated are made and recommendations for therapy given.

  3. Role of platelet derived growth factor receptor (PDGFR) over-expression and angiogenesis in ependymoma.

    PubMed

    Moreno, Lucas; Popov, Sergey; Jury, Alexa; Al Sarraj, Saffa; Jones, Chris; Zacharoulis, Stergios

    2013-01-01

    New molecularly targeted therapies are needed for childhood ependymoma. Angiogenesis and the PDGFR pathway could be potential therapeutic targets. This study aimed to screen ependymomas for the expression and clinicopathological correlates of angiogenic factors and potential therapeutic targets including VEGFR, endoglin (CD105), CD34, CD31, c-Kit, PDGFR-α and PDGFR-β. Immunohistochemistry for angiogenesis factors and PDGFR-α and β was performed in 24 archival tumor samples from children and adults treated for ependymoma at our institution. CD31 density, CD105 density and pericyte coverage index (PCI) were calculated. These findings were correlated with clinical outcome. VEGFR2 was overexpressed in tumor cells in only one out of 24 cases, but was found overexpressed in the vessels in 6 cases. PDGFR-α and β were found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases (29.2 %). CD31 density, CD105 density and PCI did not correlate with expression of PDGFRs. Overexpression of PDGFR-α and β in tumor cells and overexpression of PDGFR-α in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFR-α in tumor cells (2 year progression free survival was 16.7 ± 15.2 for cases with overexpression of PDGFR-α in the tumor vs. 74.5 ± 15.2 for those with low/no expression, hazard ratio = 5.78, p = 0.04). A number of angiogenic factors are expressed in ependymoma tumor cells and tumor endothelium. Preliminary evidence suggests that the expression of PDGFRs could have a prognostic significance in ependymoma. This data suggests that PDGFRs should be further evaluated as targets using novel PDGFR inhibitors.

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

    ClinicalTrials.gov

    2015-09-28

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

  5. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2016-10-19

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  6. A mixed choroid plexus papilloma and ependymoma.

    PubMed

    Lee, Yujin; Kim, Seong Ik; Kim, Seung-Ki; Kim, In One; Park, Sung-Hye

    2016-04-01

    We report a novel case of a mixed choroid plexus papilloma (CPP) and ependymoma with cartilaginous differentiation. This kind of mixed tumor has not been previously reported in the English literature. The patient was a 5-year-old girl, who presented with a 1-week history of fever and numbness of the right lower limb. Magnetic resonance imaging of the brain with gadolinium revealed a heterogeneously enhancing mass in the occipital horn of the left lateral ventricle. Histologically, the tumor showed an intermixed CPP area and a low-grade papillary ependymoma-like area, which was studded with cartilage islands and psammoma bodies. In many foci, direct transition of CPP and ependymoma was observed, but there were no high-grade features. We report this novel case, describe the unique microscopic and immunohistochemical features, and speculate on the pathogenesis.

  7. [Pediatric ependymomas: Current diagnosis and therapy].

    PubMed

    Frappaz, Didier; Vasiljevic, Alexandre; Beuriat, Pierre-Aurelien; Alapetite, Claire; Grill, Jacques; Szathmari, Alexandru; Faure-Conter, Cécile

    2016-10-01

    Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016 classification, pathology is enriched by localization and molecular biology. Whatever the age, total removal by one or several looks when required remains a major prognostic factor. In children, focal radiation remains a standard, while the role of chemotherapy is matter of randomized studies. In infants, front line chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is encouraged. In case of relapse, further surgery and radiation are advised, while inclusion in innovative trials including re-irradiation, and phase I-II should be encouraged. A better understanding of underlying mechanisms of ependymoma cell will provide in the close future, the key to use targeted therapies at time of relapse, and very soon as first line therapy for some subgroups of patients.

  8. Squash cytology of tanycytic ependymoma: A report of two cases.

    PubMed

    Chaudhuri, Priyanka Maity; Chaudhuri, Shubhamitra; Chakrabarty, Debashis; Chatterjee, Sandip; Datta, Chhanda; Chaudhuri, Manoj Kumar; Chatterjee, Uttara

    2017-03-01

    Tanycytic ependymoma is a rare variant of ependymoma which has a predilection for the spinal cord. It is a WHO grade II tumour with favourable outcome. Although squash cytology of ependymoma is well described, there is sparse literature available on squash cytomorphology of tanycytic variant. Here we present two cases of squash cytology of tanycytic ependymoma. In the first case the diagnosis of tanycytic ependymoma was considered. However, in the second case a diagnosis of usual ependymoma was offered. Subsequently histopathology confirmed tanycytic nature in both the cases. In this article we discuss the squash cytological features of tanycytic ependymoma along with its differential diagnosis. Diagn. Cytopathol. 2017;45:270-273. © 2016 Wiley Periodicals, Inc.

  9. Subcutaneous sacral ependymoma--a histopathological challenge.

    PubMed

    Helbig, Doris

    2016-01-01

    Subcutaneous myxopapillary or sacral ependymoma are rare tumors mostly developing in children or adolescents. The majority occurs in the sacrococcygeal region. There are numerous clinical and histopathological differential diagnoses. Owing to the fact that there have been rare reported cases that followed an aggressive course and in which the patient succumbed to metastatic disease, long term follow-up is necessary despite complete excision. We describe here a 25-year-old male patient with a histological unusual subcutaneous sacral ependymoma and discuss the differential diagnosis as well as treatment options.

  10. Intracranial Ependymomas in Children: Society of Pediatric Oncology Experience With Postoperative Hyperfractionated Local Radiotherapy

    SciTech Connect

    Conter, Cecile Carrie, Christian; Bernier, Valerie; Geoffray, Anne; Pagnier, Anne; Gentet, Jean-Claude; Lellouch-Tubiana, Arielle; Chabaud, Sylvie; Frappaz, Didier

    2009-08-01

    Purpose: To prospectively investigate the role of local hyperfractionated radiotherapy (RT) after surgical resection in the treatment of intracranial ependymomas in children. Patients and Methods: Postoperative local hyperfractionated RT was proposed for every child (>5 years old at diagnosis) with localized intracranial ependymoma. The planned dose was 60 Gy after complete resection (CR) and 66 Gy after partial resection, delivered in two daily fractions of 1 Gy, according to the early postoperative imaging findings. Results: Between November 1996 and December 2002, 24 children with infratentorial (n = 20) or supratentorial (n = 4) intracranial ependymoma were included. The median age was 8.6 years (range, 5-17). The World Health Organization grade was anaplastic in 10 of the 24 patients (not assessable in 1). After a retrospective central review, a CR was reported in 16 patients, partial resection in 4, and doubtful resection in 4. The radiation dose was 60 Gy in 18 cases (one partial resection), 66 Gy in 5 cases (one CR), and 54 Gy in 1 case (CR). The 5-year overall survival rate was 74.8%, and the progression-free survival rate was 54.2%. Of the 24 patients, 11 developed a relapse: 7 local only and 4 metastatic and local. The histological grade and extent of resection were not prognostic factors. More than 3 in 4 children had no sequelae of RT at a median follow-up of 7 years (95% confidence interval, 66.4-90.0 months). Conclusion: The results of our study have shown that hyperfractionated RT is safe but provides no outcome benefit compared with other strategies of RT such as standard fractionated regimens.

  11. Decrease in FOXJ1 expression and its ciliogenesis program in aggressive ependymoma and choroid plexus tumours

    PubMed Central

    Abedalthagafi, Malak S.; Wu, Michael P.; Merrill, Parker H.; Du, Ziming; Woo, Terri; Sheu, Shu-Hsien; Hurwitz, Shelley; Ligon, Keith L.; Santagata, Sandro

    2017-01-01

    Well-differentiated human cancers share transcriptional programs with the normal tissue counterparts from which they arise. These programs broadly influence cell behavior and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional program is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papilloma. Anaplastic ependymoma as well as choroid plexus carcinoma show decreased FOXJ1 expression and its associated ciliogenesis program genes. In ependymoma and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis program are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. PMID:26690880

  12. Cytopathologic characteristics and differential diagnostic considerations of osteolytic myxopapillary ependymoma.

    PubMed

    Hayashi, Toshitetsu; Haba, Reiji; Kushida, Yoshio; Kadota, Kyuichi; Katsuki, Naomi; Bando, Kenji; Shibuya, Shinsuke; Matsunaga, Toru

    2014-09-01

    Myxopapillary ependymoma (MPE) is a rare variant of conventional ependymoma found predominantly in the sacrococcygeal region in young adults and characterized by its distinct epithelial and stromal components (WHO grade I designation). MPE with extensive osteolysis is extremely uncommon and only up to 40 cases have been documented. A case is presented here in which imprint smears of a sacral tumor in an 18-year-old man revealed complex papillary structures, small loose clusters, or cord-like structures of bland tumor cells embedded in a myxoid or mucinous background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and occasional intracytoplasmic vacuoles were observed. A cytologic diagnosis of a MPE was suggested and histochemical and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Immunohistochemically, the tumor cells showed diffuse and strong membranous and cytoplasmic staining for cytokeratin AE1/AE3, glial fibrillary protein, and S-100 protein, but negative for epithelial membrane antigen, pan-neuroendocrine markers (i.e., NSE, chromogranin A, synaptophysin), or brachyury. The proliferative index with MIB-1 was around 10%. The diagnosis of osteolytic MPE was confirmed based on cytopathologic, histopathological, immunohistochemical results, radiologic findings, and the location of the tumor. We demonstrated here the cytopathological features of osteolytic MPE with emphasis on differential diagnostic considerations.

  13. A comparative study of ependymomas by site of origin

    SciTech Connect

    Marks, J.E.; Adler, S.J.

    1982-01-01

    Sixty-one patients with histologically proven ependymoma were irradiated between 1954 and 1976. Supra-and infratentorial tumors occurred more often in children and spinal cord- cauda equina tumors more often in adults. Local control was achieved in four of 20 supratentorial, 13 of 26 infratentorial, three of seven intramedullary spinal cord, and seven of eight cauda equina tumors. Improved local control of infratentorial tumors was noted for patients who received higher biologically effective doses of radiation but no dose-response for supratentorial, spinal cord or cauda equina tumors could be found. Five-year actuarial survival was 56% for all patients, 35% for supratentorial, 59% for infratentorial, 57% for spinal cord and 83% for cauda equina tumors. Spinal metastases were pathologically documented in 5 of 46 (11%) patients wih ependymomas above the foramen magnum. They were clinically evident in two patients and most common in patients with infratentorial tumors whose spines had not been irradiated. One patients who was irraidated externally for cauda equina tumor developed radiation myelopathy 1-1/2 years later; three of eight patients who received intrathecal gold 198 developed myelopathy and/or cauda equina syndrome 3-1/2 to 17 years later.

  14. Primary cerebral myxopapillary ependymoma presenting with intratumoral hemorrhage.

    PubMed

    Khalatbari, Mahmoud Reza; Moharamzad, Yashar

    2014-08-01

    Myxopapillary ependymoma (MPE), a benign histological variant of ependymoma, is found most commonly in the cauda equina region. Primary intracranial MPE is very rare, and most cases are a metastatic deposit from a spinal lesion. Primary cerebral MPEs are usually well-defined solid or cystic lesions without hemorrhage. We report the first case of primary cerebral MPE with intratumoral hemorrhage.

  15. Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

    ClinicalTrials.gov

    2017-03-01

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

  16. Lipomatous/Extensively Vacuolated Ependymoma with Signet-Ring Cell-Like Appearance: Analysis of a Case with Extensive Literature Review.

    PubMed

    Salazar, Miguel Fdo; Tena-Suck, Martha Lilia; Ortiz-Plata, Alma; Salinas-Lara, Citlaltepetl; Rembao-Bojórquez, Daniel

    2017-01-01

    "Lipomatous" and "extensively vacuolated" are descriptive captions that have been used to portray a curious subset of ependymomas distinctively bearing cells with a large vacuole pushing the nucleus to the periphery and, thus, simulating a signet-ring cell appearance. Here, we would like to report the first ependymoma of this kind in a Latin American institution. A 16-year-old boy experienced cephalea during three months. Magnetic resonance imaging scans showed a left paraventricular tumour which corresponded to anaplastic ependymoma. Intriguingly, it was also composed of cells with single or multiple hollow cytoplasmic vacuoles sometimes giving a signet-ring cell-like configuration. Immunolabeling of these showed membrane positivity for GFAP, PS100, and CD99, while Ki-67 expression was null. Ultrastructural examination of retrieved paraffin-embedded tissue showed the presence of scarce microlumina filled with microvilli but failed to demonstrate any content in such optically empty vacuoles as only scant granulofibrillary debris was observed. A schism prevails at present regarding these unusual morphological variants, being either "lipomatous" or "vacuolated" based mainly on the EMA immunoprofile. This, however, is a misappropriate approaching. Could it be that perhaps we are dealing with the same histopathological entity or it may simply happen that fixation and artefacts cannot allow for their proper identification?

  17. Lipomatous/Extensively Vacuolated Ependymoma with Signet-Ring Cell-Like Appearance: Analysis of a Case with Extensive Literature Review

    PubMed Central

    Tena-Suck, Martha Lilia; Ortiz-Plata, Alma; Salinas-Lara, Citlaltepetl; Rembao-Bojórquez, Daniel

    2017-01-01

    “Lipomatous” and “extensively vacuolated” are descriptive captions that have been used to portray a curious subset of ependymomas distinctively bearing cells with a large vacuole pushing the nucleus to the periphery and, thus, simulating a signet-ring cell appearance. Here, we would like to report the first ependymoma of this kind in a Latin American institution. A 16-year-old boy experienced cephalea during three months. Magnetic resonance imaging scans showed a left paraventricular tumour which corresponded to anaplastic ependymoma. Intriguingly, it was also composed of cells with single or multiple hollow cytoplasmic vacuoles sometimes giving a signet-ring cell-like configuration. Immunolabeling of these showed membrane positivity for GFAP, PS100, and CD99, while Ki-67 expression was null. Ultrastructural examination of retrieved paraffin-embedded tissue showed the presence of scarce microlumina filled with microvilli but failed to demonstrate any content in such optically empty vacuoles as only scant granulofibrillary debris was observed. A schism prevails at present regarding these unusual morphological variants, being either “lipomatous” or “vacuolated” based mainly on the EMA immunoprofile. This, however, is a misappropriate approaching. Could it be that perhaps we are dealing with the same histopathological entity or it may simply happen that fixation and artefacts cannot allow for their proper identification? PMID:28286687

  18. A Pediatric Tumor Found Frequently in the Adult Population: A Case of Anaplastic Astroblastoma in an Elderly Patient and Review of the Literature

    PubMed Central

    Batouli, Ali; Stabingas, Kristen; Alcindor, Dunbar; Abdel Aziz, Khaled; Pu, Cunfeng; Williams, Robert; Yu, Alexander

    2017-01-01

    Astroblastomas are rare, potentially curable primary brain tumors which can be difficult to diagnose. We present the case of astroblastoma in a 73-year-old male, an atypical age for this tumor, more classically found in pediatric and young adult populations. Through our case and review of the literature, we note that this tumor is frequently reported in adult populations and the presentation of this tumor in the elderly is well described. This tumor is an important consideration in the differential diagnosis when managing both pediatric and adult patients of any age who present with the imaging findings characteristic of this rare tumor. PMID:28239500

  19. Ependymoma of conus medullaris presenting as subarachnoid haemorrhage.

    PubMed

    Ulrich, C T; Beck, J; Seifert, V; Marquardt, G

    2008-02-01

    Subarachnoid haemorrhage (SAH) due to spinal ependymoma is very rare. We report a 37 year old man who presented with typical clinical signs of SAH. Lumbar puncture confirmed SAH but cerebral angiography was negative, and further diagnostic work-up revealed an ependymoma of the conus medullaris as the source of the haemorrhage. A comprehensive review of the literature was conducted. Only 17 patients with spontaneous SAH due to a spinal ependymoma have been reported since 1958. However, in cases of SAH and negative diagnostic findings for cerebral aneurysms or malformations, this aetiology should be considered and work-up of the spinal axis completed.

  20. Multisegmental diffuse intradural extramedullary ependymoma. An extremely rare case.

    PubMed

    Guarnieri, Gianluigi; Tecame, Mario; Izzo, Roberto; Zeccolini, Fabio; Genovese, Luigi; Muto, Mario

    2014-04-01

    Ependymoma has been described typically as an intramedullary tumour derived from ependymal cells with a predominance in women in the fifth decade of life. Pain is the most frequent symptom. Intradural extramedullary presentation is rarely described and almost always as a unique lesion. We describe a 53-year-old man with multi-segmental diffuse intradural extramedullary ependymoma with progressive lower leg hypoesthesia with regular motility. The patient's neurologic condition improved after surgery.

  1. Ependymoma with "granular cell" features: report of two cases.

    PubMed

    Shintaku, Masayuki; Yoshida, Makiko; Ikarashi, Toshihiko; Arakawa, Yasuaki; Nagashima, Tatsuya

    2012-12-01

    We report two cases of ependymoma which showed prominent "granular cell" changes of the cytoplasm. The patients were a 7-year-old boy with a tumor in the cerebellum (case 1) and a 70-year-old man with a tumor in the frontal lobe (case 2). The tumor of case 1 showed a histopathological appearance of ependymoma containing many focal aggregates of large polygonal cells in which the cytoplasm was stuffed with numerous eosinophilic granules. The tumor of case 2 predominantly showed the features of papillary ependymoma, and some tumor cells were swollen and contained similar eosinophilic granules. Intracytoplasmic granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were found as aggregates of membrane-bound, electron-dense, globular structures. Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies. Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and oligodendroglial neoplasms, but an appearance of similar granules is very rare in ependymoma. The two cases presented here may represent a new histopathological variant of ependymoma, and the term "granular cell ependymoma" is appropriate for them.

  2. A prognostic gene expression signature in infratentorial ependymoma.

    PubMed

    Wani, Khalida; Armstrong, Terri S; Vera-Bolanos, Elizabeth; Raghunathan, Aditya; Ellison, David; Gilbertson, Richard; Vaillant, Brian; Goldman, Stewart; Packer, Roger J; Fouladi, Maryam; Pollack, Ian; Mikkelsen, Tom; Prados, Michael; Omuro, Antonio; Soffietti, Riccardo; Ledoux, Alicia; Wilson, Charmaine; Long, Lihong; Gilbert, Mark R; Aldape, Ken

    2012-05-01

    Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

  3. Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas.

    PubMed

    Wienecke, R; Guha, A; Maize, J C; Heideman, R L; DeClue, J E; Gutmann, D H

    1997-08-01

    Individuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas. Tuberin, the protein product of the tuberous sclerosis complex-2 (TSC2) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes. To determine whether TSC2 RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase-polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas. Eighteen of 40 (45%) high-grade (World Health Organization [WHO] grade III/IV) astrocytomas and 4 of 8 (50%) adult low-grade (WHO grade II) astrocytomas demonstrated reduced or absent TSC2 expression, including 1 giant cell astrocytoma, whereas none of the 10 pediatric low-grade astrocytomas analyzed showed a reduction in TSC2 expression. Reduced or absent tuberin was observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the first time, that reduced or absent TSC2 expression may represent one of the critical genetic events associated with the development of sporadic adult, but not pediatric, astrocytomas.

  4. Anaplastic glioma: current treatment and management.

    PubMed

    Le Rhun, Emilie; Taillibert, Sophie; Chamberlain, Marc C

    2015-06-01

    Anaplastic glioma (AG) is divided into three morphology-based groups (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) as well as three molecular groups (glioma-CpG island methylation phenotype [G-CIMP] negative, G-CIMP positive non-1p19q codeleted tumors and G-CIMP positive codeleted tumors). The RTOG 9402 and EORTC 26951 trials established radiotherapy plus (procarbazine, lomustine, vincristine) chemotherapy as the standard of care in 1p/19q codeleted AG. Uni- or non-codeleted AG are currently best treated with radiotherapy only or alkylator-based chemotherapy only as determined by the NOA-04 trial. Maturation of NOA-04 and results of the currently accruing studies, CODEL (for codeleted AG) and CATNON (for uni or non-codeleted AG), will likely refine current up-front treatment recommendations for AG.

  5. [Endobronchial anaplastic large cell lymphoma in childhood].

    PubMed

    Escobosa Sánchez, O M; Herrero Hernández, A; Acha García, T

    2009-05-01

    Anaplastic large cell lymphoma is a very rare disease in childhood. The most common location of this lymphoma is lymph node and skin, with endobronchial involvement being extremely rare. We report a case of a 10-year-old boy diagnosed by chance with an endobronchial anaplastic large cell lymphoma, while he was being investigated for a a benign bone disease, due to the initial absence of respiratory symptoms.

  6. Anaplastic mandibular carcinoma in a meerkat (Suricata suricatta).

    PubMed

    Dadone, Liza I; Garner, Michael M; Klaphake, Eric; Johnston, Matthew S; Han, Sushan

    2014-06-01

    An 8-yr-old female slender-tailed meerkat (Suricata suricatta) presented with a necrotic sublingual mass and osteolysis of the mandible. After 1 mo of palliative care, the meerkat was euthanized. The mass was diagnosed histologically as an anaplastic carcinoma with extensive rostral mandibular destruction. Immunohistochemistry for vimentin and cytokeratin was validated in this nontypical species and showed that neoplastic cells expressed both mesenchymal and epithelial characteristics, suggestive of a primitive and poorly differentiated tumor. A review of 150 adult slender-tailed meerkat histopathology reports showed a 2% prevalence of orofacial neoplasia, suggesting that oral neoplasms are uncommon in meerkats.

  7. Thoracic exophytic ependymoma masquerading as a benign extra-axial tumor.

    PubMed

    Chung, Charlotte Y; Koffie, Robert M; Dewitt, John C; Aronson, Joshua P

    2016-11-01

    Spinal tumors are conventionally differentiated based on location in relation to the spinal cord. Benign spinal tumors such as schwannomas and meningiomas are typically extra-axial (intradural extramedullary) lesions, whereas more aggressive primary spinal tumors such as ependymomas are typically intramedullary masses. Rarely, ependymomas can have both intramedullary and extramedullary components (typically referred to as exophytic ependymomas). We report a case of a spinal exophytic ependymoma that radiographically masqueraded as a benign intradural extramedullary lesion causing cord compression and neurologic deficit in a 47-year-old man. The diagnosis of exophytic ependymoma was made intra-operatively, with resultant gross total resection of the extramedullary portion and subtotal resection of the intramedullary portion. Histopathological examination confirmed ependymoma with World Health Organization grade II/IV. Pre-operative suspicion of an exophytic ependymoma influences operative planning and clinical management. We review the literature and discuss clinical management strategies for these interesting spinal tumors.

  8. Multicentric intradural extramedullary ependymoma: Report of a rare case

    PubMed Central

    Vats, Atul; Ramdasi, Raghvendra; Zaveri, Gautam; Pandya, Sunil

    2015-01-01

    Spinal ependymoma commonly presents as an intramedullary tumor. We present a rare case of multicentric intradural extramedullary spinal ependymoma. A 59 years old female presented to us with spastic quadriparesis for 10 months. Magnetic resonance imaging of the spinal cord showed discretely located enhancing tumor masses from at C1-C2, C6-C7, and D4 to L3 level. Subtotal resection of the symptomatic tumor at C6-C7 and D7-D9 was done. The patient underwent radiotherapy with 50.4 Gy. At follow-up of 11 months, patient is doing well. The relevant literature is reviewed. PMID:26288550

  9. Intrasellar ependymoma: clinical, imaging, pathological, and surgical findings.

    PubMed

    Parish, Jonathan M; Bonnin, Jose M; Goodman, Julius M; Cohen-Gadol, Aaron A

    2015-04-01

    Ependymomas arising in the intrasellar compartment are extremely rare and most often are not included in the differential diagnosis of an intrasellar tumor mass. We review the literature to further advance awareness regarding unusual presentations of this type of tumor and present an illustrative case of an intrasellar cystic ependymoma that developed in an uncommon location. In our illustrative case, the patient had a 2 year history of hypopituitarism, but no headaches or visual disturbance. Preoperatively, the lesion was thought to be a pituitary macroadenoma.

  10. Oncocytic ependymoma: a new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells.

    PubMed

    Vajtai, Istvan; von Gunten, Michael; Fung, Christian; Brekenfeld, Caspar; Kappeler, Andreas; Reinert, Michael M

    2011-01-15

    Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as "dot-like" staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of "zipper-like" intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.

  11. Anaplastic lymphoma kinase status in rhabdomyosarcomas.

    PubMed

    Yoshida, Akihiko; Shibata, Tatsuhiro; Wakai, Susumu; Ushiku, Tetsuo; Tsuta, Koji; Fukayama, Masashi; Makimoto, Atsushi; Furuta, Koh; Tsuda, Hitoshi

    2013-06-01

    Rhabdomyosarcoma is a rare soft tissue sarcoma that typically affects children, adolescents, and young adults. Despite treatment via a multidisciplinary approach, the prognosis of advance-stage rhabdomyosarcomas remains poor, and a new treatment strategy is needed. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is a potential target for specific inhibitors. In this study, we investigated 116 rhabdomyosarcomas using a polymer-based ALK immunostaining method and correlated the results with clinicopathological parameters. In addition, we examined ALK status using dual-color fluorescence in situ hybridization, PCR, and sequencing. In immunohistochemical analysis, ALK was detected in 2 (6%) of 33 embryonal rhabdomyosarcomas, 42 (69%) of 61 alveolar rhabdomyosarcomas, and 0 (0%) of 22 other subtypes, including pleomorphic, adult-spindle-cell/sclerosing, and epithelioid variants. Compared with ALK-negative alveolar rhabdomyosarcomas, ALK-positive ones are presented with metastatic spread more frequently and showed a greater extent of myogenin reactivity. Overall survival was not associated with ALK expression. FOXO1 rearrangement was significantly associated with ALK immunoreactivity. The median ALK copy number was greater in ALK-positive tumors than in ALK-negative tumors. Most (93%) cases tested showed no selective increase in the ALK gene dosage. ALK selective amplification and low-level selective gain were noted in one and three cases, respectively. Further, a high-polysomy pattern (≥4 ALK copies in ≥40% of cells) was observed in seven cases. A significant increase in the ALK copy number was exclusive to the ALK-immunopositive cohort, but it was uncommon, accounting for only 30% of the 37 ALK-positive rhabdomyosarcomas. ALK gene rearrangement was not observed in either cohort, while an ALK somatic mutation (I1277T) was found in one ALK-negative embryonal case. Although it remains controversial whether ALK expression without gene rearrangement

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

    PubMed

    Cimino, Patrick J

    2015-10-01

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

  13. Acute leukaemia following malignant ependymoma: a case report

    SciTech Connect

    Pai, M.R.; Advani, S.H.; Gopal, R.; Nair, C.N.; Saikia, T.; Kamat, D.M.

    1985-05-01

    Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here the authors report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.

  14. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

    PubMed Central

    Mack, S. C.; Witt, H.; Piro, R. M.; Gu, L.; Zuyderduyn, S.; Stütz, A. M.; Wang, X.; Gallo, M.; Garzia, L.; Zayne, K.; Zhang, X.; Ramaswamy, V.; Jäger, N.; Jones, D. T. W.; Sill, M.; Pugh, T. J.; Ryzhova, M.; Wani, K. M.; Shih, D. J. H.; Head, R.; Remke, M.; Bailey, S. D.; Zichner, T.; Faria, C. C.; Barszczyk, M.; Stark, S.; Seker-Cin, H.; Hutter, S.; Johann, P.; Bender, S.; Hovestadt, V.; Tzaridis, T.; Dubuc, A. M.; Northcott, P. A.; Peacock, J.; Bertrand, K. C.; Agnihotri, S.; Cavalli, F. M. G.; Clarke, I.; Nethery-Brokx, K.; Creasy, C. L.; Verma, S. K.; Koster, J.; Wu, X.; Yao, Y.; Milde, T.; Sin-Chan, P.; Zuccaro, J.; Lau, L.; Pereira, S.; Castelo-Branco, P.; Hirst, M.; Marra, M. A.; Roberts, S. S.; Fults, D.; Massimi, L.; Cho, Y. J.; Van Meter, T.; Grajkowska, W.; Lach, B.; Kulozik, A. E.; von Deimling, A.; Witt, O.; Scherer, S. W.; Fan, X.; Muraszko, K. M.; Kool, M.; Pomeroy, S. L.; Gupta, N.; Phillips, J.; Huang, A.; Tabori, U.; Hawkins, C.; Malkin, D.; Kongkham, P. N.; Weiss, W. A.; Jabado, N.; Rutka, J. T.; Bouffet, E.; Korbel, J. O.; Lupien, M.; Aldape, K. D.; Bader, G. D.; Eils, R.; Lichter, P.; Dirks, P. B.; Pfister, S. M.; Korshunov, A.; Taylor, M. D.

    2014-01-01

    Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland. PMID:24553142

  15. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

    PubMed

    Mack, S C; Witt, H; Piro, R M; Gu, L; Zuyderduyn, S; Stütz, A M; Wang, X; Gallo, M; Garzia, L; Zayne, K; Zhang, X; Ramaswamy, V; Jäger, N; Jones, D T W; Sill, M; Pugh, T J; Ryzhova, M; Wani, K M; Shih, D J H; Head, R; Remke, M; Bailey, S D; Zichner, T; Faria, C C; Barszczyk, M; Stark, S; Seker-Cin, H; Hutter, S; Johann, P; Bender, S; Hovestadt, V; Tzaridis, T; Dubuc, A M; Northcott, P A; Peacock, J; Bertrand, K C; Agnihotri, S; Cavalli, F M G; Clarke, I; Nethery-Brokx, K; Creasy, C L; Verma, S K; Koster, J; Wu, X; Yao, Y; Milde, T; Sin-Chan, P; Zuccaro, J; Lau, L; Pereira, S; Castelo-Branco, P; Hirst, M; Marra, M A; Roberts, S S; Fults, D; Massimi, L; Cho, Y J; Van Meter, T; Grajkowska, W; Lach, B; Kulozik, A E; von Deimling, A; Witt, O; Scherer, S W; Fan, X; Muraszko, K M; Kool, M; Pomeroy, S L; Gupta, N; Phillips, J; Huang, A; Tabori, U; Hawkins, C; Malkin, D; Kongkham, P N; Weiss, W A; Jabado, N; Rutka, J T; Bouffet, E; Korbel, J O; Lupien, M; Aldape, K D; Bader, G D; Eils, R; Lichter, P; Dirks, P B; Pfister, S M; Korshunov, A; Taylor, M D

    2014-02-27

    Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

  16. Vestibular schwannoma or tanycytic ependymoma: Immunohistologic staining reveals

    PubMed Central

    Divito, Anthony; Keller, Jeffrey T.; Hagen, Matthew; Zuccarello, Mario

    2014-01-01

    Background: The cerebellopontine angle (CPA) is a common location for primary tumors, most often vestibular schwannomas, and also meningiomas, dermoids, and a host of other neoplasms. Our case report illustrates how radiologic and histopathologic presentations of an unusual variant of ependymal neoplasm can be diagnostically challenging and how accurate diagnosis can affect treatment protocols. Case History: Our patient had a CPA mass that was a variant of ependymoma known as tanycytic ependymoma that mimicked vestibular schwannoma radiologically and during intraoperative pathologic examination. Diagnosis as a World Health Organization (WHO) grade II tanycytic ependymoma was supported by its appearance on evaluation of the permanent sections, its diffuse immunoreactivity for glial fibrillary acidic protein (GFAP), and the perinuclear dot-and-ring-like staining for epithelial membrane antigen (EMA). Conclusions: Our patient's CPA mass initially believed to be a vestibular schwannoma on preoperative evaluation, surgical appearance, and intraoperative pathologic consultation was then correctly diagnosed as a WHO grade II tanycytic ependymoma on permanent histologic sections with the assistance of immunohistochemical stains, including EMA. After this definitive diagnosis, our patient's adjuvant treatment was adjusted. Earlier diagnosis could have provided guidance for goals of resection and prompt initiation of adjuvant treatment. PMID:25506503

  17. Outcome Analysis in Cases of Spinal Conus Cauda Ependymoma

    PubMed Central

    Tyagi, Devendra K; Desai, Ketan I; Dighe, Mohnish P

    2016-01-01

    Introduction One half of all central nervous system ependymomas, arise within the spinal canal and about 40% of these arise from filum terminale. The myxopapillary variant of spinal ependymoma almost exclusively occurs in the lumbosacral region and they are histologically designated as Grade I. Long term control is best achieved by gross total removal at the initial operation. There is as yet no consensus on the management of incompletely excised tumour. Opinions regarding radiotherapy are controversial and the indications are empirical. Aim In the present study, we investigated the clinical characteristics and long-term outcomes in patients with conus cauda ependymoma that were managed at our center with baseline comparison of our findings with those reported in literature. Materials and Methods A retrospective analysis of 44 cases of conus cauda ependymoma tumours treated at the Department of Neurosurgery at a tertiary care centre from January 2001 to December 2015 was done. Detailed scrutiny and analysis of the patient’s data with respect to the demographic features, clinical findings, investigative procedures, extent of surgical resection, intra and postoperative complications, efficacy of adjuvant therapy, postoperative results and long term follow-up were done. Results The analysis was done in 44 patients with conus cauda ependymoma over a period of 15 years. The mean age of presentation was 31 years. Incidence of male predominance was noted. Average duration of presenting features was 10 months. Back pain and motor weakness in the lower limbs were the commonest clinical findings. Total excision of the tumour was possible in 89% cases. Myxopapillary ependymoma was the commonest variant. Radiotherapy was only given in patients with near total to subtotal excision of tumour. Back pain and motor weakness improved in majority of patients after surgery. There is limited role of radiotherapy in cases with total tumour excision. Conclusion Conus cauda ependymomas

  18. Salvage treatment for childhood ependymoma after surgery only: Pitfalls of omitting 'at once' adjuvant treatment

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Giangaspero, Felice; Garre, Maria Luisa; Genitori, Lorenzo; Perilongo, Giorgio; Collini, Paola; Riva, Daria; Valentini, Laura; Scarzello, Giovanni; Poggi, Geraldina; Spreafico, Filippo; Peretta, Paola; Mascarin, Maurizio; Modena, Piergiorgio; Sozzi, Gabriella; Bedini, Nice; Biassoni, Veronica; Urgesi, Alessandro; Balestrini, Maria Rosa; Finocchiaro, Gaetano; Sandri, Alessandro; Gandola, Lorenza

    2006-08-01

    Purpose: To discuss the results obtained by giving adjuvant treatment for childhood ependymoma (EPD) at relapse after complete surgery only. Methods and Materials: Between 1993 and 2002, 63 children older than 3 years old entered the first Italian Association for Pediatric Hematology and Oncology protocol for EPD (group A), and another 14 patients were referred after relapsing after more tumor excisions only (group B). Prognostic factors were homogeneously matched in the two groups. We report on the outcome of group B. Results: Mean time to first local progression in group B had been 14 months. Tumors originated in the posterior fossa (PF) in 10 children and were supratentorial (ST) in 4; 11 had first been completely excised (NED) and 3 had residual disease (ED). Diagnoses were classic EPD in 9 patients, anaplastic in 5. Eight children were referred NED and 6 ED after two or more operations, 5 had cranial nerve palsy, 1 had recurrent meningitis, and 2 had persistent hydrocephalus. All received radiotherapy (RT) to tumor bed and 5 also had pre-RT chemotherapy. Six of 14 patients (6/10 with PF tumors) had a further relapse a mean 6 months after the last surgery; 4 of 6 died: progression-free survival and overall survival at 4 years after referral were 54.4% and 77%, respectively. Considering only PF tumors and setting time 0 as at the last surgery for group B, progression-free survival and overall survival were 32% and 50% for group B and 52% (p < 0.20)/70% (p < 0.29) for the 46 patients in group A with PF tumors. Local control was 32% in group B and 70.5% in group A (p = 0.02). Conclusions: Relapsers after surgery only, especially if with PF-EPD, do worse than those treated after first diagnosis; subsequent surgery for tumor relapse has severe neurologic sequelae.

  19. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  20. Ependymoma: a heterogeneous tumor of uncertain origin and limited therapeutic options.

    PubMed

    Dorfer, Christian; Tonn, Joerg; Rutka, James T

    2016-01-01

    Ependymomas are tumors that typically occur with an age-based site preference, with adults harboring supratentorial and spinal tumors and pediatric tumors being mainly in the posterior fossa. Despite their similar histologic appearance, the prognosis varies significantly by age and tumor location, with a better prognosis in increasing age. The mainstay of treatment remains surgical excision with or without radiation therapy as the tumor biology is poorly understood and chemotherapy is generally considered to be ineffective. More recently, molecular biology data have increased our understanding of the genetic and epigenetic changes that drive these tumors, but still it will take a lot of effort to find effective chemotherapeutic regimens. Currently, we are trying to define a subset of tumors, for which radiation therapy can be avoided.

  1. Fractionated stereotactic radiosurgery for recurrent ependymoma in children

    PubMed Central

    Hoffman, Lindsey M.; Plimpton, S. Reed; Foreman, Nicholas K.; Stence, Nicholas V.; Hankinson, Todd C.; Handler, Michael H.; Hemenway, Molly S.; Vibhakar, Rajeev; Liu, Arthur K.

    2013-01-01

    Outcomes for children with relapsed ependymoma are poor. Re-irradiation is a potentially viable salvage option in these patients. Data were reviewed for 12 patients (median age 5.6 years) with relapsed ependymoma who received fractionated stereotactic radiosurgery (fSRS) following maximal surgical resection from 1995 to 2012. Four patients experienced a second recurrence, including 2 in-field and 2 distant failures. Median time to second recurrence (32 months) was significantly longer than time to first recurrence (24 months) (p = 0.008). Three-year local control was 89 %, and median event free survival from fSRS was 3.4 years. Radiation necrosis was observed in 6 patients, 3 who were symptomatic. In conclusion, fSRS offers durable response with a tolerable toxicity profile in children with recurrent EPN. PMID:24078173

  2. Expression alterations define unique molecular characteristics of spinal ependymomas

    PubMed Central

    Lourdusamy, Anbarasu; Rahman, Ruman; Grundy, Richard G.

    2015-01-01

    Ependymomas are glial tumors that originate in either intracranial or spinal regions. Although tumors from different regions are histologically similar, they are biologically distinct. We therefore sought to identify molecular characteristics of spinal ependymomas (SEPN) in order to better understand the disease biology of these tumors. Using gene expression profiles of 256 tumor samples, we identified increased expression of 1,866 genes in SEPN when compared to intracranial ependymomas. These genes are mainly related to anterior/posterior pattern specification, response to oxidative stress, glial cell differentiation, DNA repair, and PPAR signalling, and also significantly enriched with cellular senescence genes (P = 5.5 × 10−03). In addition, a high number of significantly down-regulated genes in SEPN are localized to chromosome 22 (81 genes from chr22: 43,325,255 – 135,720,974; FDR = 1.77 × 10−23 and 22 genes from chr22: 324,739 – 32,822,302; FDR = 2.07 × 10−09) including BRD1, EP300, HDAC10, HIRA, HIC2, MKL1, and NF2. Evaluation of NF2 co-expressed genes further confirms the enrichment of chromosome 22 regions. Finally, systematic integration of chromosome 22 genes with interactome and NF2 co-expression data identifies key candidate genes. Our results reveal unique molecular characteristics of SEPN such as altered expression of cellular senescence and chromosome 22 genes. PMID:25909290

  3. Poorly differentiated (anaplastic) seminoma of the testis.

    PubMed

    Cockburn, A G; Vugrin, D; Batata, M; Hajdu, S; Whitmore, W F

    1984-05-01

    Anaplastic seminoma constitutes approximately 17% of total experience with seminoma at Memorial Sloan-Kettering Cancer Center. Among 25 previously untreated patients, 11 (44%) were clinical Stage I, and 14 (56%) were clinical Stage II or III. Treatment of these 25 patients with the same regimens employed for classical seminoma yielded an overall 80% 5-year apparent cure rate. Survival rates were poor in eight previously treated patients referred with recurrence.

  4. The response of spinal cord ependymomas to bevacizumab in patients with neurofibromatosis Type 2.

    PubMed

    Morris, Katrina A; Afridi, Shazia K; Evans, D Gareth; Hensiek, Anke E; McCabe, Martin G; Kellett, Mark; Halliday, Dorothy; Pretorius, Pieter M; Parry, Allyson

    2016-12-16

    OBJECTIVE People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment. METHODS The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes. RESULTS Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11-53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3-57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas. CONCLUSIONS Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

  5. Evolution of Neurological Impairment in Pediatric Infratentorial Ependymoma Patients

    PubMed Central

    Morris, E. Brannon; Li, Chenghong; Khan, Raja B.; Sanford, Robert A; Boop, Frederick; Pinlac, Renee; Xiong, Xiaoping; Merchant, Thomas E.

    2009-01-01

    Background Infratentorial ependymoma is a common central nervous system tumor of childhood and in patients > 1 year of age is treated with maximally feasible surgical resection and radiotherapy. Because of this tumor typically arises within the 4th ventricle and can invade the brainstem, patients are at risk for significant neurological impairment. Purpose To characterize the incidence, evolution, and persistence of neurologic impairment in children with infratentorial ependymoma following maximal safe surgery and conformal or intensity-modulated radiation therapy (CRT/IMRT). Patients and Methods After surgical resection, 96 children with non-metastatic infratentorial ependymoma were enrolled on a phase II study of image-guided radiation therapy and were prospectively followed with interval comprehensive neurological examinations. Late adverse neurological severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Results The most common deficits detected at baseline examination were limb dysmetria, cranial nerve VI/VII palsy, limb paresis, dysphagia, and truncal ataxia/hypotonia. When present, gait dysfunction and dysphagia were often severe. Oculomotor dysfunction, facial paresis, dysphagia, and gait impairment improved over time. With the exception of hearing loss, in the survivor cohort, very few severe late effects (CTCAE Grade 3/4/5) were present at 60 month survival. Conclusion In general, neurological deficits were maximal in the post-operative period and either remained stable or improved during radiation and the post-treatment evaluation period. With the exception of hearing, the majority of chronic residual neurological deficits in this at-risk population are mild and only minimally intrude upon daily life. PMID:19330288

  6. Histological predictors of outcome in ependymoma are dependent on anatomic site within the central nervous system.

    PubMed

    Raghunathan, Aditya; Wani, Khalida; Armstrong, Terri S; Vera-Bolanos, Elizabeth; Fouladi, Maryam; Gilbertson, Richard; Gajjar, Amar; Goldman, Stewart; Lehman, Norman L; Metellus, Phillipe; Mikkelsen, Tom; Necesito-Reyes, Mary Jo T; Omuro, Antonio; Packer, Roger J; Partap, Sonia; Pollack, Ian F; Prados, Michael D; Robins, H Ian; Soffietti, Riccardo; Wu, Jing; Miller, C Ryan; Gilbert, Mark R; Aldape, Kenneth D

    2013-09-01

    Ependymomas originate in posterior fossa (PF), supratentorial (ST) or spinal cord (SC) compartments. At present, grading schemes are applied independent of anatomic site. We performed detailed histological examination on 238 World Health Organization grade II and III ependymomas. Among PF ependymomas, the presence of hypercellular areas, necrosis, microvascular proliferation and elevated mitotic rate (all P < 0.01) were significantly associated with worse progression-free survival (PFS), while extensive ependymal canal formation was not (P = 0.89). Similar to the PF tumors, microvascular proliferation (P = 0.01) and elevated mitotic rate (P = 0.03) were significantly associated with worse PFS in the ST tumors. However, in contrast to PF tumors, extensive ependymal canals (P = 0.03) were associated with worse clinical outcome in ST ependymomas, but hypercellularity (P = 0.57) and necrosis (P = 0.47) were not. On multivariate Cox regression, after adjusting for relevant clinical variables, individual histological factors and a composite histological score remained significant among ST and PF ependymoma. In contrast to both PF and ST ependymoma, histological features were not found to be associated with PFS in SC tumors. Taken together, the clinical relevance of specific histological features in ependymoma appears to be related to the anatomic site of origin and suggests that site-specific grading criteria be considered in future classification systems.

  7. THE MANAGEMENT OF AN ORAL ANAPLASTIC SARCOMA IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) USING INTRALESIONAL CHEMOTHERAPY.

    PubMed

    Franklinos, Lydia H V; Masters, Nicholas; Feltrer, Yedra; Pocknell, Ann; Bolt, David M; Dakin, Stephanie; Berry, Karla; Molenaar, Fieke M

    2017-03-01

    An adult female captive pygmy hippopotamus (Choeropsis liberiensis) was diagnosed with an oral anaplastic sarcoma. The tumor was surgically debulked and intralesional chemotherapy with mitomycin C (0.4 mg/cm(3) of tumor) and cisplatin (1 mg/cm(3) of tumor) was administered. Chemotherapeutic treatment proved difficult due to the risks of repeated anesthetics and unknown drug efficacies. Marked proliferation of the mass was observed during estrus, and chemotherapy was repeated as an experimental treatment to slow tumor progression in order for the animal to remain in the species breeding program. Tumor proliferation was detected during the first trimester of pregnancy; however, in the lactation period, the mass became quiescent. No adverse reactions to chemotherapeutic drugs were observed and the animal continues to be monitored for tumor progression. This is the first report of an anaplastic sarcoma and of chemotherapy use in a pygmy hippopotamus and it highlights logistical considerations for treating neoplasia in this species.

  8. Phase II Pediatric Study With Dabrafenib in HGG Patients

    ClinicalTrials.gov

    2017-02-13

    Anaplastic Astrocytoma; Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Anaplastic Ependymoma; Choroid Plexus Carcinoma; Anaplastic Ganglioglioma; Pineal Parenchymal Tumor; Pineoblastoma; Medulloblastoma; PNET; Rhabdoid Tumor; Perineurioma; MPNST; Malignant Meningloma; Anaplastic Hemangiopericytoma

  9. Cervical extradural and extraspinal ependymoma mimicking dumb-bell schwannoma: an unusual tumor.

    PubMed

    Ramesh, V G; Karthikeyan, K V; Rao, K Ramesh; Balasubramanian, C

    2013-01-01

    Ependymomas are common in intramedullary location and extradural location of the spinal cord is very rare. A few cases in the lumbosacral region have been reported. This report presents a cervical dumb-bell ependymoma with a small intraspinal extradural component and a large extraspinal component in the posterior triangle of the neck. The tumor was excised in two stages. This is probably the first such case report in the cervical region in the world literature. Possible histogenesis of ependymoma in this location is also discussed.

  10. An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes.

    PubMed

    Mohankumar, Kumarasamypet M; Currle, David S; White, Elsie; Boulos, Nidal; Dapper, Jason; Eden, Christopher; Nimmervoll, Birgit; Thiruvenkatam, Radhika; Connelly, Michele; Kranenburg, Tanya A; Neale, Geoffrey; Olsen, Scott; Wang, Yong-Dong; Finkelstein, David; Wright, Karen; Gupta, Kirti; Ellison, David W; Thomas, Arzu Onar; Gilbertson, Richard J

    2015-08-01

    Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.

  11. An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

    PubMed Central

    Mohankumar, Kumarasamypet M.; Currle, David S.; White, Elsie; Boulos, Nidal; Dapper, Jason; Eden, Christopher; Nimmervoll, Birgit; Thiruvenkatam, Radhika; Connelly, Michele; Kranenburg, Tanya A.; Neale, Geoffrey; Olsen, Scott; Wang, Yong-Dong; Finkelstein, David; Wright, Karen; Gupta, Kirti; Ellison, David W.; Thomas, Arzu Onar; Gilbertson, Richard J.

    2015-01-01

    Cancers are characterized by non-random, chromosome copy number alterations that presumably contain oncogenes and tumor–suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here, we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models we validate eight new ependymoma oncogenes and 10 ependymoma TSGs that converge on a small number of cell functions including vesicle trafficking, DNA modification and cholesterol biosynthesis, pinpointing these as potential new therapeutic targets. PMID:26075792

  12. Occipital Falcine Anaplastic Hemangiopericytoma Mimicking Meningioma

    PubMed Central

    Kanesen, Davendran; Kandasamy, Regunath; Idris, Zamzuri

    2016-01-01

    The rarity of hemangiopericytoma (HPC) and its controversial histological classification result in its frequent misdiagnosis and thus make the treatment quite challenging. It is often difficult to distinguish these tumors from meningiomas based on clinical features and radiological findings. This is a case report of a man, diagnosed clinically and radiologically as meningioma, which turned out to be anaplastic HPC on histological examination. A 30-year-old man presented with 3 months of progressively worsening of headache and blurring of vision. Clinical examination revealed the right homonymous hemianopia with reduced visual acuity and papilledema bilaterally. Magnetic resonance imaging revealed a multilobulated and heterogenous extraaxial lesion attached to the occipital falx. It measured 9.0 cm (AP) × 5.5 cm (W) × 5.8 cm (CC) and expands bilaterally with major bulk on the left. An occipital craniotomy followed by a subtotal tumor excision was only achieved due to profuse bleeding intraoperatively. Histopathology confirmed an anaplastic HPC (WHO Grade 3). The importance of differentiation between HPCs and meningiomas cannot be overemphasized. A preoperative correct diagnosis is difficult, but it is important that it should be made. Multilobulated (mushroom appearance), prominent internal signal voids, relatively narrow dural attachment, and lytic destruction without calcifications are useful findings to distinguish HPCs from meningiomas. PMID:28163517

  13. Occipital Falcine Anaplastic Hemangiopericytoma Mimicking Meningioma.

    PubMed

    Kanesen, Davendran; Kandasamy, Regunath; Idris, Zamzuri

    2016-12-01

    The rarity of hemangiopericytoma (HPC) and its controversial histological classification result in its frequent misdiagnosis and thus make the treatment quite challenging. It is often difficult to distinguish these tumors from meningiomas based on clinical features and radiological findings. This is a case report of a man, diagnosed clinically and radiologically as meningioma, which turned out to be anaplastic HPC on histological examination. A 30-year-old man presented with 3 months of progressively worsening of headache and blurring of vision. Clinical examination revealed the right homonymous hemianopia with reduced visual acuity and papilledema bilaterally. Magnetic resonance imaging revealed a multilobulated and heterogenous extraaxial lesion attached to the occipital falx. It measured 9.0 cm (AP) × 5.5 cm (W) × 5.8 cm (CC) and expands bilaterally with major bulk on the left. An occipital craniotomy followed by a subtotal tumor excision was only achieved due to profuse bleeding intraoperatively. Histopathology confirmed an anaplastic HPC (WHO Grade 3). The importance of differentiation between HPCs and meningiomas cannot be overemphasized. A preoperative correct diagnosis is difficult, but it is important that it should be made. Multilobulated (mushroom appearance), prominent internal signal voids, relatively narrow dural attachment, and lytic destruction without calcifications are useful findings to distinguish HPCs from meningiomas.

  14. An integrated in vitro and in vivo high throughput screen identifies treatment leads for ependymoma

    PubMed Central

    Atkinson, Jennifer M.; Shelat, Anang A.; Carcaboso, Angel Montero; Kranenburg, Tanya A.; Arnold, Alexander; Boulos, Nidal; Wright, Karen; Johnson, Robert A.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Feau, Clementine; Phoenix, Timothy; Gibson, Paul; Zhu, Liqin; Tong, Yiai; Eden, Chris; Ellison, David W.; Priebe, Waldemar; Koul, Dimpy; Yung, W. K. Alfred; Gajjar, Amar; Stewart, Clinton F.; Guy, R. Kip; Gilbertson, Richard J.

    2011-01-01

    Summary Using a mouse model of ependymoma—a chemoresistant brain tumor—we combined multi-cell high-throughput screening (HTS), kinome-wide binding assays, and in vivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both in vitro and in vivo e.g., 5-fluoruracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation. PMID:21907928

  15. Complex cytogenetic abnormalities including telomeric associations and MEN1 mutation in a pediatric ependymoma.

    PubMed

    Urioste, M; Martínez-Ramírez, A; Cigudosa, J C; Colmenero, I; Madero, L; Robledo, M; Martínez-Delgado, B; Benítez, J

    2002-10-15

    Ependymomas are neuroectodermal tumors of the brain and spinal cord. Some recurrent cytogenetic aberrations have been reported in these tumors, including alterations involving chromosomes 22, 6, and 11. However, consistent molecular alterations have not been identified in ependymal tumors. We studied a recurrent ependymoma in a 3-year-old patient by standard cytogenetic and molecular analysis of TP53 and MEN1 genes. In the present case, we found many of the cytogenetic features previously described as being recurrent in ependymomas, including unstable telomeric alterations. Furthermore, we detected a novel acquired heterozygous mutation in the MEN1 gene. The chromosomal instability produced by the telomeric alterations and the mutation in the MEN1 gene could be important events in the tumorigenesis of ependymomas.

  16. Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells.

    PubMed

    Barszczyk, Mark; Buczkowicz, Pawel; Castelo-Branco, Pedro; Mack, Stephen C; Ramaswamy, Vijay; Mangerel, Joshua; Agnihotri, Sameer; Remke, Marc; Golbourn, Brian; Pajovic, Sanja; Elizabeth, Cynthia; Yu, Man; Luu, Betty; Morrison, Andrew; Adamski, Jennifer; Nethery-Brokx, Kathleen; Li, Xiao-Nan; Van Meter, Timothy; Dirks, Peter B; Rutka, James T; Taylor, Michael D; Tabori, Uri; Hawkins, Cynthia

    2014-12-01

    Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 ± 11 vs 64 ± 18 %; p = 0.03) and overall survival (58 ± 12 vs 83 ± 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.

  17. Intracranial extra-axial ependymoma involving the petroclival region: a rare case report

    PubMed Central

    Yang, Xiang; Ren, Yanming; Wu, Weilu; Wang, Xiang; Liu, Xuesong; Zhang, Yuekang

    2014-01-01

    Intracranial extraaxial ependymomas (IEAEs) are very rare, and extra-axial petroclival ependymoma (EAPE) has not been reported in the reviewed English-language literature by now. We present a male patient with EAPE misdiagnosed as a petroclival meningioma preoperatively, and involved recurrence at 4th months after operation though totally resection. Thereafter, we report this case and discuss the clinical characteristics of the disease by briefly review. PMID:25674289

  18. Novel Approaches in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Hsu, Kun-Tai; Yu, Xiao-Min; Audhya, Anjon W.; Jaume, Juan C.; Lloyd, Ricardo V.; Miyamoto, Shigeki; Prolla, Tomas A.

    2014-01-01

    Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future. PMID:25260367

  19. The anaplastic lymphoma kinase testing conundrum.

    PubMed

    Conde, Esther; Taniere, Philippe; Lopez-Rios, Fernando

    2015-02-01

    Given the excellent results of the clinical trials with anaplastic lymphoma kinase (ALK) inhibitors, the importance of accurately identifying ALK-positive lung carcinoma patients has never been greater. It brings with it a pressing need for harmonized development of companion diagnostics, for economic, scientific and medical reasons. Therefore, it is crucial that ALK testing assays become more standardized both in performance (analytical phase) and interpretation (post-analytical phase). We find that both methods currently recommended by College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines (FISH and Immunohistochemistry) are reasonable approaches for primary routine ALK testing, if at least 50 tumor cells are scored and protocols are strictly followed. Moreover, due to the high demand to study multiple predictive biomarkers on different assay platforms, quick and reliable approaches to achieve this are essential to guide treatment decisions.

  20. Anaplastic Carcinoma Possibly Arising from a Heterotopic Pancreas.

    PubMed

    Adachi, Yasushi; Mita, Hiroaki; Takahashi, Hideaki; Akino, Kimishige; Kikuchi, Takefumi; Ishii, Yoshifumi; Endo, Takao

    2015-01-01

    Anaplastic carcinoma is a rare pancreatic cancer, and the malignant transformation of a heterotopic pancreas is also rare. We herein report a case of an elderly woman with a mass of unknown origin in the abdominal cavity. Computed tomography identified the extent of the tumor but not the organ of origin. The abdominal tumor eventually metastasized to the liver and lung. An autopsy and immunohistochemical examination revealed an anaplastic carcinoma possibly originating in an ectopic pancreas.

  1. Primary anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma of the breast in a male patient.

    PubMed

    Ko, E S; Seol, H; Shin, J H; Ko, E Y

    2012-04-01

    Anaplastic large-cell lymphoma is an extremely rare lymphoma subtype. We describe the mammographic and ultrasonographic findings in a 51-year-old male patient who suffered from a palpable lump caused by this rare disease.

  2. Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

    ClinicalTrials.gov

    2017-04-06

    Anaplastic Large Cell Lymphoma, ALK-Positive; CD30-Positive Neoplastic Cells Present; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma

  3. Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.

    PubMed

    Karakoula, Katherine; Jacques, Thomas S; Phipps, Kim P; Harkness, William; Thompson, Dominic; Harding, Brian N; Darling, John L; Warr, Tracy J

    2014-04-28

    Promoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of gene inactivation in cancer. To identify targets of epigenetic silencing in paediatric intracranial ependymoma, we used a pharmacological unmasking approach through treatment of 3 ependymoma short-term cell cultures with the demethylating agent 5-Aza-2'-deoxycytidine followed by global expression microarray analysis. We identified 55 candidate epigenetically silenced genes, which are involved in the regulation of apoptosis, Wnt signalling, p53 and cell differentiation. The methylation status of 26 of these genes was further determined by combined bisulfite restriction analysis (COBRA) and genomic sequencing in a cohort of 40 ependymoma samples. The most frequently methylated genes were BEX1 (27/40 cases), BAI2 (20/40), CCND2 (18/40), and CDKN2A (14/40). A high correlation between promoter hypermethylation and decreased gene expression levels was established by real-time quantitative PCR, suggesting the involvement of these genes in ependymoma tumourigenesis. Furthermore, ectopic expression of brain-expressed X-linked 1 (BEX1) in paediatric ependymoma short-term cell cultures significantly suppressed cell proliferation and colony formation. These data suggest that promoter hypermethylation contributes to silencing of target genes in paediatric intracranial ependymoma. Epigenetic inactivation of BEX1 supports its role as a candidate tumour suppressor gene in intracranial ependymoma, and a potential target for novel therapies for ependymoma in children.

  4. A spinal tumor showing mixed features of ependymoma and hemangioblastoma: a case report and literature review.

    PubMed

    Cheng, Hai-Xia; Chu, Shu-Guang; Xu, Qi-Wu; Wang, Yin

    2015-04-01

    We report an intramedullary spinal tumor consisting of an ependymoma and a hemangioblastoma (HB). A 37-year-old woman presented with progressive bilateral lower limb sensory and motor deficits. Magnetic resonance imaging showed a single intramedullary mass in the thoracic cord (T4-T6 level). Clinically, the patient had no von Hippel-Lindau disease and neurofibromatosis type 2. Metastatic carcinomas including renal cell carcinoma were altogether negative. Complete surgical resection was performed. Histologically, the tumor consisted of a mixed ependymoma and HB. Tumor cells of ependymoma displayed a rather uniform appearance with round to oval nuclei having salt-and-pepper-like chromatin, forming perivascular pseudorosette structures with radially arranged, tapering cell processes extending to intratumoral blood vessels. Stromal cells of HB had vacuolated or homogeneously eosinophilic cytoplasm and variable sized hyperchromatic nuclei within a background of capillaries. Immunohistochemically, tumor cells of ependymoma were strongly positive for glial fibrillary acidic protein (GFAP), focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like or ring-like pattern. Stromal cells of HB showed immunoreactivity for S100, vimentin, inhibin-α, D2-40, EMA and cytokeratins (CK: AE1/AE3, CK19). A review of the literature, in conjunction with the present case, shows that ependymomas and HBs may have a close relationship with each other.

  5. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV

  6. Primary gastric anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma

    PubMed Central

    Tian, Chen; Zhang, Yizhuo

    2016-01-01

    Introduction Most primary stomach lymphomas are now recognized to originate from B-cell. Primary gastric anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) as shown in this case is very rare. Case report A 59-year-old man presented with a 1-month history of epigastric pain. Computed tomography showed a tumor in the stomach with perigastric lymphadenopathy. Biopsy of the tumor with gastroendoscopy showed ALCL. Bone marrow aspiration and trephine biopsy showed no infiltration. A diagnosis of primary gastric ALK-negative ALCL was made. The patient was first treated with four cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, but his condition did not show improvement. Then he was treated with two cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate and cytarabine (Hyper-CVAD/MA) regimen. In spite of these treatments, he still died of disease progression. Conclusion The prognosis of ALK-negative ALCLs is usually worse than ALK-positive ALCLs. In this case, the patient was not responsive to a multidrug chemotherapy with CHOP and Hyper-CVAD/MA. PMID:27695344

  7. Features of intraventricular tanycytic ependymoma: report of a case and review of literature.

    PubMed

    Agarwal, Shweta; Stevenson, Michael E; Sughrue, Michael E; Wartchow, Eric P; Mierau, Gary W; Fung, Kar-Ming

    2014-01-01

    Tanycytic ependymoma is the rarest variant of ependymoma and occurs primarily in the spinal cord. Intracranial cases are even rarer. Only 9 ventricular and 5 subcortical tanycytic ependymoma have been reported in the literature. Amongst the 9 ventricular cases, only one tumor arose from the third ventricle. We report here another case of tanycytic ependymoma arising from the third ventricle completed with immunohistochemical, ultrastructural, and molecular pathology study. The patient was a 44 year-old male who presented with headache, nausea and visual disturbances of a few months duration. Neuroradiological findings showed a well-defined mass arising from the posterolateral wall of third ventricle. Histologically the tumor was composed of monotonous spindle cells arranged in fascicles without definitive perivascular rosettes. The tumor cells were diffusely positive for glial fibrillary acidic protein and epithelial membrane antigen, showed faint immunoreactivity for synaptophysin but were negative for neurofilament proteins and Ki-67 was less than 1%. Molecular studies showed absence of isocitrate dehydrogenase gene 1 and 2 mutation. A diagnosis of tanycytic ependymoma (TE) was made. From literature review with our current case included, intraventricular tanycytic ependymomas ranged from 1.8 to 4.0 cm. The age of patients ranged from 3.5 to 75 years with a mean age of 37.5 and a male predominance. The tumors occurred as well-defined, solitary ventricular mass without significant peritumoral edema with or without cystic changes. Histopathology and immunohistochemical profile are rather similar among different tumors. The immediate to short term outcome is excellent but long term follow up data is lacking.

  8. Preclinical examination of clofarabine in pediatric ependymoma: intratumoral concentrations insufficient to warrant further study.

    PubMed

    Patel, Yogesh T; Jacus, Megan O; Boulos, Nidal; Dapper, Jason D; Davis, Abigail D; Vuppala, Pradeep K; Freeman, Burgess B; Mohankumar, Kumarasamypet M; Throm, Stacy L; Gilbertson, Richard J; Stewart, Clinton F

    2015-05-01

    Clofarabine, a deoxyadenosine analog, was an active anticancer drug in our in vitro high-throughput screening against mouse ependymoma neurospheres. To characterize the clofarabine disposition in mice for further preclinical efficacy studies, we evaluated the plasma and central nervous system disposition in a mouse model of ependymoma. A plasma pharmacokinetic study of clofarabine (45 mg/kg, IP) was performed in CD1 nude mice bearing ependymoma to obtain initial plasma pharmacokinetic parameters. These estimates were used to derive D-optimal plasma sampling time points for cerebral microdialysis studies. A simulation of clofarabine pharmacokinetics in mice and pediatric patients suggested that a dosage of 30 mg/kg IP in mice would give exposures comparable to that in children at a dosage of 148 mg/m(2). Cerebral microdialysis was performed to study the tumor extracellular fluid (ECF) disposition of clofarabine (30 mg/kg, IP) in the ependymoma cortical allografts. Plasma and tumor ECF concentration-time data were analyzed using a nonlinear mixed effects modeling approach. The median unbound fraction of clofarabine in mouse plasma was 0.79. The unbound tumor to plasma partition coefficient (K pt,uu: ratio of tumor to plasma AUCu,0-inf) of clofarabine was 0.12 ± 0.05. The model-predicted mean tumor ECF clofarabine concentrations were below the in vitro 1-h IC50 (407 ng/mL) for ependymoma neurospheres. Thus, our results show the clofarabine exposure reached in the tumor ECF was below that associated with an antitumor effect in our in vitro washout study. Therefore, clofarabine was de-prioritized as an agent to treat ependymoma, and further preclinical studies were not pursued.

  9. Cross-species genomics matches driver mutations and cell compartments to model ependymoma.

    PubMed

    Johnson, Robert A; Wright, Karen D; Poppleton, Helen; Mohankumar, Kumarasamypet M; Finkelstein, David; Pounds, Stanley B; Rand, Vikki; Leary, Sarah E S; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A; Gillespie, Yancey; Allen, Jeffrey C; Merchant, Thomas; Boop, Fredrick A; Sanford, Robert A; Gajjar, Amar; Ellison, David W; Taylor, Michael D; Grundy, Richard G; Gilbertson, Richard J

    2010-07-29

    Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.

  10. ‘Serpent in the spine’: a case of giant spinal ependymoma of cervicothoracic spine

    PubMed Central

    Arrifin, Arlizan; Kaliaperumal, Chandrasekaran; Keohane, Catherine; O'Sullivan, Michael

    2012-01-01

    We describe a case of giant spinal ependymoma of cervicothoracic spine in a 30-year-old lady who presented with progressive spastic paraparesis and significant combined upper and lower motor neuron signs in her lower limbs over a 1-year period. She also had upper limb small muscle wasting with absent reflexes and diminished sensation. She was wheel chair bound with involvement of sphincters. Neuroimaging revealed a uniformly enhancing intramedullary lesion from C2–T3 level with associated syringomyelia. She underwent a complete excision of this World Health Organisation (WHO) II cellular ependymoma, resulting in significant clinical outcome and improvement in bladder and bowel function. PMID:22739334

  11. 'Serpent in the spine': a case of giant spinal ependymoma of cervicothoracic spine.

    PubMed

    Arrifin, Arlizan; Kaliaperumal, Chandrasekaran; Keohane, Catherine; O'Sullivan, Michael

    2012-06-27

    We describe a case of giant spinal ependymoma of cervicothoracic spine in a 30-year-old lady who presented with progressive spastic paraparesis and significant combined upper and lower motor neuron signs in her lower limbs over a 1-year period. She also had upper limb small muscle wasting with absent reflexes and diminished sensation. She was wheel chair bound with involvement of sphincters. Neuroimaging revealed a uniformly enhancing intramedullary lesion from C2-T3 level with associated syringomyelia. She underwent a complete excision of this World Health Organisation (WHO) II cellular ependymoma, resulting in significant clinical outcome and improvement in bladder and bowel function.

  12. Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations.

    PubMed Central

    Kapp, D. S.; LiVolsi, V. A.; Sanders, M. M.

    1982-01-01

    Most cases of anaplastic thyroid carcinoma can be pathologically and often historically associated with the presence of low-grade (differentiated) cancer in the thyroid. That radiation therapy to the differentiated tumor plays an etiologic role in the transformation of a differentiated to an undifferentiated tumor has been suggested. If such therapy can be implicated, is there a difference in risk between external radiotherapy or radioactive iodine? Review of the literature discloses that more anaplastic carcinoma of the thyroid develop in patients without a history of prior radiation than in individuals who have received radiation. We report our recent experience with two patients who demonstrated the sequence of well-differentiated followed by anaplastic thyroid cancer subsequent to radiation and review the question. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:7183024

  13. The role of prophylactic spinal irradiation in localized intracranial ependymoma

    SciTech Connect

    Vanuytsel, L.; Brada, M. )

    1991-08-01

    A review of the clinical literature on ependymoma, published between 1969 and 1989, was carried out to assess the influence of tumor grade and site, tumor control at the primary site, and extent of irradiation on the incidence of spinal seeding after initial treatment. The pooled data show that the incidence of seeding was 8.4% (7/83) for high grade tumors and 4.5% (6/132) for low grade tumors. Seeding occurred more frequently in infratentorial tumors than in supratentorial tumors. For high grade tumors the incidence was 0% (0/26) for supratentorial and 15.7% (6/38) for infratentorial lesions; for low grade tumors the respective incidence was 2.7% (1/37) and 5.5% (4/73). Spinal seeding was 9.5% (15/157) in the event of failure at the primary site compared to 3.3% (4/122) when local control was achieved. The development of spinal metastases was not influenced by the extent of irradiation. For high grade tumors the incidence was 9.4% (5/53) with spinal irradiation and 6.7% (2/30) without prophylactic treatment; for low grade tumors the respective values were 9.3% (4/43) and 2.2% (2/89). These results indicate that tumor grade, tumor localization, and control of the tumor at the primary site are all factors which may influence the risk of spinal seeding. On the present evidence spinal metastases are not prevented by prophylactic spinal irradiation, regardless of tumor grade and site.

  14. Cytokine and Growth Factor Responses After Radiotherapy for Localized Ependymoma

    SciTech Connect

    Merchant, Thomas E. Li Chenghong; Xiong Xiaoping; Gaber, M. Waleed

    2009-05-01

    Purpose: To determine the time course and clinical significance of cytokines and peptide growth factors in pediatric patients with ependymoma treated with postoperative radiotherapy (RT). Methods and Materials: We measured 15 cytokines and growth factors (fibroblast growth factor, epidermal growth factor, vascular endothelial growth factor [VEGF], interleukin [IL]-1{beta}, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-{gamma}, tumor necrosis factor-{alpha}, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and macrophage inflammatory protein-{alpha}) from 30 patients before RT and 2 and 24 h, weekly for 6 weeks, and at 3, 6, 9, and 12 months after the initiation of RT. Two longitudinal models for the trend of log-transformed measurements were fitted, one during treatment and one through 12 months. Results: During RT, log IL-8 declined at a rate of -0.10389/wk (p = 0.0068). The rate of decline was greater (p = 0.028) for patients with an infratentorial tumor location. The decline in IL-8 after RT was significant when stratified by infratentorial tumor location (p = 0.0345) and more than one surgical procedure (p = 0.0272). During RT, the decline in log VEGF was significant when stratified by the presence of a ventriculoperitoneal shunt. After RT, the log VEGF declined significantly at a rate of -0.06207/mo. The decline was significant for males (p = 0.0222), supratentorial tumors (p = 0.0158), one surgical procedure (p = 0.0222), no ventriculoperitoneal shunt (p = 0.0005), and the absence of treatment failure (p = 0.0028). Conclusion: The pro-inflammatory cytokine IL-8 declined significantly during RT and the decline differed according to tumor location. The angiogenesis factor VEGF declined significantly during the 12 months after RT. The decline was greater in males, those without a ventriculoperitoneal shunt, and in those with favorable disease factors, including one surgical procedure, supratentorial tumor location, and

  15. A Retrospective Study of Surgery and Reirradiation for Recurrent Ependymoma

    SciTech Connect

    Merchant, Thomas E. Boop, Frederick A.; Kun, Larry E.; Sanford, Robert A.

    2008-05-01

    Purpose: To report disease control for patients with recurrent ependymoma (EP) treated with surgery and a second course of radiation therapy (RT{sub 2}). Patients and Methods: Thirty-eight pediatric patients (median age, 2.7 years) with initially localized EP at the time of definitive RT underwent a second course of RT after local (n = 21), metastatic (n = 13), or combined (n = 4) failure. Reirradiation included radiosurgery (n = 6), focal fractionated reirradiation (n = 13), or craniospinal irradiation (CSI; n = 19). Results: Initial time to failure was 16 months, and median age at second treatment was 4.8 years. Radiosurgery resulted in significant brainstem toxicity and one death (median dose, 18 Gy). Progression-free survival ratio was greater than unity for 4 of 6 patients; there was one long-term survivor. Three of 13 patients treated using focal fractionated reirradiation (median combined dose, 111.6 Gy) experienced metastasis. The CSI was administered to 12 patients with metastatic failure, 3 patients with local failure, and 4 patients with combined failure. The 4-year event-free survival rate was 53% {+-} 20% for 12 patients with metastatic failure treated with CSI. Failure after CSI was observed in 1 of 3 patients with a history of local failure and 3 of 4 patients with a history of combined failure. Conclusion: Patients with locally recurrent EP experience durable local tumor control, but remain at risk of metastasis. Patients with metastatic EP failure may receive salvage therapy that includes a component of CSI. Durability of disease control and long-term effects from this approach require further follow-up.

  16. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    SciTech Connect

    Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin; Cohen, Kenneth; Terezakis, Stephanie A.

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  17. Effects of epidermal growth factor receptor blockade on ependymoma stem cells in vitro and in orthotopic mouse models.

    PubMed

    Servidei, Tiziana; Meco, Daniela; Trivieri, Nadia; Patriarca, Valentina; Vellone, Valerio Gaetano; Zannoni, Gian Franco; Lamorte, Giuseppe; Pallini, Roberto; Riccardi, Riccardo

    2012-09-01

    Some lines of evidence suggest that tumors, including ependymoma, might arise from a subpopulation of cells, termed cancer stem cells (CSCs), with self-renewal and tumor-initiation properties. Given the strict dependence of CSCs on epidermal growth factor (EGF) through EGF receptor (EGFR), we investigated the effects of EGFR inhibitors in ependymoma-stem cells (SCs) in vitro and in orthotopic mouse models. We established two ependymoma-SC lines from two recurrent pediatric ependymoma. Both lines expressed markers of radial glia--the candidate SCs of ependymoma--and showed renewal ability, multipotency, and tumorigenicity after orthotopic implantation, despite markedly different expression of CD133 (94 vs. 6%). High phosphorylated-EGFR/EGFR ratio was detected, which decreased after differentiation. EGFR inhibitors (gefitinib and AEE788) reduced clonogenicity, proliferation and survival of ependymoma-SC lines dose-dependently, and blocked EGF-induced activation of EGFR, Akt and extracellular signal-regulated kinase 1/2. Overall, AEE788 was more effective than gefitinib. EGFR blockade as well as differentiation strongly reduced CD133 expression. However, ex vivo treatment with AEE788 did not impair orthotopic tumor engraftment, whereas ex vivo differentiation did, suggesting that CD133 does not absolutely segregate for tumorigenicity in ependymoma-SCs. Orally administered AEE788 prolonged survival of mice bearing ependymoma-SC-driven orthotopic xenografts from 56 to 63 days, close to statistical significance (log-rank p=0.06). Our study describes for the first time EGFR signaling in ependymoma-SCs and the effects of EGFR blockade in complementary in vitro and in vivo systems. The experimental models we developed can be used to further investigate the activity of EGFR inhibitors or other antineoplastic agents in this tumor.

  18. Intraoperative and pathological findings of intramedullary amputation neuroma associated with spinal ependymoma.

    PubMed

    Arishima, Hidetaka; Takeuchi, Hiroaki; Tsunetoshi, Kenzo; Kodera, Toshiaki; Kitai, Ryuhei; Kikuta, Ken-ichiro

    2013-07-01

    Amputation neuromas typically arise in injured peripheral nerves; rarely, however, they arise in the spinal cord. We report a rare case of intramedullary amputation neuroma associated with ependymoma in the cervical spinal cord. A 73-year-old woman presented with a 5-year history of progressive gait disturbance. Neurological examination revealed complete motor deficit of her hands and legs. Magnetic resonance imaging of the cervical spine revealed an enhancing mass within the spinal cord at the C6/7 level. The patient underwent C5-C7 laminectomy surgery. During resection of the spinal tumor, we found a whitish string resembling an aberrant nerve root or schwannoma with adhesion to the tumor on the ventral side of the spinal cord. After resecting the tumor, the surgical specimen was cut and separated into a soft greyish tumor (spinal tumor) and the tough whitish string. Histopathological and immunohistochemical examination revealed the former was a spinal ependymoma and the latter was a neuroma. An intramedullary amputation neuroma associated with a spinal ependymoma is rare, and this is the first known case in which intraoprerative findings were clearly shown. Neurosurgeons should be aware that spinal ependymomas might coexist with neuromas.

  19. Optimising treatment strategies in spinal ependymoma based on 20years of experience at a single centre.

    PubMed

    Keil, Vera C; Schmitt, Anne J; Martin, Sean C; Cadoux-Hudson, Tom A D; Pereira, Erlick A C

    2016-07-01

    Spinal ependymomas are rare tumours, with total resection favoured where possible. Several case series assessing the outcome following neurosurgical treatment for spinal ependymoma advocate the usage of adjuvant radiotherapy in cases of subtotal resection, or in unencapsulated tumours. We assessed the outcome of 61 consecutive cases of spinal ependymoma in a single centre over a 20year period using a variety of outcome measures. Sex distribution was equal, with a mean age at surgery of 43.6years (range 5-76years). Overall, most tumours occurred in the lumbosacral region (70.5%), with fewer in the thoracic (27.9%) and cervical regions (18.0%). Myxopapillary features were seen in 41.0% of tumours, and were more common when occurring in the lumbar region (51.2%). Gross total resection was achieved in 52.5%, subtotal resection in 37.7% and biopsy alone in 9.8% of patients and 31.1% received adjuvant radiotherapy. Two-thirds of patients achieved an excellent post-operative neurological outcome (Frankel grade E). Tumour recurrence was rare. Gross total resection and good preoperative neurological condition were most strongly predictive of good outcome. Post-operative radiotherapy did not seem to confer survival benefit in this case series, even in cases of incomplete resection, leading us to question its utility for all cases of spinal cord ependymoma.

  20. Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

    SciTech Connect

    MacDonald, Shannon M. Safai, Sairos; Trofimov, Alexei; Wolfgang, John; Fullerton, Barbara; Yeap, Beow Y.; Bortfeld, Thomas; Tarbell, Nancy J.; Yock, Torunn

    2008-07-15

    Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial and supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.

  1. Extra-axial ependymoma of posterior fossa extending to the Meckel's cave.

    PubMed

    Torun, Fuat; Tuna, Hakan; Bozkurt, Melih; Deda, Haluk

    2005-06-01

    An extra-axial ependymoma extending from the left cerebellopontine corner to the Meckel's cave is reported. This lesion's clinical, radiological, and histological characteristics are presented. This tumor's infrequent extra-axial location, extension to the Meckel's cave and possible origin are discussed.

  2. Anaplastic ganglioglioma: a report of three cases and review of the literature

    PubMed Central

    Lucas, John Thomas; Huang, Andrew Jonathan; Mott, Ryan T.; Lesser, Glenn J.; Tatter, Stephen Bradley; Chan, Michael David

    2015-01-01

    Gangliogliomas are rare tumors of the central nervous system that are thought to arise from a glioneuronal precursor and consist of both neuronal and glial elements. Grade III, or anaplastic ganglioglioma (AGG), most commonly affects children and young adults, generally arises in a supratentorial location, is highly epileptogenic, and often results in diffuse local and distant failure within the craniospinal axis. Pathologically, these tumors are graded by the degree of malignancy in their glial portion and radiologic diagnosis is difficult due to the wide variation in its degree of solid and cystic components, contrast uptake, and calcification patterns. This report presents three cases of AGG, with initial treatment including subtotal resection followed by conformal radio-therapy. In the case where the AGG developed in the setting of an existent low-grade astrocytoma, the patient received no chemotherapy. Both of the other de novo cases were managed with adjuvant chemoradiotherapy with temozolomide. Recurrence occurred at 6, 16, and 20 months following therapy. Two of the three patients experienced symptomatic decline at recurrence, but experienced Karnofsky performance status (KPS) improvement after salvage therapy, including the reduction of cranial neuropathy and balance. All patients had a significant reduction in presenting symptoms following salvage therapy. Patients died at 23, 20, and 22 months following initial surgical management, respectively. A review of anaplastic and malignant gangliogliomas is presented in the context of these three cases. PMID:25862009

  3. Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With Reirradiation

    SciTech Connect

    Bouffet, Eric; Ballourah, Walid; Bartels, Ute K.; Tsangaris, Elena; Huang, Annie; Mabbot, Donald J.; Laperriere, Normand; Tabori, Uri

    2012-08-01

    Purpose: The outcome of recurrent ependymoma in children is dismal. Reirradiation has been proposed as an effective modality for ependymoma at relapse. However, the toxicity and outcome benefits of this approach have not been well established. Methods and Materials: We conducted a retrospective population-based study of all patients with recurrent ependymoma treated between 1986 and 2010 in our institution. Demographic, treatment, and outcome data were analyzed for the entire cohort. Results: Of 113 patients with intracranial ependymoma, 47 patients relapsed. At the time of relapse, 29 patients were treated with surgical resection and/or chemotherapy, and 18 patients received full-dose ({>=}54 Gy focal and/or craniospinal) reirradiation with or without surgery at recurrence. Reirradiation was tolerated well with no severe acute complications noticed. Three-year overall survival was 7% {+-} 6% and 81% {+-} 12% for nonreirradiated and reirradiated patients, respectively (p < 0.0001). Time to second progression after reirradiation was significantly longer than time to first progression. This surprising phenomenon was associated with improved progression-free survival for tumors with evidence of DNA damage (n = 15; p = 0.002). At a mean follow-up of 3.73 years, only 2/18 patients had endocrine dysfunction, and 1 patient required special education support. However, a decline in intellectual function from pre- to postreirradiation assessment was observed. Conclusions: Reirradiation is an effective treatment that may change the natural history of recurrent ependymoma in children. However, this change may be associated with increased neurocognitive toxicity. Additional follow-up is needed to determine the risk of late recurrence, secondary radiation-induced tumors, and long-term functional outcome of these patients.

  4. [Anaplastic glioma. Neuropathology, molecular diagnostics and current study concepts].

    PubMed

    Wick, W; Weller, M

    2010-08-01

    According to the current WHO classification anaplastic gliomas comprise pure astrocytomas and oligodendrogliomas and mixed tumors. This review summarizes findings, discusses problems and defines new questions from the phase III trials on anaplastic gliomas. The molecular subgroup analyses of the NOA-04 trial identified three molecular parameters, which predict longer progression-free and overall survival independent from the mode of therapy, radiotherapy or alkylating chemotherapy-. These are 1p/19q codeletion, methylation of the promoter of the O(6)-methylguanyl methyltransferase (MGMT) gene and hot-spot mutations in the isocitrate dehydrogenase 1 (IDH1) gene. The prognostic relevance of these markers is not lower than that of histopathological subclassification but determination is potentially more robust. Therefore, marker profiles should be included into the next WHO brain tumor classification. The current standard of care for first-line treatment in anaplastic gliomas is radiotherapy or chemotherapy. The next steps, e.g. within the international CATNON trial, are to define the role and optimal sequencing of combined modality treatment focusing on radiotherapy and temozolomide. Inclusion in this trial is already based on the WHO grade and the 1p/19q status and not on the histopathological subtype. Furthermore, anaplastic gliomas are an important group of brain tumors for developing future molecular targeted therapies and should therefore be in the main focus of academic and industrial drug development, which aims at improved efficacy and avoiding long-term side-effects.

  5. Breast metastasis of anaplastic oligodendroglioma: a case report.

    PubMed

    Alacacioglu, Ahmet; Unal, Serkan; Canpolat, Selin; Yurt, Alaattin; Oztekin, Ozgur; Coskun, Ali; Karatas, Ayse; Postaci, Hakan; Sop, Gulten

    2012-11-01

    Extracranial metastasis of primary brain tumors is rarely observed. Of all brain malignancies, glioblastomas, medulloblastomas and astrocytomas metastasize most frequently. Metastasis of oligondendroglioma is rare. We present a case of breast metastasis in a 58-year-old man with an anaplastic oligodendroglioma.

  6. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma☆

    PubMed Central

    Gualco, Gabriela; Weiss, Lawrence M.; Bacchi, Carlos E.

    2009-01-01

    Summary Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase–negative null cell–type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma. PMID:18620733

  7. Outcomes following myxopapillary ependymoma resection: the importance of capsule integrity.

    PubMed

    Abdulaziz, Mohammed; Mallory, Grant W; Bydon, Mohamad; De la Garza Ramos, Rafael; Ellis, Jason A; Laack, Nadia N; Marsh, W Richard; Krauss, William E; Jallo, George; Gokaslan, Ziya L; Clarke, Michelle J

    2015-08-01

    OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7-68 years). The median follow-up was 51.5 months (range 12-243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy

  8. Perioperative posterior reversible encephalopathy syndrome in 2 pediatric neurosurgery patients with brainstem ependymoma.

    PubMed

    Gephart, Melanie G Hayden; Taft, Bonnie P; Giese, Anne-Katrin; Guzman, Raphael; Edwards, Michael S B

    2011-03-01

    Posterior reversible encephalopathy syndrome (PRES) has been described in pediatric neurooncology patients, although it has not been documented perioperatively in pediatric neurosurgery patients not actively receiving chemotherapy. Recently at the authors' facility, 2 cases of PRES were diagnosed perioperatively in children with brainstem ependymoma. Both patients had presented with hypertension, altered mental status, and seizures and demonstrated MR imaging features consistent with PRES. The patients were treated with antiseizure and antihypertension medications, leading to improvement in both clinical symptoms and neuroimaging findings. These cases are the first to document PRES in perioperative pediatric neurosurgery patients not actively receiving chemotherapy. Both patients had ependymoma involving the brainstem, which may have led to intra- and perioperative hemodynamic instability (including hypertension) and predisposed them to this syndrome. An awareness of PRES in similar scenarios will aid in the prevention, diagnosis, and treatment of pediatric neurosurgery patients with this syndrome.

  9. Renal Clear Cell Sarcoma - Anaplastic Variant: A Rare Entity.

    PubMed

    Walke, Vaishali Atmaram; Shende, Nitin Y; Kumbhalkar, D T

    2017-01-01

    Clear Cell Sarcoma of Kidney (CCSK) is known for its morphologic diversity, aggressive behaviour, tendency to recur and metastasis to bone. Amongst the various morphologic subtypes, anaplastic CCSK is associated with worse prognosis. Here, we report a case of this rare variant of CCSK. A five-year-old boy presented with history of lump and pain in abdomen since one week. The Computed Tomography (CT) scan revealed a large mass occupying the middle and inferior pole of right kidney. The clinical impression was Wilms tumour. Nephrectomy specimen was received and the diagnosis of CCSK anaplastic variant was offered only after excluding the differentials and after performing ancillary tests such as Immunohistochemistry (IHC). Thus, this case emphasizes the diagnostic challenges on morphology and the essential role of IHC in arriving at a definitive diagnosis, because failure to do so may deprive the child from optimal treatment.

  10. Renal Clear Cell Sarcoma - Anaplastic Variant: A Rare Entity

    PubMed Central

    Shende, Nitin Y; Kumbhalkar, D T

    2017-01-01

    Clear Cell Sarcoma of Kidney (CCSK) is known for its morphologic diversity, aggressive behaviour, tendency to recur and metastasis to bone. Amongst the various morphologic subtypes, anaplastic CCSK is associated with worse prognosis. Here, we report a case of this rare variant of CCSK. A five-year-old boy presented with history of lump and pain in abdomen since one week. The Computed Tomography (CT) scan revealed a large mass occupying the middle and inferior pole of right kidney. The clinical impression was Wilms tumour. Nephrectomy specimen was received and the diagnosis of CCSK anaplastic variant was offered only after excluding the differentials and after performing ancillary tests such as Immunohistochemistry (IHC). Thus, this case emphasizes the diagnostic challenges on morphology and the essential role of IHC in arriving at a definitive diagnosis, because failure to do so may deprive the child from optimal treatment. PMID:28273978

  11. ALK Signaling and Target Therapy in Anaplastic Large Cell Lymphoma

    PubMed Central

    Tabbó, Fabrizio; Barreca, Antonella; Piva, Roberto; Inghirami, Giorgio

    2012-01-01

    The discovery by Morris et al. (1994) of the genes contributing to the t(2;5)(p23;q35) translocation has laid the foundation for a molecular based recognition of anaplastic large cell lymphoma and highlighted the need for a further stratification of T-cell neoplasia. Likewise the detection of anaplastic lymphoma kinase (ALK) genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients. PMID:22649787

  12. Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

    SciTech Connect

    Amsbaugh, Mark J.; Grosshans, David R.; McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita

    2012-08-01

    Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

  13. Gamma knife surgery-induced ependymoma after the treatment of meningioma - a case report.

    PubMed

    Wang, Ke; Pan, Li; Che, Xiaoming; Lou, Meiqing

    2012-01-01

    Gamma knife surgery is widely used for a number of neurological disorders. However, little is known about its long-term complications such as carcinogenic risks. Here, we present a case of a radiosurgery-induced ependymoma by gamma knife surgery for the treatment of a spinal meningioma in a 7-year-old patient. In light of reviewing the previous reports, we advocate high caution in making young patients receive this treatment.

  14. Spinal Cord Ependymoma Associated with Neurofibromatosis 1 : Case Report and Review of the Literature

    PubMed Central

    Shan, Ming; Feng, Chunguo; Wang, Xiaojie

    2014-01-01

    Patients with neurofibromatosis 1 (NF1) are predisposed to develop central nervous system tumors, due to the loss of neurofibromin, an inactivator of proto-oncogene Ras. However, to our knowledge, only three cases of ependymomas with NF1 have been reported in the literature. The authors present a case of NF1 patient with a spinal cord ependymoma. She was referred for about half a year history of increasing numbness that progressed from her fingers to her entire body above the bellybutton. Magnetic resonance imaging revealed a relative-demarcated, heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7 level, a left-sided T11 spinous process heterogeneously enhanced mass in soft tissue, intervertebral disk hernia in L2-5 level, and widespread punctum enhancing lesion in her scalp and in T11-L5 level. The patient underwent C5-7 laminectomies and total excision of the tumor under operative microscope, and intraoperative ultrasonography and physiological monitoring were used during the surgery. Histopathologically, her tumor was found to be a ependymoma without malignant features (grade II in the World Health Organization classification). Therefore, no adjuvant therapy was applied. Following the operation, the patient showed an uneventful clinical recovery with no evidence of tumor recurrence after one year of follow-up. PMID:24570818

  15. Investigating Verbal and Visual Auditory Learning After Conformal Radiation Therapy for Childhood Ependymoma

    SciTech Connect

    Di Pinto, Marcos; Conklin, Heather M.; Li Chenghong; Xiong Xiaoping; Merchant, Thomas E.

    2010-07-15

    Purpose: The primary objective of this study was to determine whether children with localized ependymoma experience a decline in verbal or visual-auditory learning after conformal radiation therapy (CRT). The secondary objective was to investigate the impact of age and select clinical factors on learning before and after treatment. Methods and Materials: Learning in a sample of 71 patients with localized ependymoma was assessed with the California Verbal Learning Test (CVLT-C) and the Visual-Auditory Learning Test (VAL). Learning measures were administered before CRT, at 6 months, and then yearly for a total of 5 years. Results: There was no significant decline on measures of verbal or visual-auditory learning after CRT; however, younger age, more surgeries, and cerebrospinal fluid shunting did predict lower scores at baseline. There were significant longitudinal effects (improved learning scores after treatment) among older children on the CVLT-C and children that did not receive pre-CRT chemotherapy on the VAL. Conclusion: There was no evidence of global decline in learning after CRT in children with localized ependymoma. Several important implications from the findings include the following: (1) identification of and differentiation among variables with transient vs. long-term effects on learning, (2) demonstration that children treated with chemotherapy before CRT had greater risk of adverse visual-auditory learning performance, and (3) establishment of baseline and serial assessment as critical in ascertaining necessary sensitivity and specificity for the detection of modest effects.

  16. A 5-Year Investigation of Children's Adaptive Functioning Following Conformal Radiation Therapy for Localized Ependymoma

    SciTech Connect

    Netson, Kelli L.; Conklin, Heather M.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2012-09-01

    Purpose: Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. Methods and Materials: The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Results: Baseline IQ and VABS were below normative means (P<.05), although within the average range. Linear mixed models revealed stable IQ and VABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (-.04 points) did not correlate with annual change in VABS (-.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conclusions: Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions.

  17. Emotional and Behavioral Functioning After Conformal Radiation Therapy for Pediatric Ependymoma

    SciTech Connect

    Willard, Victoria W.; Conklin, Heather M.; Boop, Frederick A.; Wu, Shengjie; Merchant, Thomas E.

    2014-03-15

    Purpose: The standard of care for pediatric patients with ependymoma involves postoperative radiation therapy. Prior research suggests that conformal radiation therapy (CRT) is associated with relative sparing of cognitive and academic functioning, but little is known about the effect of CRT on emotional and behavioral functioning. Methods and Materials: A total of 113 patients with pediatric ependymoma underwent CRT using photons as part of their enrollment on an institutional trial. Patients completed annual evaluations of neurocognitive functioning during the first 5 years after CRT. Emotional and behavioral functioning was assessed via the Child Behavior Checklist. Results: Before CRT, emotional and behavioral functioning were commensurate with those of the normative population and within normal limits. After 5 years, means remained within normal limits but were significantly below the normative mean. Linear mixed models revealed a significant increase in attention problems over time. These problems were associated with age at diagnosis/CRT, tumor location, and extent of resection. A higher-than-expected incidence of school problems was present at all assessment points after baseline. Conclusions: The use of photon CRT for ependymoma is associated with relatively stable emotional and behavioral functioning during the first 5 years after treatment. The exception is an increase in attention problems. Results suggest that intervening earlier in the survivorship period—during the first year posttreatment—may be beneficial.

  18. Outcome of infants and young children with newly diagnosed ependymoma treated on the "Head Start" III prospective clinical trial.

    PubMed

    Venkatramani, Rajkumar; Ji, Lingyun; Lasky, Joseph; Haley, Kelley; Judkins, Alexander; Zhou, Shengmei; Sposto, Richard; Olshefski, Randal; Garvin, James; Tekautz, Tanya; Kennedy, Gloria; Rassekh, Shahrad Rod; Moore, Theodore; Gardner, Sharon; Allen, Jeffrey; Shore, Richard; Moertel, Christopher; Atlas, Mark; Dhall, Girish; Finlay, Jonathan

    2013-06-01

    This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational "Head Start" III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR. Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 ± 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 ± 13 % and 73 ± 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation.

  19. Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

    ClinicalTrials.gov

    2015-06-03

    Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor

  20. C11orf95-RELA fusion present in a primary intracranial extra-axial ependymoma: Report of a case with literature review.

    PubMed

    Nambirajan, Aruna; Malgulwar, Prit Benny; Sharma, Mehar C; Singh, Anutosh; Pathak, Pankaj; Satyarthee, Guru Dutta; Garg, Ajay

    2016-10-01

    Ependymomas are gliomas that recapitulate the ependymal cells microscopically and ultrastructurally. They commonly occur along the ventricular surfaces and central canal of the brain and spinal cord. Intracranial extra-axial ependymoma (IEAE) is a rare entity and is commonly misdiagnosed clinically and radiologically as a meningioma. The histogenesis of such IEAEs is obscure. A novel recurrent oncogenic fusion involving the C11orf95 and RELA genes was recently described in supratentorial ependymomas. A 9-year-old girl presented with a dural based parafalcine mass that, in addition to exhibiting classical immunohistochemical features of an ependymoma, also demonstrated C11orf95-RELA fusion, characteristic of supratentorial ependymomas. We suggest that IEAEs share their histogenesis with their intra-axial counterparts, arising either from dural extension of subcortical, subependymal rests or directly from ectopic dural rests.

  1. The effect of low level laser on anaplastic thyroid cancer

    NASA Astrophysics Data System (ADS)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  2. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

    PubMed Central

    Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

    2015-01-01

    Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

  3. Prophylactic irradiation in bronchogenic small cell anaplastic carcinoma

    SciTech Connect

    Hansen, H.H.; Dombernowsky, P.; Hirsch, F.R.; Hansen, M.; Rygard, J.

    1980-07-15

    A total of 114 patients with bronchogenic small cell anaplastic carcinoma and staged as having regional disease all underwent combination chemotherapy consisting of CCNU, cyclophosphamide, and methotrexate. They were randomized to receive either radiotherapy to the primary tumor and regional lymph nodes (4000 rad) or extensive radiotherapy, which included the brain, adrenals, and upper retroperitoneal lymph nodes. Fifteen patients were free of disease after 18 months of chemotherapy and the treatment was discontinued. Only 3 patients subsequently relapsed. No difference was observed between the two groups of patients in median survival time, response rate, duration of response, or relapse pattern, including the frequency of brain metastasis.

  4. Differentiation of recurrent spinal ependymoma from postradiation treatment necrosis through multiparametric PET-MR and perfusion MRI.

    PubMed

    Hojjati, Mojgan; Garg, Vasant; Badve, Chaitra A; Abboud, Salim E; Sloan, Andrew E; Wolansky, Leo J

    A 67-year-old male presented with papilledema and back pain localized to the T10 level. Initial workup revealed multifocal spinal ependymoma which was resected and treated with external beam radiotherapy. Nine years after treatment, the patient had a relapse of back pain, and MRI was inconclusive in distinguishing posttreatment radiation necrosis from recurrent tumor. We present the first described report with the utilization of multiparametric positron emission tomography-magnetic resonance imaging and perfusion MRI to distinguish recurrent spinal ependymoma from radiation necrosis.

  5. Does the real-time thermal damage estimate allow for estimation of tumor control after MRI-guided laser-induced thermal therapy? Initial experience with recurrent intracranial ependymomas.

    PubMed

    Patel, Nitesh V; Jethwa, Pinakin R; Shetty, Anil; Danish, Shabbar F

    2015-04-01

    OBJECT Although control of intracranial ependymomas is highly correlated with degree of resection, it is unknown if the same is true for MRI-guided laser-induced thermal therapy (MRgLITT). The authors report their experience with MRgLITT for ependymoma and examine the utility of the real-time thermal damage estimate (TDE), a recent software advance, with respect to completeness of ablation and impact on tumor control. To the authors' knowledge, this is the largest single-center experience utilizing MRgLITT for recurrent ependymomas. METHODS Five tumors in 4 patients were treated with the Visualase Thermal Therapy System. Two tumors were treated similarly on recurrence. Ablation was performed using a 980-nm diode laser with a real-time image acquisition system. Single-plane TDEs were calculated and compared with the original lesion area to compute percentage area ablated (PAA). Volumetric analysis was performed, and percentage volume ablated (PVA) was estimated and correlated with the TDE. Tumor control was correlated with the TDE and volumetric data during treatment. RESULTS Nine ablations were performed on 5 tumors, 2 of which had multiple recurrences. The average pretreatment lesion volume was 8.4 ± 6.3 cm(3), and the average largest 2D area was 5.3 ± 2.7 cm(2). The averaged TDE was 3.9 ± 2.1 cm(2), average PAA was 80.1% ± 34.3%, and average PVA was 64.4% ± 23.5%. For subtotal ablations, average recurrence time was 4.4 ± 5.3 months; 1 adult case remains recurrence-free at 40 months. Using TDEs, the correlation between recurrence time and PAA was r = 0.93 (p = 0.01), and for PVA was r = 0.88 (p = 0.02). Furthermore, PVA and PAA were strongly correlated (r = 0.88, p = 0.02). CONCLUSIONS Through using the PAA, the real-time TDE correlated with the volume of ablation in this initial investigation. Furthermore, the TDE and volumetric data corresponded to the level of tumor control, with time to recurrence dependent on ablation completeness. MRgLITT may have a

  6. Anaplastic lymphoma kinase: signalling in development and disease

    PubMed Central

    Palmer, Ruth H.; Vernersson, Emma; Grabbe, Caroline; Hallberg, Bengt

    2009-01-01

    RTKs (receptor tyrosine kinases) play important roles in cellular proliferation and differentiation. In addition, RTKs reveal oncogenic potential when their kinase activities are constitutively enhanced by point mutation, amplification or rearrangement of the corresponding genes. The ALK (anaplastic lymphoma kinase) RTK was originally identified as a member of the insulin receptor subfamily of RTKs that acquires transforming capability when truncated and fused to NPM (nucleophosmin) in the t(2;5) chromosomal rearrangement associated with ALCL (anaplastic large cell lymphoma). To date, many chromosomal rearrangements leading to enhanced ALK activity have been described and are implicated in a number of cancer types. Recent reports of the EML4 (echinoderm microtubule-associated protein like 4)–ALK oncoprotein in NSCLC (non-small cell lung cancer), together with the identification of activating point mutations in neuroblastoma, have highlighted ALK as a significant player and target for drug development in cancer. In the present review we address the role of ALK in development and disease and discuss implications for the future. PMID:19459784

  7. Targeting autophagy enhances the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma

    PubMed Central

    Desquesnes, Aurore; Le Gonidec, Sophie; AlSaati, Talal; Beau, Isabelle; Lamant, Laurence; Meggetto, Fabienne; Espinos, Estelle; Codogno, Patrice; Brousset, Pierre; Giuriato, Sylvie

    2015-01-01

    Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphomas (ALK+ ALCL) occur predominantly in children and young adults. Their treatment, based on aggressive chemotherapy, is not optimal since ALCL patients can still expect a 30% 2-year relapse rate. Tumor relapses are very aggressive and their underlying mechanisms are unknown. Crizotinib is the most advanced ALK tyrosine kinase inhibitor and is already used in clinics to treat ALK-associated cancers. However, crizotinib escape mechanisms have emerged, thus preventing its use in frontline ALCL therapy. The process of autophagy has been proposed as the next target for elimination of the resistance to tyrosine kinase inhibitors. In this study, we investigated whether autophagy is activated in ALCL cells submitted to ALK inactivation (using crizotinib or ALK-targeting siRNA). Classical autophagy read-outs such as autophagosome visualization/quantification by electron microscopy and LC3-B marker turn-over assays were used to demonstrate autophagy induction and flux activation upon ALK inactivation. This was demonstrated to have a cytoprotective role on cell viability and clonogenic assays following combined ALK and autophagy inhibition. Altogether, our results suggest that co-treatment with crizotinib and chloroquine (two drugs already used in clinics) could be beneficial for ALK-positive ALCL patients. PMID:26338968

  8. Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma

    PubMed Central

    Tzaridis, Theophilos; Milde, Till; Pajtler, Kristian W.; Bender, Sebastian; Jones, David T. W.; Müller, Simone; Wittmann, Andrea; Schlotter, Magdalena; Kulozik, Andreas E.; Lichter, Peter; Collins, V. Peter; Witt, Olaf; Kool, Marcel; Korshunov, Andrey; Pfister, Stefan M.; Witt, Hendrik

    2016-01-01

    Ependymomas in children can arise throughout all compartments of the central nervous system (CNS). Highly malignant paediatric ependymoma subtypes are Group A tumours of the posterior fossa (PF-EPN-A) and RELA-fusion positive (ST-EPN-RELA) tumours in the supratentorial compartment. It was repeatedly reported in smaller series that accumulation of p53 is frequently observed in ependymomas and that immunohistochemical staining correlates with poor clinical outcome, while TP53 mutations are rare. Our TP53 mutation analysis of 130 primary ependymomas identified a mutation rate of only 3%. Immunohistochemical analysis of 398 ependymomas confirmed previous results correlating the accumulation of p53 with inferior outcome. Among the p53-positive ependymomas, the vast majority exhibited a RELA fusion leading to the hypothesis that p53 inactivation might be linked to RELA positivity. In order to assess the potential of p53 reactivation through MDM2 inhibition in ependymoma, we evaluated the effects of Actinomycin-D and Nutlin-3 treatment in two preclinical ependymoma models representing the high-risk subtypes PF-EPN-A and ST-EPN-RELA. The IC-50 of the agent as determined by metabolic activity assays was in the lower nano-molar range (0.2–0.7 nM). Transcriptome analyses of high-dose (100 nM), low-dose (5 nM) and non-treated cells revealed re-expression of p53 dependent genes including p53 upregulated modulator of apoptosis (PUMA) after low-dose treatment. At the protein level, we validated the Actinomycin-D induced upregulation of PUMA, and of p53 interaction partners MDM2 and p21. Proapoptotic effects of low-dose application of the agent were confirmed by flow cytometry. Thus, Actinomycin-D could constitute a promising therapeutic option for ST-EPN-RELA ependymoma patients, whose tumours frequently exhibit p53 inactivation. PMID:27556362

  9. Ependymoma of the cauda equina starting with communicating hydrocephalus: a case report.

    PubMed

    Tzekov, Christo; Naydenov, Emanuil; Kalev, Ognian

    2007-01-01

    The presence of concomitant hydrocephalus in cases with spinal cord tumors is relatively rare. Here, we describe a case of myxopapillary ependymoma of the cauda equina starting with communicating hydrocephalus in a 14-year-old boy. The patient presented to the clinic without underlying causes of hydrocephalus on the neuroimaging data. After ventriculoperitoneal shunt placement, despite the numerous malfunction incidents, the patient was doing well. Eight years later, he developed progressive weakness and coldness of the lower limbs. Multiple cystic lesions in the cervicothoracic area were found on magnetic resonance imaging. Decompressive hemilaminectomy of the cervicothoracic region was performed with temporary improvement of the patient's condition. Because of persisting complaints, the sacral area of the spine was also observed and neuroimaging data for a tumoral lesion in the cauda equina region were found. The lesion was surgically removed and the histological result was myxopapillary ependymoma. Therefore, cases presenting with internal hydrocephalus without clear-cut intracranial etiology should have detailed neuroimaging of the whole central nervous system.

  10. Extra-axial giant falcine ependymoma with ultra-rapid growth in child: Uncommon entity with literature review

    PubMed Central

    Satyarthee, Guru Dutta; Moscote-Salazar, Luis Rafael

    2016-01-01

    Ependymoma tends to occur commonly along either on ventricular surfaces of the brain or central canal of the spinal cord. Rarely, ependymoma can develop in the cerebral cortex without attachment to the ventricular structures. However, such occurrence in the purely extra-axial compartment in the falcine region mimicking falcine meningioma is exceedingly rare. The detailed search of primary falcine ependymoma (PEFE) in Medline and PubMed yielded only five isolated case reports. All cases occurred in patient older than 17 years of age; however, our case was a 9-year-old girl. PEFE tends to occur more commonly in male with a male to female ratio of 3:2, with the mean age of 28.8 years (range 17–43 years), lesion had intra-operatively had solid consistency in all cases. All cases were subjected to surgical resection followed by adjuvant radiotherapy; however, in addition, one case also received chemotherapy, with an average follow-up period of 9 months, however, missing in one case. The mean size of the tumor was 5.25 cm (range 1.8–7.2 cm). The authors present a unique case of PEFE in a 9-year-old girl with 8.6 cm ×6 cm ×5.4 cm-sized giant primary falcine ependymoma, managed surgically successfully. To the best of the authors' knowledge, the current case is the first case of pediatric extra-axial falcine ependymoma occurring within the first decade of life in the western literature, showing rapid evolution over 1½ month's period into a giant size. Brief pathogenesis, clinical feature, and management along with the pertinent literature are reviewed briefly. PMID:28217156

  11. Array-CGH analysis of cutaneous anaplastic large cell lymphoma.

    PubMed

    Szuhai, K; van Doorn, R; Tensen, C P; Van Kester

    2013-01-01

    This chapter describes a study in which the pattern of numerical chromosomal alterations in cutaneous anaplastic large cell lymphoma (C-ALCL) tumor samples was defined using array-based comparative genomic hybridization (CGH). First, the array-based CGH technique applied is outlined in detail. Next, its application in the analysis of C-ALCL tumor specimens is described. This approach resulted in the identification of highly recurrent chromosomal alterations in C-ALCL that include gain of 7q31 and loss on 6q16-6q21 and 13q34, each affecting 45% of the patients. The pattern characteristic of C-ALCL differs markedly from chromosomal alterations observed in other CTCL such as mycosis fungoides and Sézary syndrome and yielded several candidate genes with potential relevance in the pathogenesis of C-ALCL.

  12. Racial disparities in anaplastic oligodendroglioma: An analysis on 1643 patients.

    PubMed

    Shin, Jacob Y; Yoon, Ja Kyoung; Diaz, Aidnag Z

    2017-03-01

    The objective of our study is to determine the influence of race on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1643 patients with AO were identified. 1386 (84.3%) were White, 83 (5.0%) Black, 133 (8.1%) Hispanic, and 41 (2.5%) were Asian. White and Black patients were significantly older than Hispanic and Asian patients (49.3% vs. 49.4% vs. 33.1% vs. 39.0%, p=0.003). Black patients were significantly less likely to be insured than White patients (12.8 vs. 7.2%, p<0.001) and significantly more likely to have lower income than other races (p<0.001). A trend towards higher comorbidity burden and lower rate of gross total resection was seen in Black patients. Black patients had significantly worse five-year OS compared to White, Hispanic, and Asian patients (40.3% vs. 52.3% vs. 67.8% vs. 67.7%, p=0.028). Of those who received adjuvant chemoRT, Black patients still had significantly worse OS compared to White patients (p=0.021). On multivariate analysis, Black race, older age at diagnosis, and not receiving adjuvant chemoradiotherapy were independent prognostic factors for worse OS in anaplastic oligodendroglioma. Future studies are warranted to help determine predictors for unfavorable molecular status, ways to optimize management of comorbidities, and interventions to help ensure adequate access to medical care for all patients to better care for those who may be at more risk for poorer outcome.

  13. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

    PubMed

    Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

    2015-12-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target.

  14. Therapeutic strategies and mechanisms of drug resistance in Anaplastic Lymphoma Kinase (ALK)-rearranged lung cancer.

    PubMed

    Katayama, Ryohei

    2017-02-06

    Anaplastic lymphoma kinase (ALK) gene encoding the receptor tyrosine kinase ALK is expressed as a fusion gene in a variety of carcinomas. The expression of ALK is nearly undetectable in adults, and its activation is normally regulated by its ligands, FAM150A/B. However, ALK gene rearrangements result in different ALK fusion proteins that are constitutively expressed via the active promoter of fusion partner genes. ALK fusion proteins dimerize in a ligand-independent manner and lead to the dysregulation of cell proliferation via abnormal constitutive activation of ALK tyrosine kinase. Many ALK tyrosine kinase inhibitors (TKIs) have been developed to date, are three of which are currently in clinical use for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). ALK TKIs often achieve marked tumor regression in NSCLC patients with ALK rearrangements; however, ALK TKI-resistant tumors inevitably emerge within a few years in most cases. In this review, we summarize diverse ALK TKI resistance mechanisms identified in NSCLC with ALK rearrangements, and review potential therapeutic strategies to overcome ALK TKI resistance in these patients.

  15. Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma

    SciTech Connect

    Merchant, Thomas E. . E-mail: thomas.merchant@stjude.org; Kiehna, Erin N.; Li Chenghong; Xiong Xiaoping; Mulhern, Raymond K.

    2005-12-01

    Purpose: To assess the effects of radiation dose-volume distribution on the trajectory of IQ development after conformal radiation therapy (CRT) in pediatric patients with ependymoma. Methods and Materials: The study included 88 patients (median age, 2.8 years {+-} 4.5 years) with localized ependymoma who received CRT (54-59.4 Gy) that used a 1-cm margin on the postoperative tumor bed. Patients were evaluated with tests that included IQ measures at baseline (before CRT) and at 6, 12, 24, 36, 48, and 60 months. Differential dose-volume histograms (DVH) were derived for total-brain, supratentorial-brain, and right and left temporal-lobe volumes. The data were partitioned into three dose intervals and integrated to create variables that represent the fractional volume that received dose over the specified intervals (e.g., V{sub 0-20Gy}, V{sub 20-40Gy}, V{sub 40-65Gy}) and modeled with clinical variables to develop a regression equation to estimate IQ after CRT. Results: A total of 327 IQ tests were performed in 66 patients with infratentorial tumors and 20 with supratentorial tumors. The median follow-up was 29.4 months. For all patients, IQ was best estimated by age (years) at CRT; percent volume of the supratentorial brain that received doses between 0 and 20 Gy, 20 and 40 Gy, and 40 and 65 Gy; and time (months) after CRT. Age contributed significantly to the intercept (p > 0.0001), and the dose-volume coefficients were statistically significant (V{sub 0-20Gy}, p = 0.01; V{sub 20-40Gy}, p < 0.001; V{sub 40-65Gy}, p = 0.04). A similar model was developed exclusively for patients with infratentorial tumors but not supratentorial tumors. Conclusion: Radiation dosimetry can be used to predict IQ after CRT in patients with localized ependymoma. The specificity of models may be enhanced by grouping according to tumor location.

  16. A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma.

    PubMed

    Döring, Claudia; Hansmann, Martin-Leo; Agostinelli, Claudio; Piccaluga, Pier P; Facchetti, Fabio; Pileri, Stefano; Küppers, Ralf; Newrzela, Sebastian; Hartmann, Sylvia

    2014-10-01

    Classical Hodgkin lymphoma and ALK(-) anaplastic large cell lymphoma share many features like strong CD30 expression and usually loss of B- and T-cell markers. However, their clinical course is dramatically different with curability rates of >90% for classical Hodgkin lymphoma and an unfavorable prognosis for anaplastic large cell lymphoma. Classical Hodgkin lymphoma and ALK(-) anaplastic large cell lymphoma can usually be distinguished by PAX5 expression in the Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma and expression of cytotoxic molecules in tumor cells of anaplastic large cell lymphoma. However, in some cases the differential diagnosis is difficult owing to absence of established markers. To be able to better classify these cases, we reevaluated gene expression data of microdissected tumor cells of both lymphomas for differentially expressed genes. A classifier was established, comprising four genes strongly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma (MDC/CCL22, CD83, STAT3, and TUBB2B). Applying this classifier to a test cohort, Hodgkin lymphoma was successfully distinguished from ALK(-) anaplastic large cell lymphoma with an accuracy of 97% (43/44). MDC/CCL22, CD83, and STAT3 have also been found to be expressed in antigen-presenting cells. Therefore, based on our established classifier, Hodgkin and Reed-Sternberg cells differ from tumor cells of anaplastic large cell lymphoma, which can successfully be applied for practical purposes in histopathologic diagnostics.

  17. Co-existence of L5-S1 disc herniation and conus medullaris ependymoma

    PubMed Central

    Minoğlu, Mustafa; Akkol, İsmail; Özdemir, Nail; Yıldırım, Levent

    2014-01-01

    INTRODUCTION The lumbar disc herniations are seen very common than spinal ependymomas in the neurosurgery polyclinic routine. PRESENTATION OF CASE In our case, both pathologies were seen at the most frequently located levels compatible with the literature. Aim of this case report is, to remind once more that, different pathologies can be found at the same time in a single patient; differential diagnosis must be done very carefully. DISCUSSION The routine Computed Tomography (CT) imaging for low back pain can not show the conus medullaris pathology. Spinal tumors or other similar pathologies should be kept in mind for differential diagnosis. A good medical history and a good physical examination must be completed before the final diagnosis. CONCLUSION Viewing of spinal canal with Magnetic Resonance Imaging (MRI) will be useful for the patients who we intend to do disc surgery. PMID:25460457

  18. Intraoperative squash cytology and histology of giant cell ependymoma: A diagnostic dilemma

    PubMed Central

    Cakir, Ebru; Kucuk, Ulku; Ersen, Ayca; Pala, Emel E; Senoglu, Mehmet; Binatli, Ali O; Yildirim, Zubeyde

    2017-01-01

    Giant cell ependymomas (GCE) are extremely rare tumors, with 24 cases described in the literature. Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice. We describe a rare case of GCE arising at level of L4-L5 in a 66-year-old woman and discuss the cytologic/histologic features. Intraoperative smears were highly cellular with a prominent fibrillary background and exhibited papillary structures and sheets composed of highly atypical and bizarre cells. Some of the cells showed nuclear pseudoinclusions and rarely formed pseudorosette-like arrays. Intraoperative diagnosis was high grade glial tumor. On paraffin sections, besides extensive polymorphism, there were no microvascular proliferation, necrosis, and mitosis and the final diagnosis was WHO grade II GCE. GCE may be a diagnostic challenge on intraoperative smears, frozen, and paraffin sections. It must be kept in mind in the differential diagnosis of giant cell exhibiting benign and malignant tumors of brain. PMID:28182061

  19. Superficial siderosis of the central nervous system secondary to spinal ependymoma.

    PubMed

    Pikis, Stylianos; Cohen, José E; Vargas, Andres A; Gomori, J Moshe; Harnof, Sagi; Itshayek, Eyal

    2014-11-01

    Superficial siderosis of the central nervous system is a syndrome caused by deposition of hemosiderin in the subpial layers of the central nervous system, occurring as a result of recurrent asymptomatic or symptomatic bleeding into the subarachnoid space. We report a rare case of superficial siderosis in a 33-year-old man who presented with sensorineural hearing loss. The diagnosis of superficial siderosis on MRI brain studies led to further investigations with detection of a spinal ependymoma at L1-L2, compressing the cauda equina. Gross total resection of the tumor arrested the progression of the neurological deterioration. Our report underlies the importance of early diagnosis and surgical management, with imaging examination of the full neuroaxis to identify the source of bleeding, to halt disease progression and improve prognosis.

  20. Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine's curse

    SciTech Connect

    Choi, Mehee; Thoma, Miranda; Tolekidis, George; Byrne, Richard W.; Diaz, Aidnag Z.

    2015-01-01

    Ondine's curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine's curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97 mm Hg. He was diagnosed with Ondine's curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.

  1. Anaplastic astrocytoma mimicking herpes simplex encephalitis in 13-year old girl.

    PubMed

    Talathi, Saurabh; Gupta, Neha; Reddivalla, Naresh; Prokhorov, Sergey; Gold, Menachem

    2015-11-01

    Astrocytoma is the most common childhood brain tumor. Anaplastic astrocytoma (AA) are high grade gliomas (HGG), found very rarely in pediatric patients. AA mainly results from a dedifferentiation of a low grade astrocytoma. Clinical features of supra-tentorial tumors vary according to their anatomic location, biologic aggressiveness and age of the patient. They can be either completely asymptomatic or present with signs of raised intracranial pressure, seizures (about 40% of cases), behavior changes, speech disorders, declining school performance, or hemiparesis. There have been published adult cases of brain tumor misdiagnosed as viral encephalitis. Due to variety of clinical presentations, diagnosis of AA can be challenging. Here we report a case of a 13 year old girl who presented with clinical features suggestive of viral encephalitis, such as fever, headache, dizziness, and first seizure with postictal sleep and prolonged drowsiness. However, her brain MRI findings were consistent with long standing mass effect from the underlying intracranial contents and that coupled with her history of unusual taste led to further investigations and the diagnosis of the AA. In retrospect, this presentation could have been a temporal epileptic aura. High grade astrocytomas are particularly difficult to treat with a two-year survival rates range from 10% to 30%. The treatment is multimodal with gross total surgical resection of the tumor, followed by radiotherapy with or without nitrosourea-containing chemotherapy regimen. Recent promising results seen with the use of temozolamide in adults has not been yet demonstrated in the pediatric patients. The extent of tumor resection remains the most significant indicator of survival and early recognition of this tumor is essential. This case report emphasizes the fact that mass lesions in the temporal lobe, including high-grade astrocytoma, should be considered in the differential diagnosis of suspected herpes simplex encephalitis

  2. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    ClinicalTrials.gov

    2017-01-30

    Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  3. O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy.

    PubMed

    Cheng, Y U; Li, Honglun; Li, Jianlin; Li, Jisheng; Gao, Yan; Liu, Baodong

    2016-07-01

    O-linked N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), a dynamic post-translational modification of nuclear and cytoplasmic proteins, may have a critical role in the regulation of biological cell processes and human cancer. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Accumulating evidence suggests that O-GlcNAcylation is involved in a variety of types of human cancer. However, the exact role of O-GlcNAcylation in tumor pathogenesis or progression remains to be established. Computed tomography scans of patients with anaplastic thyroid carcinoma (ATC) reveal a rapid growth rate and invasion. The present study demonstrated that O-GlcNAcylation accelerates the progression of ATC. The global O-GlcNAc level of intracellular proteins was increased by overexpression of OGT or downregulation of OGA activity with the specific inhibitor Thiamet-G. By contrast, the global O-GlcNAc level was decreased by silencing of OGT. MTT assay indicated that O-GlcNAcylation significantly promotes cell proliferation. Furthermore, O-GlcNAcylation enhanced cellular biological functions, such as colony formation ability, migration and invasion, of ATC cells in vitro. The findings of the present study suggest that O-GlcNAcylation is associated with malignant properties of thyroid cancer, and may be a potential target for the diagnosis and treatment of thyroid cancer.

  4. Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer.

    PubMed

    Zhang, Lisa; Boufraqech, Myriem; Lake, Ross; Kebebew, Electron

    2016-03-29

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with no effective treatment currently available. Previously, we identified agents active against ATC cells, both in vitro and in vivo, using quantitative high-throughput screening of 3282 clinically approved drugs and small molecules. Here, we report that combining two of these active agents, carfilzomib, a second-generation proteasome inhibitor, and CUDC-101, a histone deacetylase and multi-kinase inhibitor, results in increased, synergistic activity in ATC cells. The combination of carfilzomib and CUDC-101 synergistically inhibited cellular proliferation and caused cell death in multiple ATC cell lines harboring various driver mutations observed in human ATC tumors. This increased anti-ATC effect was associated with a synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity induced by the drug combination. Mechanistically, treatment with carfilzomib and CUDC-101 increased p21 expression and poly (ADP-ribose) polymerase protein cleavage. Our results suggest that combining carfilzomib and CUDC-101 would offer an effective therapeutic strategy to treat ATC.

  5. Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer.

    PubMed

    Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Zhang, Yaqin; Patel, Dhaval; Shen, Min; Kebebew, Electron

    2015-06-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies. Currently, there is no standard or effective therapy for ATC. Drug repurposing for cancer treatment is an emerging approach for identifying compounds that may have antineoplastic effects. The aim of this study was to use high-throughput drug library screening to identify and subsequently validate novel therapeutic agents with anticancer effects in ATC. We performed quantitative high-throughput screening (qHTS) in ATC cell lines (SW-1736, 8505C, and C-643), using a compound library of 3282 drugs. qHTS identified 100 compounds that were active in all three ATC cell lines. Proteasome inhibitors were one of the most active drug categories according to enrichment analysis. Of the three proteasome inhibitors screened, a second-generation proteasome inhibitor, carfilzomib, was the most active. Treatment of ATC cells with carfilzomib significantly inhibited cellular proliferation and induced G2/M cell cycle arrest and caspase-dependent apoptosis. Mechanistically, carfilzomib increased expression of p27 (CDKN1B) and decreased expression of the anti-apoptotic protein ATF4. Pretreatment with carfilzomib reduced in vivo metastases (lung, bone, liver, and kidney) and disease progression, and decreased N-cadherin expression. Carfilzomib treatment of mice with established, widely metastatic disease significantly increased their survival, without significant toxicity. Our findings support the use or clinical study of carfilzomib as a therapeutic option in patients with advanced and metastatic ATC.

  6. Primary Central Nervous System Anaplastic Large T-cell Lymphoma

    PubMed Central

    Splavski, Bruno; Muzevic, Dario; Ladenhauser-Palijan, Tatjana; Jr, Brano Splavski

    2016-01-01

    Introduction: Primary central nervous system lymphoma (PCNSL) of T-cell origin is an exceptionally rare, highly malignant intracranial neoplasm. Although such a tumor typically presents with a focal mass lesion. Case report: Past medical history of a 26-year-old male patient with a PCNS lymphoma of T-cell origin was not suggestive of intracranial pathology or any disorder of other organs and organic systems. To achieve a gross total tumor resection, surgery was performed via osteoplastic craniotomy using the left frontal transcortical transventricular approach. Histological and immunohistochemical analyses of the tissue removed described tumor as anaplastic large cell lymphoma of T-cells (T-ALCL). Postoperative and neurological recovery was complete, while control imaging of the brain showed no signs of residual tumor at a six-month follow-up. The patient, who did not appear immunocompromized, was referred to a hematologist and an oncologist where corticosteroids, the particular chemotherapeutic protocol and irradiation therapy were applied. Conclusion: Since PCNS lymphoma is a potentially curable brain tumor, we believe that proper selection of the management options, including early radical tumor resection for solitary PCNS lymphoma, may be proposed as a major treatment of such a tumor in selected patients, resulting in a satisfactory outcome. PMID:27703297

  7. ALK positive Anaplastic Large Cell Lymphoma of the Thoracic Spine

    PubMed Central

    Abrego, Gabriela; García, Julio; Gilbert, Bruce; Forseen, Scott; Toscano, Michael

    2016-01-01

    Primary bone lymphoma (PBL) is an uncommon extra nodal disease that represents about 1–3% of lymphoma cases. Imaging findings are variable and non-specific. Computed tomography may demonstrate lytic lesions with sequestra and periosteal reaction. On magnetic resonance imaging, lesions are T1WI hypointense and T2WI hyperintense, related to peritumoral edema or bone marrow replacement. Rarely lesions may have associated fibrosis and show a more hypointense signal pattern on T2WI. After administration of contrast, PBL tends to enhance avidly. We present a case of a 24 years old African American female patient with history of back pain. Initial imaging examinations showed lesions involving the T12 and T11 vertebral bodies with initial negative biopsy results. One month later, the patient returned with worsening back pain, and the follow up studies depicted collapse of the T12 vertebral body. A diagnosis of anaplastic large cell lymphoma in T12 was made. A brief review of the literature, imaging and pathological findings, and treatment options are also discussed. PMID:27761194

  8. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies

    PubMed Central

    Smallridge, Robert C; Marlow, Laura A; Copland, John A

    2010-01-01

    Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of ∼ 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies. PMID:18987168

  9. A New Aurora in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Baldini, Enke; D'Armiento, Massimino

    2014-01-01

    Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation. PMID:25097550

  10. Infant Ependymoma in a 10-Year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) Experience With Omitted or Deferred Radiotherapy

    SciTech Connect

    Massimino, Maura; Gandola, Lorenza; Barra, Salvina; Giangaspero, Felice; Casali, Cecilia; Potepan, Paolo; Di Rocco, Concezio; Nozza, Paolo; Collini, Paola; Viscardi, Elisabetta; Bertin, Daniele; Biassoni, Veronica; Cama, Armando; Milanaccio, Claudia; Modena, Piergiorgio; Balter, Rita; Tamburrini, Giampiero; Peretta, Paola; Mascarin, Maurizio; Scarzello, Giovanni

    2011-07-01

    Purpose: The protocols of the 1990s omitted or delayed irradiation, using upfront chemotherapy to spare the youngest children with ependymoma the sequelae of radiotherapy (RT). We treated 41 children under the age of 3 years with intracranial ependymoma between 1994 and 2003. Patients and Methods: After surgery, chemotherapy was given as follows: regimen I with four blocks of vincristine, high-dose methotrexate 5 g/m{sup 2}, and cyclophosphamide 1.5 g/m{sup 2} alternating with cisplatin 90 mg/m{sup 2} plus VP16 450 mg/m{sup 2} for 14 months; subsequently, regimen II was used: VEC (VCR, VP16 300 mg/m{sup 2}, and cyclophosphamide 3 g/m{sup 2}) for 6 months. Radiotherapy was planned for residual tumor after the completion of chemotherapy or for progression. Results: We treated 23 boys and 18 girls who were a median 22 months old; 14 were given regimen I, 27 were given regimen II; 22 underwent complete resection, 19 had residual tumor. Ependymoma was Grade 2 in 25 patients and Grade 3 in 16; tumors were infratentorial in 37 patients and supratentorial in 4. One child had intracranial metastases; 29 had progressed locally after a median 9 months. Event-free survival was 26% at 3 and 5 years and 23% at 8 years. One child died of sepsis, and another developed a glioblastoma 72 months after RT. Progression-free survival was 27% at 3, 5, and 8 years, and overall survival was 48%, 37%, and 28% at 3, 5, and 8 years, respectively. Of the 13 survivors, 6 never received RT; their intellectual outcome did not differ significantly in those children than in those without RT. Conclusions: Our results confirm poor rates of event-free survival and overall survival for up-front chemotherapy in infant ependymoma. No better neurocognitive outcome was demonstrated in the few survivors who never received RT.

  11. IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform.

    PubMed

    Singh, Neetu; Sahu, Dinesh Kumar; Chowdhry, Rebecca; Mishra, Archana; Goel, Madhu Mati; Faheem, Mohd; Srivastava, Chhitij; Ojha, Bal Krishna; Gupta, Devendra Kumar; Kant, Ravi

    2016-02-01

    Here, we sequenced and functionally annotated the long reads (1-2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes--PNMT, SNN and LAMB1 show their involvement in Ependymoma.

  12. IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform

    PubMed Central

    Singh, Neetu; Sahu, Dinesh Kumar; Chowdhry, Rebecca; Mishra, Archana; Goel, Madhu Mati; Faheem, Mohd; Srivastava, Chhitij; Ojha, Bal Krishna; Gupta, Devendra Kumar; Kant, Ravi

    2015-01-01

    Here, we sequenced and functionally annotated the long reads (1–2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes–—PNMT, SNN and LAMB1 show their involvement in Ependymoma. PMID:26862483

  13. Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases.

    PubMed

    Mellgren, K; Attarbaschi, A; Abla, O; Alexander, S; Bomken, S; Bubanska, E; Chiang, A; Csóka, M; Fedorova, A; Kabickova, E; Kapuscinska-Kemblowska, L; Kobayashi, R; Krenova, Z; Meyer-Wentrup, F; Miakova, N; Pillon, M; Plat, G; Uyttebroeck, A; Williams, D; Wróbel, G; Kontny, U

    2016-08-01

    Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.

  14. Current standards of care and future directions for "high-risk" pediatric renal tumors: Anaplastic Wilms tumor and Rhabdoid tumor.

    PubMed

    Geller, James I

    2016-01-01

    'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies.

  15. AT13387 in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2017-04-04

    Anaplastic Large Cell Lymphoma, ALK-Positive; BCL6 Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

  16. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

    PubMed Central

    Celik, Murat; Sen, Erdem; Cebeci, Hakan; Ata, Ozlem; Yavas, Cagdas

    2016-01-01

    Kaposi sarcoma (KS), a vascular tumor caused by infection with human herpesvirus 8 (HHV8), is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient. PMID:27747121

  17. Effect of Cerebellum Radiation Dosimetry on Cognitive Outcomes in Children With Infratentorial Ependymoma

    SciTech Connect

    Merchant, Thomas E.; Sharma, Shelly; Xiong, Xiaoping; Wu, Shengjie; Conklin, Heather

    2014-11-01

    Purpose: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored. Methods and Materials: Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. Results: Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; −0.190 patients/Gy/year; P=.001), math (−0.164 patients/Gy/year; P=.010), reading (−0.137 patients/Gy/year; P=.011), and spelling scores (−0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (−0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (−0.150 patients/Gy/year; P=.002), math (−0.120 patients/Gy/year; P=.023), reading (−0.111 patients/Gy/year; P=.012), and spelling (−0.117 patients/Gy/year; P=.015

  18. Factors Associated With Neurological Recovery of Brainstem Function Following Postoperative Conformal Radiation Therapy for Infratentorial Ependymoma

    SciTech Connect

    Merchant, Thomas E.; Chitti, Ramana M.; Li Chenghong; Xiong Xiaoping; Sanford, Robert A.; Khan, Raja B.

    2010-02-01

    Purpose: To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT). Methods: The study included 68 patients (median age +- standard deviation of 2.6 +- 3.8 years) who were followed for 5 years after receiving CRT (54-59.4 Gy) and were assessed for function of cranial nerves V to VII and IX to XII, motor weakness, and dysmetria. The mean (+- standard deviation) brainstem dose was 5,487 (+-464) cGy. Patients were divided into four groups representing those with normal baseline and follow-up, those with abnormal baseline and full recovery, those with abnormal baseline and partial or no recovery, and those with progressive deficits at 12 (n = 62 patients), 24 (n = 57 patients), and 60 (n = 50 patients) months. Grouping was correlated with clinical and treatment factors. Results: Risk factors (overall risk [OR], p value) associated with incomplete recovery included gender (male vs. female, OR = 3.97, p = 0.036) and gross tumor volume (GTV) (OR/ml = 1.23, p = 0.005) at 12 months, the number of resections (>1 vs. 1; OR = 23.7, p = 0.003) and patient age (OR/year = 0.77, p = 0.029) at 24 months, and cerebrospinal fluid (CSF) shunting (Yes vs. No; OR = 21.9, p = 0.001) and GTV volume (OR/ml = 1.18, p = 0.008) at 60 months. An increase in GTV correlated with an increase in the number of resections (p = 0.001) and CSF shunting (p = 0.035); the number of resections correlated with CSF shunting (p < 0.0001), and male patients were more likely to undergo multiple tumor resections (p = 0.003). Age correlated with brainstem volume (p < 0.0001). There were no differences in outcome based on the absolute or relative volume of the brainstem that received more than 54 Gy. Conclusions: Incomplete recovery of brainstem function after CRT for infratentorial ependymoma is related to surgical morbidity and the volume and the extent of tumor.

  19. ALK Positive Anaplastic Large Cell Lymphoma Presenting as Extensive Bone Involvement

    PubMed Central

    Gajendra, Smeeta; Lipi, Lipika; Goel, Shalini; Misra, Ruchira

    2015-01-01

    Anaplastic lymphoma kinase (ALK) positive Anaplastic large cell lymphoma (ALCL) represents approximately 2% of all Non-Hodgkin’s lymphomas that commonly involves nodal as well as a wide variety of extra nodal sites, as skin, soft tissue, bones and lungs, although primary or secondary involvement of bone is rare. Herein, we report a case of 14-year-old female child presented as extensive bony involvement with a clinical diagnosis of bone tumour/ small round cell tumour, which was proved to be ALK positive ALCL on histopathological examination. PMID:25738071

  20. Lipomatous ependymoma: report of a rare differentiation pattern with a comprehensive review of literature.

    PubMed

    Gaur, Kavita; Batra, Vineeta V; Gupta, Rakesh; Sharma, M C; Narang, Poonam; Pandey, P N

    2016-07-01

    We report the case of a 13-year-old girl presenting with left-sided hemiparesis, altered sensorium and episodic headache with bouts of projectile vomiting. Imaging revealed a large heterodense intraventricular mass lesion displaying focal calcification and hyperintensity on T1- and T2- weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance images suggesting the presence of intratumoral fat. Histologically, the tumour showed sheets of glial cells, focal perithelial rosettes and individual cells showing fat vacuoles. The morphological impression was of an ependymoma with lipomatous differentiation. Glial fibrillary acid protein (GFAP) immunohistochemistry revealed positivity in the cytoplasmic processes of the tumour cells as well as in the cytoplasmic rim of the cells having an adipocytic appearance. S100 and vimentin were also immunoreactive. Ultrastructural studies confirmed the ependymal differentiation of the tumour and the presence of an osmiophilic fat component confirming the diagnosis. After 1 year of follow-up, the patient presented with similar complaints and MRI evidence of recurrence of the tumour. A comprehensive literature review revealed that half of the reported cases of this pattern recurred suggesting a possibly tenacious clinical course.

  1. Canine tumour suppressor gene p53 mutation in a case of anaplastic carcinoma of the intestine.

    PubMed

    Mayr, B; Reifinger, M

    2002-01-01

    Tumours localised in the large bowel of dogs were subjected to molecular genetic studies. Highly conserved regions of the tumour suppressor gene p53, including typical tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were analysed. A mutation CGG-->TGG (arginine-->tryptophan) was present in codon 249 in an anaplastic carcinoma in the caecum.

  2. Metastatic anaplastic adenocarcinoma suspected to be of mammary origin in an intact male rabbit (Oryctolagus cuniculus)

    PubMed Central

    Summa, Noémie M.; Eshar, David; Snyman, Heindrich N.; Lillie, Brandon N.

    2014-01-01

    A 7-year-old, intact male, pet dwarf rabbit (Oryctolagus cuniculus) was presented for a ventral abdominal subcutaneous mass. Histolopathology of the resected mass was suggestive of a mammary adenocarcinoma. Six months later, the rabbit died from severe dyspnea. Necropsy showed recurrence of the original mass with hepatic and pulmonary metastasis of the anaplastic adenocarcinoma, suspected to be of mammary origin. PMID:24790235

  3. Analysis on therapeutic outcomes and prognostic factors of intracranial ependymoma: a report of 49 clinical cases in a single center.

    PubMed

    Ye, Jingliang; Zhu, Junle; Yan, Jiayi; Chen, Peiqin; Wan, Zhiping; Chen, Feng; Zhang, Lei; Qian, Jun; Luo, Chun

    2015-12-01

    Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.

  4. Anaplastic Transformation in Mandibular Metastases of Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

    PubMed

    Ambelil, Manju; Sultana, Sadia; Roy, Suvra; Gonzalez, Maria M

    2016-09-01

    Anaplastic transformation of well-differentiated thyroid carcinomas at distant metastatic sites is a rare condition. Most cases described in the literature have occurred in the thyroid or regional lymph nodes. We report a case of anaplastic transformation of the follicular variant of papillary thyroid carcinoma in mandibular metastases. A 76-year-old female presented with a painful and enlarging mandibular mass. She had been treated in the past for the follicular variant of papillary thyroid carcinoma. A palliative hemi-mandibulectomy was performed. Histology revealed a metastatic papillary thyroid carcinoma, follicular variant, with an unusual finding of solid pleomorphic epithelioid and spindle cell areas, consistent with anaplastic transformation.

  5. Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade.

    PubMed

    Altura, R A; Olshefski, R S; Jiang, Y; Boué, D R

    2003-11-03

    Survivin is a gene that is widely expressed throughout the development of the normal mammalian embryo. Subcellular localisation of Survivin to both the nucleus and cytoplasm has suggested multiple functional roles, including inhibition of cell death, especially as demonstrated within a variety of malignant cell types, as well as regulation of the mitotic spindle checkpoint. The expression of Survivin has been associated with an adverse clinical outcome in a large number of malignancies. However, nuclear Survivin expression has been described as an independent variable of favourable prognosis in two large clinical studies of breast and gastric carcinomas. Reports of Survivin expression in normal postnatal, differentiated tissues have been restricted to cell types with high proliferative capacities, including vascular endothelium, endometrium, colonic epithelium, and activated lymphocytes. Prior to this report, expression within the normal human brain had not been characterised. Here, we analyse the expression of Survivin in human brain sections obtained from perinatal and paediatric autopsy cases. We report a strikingly high level of expression of Survivin within normal ependyma and choroid plexus (CP). Analysis of corresponding neoplastic tissue in paediatric ependymomas and CP tumours shows that expression of the nuclear form of Survivin correlates with morphologic tumour grade, with a loss of nuclear expression associated with progressive cytologic anaplasia. This pattern of expression supports a hypothesis that Survivin plays a functional role in normal ependymal growth and/or neural stem cell differentiation, and that abnormally low levels of expression of the nuclear form of this protein may be a marker of more aggressive disease and/or higher morphologic grade in ependymal and CP tumours.

  6. Rare association of secondary superficial siderosis caused by a fourth ventricle hemorrhagic ependymoma mimicking a cavernoma: Case report and literature review

    PubMed Central

    Espinosa Rodríguez, Eduardo E.; Moro, Rodrigo Carrasco; Martínez San Millán, Juan S.; Pian Arias, Héctor G.

    2017-01-01

    Background: The association of a hemorrhagic tumor with secondary superficial siderosis (SS) is a relatively rare although well described phenomenon. Case Description: We present the case report of a 35-year-old male with a history of drowsiness, hypoacusia, drop attacks, and multidirectional nystagmus during the last 2 months, who presented with acute obstructive hydrocephalus caused by a fourth ventricle mass displaying radiological signs of repeated intra and extratumoral hemorrhage with SS. He underwent gross surgical removal of the solid component of the tumor. Microscopic examination revealed an ependymoma with atypical features, including prominent angiomatous formations and internal chronic hemorrhages with hemosiderin deposits, resembling a cavernoma. The scarce tumoral component, which extended around these cavernous vessels, lacked the gross typical features of fibrillary stroma or perivascular pseudorosettes. Conclusion: To our knowledge, including the present case, there are 45 published reports of tumors associating secondary SS. Besides ependymoma, no other hemorrhagic lesion, tumoral or vascular, has been previously published associating a fourth ventricle location with secondary SS. The present case represents the fifth with this finding, and we strongly suggest ependymoma as a presumptive diagnosis when this rare association is encountered. In addition, this appears to be the first case reported in the scientific literature of a hemorrhagic fourth ventricle ependymoma mimicking both, radiologically and histologically, a cavernous malformation. PMID:28217393

  7. Coexpression of EpCAM, CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

    PubMed Central

    Okada, Toshihiro; Nakamura, Teruo; Watanabe, Takayuki; Onoda, Naoyoshi; Ashida, Atsuko; Okuyama, Ryuhei; Ito, Ken-ichi

    2014-01-01

    Background Anaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma. Methodology/Principal Findings Two differentiated thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1 (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s expression and ALDH1 activity was observed in all thyroid cancer cell lines. As for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of CD44s. A positive correlation was observed between EpCAM expression and ALDH1 activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected significantly more frequently in anaplastic carcinomas. Conclusions/Significance Our study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic strategy for treatment

  8. Primary cutaneous CD 30 (+) ALK (−) anaplastic large cell lymphoma with dermoscopic findings: a case report

    PubMed Central

    Uzuncakmak, Tugba K.; Akdeniz, Necmettin; Karadag, Ayse S.; Taskin, Secil; Zemheri, Ebru I.; Argenziano, Giuseppe

    2017-01-01

    Primary cutaneous CD 30 (+) anaplastic large cell lymphoma (PCALCL) is a rare and indolent type of cutaneous T cell lymphoma, which usually presents as an asymptomatic solitary firm nodule that rapidly grows and often ulcerates without any systemic involvement. A 64-year-old female presented to our outpatient clinic with a one-year history of multiple pink nodular lesions on the chest, back and gluteal regions. Dermoscopic examination of the nodular lesions revealed pink-to-yellow structureless areas and arborizing-to-polymorphous vessels. Histopathologic examination was consistent with CD30 (+) anaplastic large cell lymphoma. Systemic involvement was not detected. Local radiotherapy for large nodules and surgical excision for small nodules were performed. The large nodules had totally regressed after 10 sessions of radiotherapy. PMID:28243498

  9. Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma

    PubMed Central

    Basheer, Aneesh; Padhi, Somanath; Nagarajan, Ramesh; Boopathy, Vinoth; Mookkappan, Sudhagar; Iqbal, Nayyar

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) has a well known association with lymphomas, especially of T cell origin. Prognosis of lymphoma associated HLH is very poor, especially in T cell lymphomas; and, therefore, early diagnosis might alter the outcome. Though association of HLH with systemic anaplastic large cell lymphoma (ALCL) is known, its occurrence in primary cutaneous ALCL (C-ALCL) is distinctly rare. We aim to describe a case of C-ALCL (anaplastic lymphoma kinase (ALK)−) in an elderly male who succumbed to the complication of associated HLH, which was possibly triggered by coexistent virus infection. We briefly present the literatures on lymphoma associated HLH and discuss the histopathological differentials of cutaneous CD30+ lymphoproliferative disorders. We do suggest that HLH may pose diagnostic challenges in the evaluation of an underlying lymphoma and hence warrants proper evaluation for the underlying etiologies and/or triggering factors. PMID:25405042

  10. Spermatocytic seminoma: review of the literature and description of a new case of the anaplastic variant.

    PubMed

    Lombardi, Mariano; Valli, Mirca; Brisigotti, Massimo; Rosai, Juan

    2011-02-01

    The aims of this paper were to review the literature of Spermatocytic Seminoma (SS) updating its clinico-pathological features and to present a new case of the exceptionally rare variant of this tumor known as anaplastic which only five cases have been reported. Many studies have confirmed that SS is a distinct neoplasm both clinically and pathologically from classical Seminoma and it differs from the latter especially in regard to behavior, characterized by an almost complete inability to metastasize with only very few convincing examples described with metastatic behavior. There is general agreement that orchidectomy is sufficient therapy for SS and that surveillance following surgery is the preferred management option. Surprisingly, the presence of an anaplastic component does not seem to impact on this excellent prognosis. Very different is the case of sarcomatous transformation, for which further therapy after orchiectomy is advisable.

  11. Autopsy of anaplastic carcinoma of the pancreas producing granulocyte colony-stimulating factor.

    PubMed

    Hayashi, Haruna; Eguchi, Noriaki; Sumimoto, Kyoku; Matsumoto, Kenta; Azakami, Takahiro; Sumida, Tomonori; Tamura, Tadamasa; Sumii, Masaharu; Uraoka, Naohiro; Shimamoto, Fumio

    2016-08-01

    A 50-year-old man presented to a nearby hospital with high fever and anorexia. An abdominal tumor was detected, and he was referred to our hospital. A pancreatic tumor was detected by computed tomography and abdominal ultrasonography. He had high fever, leukocytosis, and high serum granulocyte colony-stimulating factor (G-CSF). We performed a tumor biopsy and histological examination revealed anaplastic carcinoma of the pancreas. Based on the diagnosis, we initiated chemotherapy using gemcitabine plus S-1. However, the tumor rapidly progressed and he deteriorated and died 123 days after admission. As immunohistochemical study showed positive staining for G-CSF in the tumor cell, we diagnosed the tumor producing G-CSF during autopsy. Anaplastic carcinoma of the pancreas producing G-CSF is very rare, with 10 cases, including ours, reported in the literature.

  12. Doxorubicin has a synergistic cytotoxicity with cucurbitacin B in anaplastic thyroid carcinoma cells.

    PubMed

    Kim, Si Hyoung; Kang, Jun Goo; Kim, Chul Sik; Ihm, Sung-Hee; Choi, Moon Gi; Yoo, Hyung Joon; Lee, Seong Jin

    2017-02-01

    In this study, the combined effect of doxorubicin with cucurbitacin B on survival of anaplastic thyroid carcinoma cells was evaluated. For experiments, 8505C and CAL62 human anaplastic thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, and cytotoxic activity were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, multiplexed cytotoxicity assay, and cytotoxicity assay, respectively. Reactive oxygen species production was measured. In experiments, doxorubicin and cucurbitacin B reduced cell viability in a dose- and time-dependent manner. Cotreatment of doxorubicin and cucurbitacin B, compared with treatment of doxorubicin alone, decreased the percentage of viable cells and increased cytotoxic activity. All of the combination index values were lower than 1.0, suggesting the synergism between doxorubicin and cucurbitacin B in induction of cytotoxicity. In cells treated with both doxorubicin and cucurbitacin B, compared with doxorubicin alone, the protein levels of cleaved poly(adenosine diphosphate-ribose) polymerase and cyclooxygenase 2 and reactive oxygen species production were enhanced. In contrast, the protein levels of B-cell chronic lymphocytic leukemia/lymphoma 2 and survivin and B-cell chronic lymphocytic leukemia/lymphoma 2/B-cell chronic lymphocytic leukemia/lymphoma 2-associated x protein ratio were diminished. The protein levels of Janus kinase 2 and signal transducer and activator of transcription 3 were reduced, while phospho-extracellular signal-regulated kinase 1/2 protein levels were elevated without change in total extracellular signal-regulated kinase 1/2 protein levels. These results suggest that doxorubicin synergizes with cucurbitacin B in induction of cytotoxicity in anaplastic thyroid carcinoma cells. Moreover, synergistic cytotoxicity of doxorubicin with cucurbitacin B is mediated by B-cell chronic lymphocytic leukemia/lymphoma 2 family proteins, survivin, and reactive oxygen

  13. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    PubMed Central

    Bains, Anupama; Vedant, Deepak; Shanker, Vinay; Tegta, G. R.

    2016-01-01

    Primary cutaneous anaplastic large cell lymphoma (pcALCL) forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary. PMID:27990392

  14. Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report and Literature Review.

    PubMed

    Letter, Haley; Rop, Baiywo; Edison, Michele N; Turner, Patricia

    2016-03-26

    Introduction Anaplastic large cell lymphoma is a very rare T-cell lymphoma that has only recently been found to be associated with breast implants. It has been described in the literature mainly in the form of case reports. This article focuses on the imaging characteristics of this rare disease. We hope to increase awareness of breast imagers and referring physicians to improve early detection rates. Case Report We present the case of a 32-year-old female who presented with several weeks of pain and firmness in her right breast. MRI and ultrasound demonstrated a peri-implant fluid collection. Ultrasound-guided aspiration revealed anaplastic large cell lymphoma. The patient was treated with implant removal alone and has now been in remission for 3 years.  Conclusion Anaplastic large cell lymphoma of the breast is a very rare entity that has mainly been described in the literature as case reports. As in the case of our patient, imaging findings can be very non-specific, and it is important for surgeons, breast imagers, and oncologists to be aware of this rare disease to ensure prompt diagnosis.

  15. Breast implant-associated anaplastic large cell lymphoma: review of a distinct clinicopathologic entity.

    PubMed

    Xu, Jie; Wei, Shi

    2014-06-01

    Primary breast anaplastic large cell lymphoma (ALCL) is rare but is more commonly seen in patients with implants; fewer than 50 cases of breast implant-associated ALCL have been reported in the English language literature. Breast implant-associated ALCL is not a disease of the breast parenchyma, but instead is a disease of the fibrous capsule surrounding the implant. The patients usually present with an effusion around the implant and, rarely, with a solid mass. Morphologically, the neoplastic cells are large, epithelioid, and pleomorphic, with abundant cytoplasm, vesicular irregular nuclei, and frequent mitoses. Occasional "hallmark" cells may be present. The lesional cells typically show strong and diffuse immunoreactivity for CD30 and often express T-cell markers, cytotoxic-associated antigens, and epithelial membrane antigen. Almost all reported cases are negative for anaplastic lymphoma kinase. Molecular genetic analyses have demonstrated T-cell receptor gene rearrangements. The differential diagnosis essentially includes poorly differentiated carcinoma, other lymphomas, and chronic inflammation. Once a diagnosis of lymphoma is established, it is important to exclude systemic anaplastic lymphoma kinase-negative ALCL involving the breast, primary cutaneous ALCL, and other CD30(+) lymphoproliferative disorders. The patients with effusion-associated ALCL often have an indolent course and excellent prognosis, responding well to excision of the fibrous capsule around the implant (capsulectomy) and implant removal. In contrast, patients who present with a distinct mass may have a more aggressive course and poor prognosis, requiring chemotherapy and/or radiation therapy.

  16. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma.

    PubMed

    Coco, Simona; De Mariano, Marilena; Valdora, Francesca; Servidei, Tiziana; Ridola, Vita; Andolfo, Immacolata; Oberthuer, André; Tonini, Gian Paolo; Longo, Luca

    2012-10-01

    The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.

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

    PubMed Central

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

    2015-01-01

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

  18. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma.

    PubMed

    Heidegger, Simon; Beer, Ambros J; Geissinger, Eva; Rosenwald, Andreas; Peschel, Christian; Ringshausen, Ingo; Keller, Ulrich

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.

  19. Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma

    SciTech Connect

    Metzger, A.K.; Duyk, G.; Daneshvar, L.; Edwards, M.S.B.; Cogen, P.H. ); Sheffield, V.C. )

    1991-09-01

    The authors detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.

  20. Proton therapy dose distribution comparison between Monte Carlo and a treatment planning system for pediatric patients with ependymoma

    SciTech Connect

    Jia Yingcui; Beltran, Chris; Indelicato, Daniel J.; Flampouri, Stella; Li, Zuofeng; Merchant, Thomas E.

    2012-08-15

    Purpose: Compare dose distributions for pediatric patients with ependymoma calculated using a Monte Carlo (MC) system and a clinical treatment planning system (TPS). Methods: Plans from ten pediatric patients with ependymoma treated using double scatter proton therapy were exported from the TPS and calculated in our MC system. A field by field comparison of the distal edge (80% and 20%), distal fall off (80% to 20%), field width (50% to 50%), and penumbra (80% to 20%) were examined. In addition, the target dose for the full plan was compared. Results: For the 32 fields from the 10 patients, the average differences of distal edge at 80% and 20% on central axis between MC and TPS are -1.9 {+-} 1.7 mm (p < 0.001) and -0.6 {+-} 2.3 mm (p= 0.13), respectively. Excluding the fields that ranged out in bone or an air cavity, the 80% difference was -0.9 {+-} 1.7 mm (p= 0.09). The negative value indicates that MC was on average shallower than TPS. The average difference of the 63 field widths of the 10 patients is -0.7 {+-} 1.0 mm (p < 0.001), negative indicating on average the MC had a smaller field width. On average, the difference in the penumbra was 2.3 {+-} 2.1 mm (p < 0.001). The average of the mean clinical target volume dose differences is -1.8% (p= 0.001), negative indicating a lower dose for MC. Conclusions: Overall, the MC system and TPS gave similar results for field width, the 20% distal edge, and the target coverage. For the 80% distal edge and lateral penumbra, there was slight disagreement; however, the difference was less than 2 mm and occurred primarily in highly heterogeneous areas. These differences highlight that the TPS dose calculation cannot be automatically regarded as correct.

  1. Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine׳s curse.

    PubMed

    Choi, Mehee; Thoma, Miranda; Tolekidis, George; Byrne, Richard W; Diaz, Aidnag Z

    2015-01-01

    Ondine׳s curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine׳s curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97mmHg. He was diagnosed with Ondine׳s curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.

  2. Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

    SciTech Connect

    Gunther, Jillian R.; Sato, Mariko; Chintagumpala, Murali; Ketonen, Leena; Jones, Jeremy Y.; Allen, Pamela K.; Paulino, Arnold C.; Okcu, M. Fatih; Su, Jack M.; Weinberg, Jeffrey; Boehling, Nicholas S.; Khatua, Soumen; Adesina, Adekunle; Dauser, Robert; Whitehead, William E.; Mahajan, Anita

    2015-09-01

    Purpose: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). Methods and Materials: Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. Results: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P=.06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P=.048; OR: 0.36, P=.05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P=.019) and multivariate (OR: 3.89, P=.024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. Conclusions: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.

  3. Cardiac Tamponade Associated with the Presentation of Anaplastic Large Cell Lymphoma in a 2-Year-Old Child

    PubMed Central

    Mira-Perceval Juan, Gema; Alcalá Minagorre, Pedro J.; Huertas Sánchez, Ana M.; Segura Sánchez, Sheila; López Iniesta, Silvia; De León Marrero, Francisco J.; Costa Navarro, Estela; Niveiro de Jaime, María

    2015-01-01

    The anaplastic large cell lymphoma is a rare entity in pediatric patients. We present an unusual case of pericardial involvement, quite uncommon as extranodal presentation of this type of disorder, that provoked a life-risk situation requiring an urgent pericardiocentesis. To our knowledge, this is the first report on a child with pericardial involvement without an associated cardiac mass secondary to anaplastic large cell lymphoma in pediatric age. We report the case of a 21-month-old Caucasian male infant with cardiac tamponade associated with the presentation of anaplastic large cell lymphoma. Initially, the child presented with 24-day prolonged fever syndrome, cutaneous lesions associated with hepatomegaly, inguinal adenopathies, and pneumonia. After a 21-day asymptomatic period, polypnea and tachycardia were detected in a clinical check-up. Chest X-ray revealed a remarkable increase of the cardiothoracic index. The anaplastic large cell lymphoma has a high incidence of extranodal involvement but myocardial or pericardial involvements are rare. For this reason, we recommend a close monitoring of patients with a differential diagnosis of anaplastic large cell lymphoma. PMID:26435869

  4. Differentiation of clear cell ependymoma of the cerebellum from hemangioblastoma by thallium-201 single photon emission computed tomography-case report-.

    PubMed

    Nagamatsu, Ken-ichi; Kumabe, Toshihiro; Watanabe, Mika; Nakazato, Yoichi; Tominaga, Teiji

    2009-12-01

    A 57-year-old man suffered from dizziness for about one year and truncal ataxia for about one month. Magnetic resonance imaging demonstrated a cystic tumor with a homogeneously enhanced mural nodule located in the cerebellar vermis. Computed tomography angiography revealed a hypervascular nodule. These findings were compatible with hemangioblastoma. Thallium-201 single photon emission computed tomography ((201)Tl-SPECT) showed moderately high uptake in the early phase and moderately high retention in the delayed phase, whereas hemangioblastoma shows almost no retention in the delayed phase. The patient underwent total removal of the tumor. The histological diagnosis was clear cell ependymoma (CCE). CCE is a rare subtype of ependymoma, which resembles hemangioblastoma in histological and neuroimaging findings, but is considerably more aggressive. (201)Tl-SPECT can provide useful information for the preoperative differential diagnosis of infratentorial CCE and hemangioblastoma.

  5. Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: long term results of RTOG BR0131.

    PubMed

    Vogelbaum, Michael A; Hu, Chen; Peereboom, David M; Macdonald, David R; Giannini, Caterina; Suh, John H; Jenkins, Robert B; Laack, Nadia N; Brachman, David G; Shrieve, Dennis C; Souhami, Luis; Mehta, Minesh P

    2015-09-01

    We report on the long-term results of a phase II study of pre-irradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma. Pre-RT temozolomide was given for up to 6 cycles. RT with concurrent temozolomide was administered to patients with less than a complete radiographic response. Forty eligible patients were entered and 32 completed protocol treatment. With a median follow-up time of 8.7 years (range 1.1-10.1), median progression-free survival (PFS) is 5.8 years (95 % CI 2.0, NR) and median overall survival (OS) has not been reached (5.9, NR). 1p/19q data are available in 37 cases; 23 tumors had codeletion while 14 tumors had no loss or loss of only 1p or 19q (non-codeleted). In codeleted patients, 9 patients have progressed and 4 have died; neither median PFS nor OS have been reached and two patients who received only pre-RT temozolomide and no RT have remained progression-free for over 7 years. 3-year PFS and 6-year OS are 78 % (95 % CI 61-95 %) and 83 % (95 % CI 67-98 %), respectively. Codeleted patients show a trend towards improved 6-year survival when compared to the codeleted procarbazine/CCNU/vincristrine (PCV) and RT cohort in RTOG 9402 (67 %, 95 % CI 55-79 %). For non-codeleted patients, median PFS and OS are 1.3 and 5.8 years, respectively. These updated results suggest that the regimen of dose intense, pre-RT temozolomide followed by concurrent RT/temozolomide has significant activity, particularly in patients with 1p/19q codeleted AOs and MAOs.

  6. Analysis of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-reactive CD8(+) T cell responses in children with NPM-ALK(+) anaplastic large cell lymphoma.

    PubMed

    K Singh, V; Werner, S; Hackstein, H; Lennerz, V; Reiter, A; Wölfel, T; Damm-Welk, C; Woessmann, W

    2016-10-01

    Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8(+) T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8(+) T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM-ALK were used as antigen-presenting cells for T cell stimulation. Responder T lymphocytes were tested in interferon-gamma enzyme-linked immunospot (ELISPOT) assays with NPM-ALK-transfected autologous DCs as well as CV-1 in Origin with SV40 genes (COS-7) cells co-transfected with genes encoding the patients' HLA class I alleles and with NPM-ALK encoding cDNA to verify responses and define the HLA restrictions of specific T cell responses. NPM-ALK-specific CD8(+) T cell responses were detected in three of five ALK-positive ALCL patients tested between 1 and 13 years after diagnosis. The three patients had also maintained anti-ALK antibody responses. No reactivity was detected in samples from five healthy donors. The NPM-ALK-specific CD8(+) T cell responses were restricted by HLA-C-alleles (C*06:02 and C*12:02) in all three cases. This approach allowed for the detection of NPM-ALK-reactive T cells, irrespective of the individual HLA status, up to 9 years after ALCL diagnosis.

  7. Variant translocation partners of the anaplastic lymphoma kinase (ALK) gene in two cases of anaplastic large cell lymphoma, identified by inverse cDNA polymerase chain reaction.

    PubMed

    Takeoka, Kayo; Okumura, Atsuko; Honjo, Gen; Ohno, Hitoshi

    2014-01-01

    In anaplastic large cell lymphoma (ALCL), the anaplastic lymphoma kinase (ALK) gene is rearranged with diverse partners due to variant translocations/inversions. Case 1 was a 39-year-old man who developed multiple tumors in the mediastinum, psoas muscle, lung, and lymph nodes. A biopsy specimen of the inguinal node was effaced by large tumor cells expressing CD30, epithelial membrane antigen, and cytoplasmic ALK, which led to a diagnosis of ALK(+) ALCL. Case 2 was a 51-year-old man who was initially diagnosed with undifferentiated carcinoma. He developed multiple skin tumors eight years after his initial presentation, and was finally diagnosed with ALK(+) ALCL. He died of therapy-related acute myeloid leukemia. G-banding and fluorescence in situ hybridization using an ALK break-apart probe revealed the rearrangement of ALK and suggested variant translocation in both cases. We applied an inverse cDNA polymerase chain reaction (PCR) strategy to identify the partner of ALK. Nucleotide sequencing of the PCR products and a database search revealed that the sequences of ATIC in case 1 and TRAF1 in case 2 appeared to follow those of ALK. We subsequently confirmed ATIC-ALK and TRAF1-ALK fusions by reverse transcriptase PCR and nucleotide sequencing. We successfully determined the partner gene of ALK in two cases of ALK(+) ALCL. ATIC is the second most common partner of variant ALK rearrangements, while the TRAF1-ALK fusion gene was first reported in 2013, and this is the second reported case of ALK(+) ALCL carrying TRAF1-ALK.

  8. [Mount Fuji sign in postoperative period after surgery for ependymoma of the third ventricle (V3): case report and review of the literature].

    PubMed

    Boumadiane, Abderrahmane; Derkaoui, Ali; Shimi, Abdelkarim; Khatouf, Mohamed

    2016-01-01

    Mount Fuji sign also known as compressive pneumocephalus is a redoubtable postoperative neurosurgical complication. We report the clinical case of a 10 months-old patient, hospitalized in reanimation for postoperative management following surgery for ependymoma of the third ventricle. The evolution was marked by the occurrence of early postoperative compressive pneumocephalus, responsible for neurological and hemodynamic worsening. This study highlights the possibility of occurrence of such an adverse event, as well as the therapeutic and especially preventive measures for this complication.

  9. The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma.

    PubMed

    Kizilbash, Sani H; Giannini, Caterina; Voss, Jesse S; Decker, Paul A; Jenkins, Robert B; Hardie, John; Laack, Nadia N; Parney, Ian F; Uhm, Joon H; Buckner, Jan C

    2014-10-01

    This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3%, p = 0.02) and IDH mutation (78.9 vs. 22.0%, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.

  10. [Adolescent and Young Adults (AYAS) brain tumor national Web conference. On behalf of ANOCEF, GO-AJA and SFCE societies].

    PubMed

    Frappaz, Didier; Sunyach, Marie-Pierre; Le Rhun, Emilie; Blonski, Marie; Laurence, Valérie; Bonneville Levard, Alice; Loiseau, Hugues; Meyronnet, David; Callies, Arnaud; Laigle-Donadey, F; Faure Conter, Cecile

    2016-12-01

    The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro-oncologists are warranted to share expertise. Since 2008, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma.

  11. EphB2 activation is required for ependymoma development as well as inhibits differentiation and promotes proliferation of the transformed cell.

    PubMed

    Chen, Phylip; Rossi, Nathan; Priddy, Samuel; Pierson, Christopher R; Studebaker, Adam W; Johnson, Robert A

    2015-03-24

    Our intracranial implantation mouse model of ependymoma clearly demonstrates overexpression of the ephrin receptor EphB2 in Ink4a/Arf((-/-)) supratentorial embryonic neural stem cells (STeNSCs) to be essential for transformation and disease development; however the requirement for and consequence of receptor activation on transformation and neural stem cell function were not examined. We definitively illustrate the necessity for receptor activation in cellular transformation and the importance of implantation site and microenvironment in directing ependymoma development. In vitro assays of EphB2 overexpressing Ink4a/Arf((-/-)) STeNSCs showed no changes in their neural stem cell characteristics (stem cell marker expression and self-renewal) upon receptor activation, but EphB2 driven tumor cells were inhibited significantly in differentiation and exhibited increased tumorsphere formation and cellular proliferation in response to ephrin-B ligand mediated receptor activation. Additionally, we observed substantial differences in the phosphorylation state of several key proteins involved in Ras and p38 MAPK signaling when comparing EphB2 overexpressing Ink4a/Arf((-/-)) STeNSCs and tumor cells with relatively little change in total protein levels. We propose that EphB2 mediated ependymoma development is a multifactorial process requiring microenvironment directed receptor activation, resulting in changes in the phosphorylation status of key regulatory proteins, maintenance of a stem-like state and cellular proliferation.

  12. Meningiomas with Rhabdoid or Papillary Components : Prognosis and Comparison with Anaplastic Meningiomas

    PubMed Central

    Kim, Jeong-Kwon; Jung, Shin; Lee, Kyung-Hwa; Kim, Seul-Kee; Lee, Eun Jung

    2016-01-01

    Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (<50%) rhabdoid or papillary component (group B2). Homogeneous enhancement on MRI was associated with improved PFS compared to heterogeneous enhancement (p=0.025). Depending on pathology, the mean PFS was 134.9±31.6 months for group A, 46.6±13.4 months for group B1, and 118.7±19.2 months for group B2. The mean OS was 138.5±24.6 months for group A and 59.7±16.8 months for group B1. All recurrent tumors were of the previously diagnosed pathology, except for one tumor from group B1, which recurred as an atypical meningioma without a papillary component. Group B1 tumors showed a more aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. PMID:27446516

  13. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma.

    PubMed

    Dong, J J; Zhou, Y; Liu, Y T; Zhang, Z W; Zhou, X J; Wang, H J; Liao, L

    2013-05-06

    Anaplastic thyroid carcinoma (ATC) is a severe thyroid malignancy with poor prognosis, due to its early metastasis and unresponsiveness to both radiation and chemotherapy. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, has been used as a re-differentiation agent to treat cancers in several human cancer models. So far, the effects of nevirapine on human thyroid anaplastic carcinoma cells have not been documented. The aim of this study was to evaluate the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Cell proliferation was determined by methly thiazolyl tetrazolium (MTT) assay. Cell apoptosis was analyzed by Hoechst 33258 staining. The mRNA expression of NIS and TSHR was determined by real-time quantitative reverse transcription-polymerase chain reaction (real time RT-PCR). Iodine uptake was determined by (125)I radioactivity assay. At all doses (100, 200, 350, 500 μmol/L) tested, nevirapine significantly inhibited cell proliferation after 48 h treatment. At high dose (500 μmol/L), nevirapine significantly increased the percentage of apoptotic cells compared with control (P<0.01). At lower doses (200 μmol/L and 350 μmol/L), nevirapine did not induce cell apoptosis, but up-regulated NIS and THSR mRNA expression in a dose-dependent manner. In FRO cells pre-treated with nevirapine, the increase in NIS expression had no obvious effect on iodine uptake. These findings indicate that nevirapine has an anti-proliferative effect on FRO cells, which correlates with an induction of cell differentiation.

  14. Expression of cell adhesion molecules and doublecortin in canine anaplastic meningiomas.

    PubMed

    Ide, T; Uchida, K; Suzuki, K; Kagawa, Y; Nakayama, H

    2011-01-01

    Tumor cell invasion into the surrounding nervous tissue is one of the histologic hallmarks of anaplastic meningiomas. To identify other possible markers for aggression in canine meningiomas, the relationship between histologic features and the expression of molecules involved in cell adhesion, cell proliferation, and invasion was examined. Immunohistochemistry for epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), β-catenin, doublecortin (DCX), and Ki-67 was performed for 55 cases of canine meningioma. DCX was preferentially expressed in tumor cells invading the brain parenchyma (12 of 14 cases), suggesting its involvement in the invasion process. Regardless of the histologic type, E-cadherin and N-cadherin expression was observed in 31 of 55 and 44 of 55 cases, respectively. There was a significant positive correlation between DCX and N-cadherin expression and a significant negative correlation between E-cadherin and N-cadherin expression, suggesting that decreased E-cadherin and increased N-cadherin expression induce DCX expression. Typical membranous β-catenin expression was observed in 10 of 55 cases, whereas nuclear translocation was observed in 33 cases. Nuclear β-catenin expression was frequently found in anaplastic meningiomas (12 of 14 cases). The Ki-67 labeling indices were significantly higher in anaplastic meningiomas than in other types. These findings indicate that the expression of N-cadherin and DCX and the nuclear translocation of β-catenin are closely associated with the presence of invasion and anaplasia in canine meningiomas. Notably, granular cell meningiomas were negative for almost all the molecules examined, suggesting that they have a different tumor biology than other meningiomas.

  15. Anaplastic large cell lymphoma in a reconstructed breast using a silicone implant: a UK case report.

    PubMed

    Sørensen, K; Murphy, J; Lennard, A; Wadehra, V; Menon, G K; Collis, N

    2014-04-01

    We present case of Anaplastic Large Cell Lymphoma discovered as an incidental finding whilst revising an implant based breast reconstruction in a 55 year old woman, whom previously had undergone risk reduction mastectomies and immediate reconstruction. During the procedure a presumed seroma was present but this was macroscopically atypical giving a 'milky' coloured appearance with a pink tinge to it. The atypical fluid was sent for analysis and the diagnosis of ALCL confirmed. Treatment consisted of unilateral capsulectomy on the affected side and bilateral removal of implants with staging scans suggesting the disease being confined to the capsule. She remains in remission 12 months following the original procedure.

  16. Atypical Carcinoid Tumor with Anaplastic Lymphoma Kinase (ALK) Rearrangement Successfully Treated by an ALK Inhibitor.

    PubMed

    Nakajima, Masayuki; Uchiyama, Naoki; Shigemasa, Rie; Matsumura, Takeshi; Matsuoka, Ryota; Nomura, Akihiro

    This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement. A 70-year-old man developed a tumor in the left lung and multiple metastases to the lung and brain. The pathology of transbronchial biopsied specimens demonstrated an atypical carcinoid pattern. Combined with immunohistochemical findings, we diagnosed the tumor as atypical carcinoid. ALK gene rearrangement was observed by both immunohistochemical (IHC) and fluorescence in situ hybridization. He was treated with chemotherapy as first-line therapy, however, the tumor did not respond to chemotherapy. Thereafter, he was treated with crizotinib, which successfully reduced the tumors.

  17. Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case

    PubMed Central

    Gajavelli, Srikanth; Nakhla, Jonathan; Nasser, Rani; Yassari, Reza; Weidenheim, Karen M.; Graber, Jerome

    2016-01-01

    Background: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. Case Description: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. Conclusion: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature. PMID:27656320

  18. Disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural disease: case report.

    PubMed

    Kessler, Brice A; Bookhout, Christine; Jaikumar, Sivakumar; Hipps, John; Lee, Yueh Z

    2015-01-01

    We report the neuroimaging and histopathologic findings of a 12-year-old female patient with a disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural metastatic disease. These tumors may represent distinct pathology primarily seen in pediatric patients. Neuroimaging demonstrates diffuse, progressive enhancement of the leptomeninges often with interval development of intraparenchymal lesions on follow-up. Disease is typically confined to the central nervous system, though diffuse peritoneal disease was seen in our case, possibly through metastatic seeding of the abdomen via ventriculoperitoneal shunt.

  19. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

    PubMed

    Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

    2014-01-01

    The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

  20. Coming of Age: Breast Implant-Associated Anaplastic Large Cell Lymphoma After 18 Years of Investigation.

    PubMed

    Clemens, Mark W; Miranda, Roberto N

    2015-10-01

    Breast implant associated anaplastic large cell lymphoma (BIALCL) is a distinct clinical entity that can present in patients receiving either reconstructive or cosmetic breast implants. Presenting symptoms include onset of a delayed (>1 year after implantation) fluid collection, mass of the capsule, or lymphadenopathy. Treatment has progressed in recent years and most commonly includes implant removal and total resection of the tumor, including capsule, mass, and involved lymph nodes. Further research is warranted to determine potential malignant drivers, disease progression, and optimal treatment strategies in advanced disease.

  1. Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma.

    PubMed

    Wiestler, Benedikt; Capper, David; Sill, Martin; Jones, David T W; Hovestadt, Volker; Sturm, Dominik; Koelsche, Christian; Bertoni, Anna; Schweizer, Leonille; Korshunov, Andrey; Weiß, Elisa K; Schliesser, Maximilian G; Radbruch, Alexander; Herold-Mende, Christel; Roth, Patrick; Unterberg, Andreas; Hartmann, Christian; Pietsch, Torsten; Reifenberger, Guido; Lichter, Peter; Radlwimmer, Bernhard; Platten, Michael; Pfister, Stefan M; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang

    2014-10-01

    The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.

  2. A novel Patient Derived Tumorgraft model with TRAF1-ALK Anaplastic Large Cell Lymphoma translocation

    PubMed Central

    Abate, Francesco; Todaro, Maria; van der Krogt, Jo-Anne; Boi, Michela; Landra, Indira; Machiorlatti, Rodolfo; Tabbo’, Fabrizio; Messana, Katia; Barreca, Antonella; Novero, Domenico; Gaudiano, Marcello; Aliberti, Sabrina; Di Giacomo, Filomena; Tousseyn, Thomas; Lasorsa, Elena; Crescenzo, Ramona; Bessone, Luca; Ficarra, Elisa; Acquaviva, Andrea; Rinaldi, Andrea; Ponzoni, Maurilio; Longo, Dario Livio; Aime, Silvio; Cheng, Mangeng; Ruggeri, Bruce; Piccaluga, Pier Paolo; Pileri, Stefano; Tiacci, Enrico; Falini, Brunangelo; Pera-Gresely, Benet; Cerchietti, Leandro; Iqbal, Javeed; Chan, Wing C; Shultz, Leonard D.; Kwee, Ivo; Piva, Roberto; Wlodarska, Iwona; Rabadan, Raul; Bertoni, Francesco; Inghirami, Giorgio

    2016-01-01

    Although Anaplastic Large Cell Lymphomas (ALCL) carrying Anaplastic Lymphoma Kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human Patient Derived Tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and of NFkB pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells lacking PRDM1/Blimp-1 and with c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to down-regulation of p50/p52 and lymphoma growth inhibition. Moreover a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Moreover, a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, but the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable to validate the role of druggable molecules, predict therapeutic responses and are helpful tools for the implementation of patient specific therapies. PMID:25533804

  3. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy

    PubMed Central

    Webb, Thomas R; Slavish, Jake; George, Rani E; Look, A Thomas; Xue, Liquan; Jiang, Qin; Cui, Xiaoli; Rentrop, Walter B; Morris, Stephan W

    2009-01-01

    Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, was initially identified in constitutively activated oncogenic fusion forms – the most common being nucleophosmin-ALK – in anaplastic large-cell lymphomas, and subsequent studies have identified ALK fusions in diffuse large B-cell lymphomas, systemic histiocytosis, inflammatory myofibroblastic tumors, esophageal squamous cell carcinomas and non-small-cell lung carcinomas. More recently, genomic DNA amplification and protein overexpression, as well as activating point mutations, of ALK have been described in neuroblastomas. In addition to those cancers for which a causative role for aberrant ALK activity is well validated, more circumstantial links implicate the full-length, normal ALK receptor in the genesis of other malignancies – including glioblastoma and breast cancer – via a mechanism of receptor activation involving autocrine and/or paracrine growth loops with the reported ALK ligands, pleiotrophin and midkine. This review summarizes normal ALK biology, the confirmed and putative roles of ALK in the development of human cancers and efforts to target ALK using small-molecule kinase inhibitors. PMID:19275511

  4. Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri.

    PubMed

    Sugino, Toshiya; Mikami, Takeshi; Akiyama, Yukinori; Wanibuchi, Masahiko; Hasegawa, Tadashi; Mikuni, Nobuhiro

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.

  5. Design, synthesis, and biological activity of urea derivatives as anaplastic lymphoma kinase inhibitors.

    PubMed

    af Gennäs, Gustav Boije; Mologni, Luca; Ahmed, Shaheen; Rajaratnam, Mohanathas; Marin, Oriano; Lindholm, Niko; Viltadi, Michela; Gambacorti-Passerini, Carlo; Scapozza, Leonardo; Yli-Kauhaluoma, Jari

    2011-09-05

    In anaplastic large-cell lymphomas, chromosomal translocations involving the kinase domain of anaplastic lymphoma kinase (ALK), generally fused to the 5' part of the nucleophosmin gene, produce highly oncogenic ALK fusion proteins that deregulate cell cycle, apoptosis, and differentiation in these cells. Other fusion oncoproteins involving ALK, such as echinoderm microtubule-associated protein-like 4-ALK, were recently found in patients with non-small-cell lung, breast, and colorectal cancers. Recent research has focused on the development of inhibitors for targeted therapy of these ALK-positive tumors. Because kinase inhibitors that target the inactive conformation are thought to be more specific than ATP-targeted inhibitors, we investigated the possibility of using two known inhibitors, doramapimod and sorafenib, which target inactive kinases, to design new urea derivatives as ALK inhibitors. We generated a homology model of ALK in its inactive conformation complexed with doramapimod or sorafenib in its active site. The results elucidated why doramapimod is a weak inhibitor and why sorafenib does not inhibit ALK. Virtual screening of commercially available compounds using the homology model of ALK yielded candidate inhibitors, which were tested using biochemical assays. Herein we present the design, synthesis, biological activity, and structure-activity relationships of a novel series of urea compounds as potent ALK inhibitors. Some compounds showed inhibition of purified ALK in the high nanomolar range and selective antiproliferative activity on ALK-positive cells.

  6. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

    NASA Astrophysics Data System (ADS)

    Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

    2015-01-01

    Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

  7. Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma.

    PubMed

    Alcalá, Rebeca; Llombart, Beatriz; Lavernia, Javier; Traves, Víctor; Guillén, Carlos; Sanmartín, Onofre

    2016-07-01

    Breast implant-associated anaplastic large cell lymphoma (ALCL) is a newly described clinical and pathologic entity that typically presents as seroma in the fibrous scar around the implant. Less frequently, it presents as a solid peri-implant mass, and there have been no reports to date of cutaneous lesions as the presenting manifestation. We report the case of a 56-year-old woman with a history of bilateral breast reconstruction following breast cancer of the right breast who consulted with several papules on the right breast suggestive of metastasis. Histopathology showed a proliferation of large epithelioid lymphocytes with highly pleomorphic cells and nuclei. The neoplastic cells were CD15 and CD30 positive and ALK-1 negative. The epithelial markers were all negative except for epithelial membrane antigen (EMA), which was weakly positive. Molecular analysis showed monoclonal T-cell receptor γ gene rearrangement, confirming a diagnosis of breast implant-associated ALCL. The non-specific morphology of the skin lesions, the epithelioid nature of the neoplastic cells and the expression of EMA can lead to an erroneous diagnosis of skin metastases from a poorly differentiated adenocarcinoma of the breast. We recommend immunohistochemical staining for CD30 and ALK-1 for patients with breast implants who develop anaplastic lesions.

  8. Anaplastic thyroid cancer: outcome and the mutation/expression profiles of potential targets.

    PubMed

    Wu, Hao; Sun, Yue; Ye, Huihui; Yang, Shi; Lee, Stephanie L; de las Morenas, Antonio

    2015-07-01

    Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the thyroid. No effective treatment modalities are currently available. Targeted therapy against protein kinases showed promising results in preclinical studies. Our goal was to assess the mutational status of potential therapeutic targets, as well as the biomarker for immunotherapy in the clinical context. Using allele specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1 in anaplastic thyroid cancer specimens. Results were compared to clinical information and patient outcome to assess the utility of these biomarkers. There were 13 patients in our study with a median overall survival of 19 weeks. Of the 13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1 expression was seen in 3 (23 %) patients, none of them were surgical candidates due to unresectability and poor performance status. KRAS codon 12/13 and EGFR exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase inhibitors and immunotherapy may be useful adjuvant therapies for ATC.

  9. ANALYSIS OF HUMAN T-CELL LYMPHOTROPIC VIRUS IN CD25-POSITIVE-ANAPLASTIC LARGE CELL LYMPHOMAS IN CHILDREN

    PubMed Central

    Gualco, Gabriela; Chioato, Lucimara; Weiss, Lawrence M.; Harrington, William J.; Bacchi, Carlos E.

    2009-01-01

    T-cell lymphomas are rare in children. Anaplastic large cell lymphoma (ALCL) is the most common pediatric mature T-cell lymphoma, accounting for about 10-20% of all pediatric non-Hodgkin lymphoma. ALCL is now recognized as two distinct diseases, i.e., ALCL-ALK-positive (ALCL- ALK+) and ALCL-ALK-negative (ALCL- ALK-); ALK-positive ALCL presents at a younger age and has a better prognosis. The human T-cell lymphotropic virus (HTLV-1) is a retrovirus that mainly infects helper T lymphocytes and is linked to the development of adult T-cell leukemia/lymphoma (ATLL). The other type of lymphoma related to this virus family is hairy cell leukemia (HCL). Both of these neoplasms frequently express CD25 (alpha chain-IL-2 receptor). Recently, it was demonstrated that CD25 is significantly expressed in childhood ALCL (75%). In Brazil, HTLV-1 infection is considered endemic, and vertical transmission is responsible for spread to children, and it is important to point out that 90% or more of the HTLV-1 carriers remain asymptomatic. Some cases of HTLV-1-related lymphomas in adults are described as having characteristics of ALCL, but are considered to be CD30-positive subtypes of ATLL based on the virologic findings. No similar cases have been described in children, therefore we analyzed 33 cases of pediatric ALCL, both CD25-positive and CD25-negative, looking for the presence of proviral HTLV-1 DNA, by PCR. All cases corresponded to the common histological type of ALCL and were CD30-positive in virtually all neoplastic cells. ALK expression was observed in all but two cases (93.9%), while CD25 was positive in 27 cases (82%), including one of the ALCL-ALK-. There was a strong positive correlation between ALK and CD25 expression. None of the cases showed proviral HTLV-1-DNA presence. Our study concludes that ALCL in children has no relationship with HTLV-1 and the high frequency of CD25 expression must be explained by a different mechanism than that described in ATLL. PMID:19864230

  10. Successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy, radiation and surgery.

    PubMed

    Noguchi, Hitoshi; Yamashita, Hiroto; Murakami, Tsukasa; Hirai, Keisuke; Noguchi, Yasushi; Maruta, Junko; Yokoi, Tadao; Noguchi, Shiro

    2009-01-01

    Anaplastic thyroid carcinoma (ATC) is the most aggressive of thyroid cancers whose treatment is not yet established and mortality is extremely high. Recent in vitro studies have shown that valproic acid (VA), a newly identified histone deacetilase (HDAC) inhibitor, induces apoptosis, modulates differentiation gene expression of thyroid tumors and enhances the sensitivity of anaplastic cancer cell lines to doxorubicin. We report a case of successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy consisting of cisplatin and doxorubicin, external and intra-operative radiation and surgery. Tumor volume decreased by 50.7% under CT measurement and 44.6% under sonogram measurement over the course of the treatment. No significant rebound of tumor size was observed between each cycle of chemotherapy. Serial cytology performed via fine needle aspiration (FNA) presented a rapidly changing profile of cell types, starting with anaplastic and proceeding through increasingly well differentiated presentations. Only microscopic remnants of ATC cells were found in the histological examination of the resected thyroid. Ga scintigraphy and whole body PET scan six months after surgery revealed no evidence of recurrence or metastasis. As of Nov. 22, 2008, the patient is alive and disease free two years after diagnosis.

  11. Proliferating cell nuclear antigen expression in brain tumors, and its prognostic role in ependymomas: an immunohistochemical study.

    PubMed

    Schiffer, D; Chiò, A; Giordana, M T; Pezzulo, T; Vigliani, M C

    1993-01-01

    Proliferating cell nuclear antigen (PCNA)/cyclin is currently often investigated immunohistochemically in tumors as a marker of cell proliferation, but many problems remain open concerning its reliability as a prognostic factor. PCNA has been studied in a series of 123 brain tumors using the monoclonal antibody PC10. A clear intra- and inter-tumor variability of PCNA-positive nuclei has been found, but taking into account the tumor areas with the highest number of positive nuclei, a positive correlation between this number and the histological malignancy of tumors has been demonstrated. The staining intensity of nuclei was variable; very-intensely positive nuclei, counted separately, are hypothesized to represent nuclei in S-phase of the cell cycle. In ependymomas the investigation included a quantitative statistical analysis. The number of PCNA-positive nuclei correlated with cell density and mitotic index, but only very intensely positive nuclei showed a significant statistical correlation with survival. In spite of the many possibilities of wrong interpretation of PCNA expression, the most important of which is its deregulation, the method is useful in the practice for prognostic purposes. Its important advantages are the possibility of a retrospective application and a visual analysis of the proliferation potential of tumors.

  12. Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumor not otherwise specified

    PubMed Central

    Nowak, Johannes; Seidel, Carolin; Pietsch, Torsten; Alkonyi, Balint; Fuss, Taylor Laura; Friedrich, Carsten; von Hoff, Katja; Rutkowski, Stefan; Warmuth-Metz, Monika

    2015-01-01

    Background Ependymoblastoma (EBL), ependymoma (EP), and primitive neuroectodermal tumors of the central nervous system not otherwise specified (CNS-PNET NOS) are pediatric brain tumors that can be differentiated by histopathology in the clinical setting. Recently, we described specific MRI features of EBL. In this study, we compare standardized MRI characteristics of EBL with EP and CNS-PNET NOS in a series comprising 22 patients in each group. Methods All 66 centrally reviewed cases were obtained from the database of the German multicenter HIT trials. We systematically analyzed the initial MRI scans at diagnosis according to standardized criteria, and paired comparison was performed for EBL and EP, as well as for EBL and CNS-PNET NOS. Results We found differences between EBL and EP regarding age at diagnosis, MR signal intensity, tumor margin and surrounding edema, presence and size of cysts, and contrast enhancement pattern. Although MRI appearance of EBL shares many features with CNS-PNET NOS, we revealed significant differences in terms of age at diagnosis, tumor volume and localization, tumor margins, edema, and contrast enhancement. Conclusion This is the first study that systematically compares multiple parameters of MRI in pediatric EBL with findings in EP and CNS-PNET NOS. Although a definite differentiation by means of MRI alone might not be feasible in the individual case, we identify significant differences between these tumor entities. PMID:25916887

  13. ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study.

    PubMed

    Oschlies, Ilske; Lisfeld, Jasmin; Lamant, Laurence; Nakazawa, Atsuko; d'Amore, Emanuele S G; Hansson, Ulrika; Hebeda, Konnie; Simonitsch-Klupp, Ingrid; Maldyk, Jadwiga; Müllauer, Leonhard; Tinguely, Marianne; Stücker, Markus; Ledeley, Marie-Cecile; Siebert, Reiner; Reiter, Alfred; Brugières, Laurence; Klapper, Wolfram; Woessmann, Wilhelm

    2013-01-01

    Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty-three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lympho-proliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALK-protein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough

  14. Impact of 1p/19q Codeletion and Histology on Outcomes of Anaplastic Gliomas Treated With Radiation Therapy and Temozolomide

    SciTech Connect

    Speirs, Christina K.; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd A.; Tran, David D.; Linette, Gerry; Chicoine, Michael R.; Dacey, Ralph G.; Rich, Keith M.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H.; Huang, Jiayi

    2015-02-01

    Purpose: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. Methods and Materials: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. Results: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. Conclusions: RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.

  15. Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

    PubMed Central

    Mahuad, Carolina Valeria; Repáraz, María de los Ángeles Vicente; Zerga, Marta E.; Aizpurua, María Florencia; Casali, Claudia; Garate, Gonzalo

    2016-01-01

    The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy. PMID:27441079

  16. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2017-02-20

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor

  17. Genomically Driven Precision Medicine to Improve Outcomes in Anaplastic Thyroid Cancer

    PubMed Central

    Patel, Krupal; Mymryk, Joe S.; Barrett, John W.; Nichols, Anthony C.

    2014-01-01

    Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes. PMID:25276134

  18. Anaplastic carcinoma of the pancreas: Case report and literature review of reported cases in Japan

    PubMed Central

    Hoshimoto, Sojun; Matsui, Junichi; Miyata, Ryohei; Takigawa, Yutaka; Miyauchi, Jun

    2016-01-01

    We report a case of a 64-year-old woman with anaplastic carcinoma of the pancreas (ACP) with cyst formation and review 60 ACP cases reported in Japan. In 20% of cases, laboratory tests revealed severe anemia (hemoglobin level < 10.0 g/dL) and elevated leucocyte counts (> 12000/mm3), which were likely attributable to rapid tumor growth, intratumoral hemorrhage, and necrosis. Elevated serum CA19-9 levels were observed in 55% of cases. Cyst-like structures were observed on imaging in 47% of cases, and this finding appears to reflect subsequent cystic degeneration in the lesion. Macroscopically, hemorrhagic necrosis was observed in 77% of cases, and cyst formation was observed in 33% of cases. ACP should be considered when diagnosing pancreatic tumors with a cyst-like appearance, especially in the presence of severe anemia, elevated leucocyte counts, or elevated serum CA19-9 levels. PMID:27784976

  19. Implant-associated anaplastic large cell lymphoma of the breast: Insight into a poorly understood disease.

    PubMed

    Weathers, William M; Wolfswinkel, Erik M; Hatef, Daniel A; Lee, Edward I; Hollier, Larry H; Brown, Rodger H

    2013-01-01

    Implant-associated anaplastic large cell lymphoma (ALCL) is the subject of much debate in the field of plastic surgery. Only a few published cases have been reported and the rarity of the disease may make proving causality exceedingly difficult. Despite this, it is of utmost importance that full attention be devoted to this subject to ensure the safety and well-being of patients. The authors report one new case of implant-associated ALCL that recently presented to their institution. Implant-associated ALCL is a poorly understood disease. It should likely be considered its own clinical entity and categorized into two subtypes: one presenting as a seroma and the other as a distinct mass or masses. When reported, only textured implants have been associated with ALCL. The United States Food and Drug Administration and American Society of Plastic Surgeons have initiated a registry and have collected critical data to gain further understanding of this disease.

  20. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

    SciTech Connect

    De Crevoisier, Renaud . E-mail: rdecrevo@mdanderson.org; Baudin, Eric; Bachelot, Anne; Leboulleux, Sophie; Travagli, Jean-Paul; Caillou, Bernard; Schlumberger, Martin

    2004-11-15

    Purpose: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. Methods and materials: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m{sup 2}) and cisplatin (120 mg/m{sup 2}) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. Results: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. Conclusions: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.

  1. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

  2. Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

    PubMed

    Schliesser, Maximilian Georg; Claus, Rainer; Hielscher, Thomas; Grimm, Christiane; Weichenhan, Dieter; Blaes, Jonas; Wiestler, Benedikt; Hau, Peter; Schramm, Johannes; Sahm, Felix; Weiß, Elisa K; Weiler, Markus; Baer, Constance; Schmidt-Graf, Friederike; Schackert, Gabriele; Westphal, Manfred; Hertenstein, Anne; Roth, Patrick; Galldiks, Norbert; Hartmann, Christian; Pietsch, Torsten; Felsberg, Joerg; Reifenberger, Guido; Sabel, Michael Christoph; Winkler, Frank; von Deimling, Andreas; Meisner, Christoph; Vajkoczy, Peter; Platten, Michael; Weller, Michael; Plass, Christoph; Wick, Wolfgang

    2016-12-13

    The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas. Methylation of these candidate regions was validated in different independent patient cohorts revealing a set of miRNA promoter regions with prognostic relevance across data sets. Of those, miR-155 promoter methylation and miR-155 expression were negatively correlated and especially the methylation showed superior correlation with patient survival compared to established biomarkers.Functional examinations in malignant glioma cells further cemented the relevance of miR-155 for tumor cell viability with transient and stable modifications indicating an onco-miRNA activity. MiR-155 also conferred resistance towards alkylating temozolomide and radiotherapy as consequence of nuclear factor (NF)κB activation.Preconditioning glioma cells with an NFκB inhibitor reduced therapy resistance of miR-155 overexpressing cells. These cells resembled tumors with a low methylation of the miR-155 promoter and thus mir-155 or NFκB inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.

  3. Prognostic relevance of miRNA-155 methylation in anaplastic glioma

    PubMed Central

    Schliesser, Maximilian Georg; Claus, Rainer; Hielscher, Thomas; Grimm, Christiane; Weichenhan, Dieter; Blaes, Jonas; Wiestler, Benedikt; Hau, Peter; Schramm, Johannes; Sahm, Felix; Weiß, Elisa K.; Weiler, Markus; Baer, Constance; Schmidt-Graf, Friederike; Schackert, Gabriele; Westphal, Manfred; Hertenstein, Anne; Roth, Patrick; Galldiks, Norbert; Hartmann, Christian; Pietsch, Torsten; Felsberg, Joerg; Reifenberger, Guido; Sabel, Michael Christoph; Winkler, Frank; von Deimling, Andreas; Meisner, Christoph; Vajkoczy, Peter; Platten, Michael; Weller, Michael; Plass, Christoph; Wick, Wolfgang

    2016-01-01

    The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies. To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas. Methylation of these candidate regions was validated in different independent patient cohorts revealing a set of miRNA promoter regions with prognostic relevance across data sets. Of those, miR-155 promoter methylation and miR-155 expression were negatively correlated and especially the methylation showed superior correlation with patient survival compared to established biomarkers. Functional examinations in malignant glioma cells further cemented the relevance of miR-155 for tumor cell viability with transient and stable modifications indicating an onco-miRNA activity. MiR-155 also conferred resistance towards alkylating temozolomide and radiotherapy as consequence of nuclear factor (NF)κB activation. Preconditioning glioma cells with an NFκB inhibitor reduced therapy resistance of miR-155 overexpressing cells. These cells resembled tumors with a low methylation of the miR-155 promoter and thus mir-155 or NFκB inhibition may provide treatment options with a special focus on patients with IDH wild type tumors. PMID:27880937

  4. In contrast to agonist monoclonal antibodies, both C-terminal truncated form and full length form of Pleiotrophin failed to activate vertebrate ALK (anaplastic lymphoma kinase)?

    PubMed

    Mathivet, Thomas; Mazot, Pierre; Vigny, Marc

    2007-12-01

    Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase essentially and transiently expressed during development in specific regions of the central and peripheral nervous system. ALK expression persists at a lower level in the adult brain. Thus, it might play an important role in both the normal development and function of the nervous system. The nature of the cognate ligand of this receptor in vertebrates is still a matter of debate. Pleiotrophin and midkine have been proposed as ligands of ALK but several independent studies do not confirm this hypothesis. Interestingly, a recent study proposed that a C-terminal truncated form of Pleiotrophin (Pleiotrophin.15) and not the full length form (Pleiotrophin.18) promotes glioblastoma proliferation in an ALK-dependent fashion. These data were obviously a strong basis to conciliate the conflicting results so far reported in the literature. In the present study, we first purified to homogeneity the two forms of Pleiotrophin secreted by HEK 293 cells. In contrast to agonist monoclonal antibodies, both Pleiotrophin.15 and Pleiotrophin.18 failed to activate ALK in neuroblastoma and glioblastoma cells expressing this receptor. Thus, for our point of view, ALK is still an orphan receptor in vertebrates.

  5. Fine-needle aspiration cytology yield as a basis for morphological, molecular, and cytogenetic diagnosis in alk-positive anaplastic large cell lymphoma with atypical clinical presentation.

    PubMed

    Bogdanic, Maja; Ostojic Kolonic, Slobodanka; Kaic, Gordana; Kardum Paro, Mirjana Mariana; Lasan Trcic, Ruzica; Kardum-Skelin, Ika

    2017-01-01

    ALK positive anaplastic large cell lymphoma is a T-cell lymphoma usually occurring in children and young adults. It frequently involves lymph nodes and extranodal sites and is associated with favorable prognosis. A 20-year old man was admitted for painful mass in the left axilla with overlying skin redness. Clinical presentation and US findings were highly suspicious for sarcoma. Definitive diagnosis was established cytolologically and using ancillary technologies from cytological samples. Fine needle aspiration cytology of tumor mass (lymph node conglomerate and surrounding tissue) show predominance of large, pleomorphic, atypical cells with large nuclei and vacuolised cytoplasm. Atypical cells immunocytochemically were positive for LCA, CD30, CD3, EMA, and ALK; negative for CD15 and CD56. NPM-ALK transcript was detected by reverse transcriptase-polymerase chain reaction (RT-PCT). Molecular analysis of TCRß and TCRγ genes demonstrated clonal TCR genes rearrangement. Complex karyotype with multiple numerical and structural changes was found on conventional cytogenetics. These findings excluded sarcoma and corroborated the diagnosis of ALK positive ALCL. Cutaneous involvement in ALCL can clinically mimic sarcoma, especially in cases with localized disease without B symptoms. In those cases, immunostaining, PCR, and conventional cytogenetics are helpful to exclude sarcoma. Diagn. Cytopathol. 2017;45:51-54. © 2016 Wiley Periodicals, Inc.

  6. Acute spontaneous tumor lysis in anaplastic large T-cell lymphoma presenting with hyperuricemic acute renal failure.

    PubMed

    Hsu, Hsiang-Hao; Huang, Chiu-Ching

    2004-01-01

    Acute spontaneous tumor lysis (ASTL) syndrome, an extremely rare disease, requires prompt recognition and aggressive management because it is fulminant at its outset, associated with severe metabolic derangement, and potentially reversible. We describe an unusual case in which spontaneous tumor lysis occurred in anaplastic large T-cell lymphoma associated with acute uric acid nephropathy, persistent oliguria, and shock. This case contrasts markedly with previously reported cases of ASTL syndrome, which developed mainly in the pathologic type of Burkitt lymphoma. To our knowledge, this is the first reported occurrence of ASTL syndrome associated with anaplastic large T-cell type lymphoma. This report also chronicles our successful experience with continuous renal replacement therapy in the presence of compromised hemodynamic status.

  7. LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas

    PubMed Central

    Wang, Wen; Yang, Fan; Zhang, Lu; Chen, Jing; Zhao, Zheng; Wang, Haoyuan; Wu, Fan; Liang, Tingyu; Yan, Xiaoyan; Li, Jiye; Lan, Qing; Wang, Jiangfei; Zhao, Jizong

    2016-01-01

    Anaplastic glioma is Grade III and the median overall survival is about 37.6 months. However, there are still other factors that affect the prognosis for anaplastic glioma patients due to variable overall survival. So we screened four-lncRNA signature (AGAP2-AS1, TPT1-AS1, LINC01198 and MIR155HG) from the lncRNA expression profile from the GSE16011, CGGA and REMBRANDT datasets. The patients in low risk group had longer overall survival than high risk group (median OS 2208.25 vs. 591.30 days; P < 0.0001). Moreover, patients in the low risk group showed similar overall survival to Grade II patients (P = 0.1669), while the high risk group showed significant different to Grade IV (P = 0.0005) with similar trend. So based on the four-lncRNA, the anaplastic gliomas could be divided into grade II-like and grade IV-like groups. On the multivariate analysis, it showed the signature was an independent prognostic factor (P = 0.000). The expression of four lncRNAs in different grades showed that AGAP2-AS1, LINC01198 and MIR155HG were increased with tumor grade, while TPT1-AS1 was decreased. Knockdown of AGAP2-AS1 can inhibit the cell proliferation, migration and invasion, while increase the apoptosis cell rates in vitro. In conclusion, our results showed that the four-lncRNA signature has prognostic value for anaplastic glioma. Moreover, clinicians should conduct corresponding therapies to achieve best treatment with less side effects for two groups patients. PMID:27764782

  8. Sequentially Programmed Magnetic Field Therapy in the Management of Recurrent Anaplastic Astrocytoma: A Case Report and Literature Review

    PubMed Central

    Vasishta, V.G.

    2010-01-01

    Background Anaplastic astrocytomas are progressive brain tumors with a tendency to infiltrate the surrounding tissue. Recurrence is very common, with recurrent tumors being extremely refractory to existing therapies. Case Presentation: A 33-year-old woman presented with a history of an unprovoked fall, followed by seizures. An MRI scan revealed a mass in the fronto-temporo-parietal region of the brain, suggesting a primary tumor. She underwent craniotomy and surgical debulking of the tumor. The histology of the tumor tissue revealed an anaplastic astrocytoma. Follow-up MRI scans indicated the presence of a residual, rapidly progressing tumor. A 6-week course of fractionated radiation and concurrent chemotherapy with Temodar® (temozolomide capsules) did not stop tumor progression. Intervention: Due to the failure of conventional therapies in preventing rapid disease progression, the patient volunteered to undergo a 28-day course of Sequentially Programmed Magnetic Field (SPMF) therapy. Results Immediate post-therapy MRI scan showed a cessation of tumor growth, and follow-up imaging at 6, 12, 24 and 36 months revealed a gradual but steady decrease in the size of the tumor. The patient reported an alleviation of clinical symptoms and a subjective improvement in the quality of life at 6, 12, 24 and 36 months following SPMF therapy. Conclusion The remarkable improvement of this patient suggests that SPMF therapy may be a valuable option for anaplastic astrocytoma, especially in recurrent and rapidly progressing tumors. PMID:20740195

  9. A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.

    PubMed

    Okazaki, Mitsuyoshi; Makino, Isamu; Kitagawa, Hirohisa; Nakanuma, Shinichi; Hayashi, Hironori; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Ohta, Tetsuo

    2014-01-21

    We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.

  10. Anaplastic lymphoma kinase (ALK) inhibitors in the treatment of ALK-driven lung cancers.

    PubMed

    Roskoski, Robert

    2017-03-01

    Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors. Downstream signaling from the ALK fusion protein leads to the activation of the Ras/Raf/MEK/ERK1/2 cell proliferation module and the JAK/STAT cell survival pathways. Moreover, nearly two dozen ALK activating mutations are involved in the pathogenesis of childhood neuroblastomas. The occurrence of oncogenic ALK-fusion proteins, particularly in non-small cell lung cancer, has fostered considerable interest in the development of ALK inhibitors. Crizotinib was the first such inhibitor approved by the US Food and Drug Administration for the treatment of ALK-positive non-small cell lung cancer in 2011. The median time for the emergence of crizotinib drug resistance is 10.5 months after the initiation of therapy. Such resistance prompted the development of second-generation drugs including ceritinib and alectinib, which are approved for the treatment of non-small cell lung cancer. Unlike the single gatekeeper mutation that occurs in drug-resistant epidermal growth factor receptor in lung cancer, nearly a dozen different mutations in the catalytic domain of ALK fusion proteins have been discovered that result in crizotinib resistance. Crizotinib, ceritinib, and alectinib form a complex within the front cleft between the small and large lobes of an inactive ALK protein-kinase domain with a compact activation segment. These drugs are classified as type I½ B

  11. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  12. Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma

    PubMed Central

    Satoh, Shunpei; Takatori, Atsushi; Ogura, Atsushi; Kohashi, Kenichi; Souzaki, Ryota; Kinoshita, Yoshiaki; Taguchi, Tomoaki; Hossain, Md. Shamim; Ohira, Miki; Nakamura, Yohko; Nakagawara, Akira

    2016-01-01

    In neuroblastoma (NB), one of the most common paediatric solid tumours, activation of anaplastic lymphoma kinase (ALK) is often associated with poor outcomes. Although genetic studies have identified copy number alteration and nonsynonymous mutations of ALK, the regulatory mechanism of ALK signalling at protein levels is largely elusive. Neuronal leucine-rich repeat 1 (NLRR1) is a type 1 transmembrane protein that is highly expressed in unfavourable NB and potentially influences receptor tyrosine kinase signalling. Here, we showed that NLRR1 and ALK exhibited a mutually exclusive expression pattern in primary NB tissues by immunohistochemistry. Moreover, dorsal root ganglia of Nlrr1+/+ and Nlrr1−/− mice displayed the opposite expression patterns of Nlrr1 and Alk. Of interest, NLRR1 physically interacted with ALK in vitro through its extracellular region. Notably, the NLRR1 ectodomain impaired ALK phosphorylation and proliferation of ALK-mutated NB cells. A newly identified cleavage of the NLRR1 ectodomain also supported NLRR1-mediated ALK signal regulation in trans. Thus, we conclude that NLRR1 appears to be an extracellular negative regulator of ALK signalling in NB and neuronal development. Our findings may be beneficial to comprehend NB heterogeneity and to develop a novel therapy against unfavourable NB. PMID:27604320

  13. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    PubMed Central

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  14. Moesin-dependent cytoskeleton remodelling is associated with an anaplastic phenotype of pancreatic cancer.

    PubMed

    Abiatari, Ivane; Esposito, Irene; Oliveira, Tiago De; Felix, Klaus; Xin, Hong; Penzel, Roland; Giese, Thomas; Friess, Helmut; Kleeff, Jörg

    2010-05-01

    Cell motility is controlled by the dynamic cytoskeleton and its related proteins, such as members of the ezrin/radixin/moesin (ERM) family, which act as signalling molecules inducing cytoskeleton remodelling. Although ERM proteins have been identified as important factors in various malignancies, functional redundancy between these proteins has hindered the dissection of their individual contribution. The aim of the present study was to analyse the functional role of moesin in pancreatic malignancies. Cancer cells of different malignant lesions of human and transgenic mice pancreata were evaluated by immunohistochemistry. For functional analysis, cell growth, adhesion and invasion assays were carried out after transient and stable knock-down of moesin expression in pancreatic cancer cells. In vivo tumourigenicity was determined using orthotopic and metastatic mouse tumour models. We now show that moesin knock-down increases migration, invasion and metastasis and influences extracellular matrix organization of pancreatic cancer. Moesin-regulated migratory activities of pancreatic cancer cells were in part promoted through cellular translocation of beta-catenin, and re-distribution and organization of the cytoskeleton. Analysis of human and different transgenic mouse pancreatic cancers demonstrated that moesin is a phenotypic marker for anaplastic carcinoma, suggesting that this ERM protein plays a specific role in pancreatic carcinogenesis.

  15. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance

    PubMed Central

    Song, Zilan; Wang, Meining; Zhang, Ao

    2015-01-01

    The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b]carbazol-11(6H)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmol/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L1196M, F1174L, R1275Q and C1156Y. PMID:26579422

  16. Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

    PubMed Central

    KURATA, KENTO; ONODA, NAOYOSHI; NODA, SATORU; KASHIWAGI, SHINICHIRO; ASANO, YUKA; KAWAJIRI, HIDEMI; TAKASHIMA, TSUTOMU; TANAKA, SAYAKA; OHSAWA, MASAHIKO; HIRAKAWA, KOSEI

    2015-01-01

    The protein nestin, a neuronal stem cell marker, has been reported to indicate a poor prognosis in various tumours. Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its molecular background has not been identified. The present study evaluated the expression of nestin and its significance in ATC. Tissue samples from 23 patients with ATC were subjected to immunohistochemical staining and the staining intensity of nestin in the cytoplasm was evaluated. The expression of nestin in the tumour cytoplasm was confirmed in 6 of the 23 tissue samples (26.1%). Between the nestin-positive group (n=6) and the nestin-negative group (n=17), there were no significant differences in the clinicopathological factors of the patients. However, the nestin-positive group exhibited significantly worse prognoses than the nestin-negative group (median survival time, 86.5 vs. 306 days; P<0.01, log-rank test). The multivariate analysis indicated that nestin expression was a prognostic indicator for the ATC patients (hazard ratio, 5.59; 95% confidence interval, 1.63–19.50; P<0.01), which is independent of the known clinical indicators. Nestin expression has the potential to be an independent indicator of a poor prognosis for patients with ATC. PMID:26622582

  17. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

    PubMed Central

    Chen, Xueyan; Soma, Lorinda A; Fromm, Jonathan R

    2014-01-01

    Despite the relative success of chemotherapy for Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD)30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs) appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE). It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two Phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA) granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies. PMID:24379682

  18. Silicone implant and primary breast ALK1-negative anaplastic large cell lymphoma, fact or fiction?

    PubMed Central

    Li, Shiyong; Lee, Andrew K

    2010-01-01

    The safety of silicone-based implant for mammoplasty has been debated for decades. A series of anecdotal case reports and a recent epidemiological case-control study have suggested a possible association between silicone implant and the development of primary breast ALK1-negative anaplastic large cell lymphoma (ALCL), a rare type of peripheral T-cell lymphoma. In this report, we describe an additional case of primary breast ALK1-negative ALCL in the fibrous capsule and cystic fluid of silicone breast implant in a 58 year old woman who underwent breast reconstructive surgery after lumpectomy for her infiltrating breast adenocarcinoma. Morphologically and immunohistochemically, the lymphoma cells may be confused with recurrent infiltrating breast adenocarcinoma or other non-hematolymphoid malignancies. Molecular studies were needed to determine T-lineage differentiation of the malignant lymphoma cells. We will also review the case reports and case series published in the English literature and discuss our current understanding of silicone implant in primary breast ALK1-negative ALCL. PMID:19918336

  19. Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells.

    PubMed

    Allegri, Lorenzo; Baldan, Federica; Mio, Catia; Puppin, Cinzia; Russo, Diego; Kryštof, Vladimir; Damante, Giuseppe

    2016-04-01

    Anaplastic thyroid carcinoma (ATC) is an extremely aggressive human malignancy characterized by a marked degree of invasiveness, absense of features of thyroid differentiation and resistance to current medical treatment. It is well known that ATCs are characterized by deregulation of genes related to cell cycle regulation, i.e., cyclin-dependent kinases (CDKs) and endogenous cyclin-dependent kinase inhibitors (CDKIs). Therefore, in the present study, the effect of a novel exogenous cyclin-dependent kinase inhibitor, BP-14, was investigated in three human ATC cell lines. The ATC-derived cell lines FRO, SW1736 and 8505C were treated with BP-14 alone or in combination with the mTOR inhibitor everolimus. In all ATC cell lines, treatment with BP-14 decreased cell viability and, in two of them, BP-14 modified expression of genes involved in epithelial-mesenchymal transition. Thus, our data indicate that BP-14 is a potential new compound effective against ATC. Combined treatment with BP-14 and the mTOR inhibitor everolimus had a strong synergistic effect on cell viability in all three cell lines, suggesting that the combined used of CDK and mTOR inhibitors may be a useful strategy for ATC treatment.

  20. The role of chemotherapy for pure and mixed anaplastic oligodendroglial tumors.

    PubMed

    Dunbar, Erin M

    2009-08-01

    Pure and mixed anaplastic oligodendrogliomas (AO/mixed-AOs) remain terminal primary brain tumors, without a defined optimal initial therapy, and without sufficiently active and tolerable therapies at recurrence/progression (R/P). Very heterogeneous international therapy recommendations remain. Historical advances have resulted in only modest improvements in outcome. AO/mixed-AOs with 1p/19q co-deletion are prognostically favorable, regardless of therapy, and must be identified as early as possible. Following resection, outcome data on initial therapy with radiation (RT) remain the most mature, although controversies regarding its true toxicities and optimal timing continue. Recently, the landmark RTOG 9402 and EORTC 26951 trials showed that the addition of Procarbazine, CCNU, Vincristine chemotherapy to RT, at anytime during initial therapy, prolongs progression-free survival, but not survival, and not without moderate toxicity. Despite a lack of definitive evidence, this strategy has commonly been extrapolated to Temozolomide. Chemo-sensitivity of AO/mixed-AOs provides the rationale for the chemotherapy-only strategies being explored. In the setting of recurrence/progression (R/P), chemotherapy, small molecule (targeted), biologic, and other strategies have been relatively disappointing, toxic, and cumbersome. Partly secondary to biases regarding the relative toxicities of tumor burden vs. treatment effect, therapy remains highly individualized. Future international research must prospectively evaluate health-related quality of life, toxicity, and molecular genetic markers.

  1. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  2. Anaplastic lymphoma kinase aberrations correlate with metastatic features in pediatric rhabdomyosarcoma

    PubMed Central

    Villa, Raffaella; Collini, Paola; Alaggio, Rita; Zin, Angelica; Bonvini, Paolo; Antonescu, Cristina R; Boldrini, Renata; Caserini, Roberto; Moro, Massimo; Centonze, Giovanni; Meazza, Cristina; Massimino, Maura; Bergamaschi, Luca; Luksch, Roberto; Chiaravalli, Stefano; Bisogno, Gianni; Zaffaroni, Nadia; Daidone, MariaGrazia

    2016-01-01

    Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches. Moreover, to get insight into its possible therapeutic relevance, effects of ALK silencing on cell proliferation, invasion and apoptosis were studied in RMS cells. ALK IHC positivity was significantly correlated with gene copy number gain, the alveolar subtype, PAX3/7-FOXO1 rearrangements, the presence of metastasis at diagnosis and a worse overall outcome. Furthermore, EML4-ALK fusion gene associated with higher protein expression was identified in an embryonal RMS. ALK silencing in RH30 ALK positive cells strongly inhibited invasion capability. Overall, our data suggest a potential role of ALK in pediatric RMS. PMID:27385213

  3. Breast Implant Informed Consent Should Include the Risk of Anaplastic Large Cell Lymphoma.

    PubMed

    Clemens, Mark W; Miranda, Roberto N; Butler, Charles E

    2016-04-01

    Breast implant-associated anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma arising around breast implants. Public awareness has increased following a safety communication warning of the association of breast implant-associated ALCL by the U.S. Food and Drug Administration in 2011. Difficulty with determining an accurate assessment of risk, including diagnosis, or standardized treatment regimen has led surgeons to commonly omit preoperative discussion of this rare and frequently misunderstood cancer. Risk disclosure is a form of respect for patient autonomy, and informed consent has positive practical and moral consequences for the practice of plastic surgery. A model of breast implant-associated ALCL informed consent implementation and health care provider education are reviewed with 1-year process follow-up at a tertiary cancer center. Breast implant-associated ALCL should be included during preoperative counseling on the risks of breast implantation when obtaining informed consent. Pertinent aspects of decision-making include disease awareness, presenting symptoms, and resources for concerned patients. Education of health care professionals and provision of patient-focused materials ensures effectiveness of the informed consent process.

  4. Intracranial large vessel vasculopathy and anaplastic meningioma 19 years after cranial irradiation for acute lymphoblastic leukaemia.

    PubMed

    Foreman, N K; Laitt, R D; Chambers, E J; Duncan, A W; Cummins, B H

    1995-04-01

    A child was diagnosed in 1969 as having acute lymphoblastic leukaemia (ALL) and received chemotherapy. On bone marrow relapse in 1973, he was treated with cranial irradiation (20 Gy) in addition to chemotherapy. He continues in complete remission 19 years after his relapse. At age 25 years, he presented with headaches and left hemiparesis. Computerised tomograph demonstrated a large, enhancing right-sided intracranial tumour. Angiography was performed and showed the right internal carotid artery was occluded. Most of the right hemisphere was supplied from the external carotid via the middle meningeal artery. The left posterior cerebral artery and the left anterior cerebral artery were absent presumably as a result of radiation-induced arteritis. A resection of an anaplastic meningioma arising from the right sphenoidal ridge was achieved. There was a rapid improvement in function and he returned to work. Vasculopathy of the large intracranial arteries has been described after high dose radiation. It may occur as in this case after moderate dose radiation. There is a correlation with meningioma. There is a possibility that large artery vasculopathy will be present in a proportion of patients irradiated for ALL. The long lag time between irradiation and the development of meningioma may mean that, as survivors of childhood ALL enter their third decade since cure, this tumour may be seen increasingly.

  5. Giant cells in anaplastic mammary carcinoma of the dog and cat.

    PubMed

    Della Salda, L; Sarli, G; Benazzi, C; Marcato, P S

    1993-11-01

    Four uncommon anaplastic mammary carcinomas containing numerous giant cells are described in three dogs and one cat. The giant cells of all cases were studied by means of monoclonal and polyclonal antibodies to detect epithelial (carcinoembryonic antigen and keratin) and mesenchymal (vimentin, lysozyme and S-100 protein) differentiation. Most of them proved to have an epithelial immunophenotype. Ultrastructurally, scattered bundles of tonofilaments but no lysosome-like bodies could be detected. One tumour had an additional, different type of giant cell, which had a benign multinucleated osteoclast-like appearance, gave positive staining for acid phosphatase, had a histiocytic-stromal immunohistochemical pattern, and was, ultrastructurally, multinucleate with irregular folds and no evidence of tonofilaments. In one case some giant cells had an epithelial immunophenotype and others a stromal immunophenotype, even though their histological and ultrastructural features were the same. In the least histologically differentiated tumour the giant cells presented a coexpression of intermediate filaments. This supported the theory that there might be a stem cell origin for most canine mammary tumours.

  6. Ethanol activates midkine and anaplastic lymphoma kinase signaling in neuroblastoma cells and in the brain.

    PubMed

    He, Donghong; Chen, Hu; Muramatsu, Hisako; Lasek, Amy W

    2015-11-01

    Alcohol engages signaling pathways in the brain. Midkine (MDK) is a neurotrophic factor that is over-expressed in the prefrontal cortex of alcoholics. MDK and one of its receptors, anaplastic lymphoma kinase (ALK), also regulate behavioral responses to ethanol in mice. The goal of this study was to determine whether MDK and ALK expression and signaling are activated by ethanol. We found that ethanol treatment of neuroblastoma cells increased MDK and ALK expression. We also assessed activation of ALK by ethanol in cells and found that ALK and ALK-dependent extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) phosphorylation increased rapidly with ethanol exposure. Similarly, treatment of cells with recombinant MDK protein increased ALK, ERK and STAT3 phosphorylation, suggesting that ethanol may utilize MDK to activate ALK signaling. In support of this, transfection of cells with MDK siRNAs attenuated ALK signaling in response to ethanol. Ethanol also activates ERK signaling in the brain. We found that inhibition of ALK or knockout of MDK attenuated ethanol-induced ERK phosphorylation in mouse amygdala. These results demonstrate that ethanol engages MDK and ALK signaling, which has important consequences for alcohol-induced neurotoxicity and the regulation of behaviors related to alcohol abuse.

  7. Anaplastic T large cell lymphoma diagnosed by exfoliative cytology in a post renal transplant patient.

    PubMed

    Treaba, Diana; Assad, Lina; Goldberg, Cathryn; Loew, Jerome; Reddy, Vijaya B; Kluskens, Larry; Gattuso, Paolo

    2002-07-01

    In the last two decades posttransplant lymphoproliferative disorders (PTLDs) have been recognized as a complication of organ transplantation with immunosuppression. The reported incidence of PTLDs in renal transplant patients ranges between 0.3-3% (Birkeland et al., Transplantation 1999;67:876-881). In contrast to the reported incidence of PTLDs in post bone marrow transplant, it is 1% in HLA-matched recipients and up to 20% in HLA mismatched T-cell depleted bone marrow recipients (Curtis et al., Blood 1996;94:2208-2216). In cardiac transplant recipients the reported incidence of PTLDs is between 1.8-9.8 (Mihalov et al., Clin Transplant 1996;10:248-255). PTLDs are predominately extranodal. They have varied morphologic patterns and clonality, but almost all are associated with Epstein-Barr virus (EBV). The vast majority are of B cell lineage; only about 10% are of T-cell origin. We report a T-cell anaplastic large cell lymphoma (ALCL) presenting with bilateral pleural effusion and liver involvement in a renal transplant recipient.

  8. Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall.

    PubMed

    Ramdial, Pratistadevi K; Sing, Yetish; Naicker, Shaun; Calonje, Eduardo; Sewram, Vikash; Singh, Bhugwan

    2011-04-01

    Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.

  9. Microsurgical management of pediatric ependymomas of the fourth ventricle via the trans-cerebellomedullary fissure approach: A review of 26 cases

    PubMed Central

    QIU, BO; WANG, YONG; WANG, WEI; WANG, CHAO; WU, PENGFEI; BAO, YIJUN; OU, SHAOWU; GUO, ZONGZE; WANG, YUNJIE

    2016-01-01

    In the present study, the microsurgical management of 26 ependymomas of the fourth ventricle in children via the trans-cerebellomedullary fissure (CMF) approach was reviewed and evaluated. Clinical data were obtained from 26 ependymomas of the fourth ventricle treated with microsurgery using the trans-CMF approach from March 2006 to September 2010 at the Department of Neurosurgery of The First Affiliated Hospital of China Medical University (Shenyang, China). These data were collected and analyzed. Suboccipital median posterior fossa craniotomy and trans-CMF approach were performed in all cases for the microsurgical removal of the tumors. An additional incision was performed in the inferior medullary velum of 5 patients, in order to obtain adequate exposure of the tumors. As a result, all tumors were well exposed during surgery. Gross total resection (GTR) was achieved in 22 cases, near total resection (NTR) in 3 cases and subtotal resection (STR) in 1 case. All excised tumors were pathologically confirmed. No mortality occurred intraoperatively, and no patient presented with mutism or any other surgery-related complications. One patient suffered from postoperative hydrocephalus and received ventriculoperitoneal shunting, which relieved the symptoms. Over the 3.0–7.5-year follow-up period (mean, 4.8 years), tumor relapse occurred in 1 case with GTR, 2 cases with NTR and 1 case with STR. In total, 3 patients succumbed to tumor relapse and 4 were lost to follow-up. According to the literature and the clinical experience of the present authors, the trans-CMF approach provides safe and sufficient access to the fourth ventricle without the requirement of an incision in the inferior vermis. This approach prevents damage to the normal cerebellum and improves the surgical outcome. Tumor removal, restoration of cerebrospinal fluid circulation and preservation of brainstem function are factors that should be taken into consideration during surgery. For patients with

  10. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.

    PubMed

    Reuss, David E; Mamatjan, Yasin; Schrimpf, Daniel; Capper, David; Hovestadt, Volker; Kratz, Annekathrin; Sahm, Felix; Koelsche, Christian; Korshunov, Andrey; Olar, Adriana; Hartmann, Christian; Reijneveld, Jaap C; Wesseling, Pieter; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Herold-Mende, Christel; Aldape, Kenneth; von Deimling, Andreas

    2015-06-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A II(WHO2007)) and anaplastic astrocytoma WHO grade III (AA III(WHO2007)). Patients with A II(WHO2007) are significantly younger and survive significantly longer than those with AA III(WHO2007). So far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A II(IDHmut), 562 AA III(IDHmut) and 115 GBM(IDHmut) have been examined for age distribution and survival. In all three series patients with A II(IDHmut )and AA III(IDHmut) were of identical age at presentation of disease (36-37 years) and the difference in survival between grades was much less (10.9 years for A II(IDHmut), 9.3 years for AA III(IDHmut)) than that reported for A II(WHO2007) versus AA III(WHO2007). Our analyses imply that the differences in age and survival between A II(WHO2007) and AA III(WHO2007) predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.

  11. Treatment of Primary Cutaneous CD30+ Anaplastic Large-Cell Lymphoma With Radiation Therapy

    SciTech Connect

    Yu, James B.; McNiff, Jennifer M.; Lund, Molly W.; Wilson, Lynn D.

    2008-04-01

    Purpose: Primary cutaneous CD30+ anaplastic large-cell lymphoma (CALCL) is a relatively rare and indolent variant of cutaneous T-cell lymphoma (CTCL). This report examines the response of localized disease to radiation alone. Methods: The Yale Cancer Center records were examined, and all patients with CTCL from January 1, 2001, to September 1, 2006, evaluated in the Department of Therapeutic Radiology were identified. Only those patients with localized or single CALCL lesions, no clinical evidence or history of lymphomatoid papulosis, no history of other CTCLs, no history of other skin disorders, lack of lymph node involvement, unambiguous pathology reports, and treatment with radiation alone were included. Results: Eight patients were identified. Median age was 67 years, and gender was split evenly. Patients received radiation ranging from 34 to 44 Gy in 2-Gy fractions. Most patients (5 of 8) received 40 Gy, using 6 to 9 MeV electrons with 0.5 to 2 cm of bolus. All patients had a complete response. All patients were without evidence of disease at the most recent follow-up (median follow-up, 12 months). Radiation therapy was well tolerated, and the only recorded toxicity was Grade I to II dermatitis. Conclusions: Radiation therapy alone for localized CALCL is very well tolerated and clinical response is excellent. A dose of 40 Gy in 2-Gy fractions seems to be well tolerated and effective in inducing a complete response. Lower doses may be effective in achieving the same result, but data are not available. Longer follow-up is necessary before conclusions regarding durable disease-free survival can be made.

  12. Targeting TGF-β1 suppresses survival of and invasion by anaplastic thyroid carcinoma cells

    PubMed Central

    Sun, Wenhai; Xu, Yanyan; Zhao, Cheng; Hao, Fengyun; Chen, Dong; Guan, Jinping; Zhang, Kejun

    2017-01-01

    Background and aims: Overexpression of transforming growth factor (TGF)-β1 has been implicated in promoting cell survival, migration and invasion in many cancers, including anaplastic thyroid cancer (ATC). In the present study, we studied the effect of suppressing TGF-β1 by RNA silencing on the survival, invasion and metastasis of ATC cells. Methods: Small interfering RNA (siRNA) constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the ATC cell line, 8505C. The cells were used in several in vitro assays, including migration, invasion, survival rate, colony formation and apoptosis. A wound healing assay was used to determine the migration of cells in culture and a Boyden chamber transwell assay was used for invasion. Further, clones were used in an in vivo mouse model to study the kinetics of tumor growth and metastatic growth in lungs. Results: Targeting TGF-β1 expression in 8505C cells caused a 70% decrease in migration and a 78% decrease in invasion, as well as a 68% decrease in proliferation and a 19% increase in apoptosis in vitro. The growth of primary tumors in vivo was also inhibited when compared with parental 8505C cells; however, the number of mice bearing lung metastases was not significantly decreased. Conclusions: Targeting TGF-β1 may be effective in inhibiting primary tumor formation, but not metastasis, by ATC cells. TGF-β1 inhibition in combination with other tumor-targeted therapies may be more effective in inhibiting ATC. PMID:28386367

  13. Anaplastic large cell lymphoma associated with breast implants: a report of 13 cases.

    PubMed

    Aladily, Tariq N; Medeiros, L Jeffrey; Amin, Mitual B; Haideri, Nisreen; Ye, Dongjiu; Azevedo, Sergio J; Jorgensen, Jeffrey L; de Peralta-Venturina, Mariza; Mustafa, Eid B; Young, Ken H; You, M James; Fayad, Luis E; Blenc, Ann Marie; Miranda, Roberto N

    2012-07-01

    We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with breast implants. Patient age ranged from 39 to 68 years, and the interval from implant to ALCL was 4 to 29 years. All tumors were composed of large, pleomorphic cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell receptor γ-chain rearrangements. Two patient subgroups were identified. Ten patients presented with effusion surrounded by fibrous capsule without a grossly identifiable tumor mass. Nine patients had stage I and 1 had stage II disease. Eight patients underwent implant removal and capsulectomy. Four patients received chemotherapy and 4 radiation therapy. All patients were alive without disease at last follow-up. A second subgroup of 3 patients had effusion and a distinct mass adjacent to the implant. One patient had stage I and 2 stage II disease. One patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1-year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis of ALCL associated with breast implant. Two patients received chemotherapy and 1 radiation therapy. Two patients died 2 and 12 years after diagnosis, respectively. We conclude that the clinical behavior of ALCL associated with breast implants is heterogeneous. Patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30 lymphoproliferative disorder of skin. In contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis.

  14. A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection

    PubMed Central

    Abe, Tomoyuki; Amano, Hironobu; Hanada, Keiji; Okazaki, Akihisa; Yonehara, Shuji; Kuranishi, Fumito; Nakahara, Masahiro; Kuroda, Yoshinori; Noriyuki, Toshio

    2016-01-01

    Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed. PMID:27446572

  15. Genetic inhibition of Anaplastic Lymphoma Kinase rescues cognitive impairments in Neurofibromatosis 1 mutant mice.

    PubMed

    Weiss, Joseph B; Weber, Sydney J; Torres, Eileen Ruth S; Marzulla, Tessa; Raber, Jacob

    2017-03-15

    Heterozygous Neurofibromatosis 1 (NF1) loss of function mutations occur in approximately 90% of patients with neurofibromatosis. A major, disabling phenotypic consequence of reduced NF1 function is cognitive impairment; a possibly related behavioral phenotype is impaired sleep. Recent results in Drosophila have demonstrated a genetic interaction between Anaplastic Lymphoma Kinase (Alk) and NF1 for both associative learning and sleep. Inhibition of Alk improves associative learning and sleep in heterozygous NF1 mutant flies. The results in Drosophila provide a strong motivation to investigate NF1/Alk genetic interactions in mice. In Drosophila, activation of Alk by its ligand, Jelly belly (Jeb), is the physiologically relevant target of negative regulation by NF1. Therefore, we tested whether genetic inhibition of Alk in heterozygous NF1 mutant mice attenuates or rescues cognitive impairments in mice. Our results are consistent with the hypothesis that NF1 functions in mice biochemically to inhibit signaling from Alk through Ras. The cognitive phenotypes observed in heterozygous NF1 mutant mice are rescued or ameliorated by genetic inhibition of Alk activity. In two tests of hippocampus-dependent learning, the Morris water maze and extinction of contextual fear, mutation of one or both alleles of Alk was sufficient to improve performance to wild type or near wild type levels in NF1-/+ mice. In addition, in NF1 mice genetic inhibition of Alk improves circadian activity levels. These data are intriguing in light of the circadian alterations seen in NF1 patients and indicate that inhibition of Alk activity may cognitively benefit patients with Neurofibromatosis 1.

  16. 2-methoxyestradiol induces apoptosis in cultured human anaplastic thyroid carcinoma cells.

    PubMed

    Roswall, Pernilla; Bu, Shizhong; Rubin, Kristofer; Landström, Maréne; Heldin, Nils-Erik

    2006-02-01

    Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors in humans, and currently there is no effective treatment. In the present study we investigated the effect of an endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), on the growth of human ATC cells. 2-ME treatment had a strong growth inhibitory effect on five human ATC cell lines (HTh7, HTh 74, HTh83, C643, and SW1736), but showed no effect on one cell line (KAT-4). Cell cycle analysis of the growth-inhibited cells showed that 2-ME induced a G2/M-arrest, followed by an increased fraction of cells in sub-G1. Analysis of internucleosomal DNA laddering as well as DNA fragmentation in a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a high number of cells undergoing apoptosis after 2-ME treatment. An increased activation of caspase-3 and caspase-8 by 2-ME was observed, and inhibition of caspase-3 decreased the apoptotic effect. Addition of 2-ME increased activity of p38 mitogen-activated protein kinase (MAPK) in the sensitive HTh7 as well as the refractory KAT-4 cells, however, activation of stress-activated protein kinase/c-jun aminoterminal kinase (SAPK/JNK) was seen only in the HTh7 cells. Inhibitors of p38 MAPK and SAPK/JNK significantly attenuated the 2-ME effect. Taken together, our data demonstrate an antiproliferative and apoptotic effect of 2-ME on ATC cells involving activation of MAPKs.

  17. Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

    PubMed

    Gómez Sáez, José Manuel; Jiménez-Fonseca, Paula; Santamaría Sandi, Javier; Capdevila Castillón, Jaume; Navarro González, Elena; Zafón Llopis, Carles; Ramón Y Cajal Asensio, Teresa; Riesco Eizaguirre, Garcilaso; Grande Pulido, Enrique; Galofré Ferrater, Juan Carlos

    2015-03-01

    Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean

  18. Single Agent Nanoparticle for Radiotherapy and Radio-Photothermal Therapy in Anaplastic Thyroid Cancer

    PubMed Central

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y.; Li, Chun

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. PMID:25913249

  19. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population

    PubMed Central

    Wu, Jian; Guo, Lei; Qiu, Tian; Ling, Yun; Shan, Ling; Zhou, Haitao; Zhao, Dongbing; Wang, Jian; Liang, Jianwei; Zhao, Jianjun; Jiao, Yuchen; Lu, Ning; Zhao, Hong

    2015-01-01

    Background Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients. Patients and Methods Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner. Results Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4–ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing. Conclusions The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy. PMID:26678488

  20. Effects of selective inhibitors of Aurora kinases on anaplastic thyroid carcinoma cell lines.

    PubMed

    Baldini, Enke; Tuccilli, Chiara; Prinzi, Natalie; Sorrenti, Salvatore; Antonelli, Alessandro; Gnessi, Lucio; Morrone, Stefania; Moretti, Costanzo; Bononi, Marco; Arlot-Bonnemains, Yannick; D'Armiento, Massimino; Ulisse, Salvatore

    2014-10-01

    Aurora kinases are serine/threonine kinases that play an essential role in cell division. Their aberrant expression and/or function induce severe mitotic abnormalities, resulting in either cell death or aneuploidy. Overexpression of Aurora kinases is often found in several malignancies, among which is anaplastic thyroid carcinoma (ATC). We have previously demonstrated the in vitro efficacy of Aurora kinase inhibitors in restraining cell growth and survival of different ATC cell lines. In this study, we sought to establish which Aurora might represent the preferential drug target for ATC. To this end, the effects of two selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) on four human ATC cell lines (CAL-62, BHT-101, 8305C, and 8505C) were analysed. Both inhibitors reduced cell proliferation in a time- and dose-dependent manner, with IC50 ranges of 44.3-134.2 nM for MLN8237 and of 9.2-461.3 nM for AZD1152. Immunofluorescence experiments and time-lapse videomicroscopy yielded evidence that each inhibitor induced distinct mitotic phenotypes, but both of them prevented the completion of cytokinesis. As a result, poliploidy increased in all AZD1152-treated cells, and in two out of four cell lines treated with MLN8237. Apoptosis was induced in all the cells by MLN8237, and in BHT-101, 8305C, and 8505C by AZD1152, while CAL-62 exposed to AZD1152 died through necrosis after multiple rounds of endoreplication. Both inhibitors were capable of blocking anchorage-independent cell growth. In conclusion, we demonstrated that either Aurora-A or Aurora-B might represent therapeutic targets for the ATC treatment, but inhibition of Aurora-A appears more effective for suppressing ATC cell proliferation and for inducing the apoptotic pathway.

  1. Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer.

    PubMed

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y; Li, Chun

    2015-07-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[(64)Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[(64)Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC.

  2. CD13-positive anaplastic large cell lymphoma of T-cell origin--a diagnostic and histogenetic problem.

    PubMed

    Popnikolov, N K; Payne, D A; Hudnall, S D; Hawkins, H K; Kumar, M; Norris, B A; Elghetany, M T

    2000-12-01

    The expression of myelomonocytic-associated antigens in anaplastic large cell lymphomas (ALCLs), particularly those presenting in extranodal sites, can make their distinction from extramedullary myeloid cell tumors (EMCTs) or histiocytic tumors problematic. Yet, this distinction is clinically significant because of its therapeutic and prognostic implications. Herein, we describe a case of extranodal anaplastic lymphoma kinase-positive CD30-positive ALCL of T-cell origin in a 12-year-old boy, which was initially called an EMCT because of the expression of CD13 and HLA-DR detected by flow cytometry and the absence of other T-cell-related surface markers. However, the detection of cytoplasmic CD3 by flow cytometry prompted further studies. The tumor was composed of large cells with abundant slightly eosinophilic vacuolated cytoplasm and ovoid or reniform nuclei with a few small nucleoli. Using immunohistochemistry, the tumor was positive for CD45, CD30, CD45RO, and CD43 with a strong cytoplasmic and nuclear anaplastic lymphoma kinase stain. The tumor cells showed a T-cell clonal genotype. Electron microscopy revealed no ultrastructural features of myelomonocytic or histiocytic origin. The patient responded well to the chemotherapy and was in complete remission for 10 months at the time of submission of this manuscript. Review of the literature showed inconsistencies regarding the diagnosis, nomenclature, and, therefore, treatment and prognosis of these tumors. In addition, the CD13 expression in ALCL raises some histogenetic questions and may indicate origin from a pluripotent stem cell, misprogramming during malignant transformation, or a microenvironmental effect on lymphoid cell expression of surface antigens. Therefore, ALCL should be considered in the differential diagnosis of EMCTs or histiocytic tumors, particularly when surface marker lineage assignment is ambiguous.

  3. 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Other Thyroid Cancers: Medullary, Anaplastic, Lymphoma and So Forth

    PubMed Central

    Araz, Mine; Çayır, Derya

    2017-01-01

    Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) is used in staging, restaging, and evaluation of therapy response in many cancers as well as differentiated thyroid carcinomas especially in non-iodine avid variants. Its potential in less frequent thyroid tumors like medullary, anaplastic thyroid cancers, thyroid lymphoma and metastatic tumors of the thyroid however, is not well established yet. The aim of this review is to provide an overview on the recent applications and indications of 18F-FDG PET/CT in these tumors and to focus on the controversies in the clinical setting. PMID:28291004

  4. Bone involvement and abcess formation by neutrophil-rich CD30+ anaplastic large-cell lymphoma mimicking skeletal infection in an AIDS patient.

    PubMed

    Mira, José A; Fernández-Alonso, Jorge; Macías, Juan; Sáez, Carmen; Japón, Miguel A; Pereda, Teresa; Pineda, Juan A

    2003-07-01

    Neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) is a rare pathological entity without distinct clinical behavior. Twelve cases of neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) have been reported, three of them were HIV-infected patients. All these reports stressed the presence of neutrophil infiltration as a new morphologic feature of CD30+ ALCL. Only one case of cutaneous involvement presented with microabscess formation. We describe a case of neutrophil-rich CD30+ ALCL in an AIDS patient with a clinical picture determined by the massive neutrophil infiltration of the tumor without necrosis nor local infection, but with the formation of abscesses.

  5. Childhood Ependymoma Treatment

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  6. Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer

    PubMed Central

    Akaishi, Junko; Onda, Masamitsu; Okamoto, Junichi; Miyamoto, Shizuyo; Nagahama, Mitsuji; Ito, Kouichi; Yoshida, Akira; Shimizu, Kazuo

    2006-01-01

    Background Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII)-like 4 (TCEAL4), encodes a member of the transcription elongation factor A (SII)-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously. Methods To investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue. Results Expression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested. Conclusion To our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required. PMID:17076909

  7. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.

    PubMed

    Huang, Wei-Sheng; Liu, Shuangying; Zou, Dong; Thomas, Mathew; Wang, Yihan; Zhou, Tianjun; Romero, Jan; Kohlmann, Anna; Li, Feng; Qi, Jiwei; Cai, Lisi; Dwight, Timothy A; Xu, Yongjin; Xu, Rongsong; Dodd, Rory; Toms, Angela; Parillon, Lois; Lu, Xiaohui; Anjum, Rana; Zhang, Sen; Wang, Frank; Keats, Jeffrey; Wardwell, Scott D; Ning, Yaoyu; Xu, Qihong; Moran, Lauren E; Mohemmad, Qurish K; Jang, Hyun Gyung; Clackson, Tim; Narasimhan, Narayana I; Rivera, Victor M; Zhu, Xiaotian; Dalgarno, David; Shakespeare, William C

    2016-05-26

    In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

  8. Granulocyte Colony-stimulating Factor Producing Anaplastic Carcinoma of the Pancreas: Case Report and Review of the Literature.

    PubMed

    Vinzens, Sarah; Zindel, Joel; Zweifel, Martin; Rau, Tilman; Gloor, Beat; Wochner, Annette

    2017-01-01

    We report on the case of a 67-year-old man with granulocyte colony-stimulating factor (G-CSF) producing anaplastic carcinoma of the pancreas. Preoperative routine tests revealed an elevated white blood cell (WBC) count of 25.2 G/l, consisting almost exclusively of neutrophilic granulocytes (23.31 G/l) with a predominance of segmented neutrophils (78% of all neutrophilic granulocytes), and elevated levels of C-reactive protein at 87 mg/l. Upon surgery, local tumour infiltration was more extensive than expected from preoperative imaging. However, no peritoneal dissemination was found and curative resection was attempted. Only seven days after the operation, signs of relapse were seen upon computed tomograpy. Histology revealed an undifferentiated anaplastic carcinoma, on the basis of a poorly differentiated ductal adenocarcinoma. Immunohistochemistry demonstrated G-CSF and G-CSF-Receptor expression in some CD68-positive syncytial macrophages. Granulocyte colony-stimulating factor (G-CSF) in serum was elevated at 5.6 pg/ml, which further raised to 43 pg/ml one week after FOLFIRINOX chemotherapy (oxaliplatin, irinotecan, 5-fluorouracil), while WBC decreased from 103.3 G/l to 59.3 G/l. Granulocyte macrophage-colony stimulating factor (GM-CSF) in serum was normal (<0.5 pg/ml). The patient died on postoperative day 34.

  9. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    PubMed

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  10. Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy

    PubMed Central

    Buetti-Dinh, Antoine; O’Hare, Thomas

    2016-01-01

    A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance. PMID:27669408

  11. A model of a patient-derived IDH1 mutant anaplastic astrocytoma with alternative lengthening of telomeres

    PubMed Central

    Borodovsky, Alexandra; Meeker, Alan K.; Kirkness, Ewen F.; Zhao, Qi; Eberhart, Charles G.; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from α-ketoglutarate. Recent investigations of malignant gliomas have identified additional genetic and chromosomal abnormalities which cluster with IDH1 mutations into two distinct subgroups. The astrocytic subgroup was found to have frequent mutations in ATRX, TP53 and displays alternative lengthening of telomeres. The second subgroup with oligodendrocytic morphology has frequent mutations in CIC or FUBP1, and is linked to co-deletion of the 1p/19q arms. These mutations reflect the development of two distinct molecular pathways representing the majority of IDH1 mutant gliomas. Unfortunately, due to the scarcity of endogenously derived IDH1 mutant models, there is a lack of accurate models to study mechanism and develop new therapy. Here we report the generation of an endogenous IDH1 anaplastic astrocytoma in vivo model with concurrent mutations in TP53, CDKN2A and ATRX. The model has a similar phenotype and histopathology as the original patient tumor, expresses the IDH1 (R132H) mutant protein and exhibits an alternative lengthening of telomeres phenotype. The JHH-273 model is characteristic of anaplastic astrocytoma and represents a valuable tool for investigating the pathogenesis of this distinct molecular subset of gliomas and for preclinical testing of compounds targeting IDH1 mutations or alternative lengthening of telomeres. PMID:25471051

  12. Influence of insurance status and income in anaplastic astrocytoma: an analysis of 4325 patients.

    PubMed

    Shin, Jacob Y; Yoon, Ja Kyoung; Diaz, Aidnag Z

    2016-11-18

    To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.

  13. Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines.

    PubMed

    Hoffmann, S; Maschuw, K; Hassan, I; Reckzeh, B; Wunderlich, A; Lingelbach, S; Zielke, A

    2005-09-01

    Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of

  14. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers

    PubMed Central

    Ibrahimpasic, Tihana; Boucai, Laura; Shah, Ronak H.; Dogan, Snjezana; Ricarte-Filho, Julio C.; Krishnamoorthy, Gnana P.; Schultz, Nikolaus; Berger, Michael F.; Sander, Chris; Taylor, Barry S.; Ghossein, Ronald; Ganly, Ian; Fagin, James A.

    2016-01-01

    BACKGROUND. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next-generation sequencing of 341 cancer genes from 117 patient-derived PDTCs and ATCs and analyzed the transcriptome of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC). RESULTS. Compared to PDTCs, ATCs had a greater mutation burden, including a higher frequency of mutations in TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. BRAF and RAS were the predominant drivers and dictated distinct tropism for nodal versus distant metastases in PDTC. RAS and BRAF sharply distinguished between PDTCs defined by the Turin (PDTC-Turin) versus MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, were markedly enriched in PDTCs and ATCs and had a striking pattern of co-occurrence with RAS mutations. While TERT promoter mutations were rare and subclonal in PTCs, they were clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) revealed a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs were BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared with PDTC underscore their greater virulence and higher mortality. FUNDING. This work was supported in part by NIH grants CA50706, CA72597, P50-CA72012, P30-CA008748, and 5T32-CA160001; the Lefkovsky Family

  15. Anaplastic thyroid carcinoma and foscarnet use in a multitarget treatment documented by 18F-FDG PET/CT

    PubMed Central

    Giannetta, Elisa; Isidori, Andrea M.; Durante, Cosimo; Di Gioia, Cira; Longo, Flavia; Tombolini, Vincenzo; Bulzonetti, Nadia; Graziadio, Chiara; Pofi, Riccardo; Gianfrilli, Daniele; Verrienti, Antonella; Carletti, Raffaella; Filetti, Sebastiano; Lenzi, Andrea; Baroli, Alberto

    2017-01-01

    Abstract Rationale: The case reported the rapid remission of disease recurrence achieved adding foscarnet, a DNA polymerase inhibitor that interacts with fibroblast growth factor 2, to low molecular weight heparin and sunitinib for the first time in a patient with an anaplastic thyroid cancer (ATC). Patient concerns: A 65-year-old woman with a multinodular goiter referred for a rapid enlargement of a nodule. Histological examination revealed an ATC with a little area of papillary thyroid cancer (PTC). The patient was resistant to selective single-target treatment. DIagnoses: Immunophenotyping and gene analyses found a significant increase in FGF2 and FGFR1 expression in the primary ATC area (FGF2 = 38.2 ± 6.2% in ATC vs 34.6 ± 6.0% in the differentiated area of PTC, P < 0.05; FGFR1: 41.7 ± 6.0% in ATC vs 34.4 ± 4.2% in PTC, P < 0.001) and in metastatic neck lymph nodes (P < 0.001 vs normal control tissues). Unlike conventional imaging, 18F-FDG PET/CT with PERCIST 1.0 criteria promptly and quantitatively detected disease recurrence and remission before and after multitarget therapy, combining anatomic, metabolic, and functional data. Interventions: Foscarnet was administered given the positivity for FGF2, FGFR1 and FGFR4 in ATC. Low molecular wight heparin and Sunitinib were coadministere to limiti metastatic progression and on neck tumor masse, respectively. Outcomes: The rationale for the clinical response to this innovative multitarget association with foscarnet is based on the histological and genetic finding that fibroblast growth factors and their receptor super-family are up-regulated in the primary anaplastic thyroid tumor and in the metastatic lymph node of our patient. Lessons: We propose that fibroblast growth factors and their receptor super-family play a key role as potential therapeutic targets in anaplastic thyroid cancer and the positive relevance of this suggestion for patient care, especially for an

  16. Intermittent hypoglycemia in a horse with anaplastic carcinoma of the kidney.

    PubMed

    Baker, J L; Aleman, M; Madigan, J

    2001-01-15

    Clinically apparent hypoglycemia is rare in adult horses. Hypoglycemia is a well-recognized paraneoplastic syndrome in humans and dogs with non-insulin-secreting tumors and may occur in horses as well. Hypoglycemia associated with non-insulin-secreting tumors is believed to result from production of an abnormal form of insulin-like growth factor II. Neoplasia should be considered in the differential diagnosis for adult horses with hypoglycemia.

  17. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Report of 2 Cases and Review of the Literature.

    PubMed

    Hart, Alexandra M; Lechowicz, Mary Jo; Peters, Kendall K; Holden, Jeannine; Carlson, Grant W

    2014-08-01

    Although primary breast lymphomas are exceedingly rare, cases of breast implant-associated anaplastic large cell lymphoma (iALCL) continue to be reported. The authors describe their experience with 2 patients and review the literature. Both patients presented with periprosthetic fluid collection. Neither had evidence of systemic disease nor received systemic therapy. Both were disease free after bilateral capsulectomies and implant removal without implant replacement, and disease did not recur. During the literature review, 63 cases of iALCL (including our 2 patients) were identified. The median time from implant placement to diagnosis was 9 years. Both saline and silicone implants were associated with iALCL. Of the 26 cases for which implant surface was reported, the surface was textured in 24. Of the 58 patients with an identifiable presentation, 39 had periprosthetic fluid collection, including 7 with an associated mass; 13 had an isolated mass at presentation, including 1 with axillary adenopathy. Forty patients had capsulectomy, 7 of whom underwent implant replacement. Of the 44 patients with known treatment, 33 received chemotherapy and 23 received radiation. Of the 49 patients with known anaplastic large cell lymphoma, 15 had disease recurrence, and 4 patient deaths were reported. Of the 18 patients presenting with a mass, 11 had disease recurrence, including all 4 patients who died. This study represents the largest review of patients with iALCL described to date. Although most cases have an indolent clinical course, the variety of presentations defined as "seroma" vs "capsular involvement" emphasizes the importance of investigating a definitive method of diagnosis, management, and treatment of this disease. LEVEL OF EVIDENCE 5.

  18. Lapatinib in Treating Young Patients With Recurrent or Refractory Central Nervous System Tumors

    ClinicalTrials.gov

    2014-05-07

    Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Oligodendroglioma

  19. Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity.

    PubMed

    Nevet, Mariela Judith; Zuckerman, Tsila; Sahar, Dvora; Bergman, Reuven

    2015-01-01

    Alemtuzumab is a humanized mouse antibody targeting the CD52 cell surface, which has been effective in patients with advanced stage mycosis fungoides (MF) including erythrodermic MF and Sézary syndrome. There are a few descriptions of large cell transformation after its administration. A young patient with an acute onset of Sézary syndrome treated initially unsuccessfully with fludarabine and cyclophosphamide and later on successfully with alemtuzumab has been described. Three weeks after the beginning of therapy, however, she developed transformed T-cell lymphoma indistinguishable from CD30 anaplastic large-cell lymphoma. After bone marrow transplantation, the transformed CD30 cutaneous T-cell lymphoma recurred as a transformed CD30 plaque MF. All 3 types of lesions showed the same T-cell receptor clonal gene rearrangement, which supports the notion that Sézary syndrome, CD30 anaplastic large-cell lymphoma, and MF are interrelated.

  20. Microcomputer-based technique for 3-D reconstruction and volume measurement of computed tomographic images. Part 2: Anaplastic primary brain tumors.

    PubMed

    Albright, R E; Fram, E K

    1988-12-01

    Serial computed tomography (CT) plays an integral part in monitoring effects of therapy for primary anaplastic brain tumors. Despite advances in CT technology, clinicians often cannot obtain accurate quantitative volume information to complement the qualitative assessment of tumor change. This paper presents a microcomputer-based method that provides both quantitative volume measurements and 3-D reconstructions of primary anaplastic brain tumors based on their hard copy CT or magnetic resonance imaging studies. The findings of this study demonstrate that planimetry is feasible for routine clinical use and is superior in accuracy to the spherical geometric model, which is shown to significantly overestimate tumor volume. The findings of 62 quantitative tumor studies (17 patients) showed a direct relationship between the total tumor volume and the volume of the hypodense intratumor core. There was no evidence of a relationship between the total tumor volume and the amount of peritumor low density (edema).

  1. ALK-negative anaplastic large cell lymphoma with urinary bladder involvement diagnosed in urine cytology: A case report and literature review.

    PubMed

    Lobo, João; Henrique, Rui; Monteiro, Paula; Lobo, Cláudia

    2017-04-01

    Anaplastic large cell lymphoma is an aggressive T-cell neoplasm. It rarely involves the urinary bladder, with just twelve cases reported thus far and only one being ALK-negative. Immunophenotyping (particularly for ALK) is mandatory, both for prognostic and therapeutic reasons. Herein, we report the case of a patient with an ALK-negative anaplastic large cell lymphoma involving the bladder which was diagnosed and fully characterized by immunocytochemistry in urine cytology. The patient underwent a cystoscopy and the urine sample disclosed tumor diathesis background and aggregates of atypical cells, with evidence of multinucleation and mitotic figures. Immunocytochemistry revealed strong membrane/Golgi positivity for CD30 and negativity for ALK. The patient was submitted to transurethral resection for therapeutic purposes, which confirmed the diagnosis. To the best of our knowledge, this represents only the third case of anaplastic large cell lymphoma with bladder involvement diagnosed in urine cytology and the very first with diagnostic findings allowing for immunophenotyping of the disease in a bladder wash. The present report reinforces the role of urine cytology as a suitable method for establishing an earlier diagnosis and characterization of the disease, avoiding submitting patients to invasive procedures like transurethral resections. Diagn. Cytopathol. 2017;45:354-358. © 2016 Wiley Periodicals, Inc.

  2. The Results of Surgery, With or Without Radiotherapy, for Primary Spinal Myxopapillary Ependymoma: A Retrospective Study From the Rare Cancer Network

    SciTech Connect

    Pica, Alessia; Miller, Robert; VillA, Salvador; Kadish, Sidney P.; Anacak, Yavuz; Abusaris, Huda; Ozyigit, Gokhan; Baumert, Brigitta G. M.D. Ph.D; Zaucha, Renata; Haller, Guy; Weber, Damien C.

    2009-07-15

    Purpose: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). Materials and Methods: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). Results: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose ({>=}50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size {>=}25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). Conclusions: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

  3. Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation.

    PubMed

    Vaubel, Rachael A; Caron, Alissa A; Yamada, Seiji; Decker, Paul A; Eckel Passow, Jeanette E; Rodriguez, Fausto J; Nageswara Rao, Amulya A; Lachance, Daniel; Parney, Ian; Jenkins, Robert; Giannini, Caterina

    2017-02-09

    Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n=33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50-60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n=15), +2 (n=11), +5 (n=10), +21 (n=10), +20 (n=9), +12 (n=8), +15 (n=8) and losses -22 (n=11), -14 (n=7), -13 (n=5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (p=0.009) and 14 (p=0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (p=0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n=2), matched primary/tumor recurrence (n=7), or both (n=1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not

  4. Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2015-05-29

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  5. Successful Cord Blood Stem Cell Transplantation for an Adult Case of Chronic Active Epstein-Barr Virus Infection

    PubMed Central

    Saburi, Masuho; Ogata, Masao; Satou, Takako; Yoshida, Natsumi; Nagamatsu, Kentaro; Nashimoto, Yuko; Moroga, Yui; Takano, Kuniko; Kohno, Kazuhiro; Shirao, Kuniaki

    2016-01-01

    A 41-year-old man was referred to our hospital for treatment of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Chronic active Epstein-Barr virus (CAEBV) was diagnosed based on the findings of elevated EBV antibody titers and positive EBV-DNA in the peripheral blood, and cord blood stem cell transplantation (CBT) was performed. The EBV-DNA levels in the blood fell below the limit of detection. His lymphoma relapsed on Day 165 with the appearance of eruptions, which disappeared after the withdrawal of tacrolimus. One year after transplantation, there were no signs of recurrence. This encouraging result suggests that CBT should be considered for adult cases of CAEBV with aggressive clinical manifestations. PMID:27904117

  6. The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met.

    PubMed

    Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Heiden, Katherine B; Xing, Mingzhao; Li, Yi; Prinz, Richard A; Xu, Xiulong

    2016-03-01

    The sonic hedgehog (Shh) pathway is highly activated in thyroid neoplasms and promotes thyroid cancer stem-like cell phenotype, but whether the Shh pathway regulates thyroid tumor cell motility and invasiveness remains unknown. Here, we report that the motility and invasiveness of two anaplastic thyroid tumor cell lines, KAT-18 and SW1736, were inhibited by two inhibitors of the Shh pathway (cyclopamine and GANT61). Consistently, the cell motility and invasiveness was decreased by Shh and Gli1 knockdown, and was increased by Gli1 overexpression in KAT-18 cells. Mechanistic studies revealed that Akt and c-Met phosphorylation was decreased by a Gli1 inhibitor and by Shh and Gli1 knockdown, but was increased by Gli1 overexpression. LY294002, a PI-3 kinase inhibitor, and a c-Met inhibitor inhibited the motility and invasiveness of Gli1-transfected KAT-18 cells more effectively than the vector-transfected cells. Knockdown of Snail, a transcription factor regulated by the Shh pathway, led to decreased cell motility and invasiveness in KAT-18 and SW1736 cells. However, key epithelial-to-mesenchymal transition (EMT) markers including E-cadherin and vimentin as well as Slug were not affected by cyclopamine and GANT61 in either SW1736 or WRO82, a well differentiated follicular thyroid carcinoma cell line. Our data suggest that the Shh pathway-stimulated thyroid tumor cell motility and invasiveness is largely mediated by AKT and c-Met activation with little involvement of EMT.

  7. Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor

    PubMed Central

    Stylianou, DC; Auf der Maur, A; Kodack, DP; Henke, RT; Hohn, S; Toretsky, JA; Riegel, AT; Wellstein, A

    2013-01-01

    The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) and its ligand, the growth factor pleiotrophin (PTN), are highly expressed during the development of the nervous system and have been implicated in the malignant progression of different tumor types. Here, we describe human single-chain variable fragment (scFv) antibodies that target the ligand-binding domain (LBD) in ALK and show the effect in vitro and in vivo. The ALK LBD was used as a bait in a yeast two-hybdrid system to select human scFv from a library with randomized complementarity-determining region 3 domains. Surface plasmon resonance showed high-affinity binding of the selected scFv. The anti-ALK scFv competed for binding of PTN to ALK in intact cells and inhibited PTN-dependent signal transduction through endogenous ALK. Invasion of an intact endothelial cell monolayer by U87MG human glioblastoma cells was inhibited by the anti-ALK scFv. In addition, the growth of established tumor xenografts in mice was reversed after the induction of the conditional expression of the anti-ALK scFv. In archival malignant brain tumors expression levels of ALK and PTN were found elevated and appear correlated with poor patient survival. This suggests a rate-limiting function of the PTN/ALK interaction that may be exploited therapeutically. PMID:19633684

  8. Allelic loss of 9p21.3 is a prognostic factor in 1p/19q codeleted anaplastic gliomas

    PubMed Central

    Alentorn, Agustí; Dehais, Caroline; Ducray, François; Carpentier, Catherine; Mokhtari, Karima; Figarella-Branger, Dominique; Chinot, Olivier; Cohen-Moyal, Elisabeth; Ramirez, Carole; Loiseau, Hugues; Elouahdani-Hamdi, Selma; Beauchesne, Patrick; Langlois, Olivier; Desenclos, Christine; Guillamo, Jean-Sébastien; Dam-Hieu, Phong; Ghiringhelli, François; Colin, Philippe; Godard, Joel; Parker, Fabrice; Dhermain, Frédéric; Carpentier, Antoine F.; Frenel, Jean-Sebastien; Menei, Philippe; Bauchet, Luc; Faillot, Thierry; Fesneau, Mélanie; Fontaine, Denys; Motuo-Fotso, Marie-Jeannette; Vauleon, Elodie; Gaultier, Claude; Le Guerinel, Caroline; Gueye, Edouard-Marcel; Noel, Georges; Desse, Nicolas; Durando, Xavier; Barrascout, Eduardo; Wager, Michel; Ricard, Damien; Carpiuc, Ioana; Delattre, Jean-Yves

    2015-01-01

    Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate (p = 0.008 and p < 0.001, respectively) and multivariate analyses (p = 0.009 and p = 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis (p = 0.01 and p = 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding. PMID:26385879

  9. Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co-deleted anaplastic gliomas.

    PubMed

    Bielle, Franck; Ducray, François; Mokhtari, Karima; Dehais, Caroline; Adle-Biassette, Homa; Carpentier, Catherine; Chanut, Anaïs; Polivka, Marc; Poggioli, Sylvie; Rosenberg, Shai; Giry, Marine; Marie, Yannick; Duyckaerts, Charles; Sanson, Marc; Figarella-Branger, Dominique; Idbaih, Ahmed

    2016-08-20

    The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co-deleted, grade III (O3(id) ) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage-oriented, heterogeneity in O3(id) . Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3(id) overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3(id) is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3(id) recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3(id) and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3(id) . A better understanding of spatial and temporal intratumor cell heterogeneity in O3(id) will open new therapeutic avenues overcoming resistance to current antitumor treatments.

  10. Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines.

    PubMed

    Rodrigues, R F; Roque, L; Krug, T; Leite, V

    2007-04-23

    Information on gene alterations associated to poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) is scarce. Using human cancer cell lines as a tool for gene discovery, we performed a cytogenetic and oligo-array analysis in five new cell lines derived from two PDTC and three ATC. In PDTC we evidenced, as important, the involvement of the MAPK/ERK kinase pathway, and downregulation of a group of suppressor genes that include E-cadherin. In ATC, downregulation of a specific group of oncosuppressor genes was also observed. Our ATC cell lines presented chromosomal markers of gene amplification, and we were able to identify for the first time the nature of the involved amplicon target genes. We found that the main molecular differences between the two cell line types were related to signal transduction pathways, cell adhesion and motility process. TaqMan experiments performed for five amplicon target genes and for two genes, which allowed a clear distinction between ATC and PDTC: CDH13 and PLAU corroborated array results, not only in the cell lines, but also in an additional set of primary 14 PDTC and three ATC. We suggest that our findings may represent new tools for the development of more effective therapies to the hitherto untreatable ATC.

  11. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

    SciTech Connect

    Shao, Mingchen; Geng, Yiwei; Lu, Peng; Xi, Ying; Wei, Sidong; Wang, Liuxing; Fan, Qingxia; Ma, Wang

    2015-09-04

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells.

  12. Dysphasia and Phantosmia as First Presentation of Multifocal Cerebral Anaplastic Astrocytomas: Case Report and Review of the Literatures

    PubMed Central

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Lu, Zhaohui; Wu, Huanwen; Mao, Xinxin; Cheng, Xin; Gao, Jun; Guan, Jian; Yang, Yi; Li, Yongning; Xing, Bing; Ma, Wenbin; Wang, Renzhi

    2015-01-01

    Abstract Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are frequently mistaken as metastases of an unknown primary cancer site. Most MCGs are glioblastomas with <4 lesions supratentorially, and are lack of typical symptoms and special detections. Through a rare MCG case, we aim to present this rarity and emphasize the need to correctly diagnose multiple intracranial lesions using a variety of diagnostic modalities to ensure that the patient receives proper treatment. We present a case of multifocal cerebral anaplastic astrocytomas with a total of 8 lesions located in the left frontal lobe and invading the lateral ventricle, presenting with dysphasia and phantosmia. The disease course, including diagnosis and treatment, is presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. After an initial impression of brain metastasis from lung cancer because of the magnetic resonance imaging (MRI) resemblance and history of chronic bronchitis, we were able to use positron emission tomography (PET) and excisional biopsy to get the final diagnosis. After 10 months, the patient's overall condition deteriorated and succumbed to his disease. MCGs are easy to be misdiagnosed as metastatic diseases. In addition to MRI, PET adds more biochemical and molecular information and is helpful in the differentiation. Although uncommon, if multiple lesions are present in various locations in the hemispheres, MCG should be kept in mind. PMID:25997068

  13. Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan.

    PubMed

    Fukano, Reiji; Mori, Tetsuya; Kobayashi, Ryoji; Mitsui, Tetsuo; Fujita, Naoto; Iwasaki, Fuminori; Suzumiya, Junji; Chin, Motoaki; Goto, Hiroaki; Takahashi, Yoshiyuki; Hara, Junichi; Park, Yong-Dong; Inoue, Masami; Koga, Yuhki; Inagaki, Jiro; Sakamaki, Hisashi; Adachi, Souichi; Kawa, Keisei; Kato, Koji; Suzuki, Ritsuro

    2015-02-01

    To evaluate haematopoietic stem cell transplantation (HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission (CR) was less common in allogeneic HSCT recipients (n = 24) than in autologous HSCT recipients (n = 23) (P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5-year event-free survival (EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment-related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non-CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non-CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced-intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non-CR. These three patients achieved CR, surviving 32-65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy.

  14. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    PubMed Central

    Katayama, Ryohei; Sakashita, Takuya; Yanagitani, Noriko; Ninomiya, Hironori; Horiike, Atsushi; Friboulet, Luc; Gainor, Justin F.; Motoi, Noriko; Dobashi, Akito; Sakata, Seiji; Tambo, Yuichi; Kitazono, Satoru; Sato, Shigeo; Koike, Sumie; John Iafrate, A.; Mino-Kenudson, Mari; Ishikawa, Yuichi; Shaw, Alice T.; Engelman, Jeffrey A.; Takeuchi, Kengo; Nishio, Makoto; Fujita, Naoya

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression. PMID:26870817

  15. Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3

    PubMed Central

    Kasprzycka, Monika; Marzec, Michal; Liu, Xiaobin; Zhang, Qian; Wasik, Mariusz A.

    2006-01-01

    The mechanisms of malignant cell transformation mediated by the oncogenic, chimeric nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) tyrosine kinase remain only partially understood. Here we report that the NPM/ALK-carrying T cell lymphoma (ALK+TCL) cells secrete IL-10 and TGF-β and express FoxP3, indicating their T regulatory (Treg) cell phenotype. The secreted IL-10 suppresses proliferation of normal immune, CD3/CD28-stimulated peripheral blood mononuclear cells and enhances viability of the ALK+TCL cells. The Treg phenotype of the affected cells is strictly dependent on NPM/ALK expression and function as demonstrated by transfection of the kinase into BaF3 cells and inhibition of its enzymatic activity and expression in ALK+TCL cells. NPM/ALK, in turn, induces the phenotype through activation of its key signal transmitter, signal transducer and activator of transcription 3 (STAT3). These findings identify a mechanism of NPM/ALK-mediated oncogenesis based on induction of the Treg phenotype of the transformed CD4+ T cells. These results also provide an additional rationale to therapeutically target the chimeric kinase and/or STAT3 in ALK+TCL. PMID:16766651

  16. miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8

    PubMed Central

    Liu, Yao; Zhang, Bing; Shi, Tiefeng; Qin, Huadong

    2017-01-01

    Chemotherapy is one of the most effective forms of cancer treatment and has been used in the treatment of various malignant tumors. We have gained significant insight into the mechanisms of chemoresistance but the details of the molecular mechanisms remain unclear. In the present study, we found that tripartite motif 8 (TRIM8) expression was downregulated in anaplastic thyroid cancer (ATC) tissues and cell lines. This downregulation of TRIM8 was significantly correlated with the upregulation of miR-182 in human ATC tissues. Bioinformatic analysis and luciferase reporter assays identified TRIM8 as a direct target of miR-182 in ATC. A functional assay using an MTT assay and colony formation showed that miR-182 induced cellular growth by repressing TRIM8 expression. Additionally, overexpressed miR-182 contributed to the chemoresistance of ATC cells by the repression of TRIM8 expression. In conclusion, these results demonstrate that miR-182/TRIM8 may be a therapeutic target for the treatment of chemoresistant human thyroid papillary cancer. PMID:28280352

  17. Development of secondary anaplastic oligoastrocytoma after matched unrelated bone marrow transplantation in a child with acute myeloid leukemia.

    PubMed

    Panigrahi, Soumya; Das, Mayukh; Stagler, Dalia; Konstantini, Shlomi; Gmori, Moshe; Slavin, Shimon; Nagler, Arnon

    2003-01-01

    The growing incidences of secondary malignancies in long-term survivors of childhood leukemia following allogeneic bone marrow transplantation (alloBMT) are increasingly being reported. Among the late complications of conventional myeloablative alloBMT, the occurrence of secondary malignant solid tumors is of major concern. Secondary malignant and benign brain tumors such as astrocytoma, meningioma and glioblastoma have been described in long-term survivors of conventional myeloablative alloBMT. Here we report a case of secondary anaplastic oligoastrocytoma that developed 7 years after matched unrelated alloBMT for relapsing childhood acute myeloid leukemia (AML) with CNS involvement. Although isolated CNS relapse of primary leukemia following alloBMT is not uncommon, it is important to identify and define potential risk factors that may lead to the development of secondary brain tumors in children who received high-dose chemotherapy and irradiation prior to alloBMT presenting with progressive neurological symptoms and to differentiate them from leukemia relapse with CNS involvement.

  18. Occurrence of anaplastic oligodendroglioma in a patient with Williams syndrome: a case report with analysis of mutational profile of tumor.

    PubMed

    Omalu, B I; Nnebe-Agumadu, U H

    2009-06-01

    Williams syndrome is a rare congenital developmental disorder characterized by a constellation of distinctive facial dysmorphisms, mental retardation, cardiovascular anomalies, infantile hypercalcemia, delayed developmental milestones, dental and musculoskeletal anomalies and distinctive personality traits. A majority of patients with Williams syndrome exhibit a hemizygous micro-deletion of chromosome 7q11.23, which is the locus of some 20-30 genes including the ELN gene that encodes the structural protein elastin. Chromosome 7q contains putative tumor suppressor genes and is one of the chromosomes that are frequently involved in chromosomal aberrations in human malignancies. A paucity of tumors (three) has been reported in the literature to occur in patients with Williams syndrome. We report a case of anaplastic oligodendroglioma that occurred in a 31-year-old man with Williams syndrome. Mutational profiling by loss of heterozygosity analysis using a panel of polymorphic micro-satellite markers indicated combined deletion of chromosome 1p and 19q. We draw attention to this apparently rare or possibly under-reported occurrence of tumors in patients with Williams syndrome and suggest that Central Nervous System [CNS] tumors be considered as differential diagnoses in such patients when they present with unanticipated neurologic symptoms that are not attributable to those commonly associated with Williams syndrome.

  19. CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation.

    PubMed

    Miyagaki, Tomomitsu; Sugaya, Makoto; Murakami, Takashi; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Okochi, Hitoshi; Tamaki, Kunihiko; Sato, Shinichi

    2011-03-15

    CCR3 is a specific marker of anaplastic large cell lymphoma (ALCL) cells. ALCL cells also express CCL11, a ligand for CCR3, leading to the hypothesis that CCL11 may play an autocrine role in ALCL progression. In this study, we investigated a role of CCL11 in cell survival and growth of human Ki-JK cells, established from an ALCL patient, and murine EL-4 lymphoma cells. Both Ki-JK and EL-4 cells expressed cell surface CCR3. CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner, whereas it promoted EL-4 cell proliferation. Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation. CCL11 induced expression of antiapoptotic proteins, Bcl-xL and survivin, in Ki-JK cells. CCL11 also enhanced tumor growth of EL-4 and Ki-JK cells in vivo. Consistent with these results, tumor cells of cutaneous ALCL expressed CCR3 and increased levels of phosphorylated ERK1/2, Bcl-xL, and survivin in situ. Thus, our findings prompt a novel therapeutic approach to treat relapses of an aggressive form of lymphoma based on the discovery that a cell surface marker of disease functions as a critical autocrine growth receptor.

  20. The long non-coding RNA LINC01013 enhances invasion of human anaplastic large-cell lymphoma.

    PubMed

    Chung, I-Hsiao; Lu, Pei-Hsuan; Lin, Yang-Hsiang; Tsai, Ming-Ming; Lin, Yun-Wen; Yeh, Chau-Ting; Lin, Kwang-Huei

    2017-03-22

    Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines. Knockdown of LINC01013 suppressed tumor cell invasion; conversely, its overexpression enhanced tumor cell invasion. LINC01013-induced invasion was mediated by activation of the epithelial-to-mesenchymal transition (EMT)-associated proteins, snail and fibronectin. Specifically, LINC01013 induced snail, resulting in activation of fibronectin and enhanced ALCL cell invasion. Collectively, these findings support a potential role for LINC01013 in cancer cell invasion through the snail-fibronectin activation cascade and suggest that LINC01013 could potentially be utilized as a metastasis marker in ALCL.

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

    ClinicalTrials.gov

    2014-07-09

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

  2. Intracoelomic anaplastic sarcoma in an intersex Madagascar tree boa (Sanzinia madagascariensis).

    PubMed

    Sharpe, Sam; Lamm, Catherine G; Killick, Rowena

    2013-01-01

    An adult Madagascar tree boa (Sanzinia madagascariensis) underwent coeliotomy for investigation of a coelomic mass. At surgery, a large mass originating from the peri-pancreatic adipose tissue and involving the gall bladder was removed. The snake did not recover from general anesthesia. A complete postmortem was performed, and samples were submitted to the University of Glasgow for histopathology. On histological examination, the mass was composed of adipose tissue infiltrated with a poorly demarcated spindle cell neoplasm. The neoplastic cells were highly pleomorphic with abundant cytoplasm and frequent clear cytoplasmic vacuoles, suggestive of adipocyte origin. Immunohistochemical characterization of the mass was inconclusive. Metastatic neoplastic cells were present within vessels in the liver, lungs, and brain. As an incidental finding, the gonads contained both maturing ovarian follicles and seminiferous tubules with intact germinal epithelium and evidence of spermatogenesis, along with other features of male and female gonad anatomy. The current report describes a rare neoplasm in snakes within an intersex Madagascar tree boa.

  3. Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    PubMed

    Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

    2017-03-24

    As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

  4. Analysis of clinical characteristics and prognosis of patients with anaplastic lymphoma kinase‐positive and surgically resected lung adenocarcinoma

    PubMed Central

    Tao, Hong; Cai, Yiran; Shi, Liang; Tang, Junfang; Liu, Zhidong; Wang, Zitong; Bai, Lianqi

    2016-01-01

    Background Recent research into lung cancer‐related driver genes has identified a distinctive molecular subtype of non‐small cell lung cancer (NSCLC) – anaplastic lymphoma kinase (ALK)‐positive NSCLC. We evaluated the clinical features and survival rates of ALK‐positive lung adenocarcinoma patients who had undergone surgery but had not received ALK inhibitor therapy, along with the characteristics of patients with distant metastases. Methods Clinical data of 40 patients with ALK‐positive, postsurgical lung adenocarcinoma were retrospectively analyzed. Relationships between the patients’ clinical characteristics, distant metastases, and their disease‐free survival (DFS) and overall survival (OS) rates were assessed. Results Most patients were relatively young, never‐smokers, had peripheral tumors, and the tumors were either moderately or poorly differentiated. The most common organ of distant metastases was the brain. The median time from surgery to brain metastasis was 17.2 months. The median OS following brain metastasis was 9.4 months. DFS in patients with early stage disease, peripheral tumors, no lymph node metastases, and treated with adjuvant therapy was significantly longer than for those with late stage disease (P = 0.015), central tumors (P = 0.000), lymph node metastases (P = 0.026), and not treated with adjuvant therapy (P = 0.000). Patients with early stage disease, peripheral tumors, and treated with adjuvant therapy obtained markedly longer OS than those with late stage disease (P = 0.021), central tumors (P = 0.003), and not treated with adjuvant therapy (P = 0.006). Conclusion Patients with ALK‐positive surgically resected lung adenocarcinoma have distinctive clinical characteristics. The brain is the most common site of extrapulmonary metastasis. Survival is associated with stage, tumor location, and the administration of adjuvant therapy. PMID:27779369

  5. Network analysis of microRNAs, transcription factors, target genes and host genes in human anaplastic astrocytoma

    PubMed Central

    XUE, LUCHEN; XU, ZHIWEN; WANG, KUNHAO; WANG, NING; ZHANG, XIAOXU; WANG, SHANG

    2016-01-01

    Numerous studies have investigated the roles played by various genes and microRNAs (miRNAs) in neoplasms, including anaplastic astrocytoma (AA). However, the specific regulatory mechanisms involving these genes and miRNAs remain unclear. In the present study, associated biological factors (miRNAs, transcription factors, target genes and host genes) from existing studies of human AA were combined methodically through the interactions between genes and miRNAs, as opposed to studying one or several. Three regulatory networks, including abnormally expressed, related and global networks were constructed with the aim of identifying significant gene and miRNA pathways. Each network is composed of three associations between miRNAs targeted at genes, transcription factors (TFs) regulating miRNAs and miRNAs located on their host genes. Among these, the abnormally expressed network, which involves the pathways of previously identified abnormally expressed genes and miRNAs, partially indicated the regulatory mechanism underlying AA. The network contains numerous abnormal regulation associations when AA emerges. By modifying the abnormally expressed network factors to a normal expression pattern, the faulty regulation may be corrected and tumorigenesis of AA may be prevented. Certain specific pathways are highlighted in AA, for example PTEN which is targeted by miR-21 and miR-106b, regulates miR-25 which in turn targets TP53. PTEN and miR-21 have been observed to form feedback loops. Furthermore, by comparing and analyzing the pathway predecessors and successors of abnormally expressed genes and miRNAs in three networks, similarities and differences of regulatory pathways may be identified and proposed. In summary, the present study aids in elucidating the occurrence, mechanism, prevention and treatment of AA. These results may aid further investigation into therapeutic approaches for this disease. PMID:27347075

  6. Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer.

    PubMed

    Haghpanah, Vahid; Fallah, Parviz; Tavakoli, Rezvan; Naderi, Mahmood; Samimi, Hilda; Soleimani, Masoud; Larijani, Bagher

    2016-01-01

    Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin (TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy.

  7. p21 participates in the regulation of anaplastic thyroid cancer cell proliferation by miR-146b

    PubMed Central

    Wang, Shiyang; Chen, Yangjing; Bai, Yanxia

    2016-01-01

    Anaplastic thyroid carcinoma (ATC) originates from completely undifferentiated cells, and is the most lethal type of thyroid-derived tumor. Numerous microRNAs have significant roles in tumorigenesis by targeting relevant genes. The role of microRNA 146b (miR-146b) in ATC remains to be elucidated. In order to characterize the role of miR-146b in ATC, overexpression or interference of miR-146b was induced in ATC cell lines, and cell proliferation and migration were evaluated. The potential targets of miR-146b were searched in the Gene Expression Omnibus database for ATC and matched non-tumor control samples. The expression level of potential targets was detected following overexpression or interference of miR-146b in ATC cell lines. In the present study, cell proliferation was promoted when overexpression of miR-146b was induced in ATC, and inhibited when interference of miR-146b was induced, which indicated that miR-146b affects the proliferation of ATC cells in vitro. In addition, cell migration of ATC was also affected by miR-146b. During the search for potential targets of miR-146b in ATC, p21 (also known as p21Waf1/Cip1 or CDKN1A) was noted for its role in cell cycle progression and tumor pathogenesis. The expression level of p21 was influenced by the level of miR-146b, and the results of the present study demonstrated that the level of p21 was increased when FRO cells were transformed with miR-146b mimic, and p21 was downregulated when FRO cells transformed with anti-miR-146b. In conclusion, p21 may participate in the regulation of ATC cell proliferation by miR-146b. PMID:27602131

  8. Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis.

    PubMed

    George, Eva V; Pharm, John; Houston, Courtney; Al-Quran, Semar; Brian, Grey; Dong, Huijia; Hai, Wang; Reeves, Westley; Yang, Li-Jun

    2013-01-01

    Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized clinical entity, with only 39 well-documented cases reported worldwide, including 3 fatalities. Because of its rarity, the clinical and pathologic features of this malignancy have yet to be fully defined. Moreover, the pathogenesis of ALCL in association with textured silicone gel breast implants is poorly understood. Here we report a case of BIA-ALCL arising in a 67-year-old woman with a mastectomy due to breast cancer followed by implantation of textured silicone gel breast prosthesis. The patient presented with breast enlargement and tenderness 8 years following reconstructive surgery. MRI revealed a fluid collection surrounding the affected breast implant. Pathologic examination confirmed the presence of malignant ALCL T cells that were CD30+, CD8+, CD15+, HLA-DR+, CD25+ ALK- and p53. A diagnosis of indolent BIA-ALCL was made since tumor cells were not found outside of the capsule. Interestingly, an extensive mixed lymphocytic infiltrate and ectopic lymphoid tissue (lymphoid neogenesis) adjacent to the fibrous implant capsule were present. The patient was treated with capsulectomy and implantation of new breast prostheses. Six months later, the patient was found to have BIA-ALCL involvement of an axillary lymph node with cytogenetic evolution of the tumor. To our knowledge, this is the sixth reported case of aggressive BIA-ALCL. Unique features of this case include the association with lymphoid neogenesis and the in vivo cytogenetic progression of the tumor. This case provides insight into the potential role of chronic inflammation and genetic instability in the pathogenesis of BIA-ALCL.

  9. Anaplastic large-cell lymphoma associated with breast implants: a unique entity within the spectrum of peri-implant effusions.

    PubMed

    Chai, Siaw Ming; Kavangh, Simon; Ooi, Sin Sin; Sterrett, Gregory F; Cull, Gavin; Plunkett, Myfanwy; Spagnolo, Dominic; Amanuel, Benhur; Joske, David; Leslie, Connull; Barham, Tony; Frost, Felicity

    2014-11-01

    Anaplastic large-cell lymphoma (ALCL) is a rare and newly described complication associated with breast implants. Patients often present with a peri-implant effusion, which is amenable to fine-needle aspiration. The laboratory handling of peri-implant effusions for cytology and ancillary studies is as crucial as recognizing the characteristic cytology of ALCL. All cases of peri-implant effusions were retrieved from the PathWest database between January 2003 and May 2013, yielding four cases of breast implant-associated ALCL and six benign samples. The cytological features were evaluated and information from ancillary studies collated. Clinical and follow-up histology was available in all cases. All ALCL cases contained highly atypical lymphoid cells including 'hallmark' cells. In contrast, benign peri-implant effusions showed a mixture of inflammatory cells, being either neutrophil-rich (three cases) or lymphocyte-rich (three cases). A CD30 positive, ALK1 negative immunophenotype was demonstrated in all cases on cell block immunohistochemistry. Flow cytometry and T-cell receptor clonality studies confirmed aberrant T-cell immunophenotype in four of four and clonally rearranged T-cell receptor antigens in three of three cases. ALCL was identified in three of four subsequent capsulectomies. Staging confirmed disease limited to the capsular tissue or peri-implant effusion in all cases. None of the six patients with benign peri-implant effusions developed lymphoma during follow-up. Cases of ALCL accounted for 40% of peri-implant effusions received over a 10-year period, indicating the rarity of these samples and the high likelihood of malignancy. Awareness of this entity and its presentation should allow for appropriate triage of these specimens and definitive diagnosis on effusion specimens.

  10. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

    PubMed Central

    Miranda, Roberto N.; Aladily, Tariq N.; Prince, H. Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E.; Amin, Mitual B.; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S.; Shifrin, David A.; O'Malley, Dennis P.; Cheah, Chan Y.; Bacchi, Carlos E.; Gualco, Gabriela; Li, Shiyong; Keech, John A.; Hochberg, Ephram P.; Carty, Matthew J.; Hanson, Summer E.; Mustafa, Eid; Sanchez, Steven; Manning, John T.; Xu-Monette, Zijun Y.; Miranda, Alonso R.; Fox, Patricia; Bassett, Roland L.; Castillo, Jorge J.; Beltran, Brady E.; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H.; Medeiros, L. Jeffrey

    2014-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. PMID:24323027

  11. Granulocyte colony-stimulating factor-producing pancreatic anaplastic carcinoma in ascitic fluid at initial diagnosis: A case report.

    PubMed

    Kubota, Nao; Naito, Yoshiki; Kawahara, Akihiko; Taira, Tomoki; Yamaguchi, Tomohiko; Yoshida, Tomoko; Abe, Hideyuki; Takase, Yorihiko; Fukumitsu, Chihiro; Murata, Kazuya; Ishida, Yusuke; Okabe, Yoshinobu; Kimura, Yoshizo; Tanigawa, Masahiko; Mihara, Yutaro; Nakayama, Masamichi; Yamaguchi, Rin; Akiba, Jun; Yano, Hirohisa

    2017-02-10

    Granulocyte colony-stimulating factor (G-CSF)-producing pancreatic tumors are extremely rare. These tumors have an aggressive clinical course and no established treatment. Here, we report an autopsy case of G-CSF-production in pancreatic anaplastic carcinoma (PAC). A 72-year-old woman presented with a large pancreatic head mass and multiple liver metastases. Laboratory data showed leukocytosis (leukocyte count 113.3 × 10(3) /µL) and high serum G-CSF levels (441 pg/mL; normal range: <39.0 pg/mL). The ascitic fluid was submitted to our pathology laboratory at initial diagnosis. Cytopathology showed that smears from the ascitic fluid were highly cellular and contained numerous malignant cells, mainly in loose groupings. Occasional pseudoglandular formations and giant cells were also present. The malignant cells were round, and no spindle-shaped cells were visible. The nuclei were round to ovoid with coarsely granular chromatin and large prominent nucleoli. Upon immunocytochemistry, tumor cells were positive for G-CSF and vimentin; there was no E-cadherin expression. Histopathological examination of the tumor showed a mixed composition of adenocarcinomatous and sarcomatous regions. Upon immunohistochemistry, both components were positive for G-CSF. Few CD34-positive myeloblasts were observed in the bone marrow. Thus, we diagnosed this as a case of G-CSF production in PAC with leukocytosis. To the best of our knowledge, this is the first report on G-CSF expression immunocytochemically confirmed in PAC. Diagn. Cytopathol. © 2017 Wiley Periodicals, Inc.

  12. Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma

    PubMed Central

    Wurster, K D; Hummel, F; Richter, J; Giefing, M; Hartmann, S; Hansmann, M-L; Kreher, S; Köchert, K; Krappmann, D; Klapper, W; Hummel, M; Wenzel, S-S; Lenz, G; Janz, M; Dörken, B; Siebert, R; Mathas, S

    2017-01-01

    Apart from its unique histopathological appearance with rare tumor cells embedded in an inflammatory background of bystander cells, classical Hodgkin lymphoma (cHL) is characterized by an unusual activation of a broad range of signaling pathways involved in cellular activation. This includes constitutive high-level activity of nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), activator protein-1 (AP-1) and interferon regulatory factor (IRF) transcription factors (TFs) that are physiologically only transiently activated. Here, we demonstrate that inactivation of the putative ubiquitin E3-ligase PDLIM2 contributes to this TF activation. PDLIM2 expression is lost at the mRNA and protein levels in the majority of cHL cell lines and Hodgkin and Reed–Sternberg (HRS) cells of nearly all cHL primary samples. This loss is associated with PDLIM2 genomic alterations, promoter methylation and altered splicing. Reconstitution of PDLIM2 in HRS cell lines inhibits proliferation, blocks NF-κB transcriptional activity and contributes to cHL-specific gene expression. In non-Hodgkin B-cell lines, small interfering RNA-mediated PDLIM2 knockdown results in superactivation of TFs NF-κB and AP-1 following phorbol 12-myristate 13-acetate (PMA) stimulation. Furthermore, expression of PDLIM2 is lost in anaplastic large cell lymphoma (ALCL) that shares key biological aspects with cHL. We conclude that inactivation of PDLIM2 is a recurrent finding in cHL and ALCL, promotes activation of inflammatory signaling pathways and thereby contributes to their pathogenesis. PMID:27538486

  13. Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer

    PubMed Central

    Liu, Yanlan; Gunda, Viswanath; Zhu, Xi; Xu, Xiaoding; Wu, Jun; Askhatova, Diana; Farokhzad, Omid C.; Parangi, Sareh; Shi, Jinjun

    2016-01-01

    Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a promising strategy for cancer therapy through nanoparticle (NP) -mediated delivery of RNAi agents (e.g., siRNA) to solid tumors for specific silencing of target genes driving growth and/or metastasis. Nevertheless, the clinical success of RNAi cancer nanotherapies remains elusive in large part because of the suboptimal systemic siRNA NP delivery to tumors and the fact that tumor heterogeneity produces variable NP accumulation and thus, therapeutic response. To address these challenges, we here present an innovative theranostic NP platform composed of a near-infrared (NIR) fluorescent polymer for effective in vivo siRNA delivery to ATC tumors and simultaneous tracking of the tumor accumulation by noninvasive NIR imaging. The NIR polymeric NPs are small (∼50 nm), show long blood circulation and high tumor accumulation, and facilitate tumor imaging. Systemic siRNA delivery using these NPs efficiently silences the expression of V-Raf murine sarcoma viral oncogene homolog B (BRAF) in tumor tissues and significantly suppresses tumor growth and metastasis in an orthotopic mouse model of ATC. These results suggest that this theranostic NP system could become an effective tool for NIR imaging-guided siRNA delivery for personalized treatment of advanced malignancies. PMID:27342857

  14. Expression of the Chemokine Receptor Gene, CCR8, is Associated with DUSP22 Rearrangements in Anaplastic Large Cell Lymphoma

    PubMed Central

    Xing, Xiaoming; Flotte, Thomas J.; Law, Mark E.; Blahnik, Anthony J.; Chng, Wee-Joo; Huang, Gaofeng; Knudson, Ryan A.; Ketterling, Rhett P.; Porcher, Julie C.; Ansell, Stephen M.; Sidhu, Jagmohan; Dogan, Ahmet; Feldman, Andrew L.

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is one of the most common T-cell non-Hodgkin lymphomas and has two main subtypes: an ALK-positive subtype characterized by ALK gene rearrangements and an ALK-negative subtype that is poorly understood. We recently identified recurrent rearrangements of the DUSP22 locus on 6p25.3 in both primary cutaneous and systemic ALK-negative ALCLs. This study aimed to determine the relationship between these rearrangements and expression of the chemokine receptor gene, CCR8. CCR8 has skin-homing properties, and has been suggested to play a role in limiting extracutaneous spread of primary cutaneous ALCLs. However, overexpression of CCR8 also has been reported in systemic ALK-negative ALCLs. As available antibodies for CCR8 have shown lack of specificity, we examined CCR8 expression using quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH) in paraffin tissue. Both approaches showed higher CCR8 expression in ALCLs with DUSP22 rearrangements than in non-rearranged cases (PCR: 19.5-fold increase, p=0.01; ISH: 3.3-fold increase, p=0.0008). CCR8 expression was not associated with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement during the disease course. These findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 rearrangements than to cutaneous involvement, and that the function of CCR8 may extend beyond its skin-homing properties in this disease. This study also underscores the utility of RNA-ISH as a paraffin-based method for investigating gene expression when reliable antibodies for immunohistochemistry are not available. PMID:25390351

  15. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

    PubMed Central

    Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.

    2016-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

  16. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    SciTech Connect

    Gan, Gregory N.; Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C.; Gaspar, Laurie E.; Kavanagh, Brian D.; Camidge, D. Ross

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  17. EXTRINSIC APOPTOTIC PATHWAYS: A NEW POTENTIAL “TARGET” FOR MORE SUFFICIENT THERAPY IN A CASE OF CUTANEOUS ANAPLASTIC LARGE CD30+ ALK–T-CELL LYMPHOMA

    PubMed Central

    Georgi, Tchernev; Carlos, Cardoso José; Lubomir, Arseniev; Hiroyuki, Okamoto

    2011-01-01

    The primary cutaneous T-cell lymphomas (CTCL) represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the “tumor lymphocytes”. The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30+/ALK− anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation) combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vincristin (Oncovin®), Predniso(lo)n). Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF)-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30+ cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis. PMID:21572802

  18. Detection of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer and related issues in ALK inhibitor therapy: a literature review.

    PubMed

    Yi, Eunhee S; Chung, Jin-Haeng; Kulig, Kimary; Kerr, Keith M

    2012-06-01

    Anaplastic lymphoma kinase (ALK) encodes a receptor tyrosine kinase, and ALK gene rearrangement (ALK+) is implicated in the oncogenesis of non-small cell lung carcinomas (NSCLCs), especially adenocarcinomas. The ALK inhibitor crizotinib was approved in August 2011 by the US Food and Drug Administration (FDA) for treating late-stage NSCLCs that are ALK+, with a companion fluorescent in situ hybridization (FISH) test using the Vysis ALK Break Apart FISH Probe Kit. This review covers pertinent issues in ALK testing, including approaches to select target patients for the test, pros and cons of different detection methods, and mechanisms as well as monitoring of acquired crizotinib resistance in ALK+ NSCLCs.

  19. AT-57LONG-TERM CLINICAL RESULTS OF EXTENSIVE TUMOR REMOVAL FOLLOWED BY ACNU-BASED CHEMORADIOTHERAPY FOR 147 ANAPLASTIC GLIOMAS

    PubMed Central

    Takayuki, Yasuda; Masayuki, Nitta; Takashi, Maruyama; Taichi, Saito; Satoko, Ikuta; Yoshikazu, Okada; Hiroshi, Iseki; Yoshihiro, Muragaki

    2014-01-01

    INTRODUCTION: Recent randomized trials showed that highly extent of resection (EOR) and PCV chemoradiotherapy had therapeutic long-term efficacy to anaplastic glioma (AG). From 2000, we have consistently enforced extensive removal and ACNU-based chemoradiotherapy for AG. We report retrospective clinical results of a single institution. METHODS: We reviewed 147 cases of primary AG between 2000 and 2011 (Male : Female = 94:53, average age; 43.9 year-old). 69 were anaplastic astrocytoma (41%), 43 were anaplastic oligoastrocytoma (29%), and 44 were anaplastic oligodendroglioma (30%). The intraoperative MRI was performed in 133 cases (90%), and awake surgery was performed in 58 cases (39%). Gross-total removal was 46 (31%), partial removal was 89 (61%), and biopsy was 12 (8%) (average; 83%, median; 95%). After resection, 60 Gy radiotherapy and ACNU or PAV chemotherapy were performed. The average Mib-1 index was 15%. The mean observation periods were 57 months and 95% follow-up rate. RESULTS: Overall survival (OS) wasn't reached median. The 3y-OS was 82%, 5y-OSs was 72%, and 10y-OS was 66%. There was no statistical significance among AA, AOA, AO (5y-OS; 64%, 79%, 77%). The each 5 years survival rate of gross-total resection, partial resection, and biopsy were 83%, 70%, 39%, and there was statistical significance (P = 0.0024). Extent of resection (EOR) correlated OS in AA (P = 0.02) but not in oligodendroglial subtypes (P = 0.6). Statistical significant factors were EOR (P = 0.0024) and Mib-1 index (P = 0.013). The significant factors in multi variable analysis were EOR (more than 95% or not, HR 2.5) and Mib-1 index (more than 13% or not, HR 2.3). The median PFS was 8.3, and 5y-PFS was 59%,and 10y-PFS was 45%. CONCLUSION: Our long-term clinical results of AG treated with extensive resection and ACNU-based chemoradiotherapy were better than previous reports. The EOR contributed better prognosis especially for AA.

  20. Long-term stabilization by radiosurgery of a secondary focal anaplastic transformation in a surgically treated WHO grade II oligodendroglioma. A case report.

    PubMed

    Yordanova, Y N; Rodriguez-Arribas, M-A; Duffau, H

    2015-02-01

    We report on a young woman with a left temporal diffuse low-grade glioma treated initially by a subtotal resection. A focal anaplastic area appeared 5years later and was treated by radiosurgery. A long-time stabilization was therefore obtained and lasted even after pregnancy, which is a known factor of faster tumour progression. This report shows that radiosurgery could be an option in the multimodal treatment of a selected group of patients with focal malignant transformation of diffuse low-grade glioma. It could permit long-term stabilization of the tumour without any other adjuvant treatment and without compromising the quality of life.

  1. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    ClinicalTrials.gov

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  2. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  3. Immunocytochemical analysis of glucose transporter protein-1 (GLUT-1) in typical, brain invasive, atypical and anaplastic meningioma.

    PubMed

    van de Nes, Johannes A P; Griewank, Klaus G; Schmid, Kurt-Werner; Grabellus, Florian

    2015-02-01

    Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and "spontaneous" necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1-4) and to be consistently strong in WHO grade III meningiomas (IRS = 6-12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS = 1-9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS = 0-4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) "Spontaneous" necrosis and small cell change typically occurred away from the intratumoral capillary

  4. Anaplastic Large Cell Lymphoma

    MedlinePlus

    ... and support programs: • Lymphoma Helpline • Clinical Trials Information Service • Lymphoma Support Network • Publications • Teleconferences • Webcasts & podcasts • In-person conferences Medical ...

  5. Nodal anaplastic large-cell lymphoma ALK-1- with CD30+ cutaneous lymphoproliferation treated with mistletoe: spontaneous remission or treatment response?

    PubMed

    Kameda, G; Kempf, W; Oschlies, I; Michael, K; Seifert, G; Längler, A

    2011-11-01

    A 12-year old girl presented with general weakness and weight loss, a localised cervical lymph node enlargement and cutaneous lesions compatible with lymphomatoid papulosis (LyP). Biopsies from lymph node and skin revealed a histological diagnosis of nodal large cell ALK-1- anaplastic lymphoma (ALCL) with a synchronous CD30+ cutaneous lymphoproliferation consistent with lymphomatoid papulosis (LyP). The girl was treated with mistletoe (MT) as monotherapy. Within 1 week after initiation of MT-treatment the skin lesions and lymph node enlargement improved. Under continuing MT-therapy 30 months after diagnosis the patient is still in complete remission. It is not possible to know whether this was a rare case of spontaneous remission of the nodal and skin-manifestations of this CD30+ T-cell lymphoproliferation or whether the observed effect was a specific therapeutic response to MT-treatment.

  6. A Unique "Composite" PTLD with Diffuse Large B-Cell and T/Anaplastic Large Cell Lymphoma Components Occurring 17 Years after Transplant.

    PubMed

    La Fortune, Kristin; Zhang, Dahua; Raca, Gordana; Ranheim, Erik A

    2013-01-01

    Posttransplant lymphoproliferative disorder (PTLD) comprises a spectrum ranging from polyclonal hyperplasia to aggressive monoclonal lymphomas. The majority of PTLDs are of B-cell origin while T-cell PTLDs and Hodgkin lymphoma-like PTLDs are uncommon. Here, we report a unique case of a 56-year-old man in whom a lymphoma with two distinct components developed as a duodenal mass seventeen years following a combined kidney-pancreas transplant. This PTLD, which has features not previously reported in the literature, consisted of one component of CD20 positive and EBV negative monomorphic diffuse large B-cell lymphoma. The other component showed anaplastic morphology, expressed some but not all T-cell markers, failed to express most B-cell markers except for PAX5, and was diffusely EBV positive. Possible etiologies for this peculiar constellation of findings are discussed and the literature reviewed for "composite-like" lymphomas late in the posttransplant setting.

  7. Therapeutic efficacy of the bromodomain inhibitor OTX015/MK-8628 in ALK-positive anaplastic large cell lymphoma: an alternative modality to overcome resistant phenotypes

    PubMed Central

    Vurchio, Valentina; Yang, Shao Ning; Moon, John; Kwee, Ivo; Rinaldi, Andrea; Pan, Heng; Crescenzo, Ramona; Cheng, Mangeng; Cerchietti, Leandro; Elemento, Olivier; Riveiro, Maria E.; Cvitkovic, Esteban; Bertoni, Francesco; Inghirami, Giorgio

    2016-01-01

    Anaplastic large cell lymphomas (ALCL) represent a peripheral T-cell lymphoma subgroup, stratified based on the presence or absence of anaplastic lymphoma kinase (ALK) chimeras. Although ALK-positive ALCLs have a more favorable outcome than ALK-negative ALCL, refractory and/or relapsed forms are common and novel treatments are needed. Here we investigated the therapeutic potential of a novel bromodomain inhibitor, OTX015/MK-8628 in ALK-positive ALCLs. The effects of OTX015 on a panel of ALK+ ALCL cell lines was evaluated in terms of proliferation, cell cycle and downstream signaling, including gene expression profiling analyses. Synergy was tested with combination targeted therapies. Bromodomain inhibition with OTX015 led primarily to ALCL cell cycle arrest in a dose-dependent manner, along with downregulation of MYC and its downstream regulated genes. MYC overexpression did not compensate this OTX015-mediated phenotype. Transcriptomic analysis of OTX015-treated ALCL cells identified a gene signature common to various hematologic malignancies treated with bromodomain inhibitors, notably large cell lymphoma. OTX015-modulated genes included transcription factors (E2F2, NFKBIZ, FOS, JUNB, ID1, HOXA5 and HOXC6), members of multiple signaling pathways (ITK, PRKCH, and MKNK2), and histones (clusters 1-3). Combination of OTX015 with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib led to cell cycle arrest then cell death, and combination with suboptimal doses of the ALK inhibitor CEP28122 caused cell cycle arrest. When OTX015 was associated with GANT61, a selective GLI1/2 inhibitor, C1156Y-resistant ALK ALCL growth was impaired. These findings support OTX015 clinical trials in refractory ALCL in combination with inhibitors of interleukin-2-inducible kinase or SHH/GLI1. PMID:27793034

  8. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    ClinicalTrials.gov

    2016-01-29

    Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

  9. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    PubMed Central

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

  10. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    PubMed

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  11. Polymyositis - adult

    MedlinePlus

    ... rash is a sign of a similar condition, dermatomyositis . Common symptoms include: Muscle weakness in the shoulders ... in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. ...

  12. Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation.

    PubMed

    Capdevila, Laia; Cros, Sara; Ramirez, Jose-Luis; Sanz, Carolina; Carrato, Cristina; Romeo, Margarita; Etxaniz, Olatz; Hostalot, Cristina; Massuet, Ana; Cuadra, Jose Luis; Villà, Salvador; Balañà, Carmen

    2014-03-01

    Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.

  13. Consequences of heat shock protein 72 (Hsp72) expression and activity on stress-induced apoptosis in CD30+ NPM-ALK+ anaplastic large-cell lymphomas.

    PubMed

    Bonvini, P; Zorzi, E; Mussolin, L; Pillon, M; Romualdi, C; Peron, M; d'Amore, E S G; Lamant, L; Rosolen, A

    2012-06-01

    Understanding the mechanisms that control stress-induced apoptosis is critical to explain how tumours respond to treatment, as cancer cells frequently escape drug toxicity by regulating stress response through heat shock protein (HSP) expression. The overexpression of Hsp72, in particular, results in increased incidence of cell transformation, and correlates with poor prognosis in a wide range of cancers. We have shown that Hsp72 assists folding of oncogenic NPM-ALK kinase in anaplastic large-cell lymphomas (ALCLs), but its role in the maintenance of the malignant phenotype remains uncertain. Therefore, we assessed Hsp72 expression in ALCLs, investigating more in detail the mechanisms that regulate its status and activity. We found that Hsp72 is unique among the HSPs involved in tumourigenesis to be overexpressed in ALK(+) tumours and cell lines and to be induced by stress. Different from other HSPs, Hsp72 prevents cell injury, Bax activation and death by apoptosis in ALK(+) cells, acting both upstream and downstream of mitochondria. Conversely, Hsp72 is underexpressed in ALK(-) ALCL cells, and it is unable to protect cells from apoptosis under stress. Moreover, when Hsp72 expression is reduced following NPM-ALK inhibition, lymphoma cells undergo apoptosis, demonstrating the importance of Hsp72 in regulating ALCL stress response and drug sensitivity.

  14. Combination of the human anti-CD30 antibody 5F11 with cytostatic drugs enhances its antitumor activity against Hodgkin and anaplastic large cell lymphoma cell lines.

    PubMed

    Heuck, Friederike; Ellermann, Julia; Borchmann, Peter; Rothe, Achim; Hansen, Hinrich; Engert, Andreas; von Strandmann, Elke Pogge

    2004-01-01

    Due to its selective overexpression on the malignant cells of Hodgkin's lymphoma (HL) and large cell anaplastic lymphoma (ALCL), CD30 is an excellent target for immunotherapy of these diseases. The fully human monoclonal anti-CD30-antibody 5F11 has been shown to be effective against CD30-expressing cell lines both in vitro and in vivo. In addition, 5F11 shows promising antitumor activity in phase 1/2 clinical trials. To extend these promising results, the authors evaluated combinations of 5F11 with conventional cytostatic drugs against a variety of lymphoma cell lines in vitro. Most combinations tested showed at least additive cytotoxic effects on the HL-derived cell lines L428, L540, and L1236 and the ALCL-derived cell line Karpas 299 as measured by proliferation assays (XTT) and the induction of apoptosis (annexin-V FACS analysis). The most impressive results were detected with the combination of 5F11 and gemcitabine or etoposide. The data suggest that the combination of the human antibody 5F11 with conventional chemotherapy might be beneficial in the combined chemo-immunotherapy of CD30-positive lymphomas.

  15. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

    PubMed Central

    Pugliese, Mariateresa; Gallo, Marco; Brignardello, Enrico; Milla, Paola; Orlandi, Fabio; Limone, Paolo Piero; Arvat, Emanuela; Boccuzzi, Giuseppe; Piovesan, Alessandro

    2016-01-01

    Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11. PMID:27766105

  16. An interaction map of small-molecule kinase inhibitors with anaplastic lymphoma kinase (ALK) mutants in ALK-positive non-small cell lung cancer.

    PubMed

    Ai, Xinghao; Shen, Shengping; Shen, Lan; Lu, Shun

    2015-05-01

    Human anaplastic lymphoma kinase (ALK) has become a well-established target for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Here, we have profiled seven small-molecule inhibitors, including 2 that are approved drugs, against a panel of clinically relevant mutations in ALK tyrosine kinase (TK) domain, aiming at a comprehensive understanding of molecular mechanism and biological implication underlying inhibitor response to ALK TK mutation. We find that (i) the gatekeeper mutation L1196M causes crizotinib resistance by simultaneously increasing and decreasing the binding affinities of, respectively, ATP and inhibitor to ALK, whereas the secondary mutation C1156Y, which is located far away from the ATP-binding site of ALK TK domain, causes the resistance by inducing marked allosteric effect on the site, (ii) the 2nd and 3rd generation kinase inhibitors exhibit relatively high sensitivity towards ALK mutants as compared to 1st generation inhibitors, (iii) the pan-kinase inhibitor staurosporine is insensitive for most mutations due to its high structural compatibility, and (iv) ATP affinity to ALK is generally reduced upon most clinically relevant mutations. Furthermore, we also identify six novel mutation-inhibitor pairs that are potentially associated with drug resistance. In addition, the G1202R and C1156Y mutations are expected to generally cause resistance for many existing inhibitors, since they can address significant effect on the geometric shape and physicochemical property of ALK active pocket.

  17. U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.

    PubMed

    Malik, Shakun M; Maher, Virginia Ellen; Bijwaard, Karen E; Becker, Robert L; Zhang, Lijun; Tang, Shenghui W; Song, Pengfei; Liu, Qi; Marathe, Anshu; Gehrke, Brenda; Helms, Whitney; Hanner, Diane; Justice, Robert; Pazdur, Richard

    2014-04-15

    On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (≥25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.

  18. Involvement of cysteine-rich protein 61 in the epidermal growth factor-induced migration of human anaplastic thyroid cancer cells.

    PubMed

    Chin, Li-Han; Hsu, Sung-Po; Zhong, Wen-Bin; Liang, Yu-Chih

    2016-05-01

    Anaplastic thyroid cancer (ATC) is among the most aggressive types of malignant cancer. Epidermal growth factor (EGF) plays a crucial role in the pathogenesis of ATC, and patients with thyroid carcinoma typically exhibit increased cysteine-rich protein 61 (Cyr61). In this study, we found that EGF treatment induced cell migration, stress fiber formation, Cyr61 mRNA and protein expressions, and Cyr61 protein secretion in ATC cells. The recombinant Cyr61 protein significantly induced cell migration; however, inhibition of Cyr61 activity by a Cyr61-specific antibody abrogated EGF-induced cell migration. EGF treatment also affected epithelial-to-mesenchymal transition (EMT)-related marker protein expression, as evidenced by an increase in vimentin and a decrease in E-cadherin expression. Inhibition of Cyr61 expression by Cyr61 siRNA decreased cell migration and reversed the EMT-related marker protein expression. EGF treatment increased the phosphorylation of the extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), and finally activated Cyr61 promoter plasmid activity. Our results suggest that Cyr61 is induced by EGF through the ERK/CREB signal pathway and that it plays a crucial role in the migration and invasion of ATC cells; moreover, Cyr61 might be a therapeutic target for metastatic ATC.

  19. Silicone-induced granuloma of breast implant capsule (SIGBIC): similarities and differences with anaplastic large cell lymphoma (ALCL) and their differential diagnosis

    PubMed Central

    Fleury, Eduardo de Faria Castro; Rêgo, Milena Morais; Ramalho, Luciana Costa; Ayres, Veronica Jorge; Seleti, Rodrigo Oliveira; Ferreira, Carlos Alberto Pecci; Roveda, Decio

    2017-01-01

    Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL) is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease. PMID:28331364

  20. Silicone-induced granuloma of breast implant capsule (SIGBIC): similarities and differences with anaplastic large cell lymphoma (ALCL) and their differential diagnosis.

    PubMed

    Fleury, Eduardo de Faria Castro; Rêgo, Milena Morais; Ramalho, Luciana Costa; Ayres, Veronica Jorge; Seleti, Rodrigo Oliveira; Ferreira, Carlos Alberto Pecci; Roveda, Decio

    2017-01-01

    Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL) is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease.

  1. Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation

    PubMed Central

    Jiang, Yue; Sun, Ruimei; Chen, Xue; Chu, Hongying; Zeng, Musheng; Sun, Chuanzheng

    2016-01-01

    Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored. PMID:27487122

  2. Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex.

    PubMed

    Piazza, Rocco; Magistroni, Vera; Mogavero, Angela; Andreoni, Federica; Ambrogio, Chiara; Chiarle, Roberto; Mologni, Luca; Bachmann, Petra S; Lock, Richard B; Collini, Paola; Pelosi, Giuseppe; Gambacorti-Passerini, Carlo

    2013-05-01

    BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  3. Diagnosis of anaplastic lymphoma kinase rearrangement in cytological samples through a fluorescence in situ hybridization-based assay: Cytological smears versus cell blocks.

    PubMed

    Zito Marino, Federica; Rossi, Giulio; Brunelli, Matteo; Malzone, Maria Gabriella; Liguori, Giuseppina; Bogina, Giuseppe; Morabito, Alessandro; Rocco, Gaetano; Franco, Renato; Botti, Gerardo

    2017-02-14

    Anaplastic lymphoma kinase (ALK) status analysis of lung cytological specimens should be successfully encouraged in routine practice because biopsy specimens are not always available. To date, the US Food and Drug Administration has approved both fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) as diagnostic tests for identifying ALK-positive patients eligible for treatment with crizotinib. Although ALK IHC is an optimal diagnostic tool, FISH becomes mandatory in equivocal cases. ALK FISH of paraffin-embedded tissue material is still the gold standard, whereas the cytological specimen assay has not yet been completely standardized. Many controversial data have been reported on the adequacy of cytology cell blocks (CBs) versus conventional smears for FISH testing. This review discusses some critical issues related to ALK FISH of cytological samples, including the triaging of collected specimens to optimize the material, the use of CBs versus conventional smears, and alternative methods for an ALK rearrangement diagnosis. Conventional smears have the advantages of an immediate evaluation, no probe tissue-related artifactual loss, no fixation-related alterations, and usually sufficient material for an analytic preparation. On the other hand, CBs have several advantages, including the appropriate conservation of the tissue architecture, an absence of problems related to cell overlapping, and the ability to evaluate neoplastic cells in a dark field. Cancer Cytopathol 2017. © 2017 American Cancer Society.

  4. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis

    PubMed Central

    Carina, Valeria; Tomasello, Laura; Pitrone, Maria; Baiamonte, Concetta; Amato, Marco Calogero

    2015-01-01

    It has been suggested that cancer stem cells (CSC) may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC) has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA) analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2), in the control cell cycle (TP53, CCND1), and in mitochondrial activity (COX8A). The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated. PMID:25705224

  5. Alectinib-Induced Erythema Multiforme and Successful Rechallenge with Alectinib in a Patient with Anaplastic Lymphoma Kinase-Rearranged Lung Cancer

    PubMed Central

    Kimura, Tatsuo; Sowa-Osako, Junko; Nakai, Toshiyuki; Ohyama, Ayako; Kawaguchi, Tomoya; Tsuruta, Daisuke; Ohsawa, Masahiko; Hirata, Kazuto

    2016-01-01

    Background Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. Case Presentation A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK. The skin reaction was observed on the anterior chest, upper arms, and ear auricles on day 11 of treatment with oral alectinib. The skin event presented as widely distributed erythematous macules that were confluent, indicating a severe and life-threatening form. The skin lesions started to resolve after the initiation of treatment with 40 mg prednisolone. After regrowth of the tumor, she received a rechallenge program for alectinib for 2 weeks; thereafter, alectinib treatment was successfully reinitiated. Conclusion To the best of our knowledge, we present the first case in which alectinib, which binds to the adenosine triphosphate site of EML4-ALK, induced erythema multiforme. Moreover, successful readministration of alectinib through our rechallenge program has not been reported so far. PMID:28101031

  6. AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

    ClinicalTrials.gov

    2016-03-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

  7. Inhibition of p21 and Akt potentiates SU6656-induced caspase-independent cell death in FRO anaplastic thyroid carcinoma cells.

    PubMed

    Kim, S H; Kang, J G; Kim, C S; Ihm, S-H; Choi, M G; Yoo, H J; Lee, S J

    2013-06-01

    SU6656 is a small-molecule indolinone that selectively inhibits Src family kinase and induces death of cancer cells. The aim of the present study was to investigate the influence of SU6656 on cell survival and to assess the role of p21 and PI3K/Akt signaling in cell survival resulting from SU6656 treatment in anaplastic thyroid carcinoma (ATC) cells. When 8505C, CAL62, and FRO ATC cells were treated with SU6656, the viability of 8505C and CAL62 ATC cells decreased only after treatment with SU6656 at a dosage of 100 μM for 72 h, while the viability of FRO ATC cells decreased after treatment with SU6656 in a concentration- and time-dependent manner. Cell viability was not changed by pretreatment with the broad-spectrum caspase inhibitor z-VAD-fmk. Phospho-Src protein levels were reduced, and p21 protein levels were elevated. Phospho-ERK1/2 protein levels were multiplied without alteration of total ERK1/2, total Akt, and phospho-Akt protein levels. Regarding FRO ATC cells, the decrement of cell viability, the increment of cleaved PARP-1 protein levels, and the decrement of phospho-Src protein levels were shown in p21 siRNA- or LY294002-pretreated cells compared to SU6656-treated control cells. ERK1/2 siRNA transfection did not affect cell viability and protein levels of cleaved PARP-1, p21, and Akt. In conclusion, these results suggest that SU6656 induces caspase-independent death of FRO ATC cells by overcoming the resistance mechanism involving p21 and Akt. Suppression of p21 and Akt enhances the cytotoxic effect of SU6656 in FRO ATC cells.

  8. Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature.

    PubMed

    Freeman, Alex; Geddes, Nicola; Munson, Philippa; Joseph, Jean; Ramani, Pramila; Sandison, Ann; Fisher, Cyril; Parkinson, M Connie

    2004-07-01

    Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.

  9. Cognition and Quality of Life After Chemotherapy Plus Radiotherapy (RT) vs. RT for Pure and Mixed Anaplastic Oligodendrogliomas: Radiation Therapy Oncology Group Trial 9402

    SciTech Connect

    Wang Meihua; Cairncross, Gregory; Shaw, Edward

    2010-07-01

    Purpose: Radiation Therapy Oncology Group 9402 compared procarbazine, lomustine, and vincristine (PCV) chemotherapy plus radiation therapy (PCV + RT) vs. RT alone for anaplastic oligodendroglioma. Here we report longitudinal changes in cognition and quality of life, effects of patient factors and treatments on cognition, quality of life and survival, and prognostic implications of cognition and quality of life. Methods and Materials: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL). Scores were analyzed for survivors and within 5 years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those who died, MMSE scores remained stable initially, whereas B-QOL slowly declined; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (p = 0.0413 for MMSE; p = 0.0016 for B-QOL) and were superior with age <50 years (p < 0.001 for MMSE; p = 0.0554 for B-QOL) and Karnofsky Performance Score (KPS) 80-100 (p < 0.001). Younger age and higher KPS were associated with longer survival. After adjusting for patient factors and drop-out, survival was longer after PCV + RT (HR = 0.66, 95% CI = 0.49-0.9, p = 0.0084; HR = 0.74, 95% CI = 0.54-1.01, p = 0.0592) in models with MMSE and B-QOL. In addition, there were no differences in MMSE and B-QOL scores between arms (p = 0.4752 and p = 0.2767, respectively); higher scores predicted longer survival. Conclusion: MMSE and B-QOL scores held steady in the upper range in both arms for survivors. Younger, fitter patients had better MMSE and B-QOL and longer survival.

  10. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

    PubMed Central

    Figarella-Branger, Dominique; Mokhtari, Karima; Dehais, Caroline; Jouvet, Anne; Uro-Coste, Emmanuelle; Colin, Carole; Carpentier, Catherine; Forest, Fabien; Maurage, Claude-Alain; Vignaud, Jean-Michel; Polivka, Marc; Lechapt-Zalcman, Emmanuelle; Eimer, Sandrine; Viennet, Gabriel; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Loussouarn, Delphine; Lacroix, Catherine; Rigau, Valérie; Laquerrière, Annie; Vandenbos, Fanny; Michalak, Sophie; Sevestre, Henri; Peoch, Michel; Labrousse, François; Christov, Christo; Kemeny, Jean-Louis; Chenard, Marie-Pierre; Chiforeanu, Danchristian; Ducray, François; Idbaih, Ahmed; Desenclos, Christine; Menei, Philippe; Al Nader, Edmond; Godard, Joel; Servagi-Vernat, Stéphanie; Carpentier, Antoine; Loiseau, Hugues; Dam-Hieu, Phong; Guillamo, Jean Sebastien; Emery, Evelyne; Verelle, Pierre; Durando, Xavier; Faillot, Thierry; Le Guerinel, Caroline; Ghiringhelli, François; Parker, Fabrice; Adam, Clovis; Dubois, François; Ramirez, Carole; Gueye, Edouard Marcel; Honnorat, Jerome; Chinot, Olivier; Bauchet, Luc; Beauchesne, Patrick; Campone, Mario; Frenel, Jean Sébastien; Fontaine, Denys; Campello, Chantal; Roger, Pascal; Heitzmann, Anne; Fesneau, Mélanie; Delattre, Jean Yves; Elouadhani-Hamdi, Selma; Ricard, Damien; Colin, Philippe; Vauléon, Elodie; Langlois, Olivier; Fotso, Marie Janette Motsuo; Andraud, Marie; Mouton, Servane; Noel, Georges; Desse, Nicolas; Soulard, Raoulin; Cohen-Moyal, Elisabeth; Lubrano, Vincent; Dhermain, Frederic

    2014-01-01

    Background The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). Methods The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. Results 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10−4), IDH1/2 mutation (P < 10−4), chromosome 4 loss (P < 10−3), and better overall survival (P < 10−4). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). Conclusions The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations. PMID:24723566

  11. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    SciTech Connect

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Juergen; Deimling, Andreas von; Hartmann, Christian

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  12. Effect of Slug-Mediated Down-Regulation of E-Cadherin on Invasiveness and Metastasis of Anaplastic Thyroid Cancer Cells

    PubMed Central

    Sheng, Li; Zhang, Shanjuan; Xu, Hui

    2017-01-01

    Background Slug has been found to promote migration and invasion of many cancer cells, including anaplastic thyroid cancer (ATC). Thus, targeting Slug expression could provide new approaches for the treatment of patients with ATC. Material/Methods Small interfering RNA (siRNA) targeting Slug (Slug siRNA) was used to construct clonal derivatives in the metastatic ATC SW1736 cells. Slug cDNA transfection was used to restore the Slug expression in the Slug siRNA-transfected SW1736 cells (Slug siRNA/SW1736). E-cadherin siRNA was used to inhibit E-cadherin expression in the Slug siRNA/SW1736 cells. The SW1736 cell migration, invasion, and signaling pathway was analyzed in vitro. Furthermore, the stable Slug siRNA-transfected SW1736 clones were used for the lung metastasis assay in an in vivo mouse model. Results Targeting Slug expression in SW1736 cells showed a 45% decrease in migration and an 85% decrease in invasiveness in vitro. Knockdown of E-cadherin by E-cadherin siRNA transfection or Slug overexpression by Slug cDNA transfection restored the invasive and migrative ability in SW1736 cells. In addition, we found an 80% decrease in the number of macroscopic lung metastases nodes of mice by in vivo analysis. Western blot assay showed that Slug expression was inhibited and E-cadherin expression was increased in the Slug siRNA-transfected tumors. Conclusions Targeting Slug signaling pathway is effective in preventing lung metastasis in ATC. PMID:28070118

  13. Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation

    PubMed Central

    ONODA, NAOYOSHI; NAKAMURA, MASANORI; AOMATSU, NAOKI; NODA, SATORU; KASHIWAGI, SHINICHIRO; KURATA, KENTO; UCHINO, SHINYA; HIRAKAWA, KOSEI

    2015-01-01

    We previously demonstrated the efficacy of gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), on an anaplastic thyroid cancer (ATC) cell line. We also observed that gefitinib was not effective in regulating cell growth in a different ATC cell line that exhibited an altered EGFR-initiated signal transduction pathway. In the present study, we attempted to regulate the downstream effector of EGFR-Akt-mammalian target of rapamycin (mTOR) pathway by an mTOR inhibitor, everolimus. A total of 8 ATC cell lines were employed, 7 of which were established in our institute. OCUT-2 was known to carry a mutation in the phosphoinositide-3-kinase, catalytic, α polypeptide gene (PI3KCA) and to be gefitinib-resistant, whereas ACT-1 exhibited a remarkable growth arrest by gefitinib. All the cell lines were tested for the cytotoxic effect of everolimus. The mechanisms of cellular toxicity were investigated by EGFR stimulation, cell cycle and concurrent exposure to paclitaxel. In OCUT-2, but not in any of the other cell lines, everolimus achieved a significant growth inhibition (inhibition of 30 and 50% was achieved by concentrations of 0.8 and 5 nM, respectively). The growth in OCUT-2 was inhibited by everolimus, even with concordant EGFR stimulation. This effect was demonstrated by a G2M cell cycle arrest. An additive effect of everolimus onto the cytotoxic effect of paclitaxel was demonstrated at a dose of 1–2 nM. A significant growth inhibitory effect of everolimus on the gefitinib-resistant ATC cell line was demonstrated, suggesting a possible correlation between the efficacy of everolimus and PI3KCA gene mutation and the significance of molecular-targeted therapy in the management of ATC. PMID:26137260

  14. Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells.

    PubMed

    Asghar, Muhammad Yasir; Viitanen, Tero; Kemppainen, Kati; Törnquist, Kid

    2012-10-01

    Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a'-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P(1-3) receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P(1,3) inhibitor VPC-23019, the S1P(2) inhibitor JTE-013, and the S1P(2) receptor siRNA, we showed that the effect was mediated through S1P(2). Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P(2) and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.

  15. Lovastatin inhibits proliferation of anaplastic thyroid cancer cells through up-regulation of p27 by interfering with the Rho/ROCK-mediated pathway.

    PubMed

    Zhong, Wen-Bin; Hsu, Sung-Po; Ho, Pei-Yin; Liang, Yu-Chih; Chang, Tien-Chun; Lee, Wen-Sen

    2011-12-01

    Previously, we demonstrated that lovastatin, a HMG-CoA reductase inhibitor, induced apoptosis, differentiation, and inhibition of invasiveness of human anaplastic thyroid carcinoma cells (ATCs). Here, we further examined the effect of lovastatin on the growth of ARO cells. Lovastatin (0-20μM) concentration-dependently decreased cell number in cultured ATC and arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that lovastatin caused an increase of the protein level of p27 and cyclin-dependent kinase (CDK)4 and a decrease of the protein level of cyclin A2, cyclin D3, and phosphorylated Rb (pRb), but did not significantly change the protein levels of p21, cyclins D1 and E, and CDK2, in ARO cells. The formation of the CDK2-p27 complex was increased and the CDK2 activity was decreased in the lovastatin-treated ARO cells. Pretreatment of ARO cells with a p27, but not p21, antisense oligonucleotide prevented the lovastatin-induced G0/G1 arrest in ARO cells. The lovastatin-induced growth inhibition and translocation of RhoA and Rac1 in ARO cells were completely prevented by mevalonate and partially by geranylgeranyl pyrophosphate. Treatment of ARO cells with Y27632, an inhibitor of Rho-associated kinase, abolished the GGPP-mediated prevention of lovastatin-induced anti-proliferation and up-regulation and prolonged degradation of p27. Taken together, these data suggest that lovastatin treatment caused a reduction of Rho geranylgeranylation, which in turn increased the expression and stability of p27, and then inhibited ARO cell proliferation. These data suggest that lovastatin merits further investigation as multipotent therapy for treatment ATC.

  16. Clinicopathological features and relation between anaplastic lymphoma kinase (ALK) mutation and histological subtype of lung adenocarcinoma in Eastern European Caucasian population

    PubMed Central

    Zaric, Bojan; Stojsic, Vladimir; Panjkovic, Milana; Tegeltija, Dragana; Stepanov, Vanesa; Kovacevic, Tomi; Sarcev, Tatjana; Radosavljevic, Davorin; Milovancev, Aleksandar; Adamidis, Vasilis; Zarogoulidis, Paul; Hohenforst-Schmidt, Wolfgang; Trakada, Georgia; Rapti, Aggeliki; Perin, Branislav

    2016-01-01

    Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation. PMID:27994656

  17. Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma.

    PubMed

    Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Keiko; Kagotani, Akiko; Iwai, Muneo; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Yoshida, Takashi; Okabe, Hidetoshi

    2013-01-01

    IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4-related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder.

  18. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing

    PubMed Central

    Mineva, Ivelina; Gartner, Wolfgang; Hauser, Peter; Kainz, Alexander; Löffler, Michael; Wolf, Gerhard; Oberbauer, Rainer; Weissel, Michael; Wagner, Ludwig

    2005-01-01

    Expression of the small heat shock protein alphaB-crystallin in differentiated thyroid tumors has been described recently. In this study, we investigated the molecular mechanisms that affect the expression of alphaB-crystallin in benign goiters (n = 7) and highly malignant anaplastic thyroid carcinomas (ATCs) (n = 3). AlphaB-crystallin expression was compared with that of Hsp27-1. Immunoblot and quantitative real-time (RT) polymerase chain reaction revealed marked downregulation of alphaB-crystallin in all the tested ATCs and the ATC-derived cell line C-643 . In contrast, considerable expression of Hsp27-1 in benign and malignant thyroid tissue was demonstrated. Immunofluorescence analysis revealed no relevant topological differences between benign and malignant thyrocytes in the cytoplasmic staining of both proteins. Consistent and marked downregulation of TFCP2L1 was identified as one of the main mechanisms contributing to CRYAB gene silencing in ATCs. In addition, CRYAB gene promoter methylation seems to occur in distinct ATCs. In silico analysis revealed that the differential expression of alphaB-crystallin and Hsp27-1 results from differences between the alphaB-crystallin and Hsp27-1 promoter fragments (712 bp upstream from the transcriptional start site). Biological activity of the analyzed promoter element is confirmed by its heat shock inducibility. In conclusion, we demonstrate downregulation of alphaB-crystallin expression in highly dedifferentiated ATCs because of a tumor-specific transcription factor pattern. The differential expression of alphaB-crystallin and Hsp27-1 indicates functional differences between both proteins. PMID:16184762

  19. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing.

    PubMed

    Mineva, Ivelina; Gartner, Wolfgang; Hauser, Peter; Kainz, Alexander; Löffler, Michael; Wolf, Gerhard; Oberbauer, Rainer; Weissel, Michael; Wagner, Ludwig

    2005-01-01

    Expression of the small heat shock protein alphaB-crystallin in differentiated thyroid tumors has been described recently. In this study, we investigated the molecular mechanisms that affect the expression of alphaB-crystallin in benign goiters (n = 7) and highly malignant anaplastic thyroid carcinomas (ATCs) (n = 3). AlphaB-crystallin expression was compared with that of Hsp27-1. Immunoblot and quantitative real-time (RT) polymerase chain reaction revealed marked downregulation of alphaB-crystallin in all the tested ATCs and the ATC-derived cell line C-643 . In contrast, considerable expression of Hsp27-1 in benign and malignant thyroid tissue was demonstrated. Immunofluorescence analysis revealed no relevant topological differences between benign and malignant thyrocytes in the cytoplasmic staining of both proteins. Consistent and marked downregulation of TFCP2L1 was identified as one of the main mechanisms contributing to CRYAB gene silencing in ATCs. In addition, CRYAB gene promoter methylation seems to occur in distinct ATCs. In silico analysis revealed that the differential expression of alphaB-crystallin and Hsp27-1 results from differences between the alphaB-crystallin and Hsp27-1 promoter fragments (712 bp upstream from the transcriptional start site). Biological activity of the analyzed promoter element is confirmed by its heat shock inducibility. In conclusion, we demonstrate downregulation of alphaB-crystallin expression in highly dedifferentiated ATCs because of a tumor-specific transcription factor pattern. The differential expression of alphaB-crystallin and Hsp27-1 indicates functional differences between both proteins.

  20. The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma

    PubMed Central

    Vastolo, Viviana; Di Somma, Sarah; Scamardella, Eloise; Gigantino, Vincenzo; Franco, Renato; Marone, Gianni; Portella, Giuseppe

    2016-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy. PMID:26625205

  1. CPR: Adult

    MedlinePlus

    Refresher Center Home FIRST AID, CPR and AED LIFEGUARDING Refresher Putting It All Together: CPR—Adult (2:03) Refresher videos only utilize this player QUICK LINKS Home RedCross.org Purchase Course ...

  2. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project.

    PubMed

    Savage, Kerry J; Harris, Nancy Lee; Vose, Julie M; Ullrich, Fred; Jaffe, Elaine S; Connors, Joseph M; Rimsza, Lisa; Pileri, Stefano A; Chhanabhai, Mukesh; Gascoyne, Randy D; Armitage, James O; Weisenburger, Dennis D

    2008-06-15

    The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-) ALCL (5-year failure-free survival [FFS], 60% vs 36%; P = .015; 5-year overall survival [OS], 70% vs 49%; P = .016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P = .012) and OS (49% vs 32%; P = .032) were superior for ALK(-) ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-) ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course.

  3. Adult Psychology.

    ERIC Educational Resources Information Center

    Bischof, Ledford J.

    This volume comprehensively reviews the research on the psychology of the middle aged (ages 40-65). Topics include the concept of maturity and maturation models, the measurement and influences of adult self image; marriage and sexual patterns; intergenerational relationships between and children; vocations and avocations (work, retirement, play,…

  4. Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

    ClinicalTrials.gov

    2014-04-21

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma

  5. ADULT EDUCATION OF MIGRANT ADULTS.

    ERIC Educational Resources Information Center

    BEAL, CATHERINE; AND OTHERS

    UNITS ON MIGRANT ADULT EDUCATION, AND A UNIT ON ORGANIZING INFORMAL GROUPS OF MIGRANT WOMEN TO DISCUSS MAINTAINING AND IMPROVING THEIR TEMPORARY HOMES, ARE PRESENTED. THE GOALS OF THE UNIT ON EDUCATION FOR MIGRANT MEN ARE ECONOMIC INDEPENDENCE, BETTER HEALTH AND WELL-BEING, AND BETTER HANDLING OF RESPONSIBILITIES. THE MAIN DIVISIONS OF THE…

  6. Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors.

    PubMed

    Tardy, Sébastien; Orsato, Alexandre; Mologni, Luca; Bisson, William H; Donadoni, Carla; Gambacorti-Passerini, Carlo; Scapozza, Leonardo; Gueyrard, David; Goekjian, Peter G

    2014-02-15

    Chromosomal translocations involving anaplastic lymphoma kinase (ALK) are the driving mutations for a range of cancers and ALK is thus considered an attractive therapeutic target. We synthesized a series of functionalized benzo[4,5]imidazo[1,2-c]pyrimidines and benzo[4,5]imidazo[1,2-a]pyrazines by an aza-Graebe-Ullman reaction, followed by palladium-catalyzed cross-coupling reactions. A sequential regioselective cross-coupling route is reported for the synthesis of unsymmetrically disubstituted benzo[4,5]imidazo[1,2-a]pyrazines. The inhibition of ALK was evaluated and compound 19 in particular showed good activity against both the wild type and crizotinib-resistant L1196M mutant in vitro and in ALK-transfected BaF3 cells.

  7. Thrombospondin-1 Silencing Down-Regulates Integrin Expression Levels in Human Anaplastic Thyroid Cancer Cells with BRAFV600E: New Insights in the Host Tissue Adaptation and Homeostasis of Tumor Microenvironment

    PubMed Central

    Duquette, Mark; Sadow, Peter M.; Lawler, Jack; Nucera, Carmelo

    2013-01-01

    Background and Rationale: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross-talk in the tumor microenvironment. Goals: Our goal was to understand whether TSP-1 could affect protein levels of its integrin receptors (e.g., ITGα3, α6, and β1) and cell morphology in BRAFV600E-ATC cells in vitro and in vivo. Experimental Design: Anaplastic thyroid cancer-derived cell cultures and western blotting were used to assess integrin protein expression upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein expression levels. Results: TSP-1 knock-down down-regulates ITGα3, α6, and β1 in BRAFV600E-human ATC cells. BRAFV600E-ATC cells with TSP-1 knock-down were rounded compared to control cells, which displayed a spread morphology. TSP-1 knock-down also reduced TSP-1, ITGα3, α6, and β1 protein expression levels in vivo in the ATC microenvironment, which is enriched in stromal and inflammatory cells. Conclusion: TSP-1 silencing causes changes in ITG levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might contribute to earlier metastatic potential of BRAFV600E-positive aggressive thyroid cancers, and allow improved patient selection for clinical trials. PMID:24348463

  8. Panic Disorder among Adults

    MedlinePlus

    ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ...

  9. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  10. Adult Development and Learning of Older Adults

    ERIC Educational Resources Information Center

    Roberson, Donald N., Jr.

    2005-01-01

    This summary of adult development covers a wide range of authors. Adult development is one way of understanding how the internal and external changes in our lives have an impact on learning. Of particular importance in this work are the developmental issues of older adults. I present various theories of adult development such as linear and…

  11. Preparing Educators of Adults.

    ERIC Educational Resources Information Center

    Grabowski, Stanley M.; And Others

    Model programs are described for two areas of adult education--the preparation of adult educators and the training conducted by adult educators. In Chapter One, Phyllis Caldwell reviews the literature concerning the preservice training of adult educators, concentrating on the competencies of adult education administrators and teachers. In Chapter…

  12. Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Primary Hepatocellular Carcinoma; Adult Subependymoma; Advanced Adult Primary Liver Cancer; Advanced Malignant Mesothelioma; Male Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Malignant Mesothelioma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage II Esophageal Cancer; Stage II Pancreatic Cancer; Stage III Esophageal Cancer

  13. Adults Need Vaccines, Too!

    MedlinePlus

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  14. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  15. Adult Day Care

    MedlinePlus

    ... Page Resize Text Printer Friendly Online Chat Adult Day Care Adult Day Care Centers are designed to provide care and ... adults who need assistance or supervision during the day. Programs offer relief to family members and caregivers, ...

  16. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  17. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    PubMed

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.

  18. Adult Recruitment Practices.

    ERIC Educational Resources Information Center

    Kaufman, Juliet, Ed.; And Others

    Findings of an American College Testing Program 1981 survey on college recruitment of adult students are summarized, and 12 articles on adult recruitment are presented. Titles and authors are as follows: "Adult Recruitment Practices: A Report of a National Survey" (Patricia Spratt, Juliet Kaufmann, Lee Noel); "Three Programs for Adults in Shopping…

  19. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  20. Clueless? Adult Mysteries with Young Adult Appeal.

    ERIC Educational Resources Information Center

    Charles, John; Morrison, Joanna

    1997-01-01

    Presents a list of adult mystery titles for young adult readers. Includes first titles in a series (for reading in order); new and lesser-known mystery authors' works are the focus. Annotations include plot summary. The rest of each annotation is for professional use (includes date and name of award bestowed). (AEF)

  1. Young Adult Literature for Young Adult Males.

    ERIC Educational Resources Information Center

    Gill, Sam D.

    1999-01-01

    Argues that young adult literature can play a significant role in the emotional and mental health of an adolescent as well as help young males become more literate. Offers a 19-item annotated list of young adult novels with male protagonists, sorted by themes: nature and adventure stories, sports stories, genre stories, historical stories, and…

  2. Natural history and management of brainstem gliomas in adults. A retrospective Italian study.

    PubMed

    Salmaggi, A; Fariselli, L; Milanesi, I; Lamperti, E; Silvani, A; Bizzi, A; Maccagnano, E; Trevisan, E; Laguzzi, E; Rudà, R; Boiardi, A; Soffietti, R

    2008-02-01

    Brainstem gliomas in adults are rare tumors, with heterogeneous clinical course; only a few studies in the MRI era describe the features in consistent groups of patients. In this retrospective study, we report clinical features at onset, imaging characteristics and subsequent course in a group of 34 adult patients with either histologically proven or clinico-radiologically diagnosed brainstem gliomas followed at two centers in Northern Italy. Of the patients 18 were male, 14 female, with a median age of 31. In 21 of the patients histology was obtained and in 20 it was informative (2 pilocytic astrocytoma, 9 low-grade astrocytoma, 8 anaplastic astrocytoma and 1 glioblastoma). Contrast enhancement at MRI was present in 14 patients. In all of the 9 patients who were investigated with MR spectroscopy, the Cho/NAA ratio was elevated at diagnosis. In 8 of the patients, an initial watch and wait policy was adopted, while 24 were treated shortly after diagnosis with either radiotherapy alone [4] or radiotherapy and chemotherapy [20] (mostly temozolomide). Only minor radiological responses were observed after treatments; in a significant proportion of patients (9 out of 15) clinical improvement during therapy occurred in the context of radiologically (MRI) stable disease. Grade III or IV myelotoxicity was observed in 6 patients. After a follow-up ranging from 9 to 180 months, all but 2 patients have progressed and 14 have died (12 for disease progression, 2 for pulmonary embolism). Median overall survival time was of 59 months. Investigation of putative prognostically relevant parameters showed that a short time between disease onset and diagnosis was related to a shorter survival. Compared with literature data, our study confirms the clinical and radiological heterogeneity of adult brainstem gliomas and underscores the need for multicenter trials in order to assess the efficacy of treatments in these tumors.

  3. Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method.

    PubMed

    Zhao, Jing; Zhao, Jin-Yin; Chen, Zhi-Xia; Zhong, Wei; Li, Long-Yun; Liu, Li-Cheng; Hu, Xiao-Xu; Chen, Wei-Jun; Wang, Meng-Zhao

    2016-12-20

    Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/μl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/μl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

  4. Cytological Diagnosis of Bilateral Breast Implant-Associated Lymphoma of the ALK-Negative Anaplastic Large-Cell Type. Clinical Implications of Peri-Implant Breast Seroma Cytological Reporting.

    PubMed

    Granados, Rosario; Lumbreras, Eva M; Delgado, Manuel; Aramburu, José A; Tardío, Juan C

    2016-07-01

    The cytological examination of peri-prosthetic breast effusions allowed the diagnosis of bilateral breast-implant ALK-negative anaplastic large cell lymphoma (BI-ALCL) in the case reported. Ten years after reconstructive surgery with bilateral breast implants, a large unilateral seroma developed and was cytologically analyzed. The presence of CD30 and CD4-positive large-sized atypical lymphoid cells exhibiting horseshoe-shaped nuclei and a brisk mitotic activity rendered the diagnosis of BI-ALCL. Similar cells were seen in the peri-prosthetic fluid intraoperatively collected from the contralateral breast. Although initial histological analysis of the capsulectomy specimens showed unilateral tumor, the cytological findings prompted a more thorough tissue sampling, resulting in the diagnosis of bilateral disease. BI-ALCL usually follows an indolent clinical course; however, there are reported cases with an aggressive behavior. While the presence of bilateral disease is a putative risk factor for a bad prognosis, the small number of cases reported precludes a definitive assessment of this risk. Since most BI-ALCL present with late seromas, cytologic analysis of these effusions in women with breast implants should be mandatory. Cytology is a safe tool for diagnosis and follow-up of patients with breast implant-related late seromas, sometimes proven more sensitive than histological analysis. Complete bilateral capsulectomy and a detailed histological analysis should follow a cytological diagnosis of BI-ALCL in a breast effusion in order to avoid false negative diagnoses. Our case constitutes the first published report of a bilateral BI-ALCL diagnosed by cytology. Diagn. Cytopathol. 2016;44:623-627. © 2016 Wiley Periodicals, Inc.

  5. Imaging diagnosis and fundamental knowledge of common brain tumors in adults.

    PubMed

    Tanaka, Akio

    2006-07-01

    The most common primary brain tumors in Japanese adults are meningiomas, gliomas, pituitary adenomas, and schwannomas, which together account for 84.0% of all primary brain tumors. The typical imaging findings of these tumors are well known by radiologists; therefore, the clinical and pathological issues, including terminology, genetics, and relation to hormones are discussed in this article. Other diseases important for the differential diagnoses are also mentioned. The molecular genetic analysis of brain tumors has recently become important. For instance, genetic analysis is important for differentiating oligodendroglial tumors from astrocytic tumors, and the gene mutation predicts response to chemotherapy for anaplastic oligodendrogliomas. Background factors such as hormones, history of cranial irradiation, and medications influence oncogenesis, tumor growth, and tumor appearances as seen by imaging modalities. A differential diagnosis with knowledge of the above may have some advantages over diagnoses based on imaging findings alone. Nonneoplastic diseases such as abscesses and demyelinating diseases may mimic gliomas. Pituitary adenomas may be confused with nonneoplastic conditions such as physiological hypertrophy and Rathke's cleft cyst. Such misdiagnoses would result in a treatment protocol very different from what would be suitable. Such conditions should be carefully distinguished from neoplasms.

  6. Depression in Older Adults

    ERIC Educational Resources Information Center

    Stickle, Fred; Onedera, Jill D.

    2006-01-01

    The purpose of this article is to address selected aspects of depression in older adults. Specifically, symptoms, risk factors, diagnosis, and interventions for depression in older adults are reviewed.

  7. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  8. Adult Education Update

    ERIC Educational Resources Information Center

    Hall, Clyde W.

    1975-01-01

    Summarized are speeches dealing with adult education's stiff-necked adherence to middle-class values; the need for upgraded management skills; and a report of a study of adult education in area vocational schools in Georgia. (Author/AJ)

  9. Adult Education in Sweden.

    ERIC Educational Resources Information Center

    Miller, Harry; And Others

    Folk high schools, study circles, labor market training, union education, and municipal adult schools are the major providers of adult education in Sweden. For the most part, these programs are financed by the government and are tuition free. Folk high schools, which are the oldest type, were founded to provide young adults with a general civic…

  10. The Adult Experience.

    ERIC Educational Resources Information Center

    Belsky, Janet

    The 14 chapters of this textbook chronicle adult development from youth through old age, emphasizing both research and interviews with adults at various stages in their lives. Topics covered include the following: (1) the academic field of adult development; (2) theories and research methods; (3) aging and disease prevention; (4) sexuality and…

  11. Adult Survival Skills Assessment.

    ERIC Educational Resources Information Center

    Walsko, Gregory M.

    The purpose of this instrument is to supplement data from the Adult Basic Learning Examination in assessing the functional level of adults in daily situations. It may also be used as a teaching tool for adults requesting tutoring in specific concepts and skills presented in the instrument. This instrument is an informal assessment instrument and…

  12. Kids Who Outwit Adults.

    ERIC Educational Resources Information Center

    Seita, John R.; Brendtro, Larry K.

    Kids who distrust adults are highly skilled at hiding their real nature and resisting change. Most adults shun such youths or get mired in conflict with them. Punitive get tough practices as well as traditional flaw-fixing treatment are reactive strategies that often drive these youths further from adult bonds and reinforce oppositional and…

  13. Urbanization and Adult Education

    ERIC Educational Resources Information Center

    Short, W. Fisher

    1974-01-01

    The impact of urbanization, the main tasks facing the adult educator in an urban context, identifying the casualties of urbanization, recognizing and dealing with social deprivation, and the various agencies involved in adult education are relevant considerations for adult educators. (MW)

  14. Dimensions of Adult Learning

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    2004-01-01

    This broad introduction to adult and postcompulsory education offers an overview of the field for students, adult educators and workplace trainers. The book establishes an analytical framework to emphasize the nature of learning and agency of learners; examines the core knowledge and skills that adult educators need; discusses policy, research and…

  15. Adult Learning: A Reader.

    ERIC Educational Resources Information Center

    Sutherland, Peter, Ed.

    This book on adult learning is divided into six sections. Section 1, Cognitive Processes, includes the following chapters: "Cognitive Processes: Contemporary Paradigms of Learning" (Jack Mezirow); "Information Processing, Memory, Age and Adult Learning" (Gillian Boulton-Lewis); "Adult Learners' Metacognitive Behaviour in Higher Education" (Barry…

  16. Adult Education in Israel.

    ERIC Educational Resources Information Center

    Kirmayer, Paul, Ed.; And Others

    This volume contains 13 articles that reflect the development of adult education in Israel during recent years. The material relates to the principal areas with which the Division of Adult Education deals: formal and nonformal education for adults, language and cultural absorption of new immigrants, and training of facilitators for parental…

  17. Adults Role in Bullying

    ERIC Educational Resources Information Center

    Notar, Charles E.; Padgett, Sharon

    2013-01-01

    Do adults play a role in bullying? Do parents, teachers, school staff, and community adult leaders influence bullying behavior in children and teenagers? This article will focus on research regarding all adults who have almost daily contact with children and teens and their part in how bullying is identified, addressed, and prevented. This article…

  18. Adult Education in Greece

    ERIC Educational Resources Information Center

    Kokkos, Alexios

    2008-01-01

    The central aim of this article is to analyse the current situation of adult education in Greece. The article focuses on the following points: (a) the degree of participation in programmes of continuing professional training and general adult education courses, (b) the quality and the outcomes of the adult education provision in Greece, and (c)…

  19. Adult Competency Education Profile.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of abstracts of 120 current Adult Performance Level (APL) and Adult Competency Education (ACE) federally supported projects being conducted in 34 States and the District of Columbia, this project profile was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are currently…

  20. Adult Competency Education Resources.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of brief descriptions of 20 current resources for Adult Performance Level (APL) and Adult Competency Education (ACE) programs, this guide was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are already involved with APL/ACE programs. Each citation contains information…

  1. Adult Academy Volunteer Manual.

    ERIC Educational Resources Information Center

    Cora, Marie T., Ed.; Wood, Nicole R., Ed.

    This handbook was written specifically for volunteer tutors but is appropriate for teachers, student interns, coordinators, and others working with Adult Basic Education (ABE) and English-as-a-Second-Language (ESL) adult learners. It presents an overview of adult and non-traditional education models, some principles of reading and writing, a…

  2. Canadian Adult Basic Education.

    ERIC Educational Resources Information Center

    Brooke, W. Michael, Comp.

    "Trends," a publication of the Canadian Association for Adult Education, is a collection of abstracts on selected subjects affecting adult education; this issue is on adult basic education (ABE). It covers teachers and teacher training, psychological factors relating to the ABE teacher and students, manuals for teachers, instructional…

  3. Young Adult Services Manual.

    ERIC Educational Resources Information Center

    Boegen, Anne, Ed.

    Designed to offer guidelines, ideas and help to those who provide library service to young adults, this manual includes information about the provision of young adult (YA) services in six sections. The first section, which addresses planning and administration, includes a definition of a young adult and a checklist for determining community needs…

  4. Adult Educators' Core Competences

    ERIC Educational Resources Information Center

    Wahlgren, Bjarne

    2016-01-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned…

  5. An Adult ESL Curriculum.

    ERIC Educational Resources Information Center

    South Carolina Literacy Resource Center, Columbia.

    This curriculum framework for adult literacy was written by 21 South Carolina adult English-as-a-Second-Language (ESL) instructors, as submitted to the South Carolina Literacy Resource Center. It is based on current theories in the fields of adult education and second language acquisition and is designed to be flexible so that it may be adapted to…

  6. Obsessive Compulsive Disorder among Adults

    MedlinePlus

    ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ...

  7. The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide.

    PubMed

    Strowd, Roy E; Abuali, Inas; Ye, Xiaobu; Lu, Yao; Grossman, Stuart A

    2016-03-01

    Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23-43). Survival was longer in the post-2004 cohort (37 mo, 24-64) than pre-2004 (27 mo, 19-40; HR 0.75, 0.53-1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44-0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of

  8. Effects of adenovirus-mediated expression of p27Kip1, p21Waf1 and p16INK4A in cell lines derived from t(2;5) anaplastic large cell lymphoma and Hodgkin's disease.

    PubMed

    Turturro, Franceso; Arnold, Marilyn D; Frist, Audrey Y; Seth, Prem

    2002-06-01

    We investigated the response of SUDHL-1 and L428 cells, derived from t(2;5)-anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD), respectively, to recombinant adenoviruses expressing cyclin-dependent kinase inhibitors (CDKIs) p27Kip1 (Adp27), p21Waf1 (Adp21) and p16INK4A (Adp16). Cell cycle analysis of SUDHL-1 cells after 24 h of infection with 200 multiplicity of infection (MOI) of Adp27, Adp21, and Adp16, showed very high levels of cell debris in the subG1 area. The magnitude of cell debris-events was Adp27/Adp21 > Adp16. Cell cycle analysis of L428 cells revealed absence of cell debris and increased G2 phase in all the groups of cells tested as compared to the controls (mock and AdNull). A minimal increase in G1 phase was also evident in cells infected with Adp27 (52%) compared to uninfected cells (43%), AdNull (45%) and to cells infected with Adp21 (37%) and Adp16 (31%). The presence of significant levels of Coxsackie-adenovirus receptor (CAR) on the cell surface of L428 cells excluded the cell membrane-barrier as responsible for the differences in cell observed in response to the recombinant adenovirus-mediated CDKIs expression as compared to SUDHL-1. We also showed that the recombinant adenovirus-mediated cytotoxicity measured as apoptosis was MOI- and vector-dependent in SUDHL-1 cells at lower MOI (100). In conclusion, the therapeutic effect induced by recombinant adenoviruses expressing p27Kip1, p21Waf1 and p16INK4A is cell-dependent in cells derived from selected lymphoid malignancies. Biochemical cellular differences more than cell surface barriers seem to be responsible for differences in response to recombinant adenovirus-mediated expression of cytotoxic genes. Moreover, the cytotoxicity of recombinant adenoviruses expressing p27Kip1, p21Waf1 and p16INK4A may be further explored as a tool for gene therapy of t(2;5)-derived ALCL.

  9. Adult Education Regional Planning

    ERIC Educational Resources Information Center

    California Community Colleges, Chancellor's Office, 2015

    2015-01-01

    For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

  10. Young Adult Library Services.

    ERIC Educational Resources Information Center

    The Bookmark, 1985

    1985-01-01

    Eight articles in this Spring 1985 issue of The Bookmark focus on young adult library services. In addition to these thematic articles, an introduction and three reports are presented. The issue contains: (1) "In Perspective" (E. J. Josey); (2) "Young Adult Literature in the 1980's--Awesome!" (Ellin Chu); (3) "Young Adult…

  11. Toward Transpersonal Adult Development

    ERIC Educational Resources Information Center

    Boucouvalas, Marcie

    2016-01-01

    As a foundation for discussing transpersonal adult development, the author traces her trajectory, involvement in, and contribution to the modern transpersonal movement and her introduction of it to the adult learning literature, beginning during the early 1980s. Highlighted are the transpersonal domain and a differentiation between transpersonal…

  12. Adult Day Services

    MedlinePlus

    A Smart Choice Adult Day Services Comparison At-a-Glance 1 Adult Day Services Assisted Living Home Care Nursing Homes Live at home with family ... supervision Nursing care available as needed during the day Flexibility to receive care only on days when ...

  13. Adult Tech Prep.

    ERIC Educational Resources Information Center

    Schaad, Donna

    For over 2 years, Blak Hawk College (Illinois) has provided high school equivalency (GED) candidates and recipients, older returning students, and underprepared high school graduates with a Tech Prep curriculum to give them the skills to make the transition from adult basic education to college or work. The Adult Tech Prep (ATP) core curriculum…

  14. Authenticity in Adult Learning

    ERIC Educational Resources Information Center

    Ashton, Sam

    2010-01-01

    This paper is concerned with the relationship between authenticity and adult learning and prompted by some studies in which adult "authentic learning" is a central concept. The implication revealed by them is that real-worldness of learning contexts, learning content and learning tasks is perceived as conferring authenticity on learning. Here,…

  15. Adult Learning and Education

    ERIC Educational Resources Information Center

    Rubenson, Kjell, Ed.

    2011-01-01

    As individuals and societies try to respond to fundamental economic and social transformation, the field of adult learning and education is rapidly getting increased attention and new topics for research on adult learning have emerged. This collection of articles from the International Encyclopedia of Education 3e offers practitioners and…

  16. Today's Adult Students

    ERIC Educational Resources Information Center

    Reese, Susan

    2012-01-01

    Who are the adult students in career and technical education (CTE) today? There is not one simple answer to that question. Some are young with little life experience, while others are returning to the workforce and learning new skills to reinvent themselves. Whatever the case, educating adult students is an integral part of ACTE's mission, and the…

  17. Adult Literacy in Zanzibar.

    ERIC Educational Resources Information Center

    Saadat, Ahmed H.

    The philosophy behind adult literacy in Zanzibar is that adult literacy is a process whereby the illiterate is empowered to become aware of his or her potential. Literacy activities emphasize a relation to work, sometimes known as functional literacy. Specific objectives of literacy programs are to improve living conditions, impart self-reliant…

  18. Adult Vocational Trajectory.

    ERIC Educational Resources Information Center

    Riverin-Simard, Danielle

    1990-01-01

    Proposes a "spatial-temporal" model conceiving adult vocational development as a complex and constant readjustment in always changing perception of personal space-time, based on interviews of 786 adults. Presents two propositions of this model: the continuous alternation between states of instability and interaction of influences.…

  19. Counseling Adult Adoptees

    ERIC Educational Resources Information Center

    Corder, Kate

    2012-01-01

    This review presents various resources about working with adult adoptees in order to inform counselors in their practice. Topics covered include basics of adoption, including types of adoption and adoption statistics; possible issues adult adoptees may face; and suggestions and implications for counselors. The article addresses some of the serious…

  20. Alternative Programming for Adults.

    ERIC Educational Resources Information Center

    Flint, Thomas A.; Frey, Ruth

    2003-01-01

    The Council for Adult and Experiential Learning is currently cataloguing alternative programming features that are most effective with adult students in a best practices inventory organized around a framework of high-level descriptive principles of effectiveness. This chapter identifies a few interesting features from a quick survey of this…

  1. Adult Education and Development.

    ERIC Educational Resources Information Center

    Hinzen, Heribert, Ed.

    2002-01-01

    This document contains 19 papers on adult education and development worldwide. The following papers are included: "Editorial" (Heribert Hinzen); "Lifelong Learning in Europe: Moving towards EFA (Dakar Framework for Action on Education for All) Goals and the CONFINTEA V Agenda" (Sofia Conference on Adult Education);…

  2. Adult Education in Finland

    ERIC Educational Resources Information Center

    Szekely, Radu

    2006-01-01

    Ever since the first ideas of national independence appeared in Finland, adult education has played an essential role in shaping the destiny of the Finns. With a history of almost 130 years, during which it has continuously increased in quality and quantity, the Finnish adult education system has ensured that Finland stays among the most…

  3. Financing of Adult Education

    ERIC Educational Resources Information Center

    Archer, David

    2007-01-01

    The 2008 EFA Global Monitoring Report recognises adult literacy as the most neglected of the EFA goals. It is neglected most obviously in respect of the financial allocations made by governments and donors. This shortage of financing creates a dangerous situation in which adult educators seek to convince politicians to invest, based on false…

  4. Gender Dysphoria in Adults.

    PubMed

    Zucker, Kenneth J; Lawrence, Anne A; Kreukels, Baudewijntje P C

    2016-01-01

    Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater client autonomy, and improved understanding of the benefits and limitations of current treatment modalities.

  5. Depression in Older Adults

    PubMed Central

    Fiske, Amy; Wetherell, Julie Loebach; Gatz, Margaret

    2010-01-01

    Depression is less prevalent among older adults than among younger adults but can have serious consequences. Over half of cases represent a first onset in later life. Although suicide rates in the elderly are declining, they are still higher than in younger adults and more closely associated with depression. Depressed older adults are less likely to endorse affective symptoms and more likely to display cognitive changes, somatic symptoms, and loss of interest than are younger adults. Risk factors leading to the development of late life depression likely comprise complex interactions among genetic vulnerabilities, cognitive diathesis, age-associated neurobiological changes, and stressful events. Insomnia is an often overlooked risk factor for late life depression. We suggest that a common pathway to depression in older adults, regardless of which predisposing risks are most prominent, may be curtailment of daily activities. Accompanying self-critical thinking may exacerbate and maintain a depressed state. Offsetting the increasing prevalence of certain risk factors in late life are age-related increases in psychological resilience. Other protective factors include higher education and socioeconomic status, engagement in valued activities, and religious or spiritual involvement. Treatments including behavioral therapy, cognitive behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy, and life review/reminiscence therapy are effective but too infrequently used with older adults. Preventive interventions including education for individuals with chronic illness, behavioral activation, cognitive restructuring, problem-solving skills training, group support, and life review have also received support. PMID:19327033

  6. Mosquito, adult (image)

    MedlinePlus

    This illustration shows an adult southern house mosquito. This mosquito feeds on blood and is the carrier of many diseases, such as encephalitis, West Nile, dengue fever, yellow fever, and others. ( ...

  7. Older Adults and Alcohol

    MedlinePlus

    ... Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & Fact Sheets NIAAA ... are here Home » Alcohol & Your Health » Special Populations & Co-occurring Disorders » Older Adults In this Section Underage ...

  8. Speech impairment (adult)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  9. Motivation and Adult Education

    ERIC Educational Resources Information Center

    Veeraraghavan, J.

    1974-01-01

    The paper examines the role of adult education and the contribution it can make to the solution of current problems in developing countries, particularly the problems of economic under-development and over-population. (Author/AG)

  10. Motivation and Adult Education.

    ERIC Educational Resources Information Center

    Taylor, J. Rodney

    1982-01-01

    The author reviews theories of human motivation: Lewin's force field analysis, Skinner's operant reinforcement theory, and Maslow's hierarchy of needs. He then extracts the implications of these theories for adult learning. SK)

  11. Older Adults and Depression

    MedlinePlus

    ... find more information? Reprints Share Older Adults and Depression Download PDF Download ePub Order a free hardcopy ... depression need treatment to feel better. Types of Depression There are several types of depression. The most ...

  12. Young Adult Books.

    ERIC Educational Resources Information Center

    Epstein, Connie C.

    1987-01-01

    Considers the similarities between science fiction writing and young adult literature, and points out that several well-known authors, such as Robert Heinlein and Jane Yolen, write in both genres. (NKA)

  13. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  14. Adult educators' core competences

    NASA Astrophysics Data System (ADS)

    Wahlgren, Bjarne

    2016-06-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or "core" requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students' prior learning into account; (3) supporting a learning environment; and (4) the adult educator's reflection on his or her own performance. At the end of his analysis of different competence profiles, the author notes that adult educators' ability to train adult learners in a way which then enables them to apply and use what they have learned in practice (thus performing knowledge transfer) still seems to be overlooked.

  15. [Orthodontic treatment for adults].

    PubMed

    Kuitert, R B

    2000-04-01

    The number of adults undergoing orthodontic treatment has increased strongly and the average age that adult patients undergo orthodontic treatment increased steadily although 3/4 is still younger than 27 years. In adults the facial skeletal pattern can only be changed in a very confined way, consequently in case of an abnormal skeletal pattern one has to choose between a combined orthodontic-surgical approach (which is the case in 18% of the patients) and a compromised orthodontic treatment, if necessary combined with other disciplines. It is still controversial whether tooth movement in adults is slower and more difficult than in adolescents. The same holds true for the risk for loss of periodontal support, for root resorption, for gnathologic problems and for relapse. As related to these variables there appears to be a large individual variation. Many adults show one or more problems in their dentition that may influence their orthodontic treatment. About 60% of the adult patients need a multidisciplinary approach. The development of implantology and of bone regeneration and bone grafting has lead to more combined treatments. The risks of such complex treatment plans are generally larger than those for more simple kinds of treatment. A very careful treatment planning and good communication between the different specialists is essential. Moreover the treatment plan with all its (dis)advantages has to be extensively discussed with the patient.

  16. P17.41CLINICAL MANAGEMENT AND OUTCOME OF HISTOLOGICALLY VERIFIED ADULT BRAINSTEM GLIOMAS IN SWITZERLAND: A RETROSPECTIVE ANALYSIS OF 21 PATIENTS

    PubMed Central

    Hundsberger, T.; Tonder, M.; Andreas, H.; Brügge, D.; Roelcke, U.; Putora, P.M.; Stupp, R.; Weller, M.

    2014-01-01

    BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (>age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

  17. The State of Adult Education

    ERIC Educational Resources Information Center

    Fleming, Ted

    2004-01-01

    In this paper, the author looks at the state of adult education in Ireland. He is suggesting that the state here means both the condition in which one now finds adult education and the role of the Irish State in adult education. He briefly outlines some recent developments in adult education, makes some critical comments on the state of adult…

  18. The ABC's of Adult Ed

    ERIC Educational Resources Information Center

    Roehrig, Lucy

    2010-01-01

    According to the 2003 National Assessment of Adult Literacy, it is estimated that 93 million adults in the United States have basic or below basic literacy skills. Those individuals found most lacking in literacy skills were adults living in poverty, adults lacking a high school diploma, seniors and the elderly aged 65 and older, the more than one…

  19. Designing an Adult Education Program.

    ERIC Educational Resources Information Center

    Rand, Margaret

    Intended for planners of adult education curriculums, this literature review explains the concepts involved in designing an adult education program, provides information about the roles of the people involved in the adult education process, cites some program planning models, and applies the program planning principles to an Adult Basic Education…

  20. The Adult Learner: Four Aspects.

    ERIC Educational Resources Information Center

    Lucas, John A., Ed.

    1986-01-01

    Topics concerning the adult learner that are relevant to institutional researchers are addressed in four articles: marketing, predicting success for adult students, enrollment projection, and follow-up studies of adult learners. In "Institutional Research in Support of Marketing the Adult Student," Lydia Jurand notes the importance of…

  1. Rich Environments for Adult Learners

    ERIC Educational Resources Information Center

    Bentham, Renee

    2008-01-01

    Unaware of the messages a bare adult learning environment sends and its effect on adult learners, a trainer attends an intensive Reggio Emilia course and learns that the physical environment is the "third teacher"--for adults as well as for children. Using principles of Reggio, she offers suggestions for enhancing adult learning spaces and…

  2. Adult-onset Atopic Dermatitis

    PubMed Central

    Kanwar, Amrinder Jit

    2016-01-01

    Adult-onset atopic dermatitis is still an under recognized condition as there are only few studies regarding this entity. As compared to childhood onset atopic dermatitis, clinical features of adult onset atopic dermatitis are still not categorized. Adult atopic dermatitis can present for the first time in adult age with atypical morphology or may progress from childhood onset. This article reviews the characteristic clinical features of adult atopic dermatitis, associated risk factors and management. PMID:27904186

  3. Adult onset retinoblastoma

    PubMed Central

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-01-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  4. Adult Seborrheic Dermatitis

    PubMed Central

    2011-01-01

    Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal “device ”cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population. PMID:21607192

  5. Electroporation of adult zebrafish.

    PubMed

    Rao, N Madhusudhana; Rambabu, K Murali; Rao, S Harinarayana

    2008-01-01

    We generated transient transgenic zebrafish by applying electrical pulses subsequent to injection of DNA into muscle tissue of 3-6-month old adult zebrafish. Electroporation parameters, such as number of pulses, voltage, and amount of plasmid DNA, were optimized and found that 6 pulses of 40 V/cm at 15 mug/fish increased the luciferase expression by 10-fold compared with those in controls. By measuring the expression of luciferase, in vivo by electroporation in adult zebrafish and in vitro using fish cell line (Xiphophorus xiphidium A2 cells), the strength of three promoters (CMV, human EF-1alpha, and Xenopus EF-1alpha) was compared. Subsequent to electroporation after injecting DNA in the mid region of zebrafish, expression of green fluorescent protein was found far away from the site of injection in the head and the tail sections. Thus, electroporation in adult zebrafish provides a rapid way of testing the behavior of gene sequences in the whole organism.

  6. Back pain in adults.

    PubMed

    Becker, Jonathan A; Stumbo, Jessica R

    2013-06-01

    This article provides a summary of the many causes of back pain in adults. There is an overview of the history and physical examination with attention paid to red flags that alert the clinician to more worrisome causes of low back pain. An extensive differential diagnosis for back pain in adults is provided along with key historical and physical examination findings. The various therapeutic options are summarized with an emphasis on evidence-based findings. These reviewed treatments include medication, physical therapy, topical treatments, injections, and complementary and alternative medicine. The indications for surgery and specialty referral are also discussed.

  7. [Adult oligosymptomatic coeliac disease].

    PubMed

    Cabral Rodríguez, R; Arrieta Blanco, F J; Vicente Sánchez, F; Cordobés Martín, F J; Moreno Caballero, B

    2004-12-01

    Coeliac disease is a chronic pathology of the small intestine. The pathogenic mechanism is caused by gluten intolerance. This disease present a characteristic and unspecific injury that causes nutrients and vitamins malabsorption. In adults is an underdiagnosed entity due to atypical forms. To make a premature diagnosis is basic because gluten-free diet prevent the complications after long-term like the intestinal T lymphoma and other digestives malignancies, and decrease the mortality of these patients. We present a case of adult oligosymptomatic coeliac disease in a patient with iron deficiency anaemia and vaginal bleeding. We study the clinic-nutrition and the alterations evolution of the patient.

  8. Adult Learning Matters

    ERIC Educational Resources Information Center

    Adults Learning, 2009

    2009-01-01

    The Campaigning Alliance for Lifelong Learning is to lobby parliament for the restoration of the 1.5 million adult learning places lost over the past two years. The campaign has attracted supporters from an astonishingly wide range of backgrounds. In this article, Gordon Marsden, Caroline Biggins, Beth Walker, Mike Chaney, Peter Davies, Sian…

  9. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  10. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  11. Older Adult Education.

    ERIC Educational Resources Information Center

    Forman, Jeffrey

    In an effort to improve the quality of life for area senior citizens, De Anza College has established an older adult education program which combines adaptive physical education with holistic health care principles to instruct students in relaxation, nutrition, and physical activity. Classes are held in convalescent hospitals, retirement homes,…

  12. Adult Education in Brazil.

    ERIC Educational Resources Information Center

    Ministerio da Educacao e Cultura, Rio de Janeiro (Brazil).

    The status and goals of adult education programs in Brazil are discussed in this report. Supplemental systems such as the Brazilian Literacy Movement (Mobral) and their results are described and evaluated. Charts detailing the evolution of literacy are shown and priorities in education are suggested. The progress of other educational entities is…

  13. Adult Basic Education Curriculum.

    ERIC Educational Resources Information Center

    Massachusetts Career Development Inst., Springfield.

    This booklet, aimed at adult basic education students, pinpoints and summarizes a few common spelling rules to help make spelling easier, and includes a component on using the dictionary. In the text, each rule is presented with many examples. Exercises follow each spelling rule, allowing students the opportunity to apply the rule to specific…

  14. Police and Adult Education.

    ERIC Educational Resources Information Center

    Sims, Vic

    The literature on adult education for police is reviewed and criticized. Among the publications that have been influential in debating the need for police education are Charles B. Saunder's "The Challenge of Crime in a Free Society" (1976), which endorses the Presidential Commission on Law Enforcement's recommendations regarding the vital…

  15. Dance for Older Adults.

    ERIC Educational Resources Information Center

    Pruett, Diane Milhan, Ed.; And Others

    1983-01-01

    Dance programs for older adults that encourage exercise and socializing are described in six articles. Program guidelines of the American Alliance Committee on Aging are explained, and other articles emphasize a movement education approach that may involve intergenerational contact. A dance program held in a worship setting is also discussed. (PP)

  16. Migration and Adult Education

    ERIC Educational Resources Information Center

    Gois, William

    2007-01-01

    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  17. How Do Adults Learn?

    ERIC Educational Resources Information Center

    Rogers, Alan; Illeris, Knud

    2003-01-01

    This dialog between Alan Rogers and Knud Illeris debates arguments Rogers made in a previous article about the differences between adult and child learning. Rogers emphasizes differences in teacher-learner relationships. Illeris believes the differences result from different motivations for learning. (SK)

  18. Encyclopedia of Adult Development.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert, Ed.

    This encyclopedia contains 106 articles on adult development that were written by more than 75 specialists in such diverse fields as anthropology, communication, education, health sciences, history, and psychology. In a guide to related topics that is presented at the beginning of the encyclopedia, the 106 articles are grouped under the following…

  19. Sinusitis in adults - aftercare

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000563.htm Sinusitis in adults - aftercare To use the sharing features on this page, please enable JavaScript. Your sinuses are chambers in ... They are filled with air. Sinusitis is an infection of these chambers, which causes ...

  20. Helping Adults to Spell.

    ERIC Educational Resources Information Center

    Moorhouse, Catherine

    This book presents a range of strategies for adult literacy tutors and offers a wealth of practical advice on teaching spelling within the context of writing. Chapters 1-3 offer basic information on talking with the student about spelling, finding out how the student spells and helping the student to see himself/herself as a "good" speller, and…