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Sample records for adult anaplastic oligodendroglioma

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Clinical management of grade III oligodendroglioma

    PubMed Central

    Simonetti, G; Gaviani, P; Botturi, A; Innocenti, A; Lamperti, E; Silvani, A

    2015-01-01

    Oligodendrogliomas represent the third most common type of glioma, comprising 4%–15% of all gliomas and can be classified by degree of malignancy into grade II and grade III, according to WHO classification. Only 30% of oligodendroglial tumors have anaplastic characteristics. Anaplastic oligodendroglioma (AO) is often localized as a single lesion in the white matter and in the cortex, rarely in brainstem or spinal cord. The management of AO is deeply changed in the recent years. Maximal safe surgical resection followed by radiotherapy (RT) was considered as the standard of care since paramount findings regarding molecular aspects, in particular co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19, revealed that these subsets of AO, benefit in terms of overall survival (OS) and progression-free survival (PFS), from the addition of chemotherapy to RT. Allelic losses of chromosomes 1p and 19q occur in 50%–70% of both low-grade and anaplastic tumors, representing a strong prognostic factor and a powerful predictor of prolonged survival. Several other molecular markers have potential clinical significance as IDH1 mutations, confirming the strong prognostic role for OS. Malignant brain tumors negatively impacts on patients’ quality of life. Seizures, visual impairment, headache, and cognitive disorders can be present. Moreover, chemotherapy and RT have important side effects. For these reasons, “health-related quality of life” is becoming a topic of growing interest, investigating on physical, mental, emotional, and social well-being. Understanding the impact of medical treatment on health-related quality of life will probably have a growing effect both on health care strategies and on patients. PMID:26251628

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma.

    PubMed

    Reuss, David E; Sahm, Felix; Schrimpf, Daniel; Wiestler, Benedikt; Capper, David; Koelsche, Christian; Schweizer, Leonille; Korshunov, Andrey; Jones, David T W; Hovestadt, Volker; Mittelbronn, Michel; Schittenhelm, Jens; Herold-Mende, Christel; Unterberg, Andreas; Platten, Michael; Weller, Michael; Wick, Wolfgang; Pfister, Stefan M; von Deimling, Andreas

    2015-01-01

    Diffuse gliomas are represented in the 2007 WHO classification as astrocytomas, oligoastrocytomas and oligodendrogliomas of grades II and III and glioblastomas WHO grade IV. Molecular data on these tumors have a major impact on prognosis and therapy of the patients. Consequently, the inclusion of molecular parameters in the WHO definition of brain tumors is being planned and has been forwarded as the "ISN-Haarlem" consensus. We, here, analyze markers of special interest including ATRX, IDH and 1p/19q codeletion in a series of 405 adult patients. Among the WHO 2007 classified tumors were 152 astrocytomas, 61 oligodendrogliomas, 63 oligoastrocytomas and 129 glioblastomas. Following the concepts of the "ISN-Haarlem", we rediagnosed the series to obtain "integrated" diagnoses with 155 tumors being astrocytomas, 100 oligodendrogliomas and 150 glioblastomas. In a subset of 100 diffuse gliomas from the NOA-04 trial with long-term follow-up data available, the "integrated" diagnosis had a significantly greater prognostic power for overall and progression-free survival compared to WHO 2007. Based on the "integrated" diagnoses, loss of ATRX expression was close to being mutually exclusive to 1p/19q codeletion, with only 2 of 167 ATRX-negative tumors exhibiting 1p/19q codeletion. All but 4 of 141 patients with loss of ATRX expression and diffuse glioma carried either IDH1 or IDH2 mutations. Interestingly, the majority of glioblastoma patients with loss of ATRX expression but no IDH mutations exhibited an H3F3A mutation. Further, all patients with 1p/19 codeletion carried a mutation in IDH1 or IDH2. We present an algorithm based on stepwise analysis with initial immunohistochemistry for ATRX and IDH1-R132H followed by 1p/19q analysis followed by IDH sequencing which reduces the number of molecular analyses and which has a far better association with patient outcome than WHO 2007.

  2. Vascular Endothelial Growth Factor as an Angiogenic Marker in Malignant Astrocytoma and Oligodendroglioma: An Indian Scenario

    PubMed Central

    Vokuda, Ramya S; Srinivas, Bheemanathi Hanuman; Madhugiri, Venkatesh S

    2017-01-01

    Introduction The role of Vascular Endothelial Growth Factor (VEGF) in angiogenesis has been extensively studied in gliomas, such as astrocytoma and oligodendrogliomas, worldwide. However, there is limited information available with regard to the Indian population. Aim To study, whether VEGF is expressed in the Indian population in a pattern similar to that in other population. Materials and Methods In this prospective study approved by the Institute Ethics Committee for Human Studies at Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER) the patients operated for glioma in 2014 and 2015 (n = 60) were included. Tumours were graded as per the World Health Organization (WHO) grading system. VEGF expression in various grades was analysed using immunohistochemistry. Results Of the 60 patients included in this study, 15 were Grade II- (diffuse astrocytomas – 12; oligodendrogliomas- 3), 15 were Grade III-(anaplastic astrocytomas- 2; anaplastic oligodendrogliomas – 13) and 30 were Grade IV-glioblastomas. For VEGF antibody staining, two patients (3.33%) showed negative results and 58 patients (96%) showed positive results. VEGF positivity was 100% in Grade II and III, while it was 93.3% (28/30) in Grade IV tumours (p=0.012). Conclusion The expression of VEGF was associated with the grade of tumour, which gradually increased from Grade II to Grade IV. We conclude that VEGF-regulated angiogenesis plays an important role in tumour progression of astrocytomas and oligodendrogliomas in the Indian population as observed worldwide.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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 ...

  9. 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

  10. 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

  11. 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

  12. Oligodendroglioma

    MedlinePlus

    ... The most common symptoms are seizures, headaches, and personality changes. Other symptoms vary by location and size ... cause weakness on one side of the body, personality or behavior changes, and difficulty with short-term ...

  13. Recurrent Oligodendroglioma Treated with Acupuncture and Pharmacopuncture.

    PubMed

    Kim, Jae Soo; Lee, Hyun Jong; Lee, Sang Hoon; Lee, Bong Hyo

    2015-06-01

    Acupuncture and pharmacopuncture have been shown to be effective in tumor treatment. However, their effectiveness for treating oligodendroglioma has not been reported yet. The purpose of this study was to provide an initial report on the effectiveness of acupuncture and pharmacopuncture for the treatment of an oligodendroglioma by presenting a case that was treated successfully. A 54-year-old man, who had experienced intracranial hemorrhage, was diagnosed with recurrent oligodendroglioma. His expected survival period was 3-6 months. The patient received daily acupuncture and weekly pharmacopuncture of mountain ginseng and bee venom. After treatment for 18 months, the tumor size was decreased markedly on brain magnetic resonance imaging, and severe seizures had disappeared. In this case, a combination of acupuncture and pharmacopuncture was shown to be effective for the treatment of recurrent oligodendroglioma.

  14. 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

  15. 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

  16. 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

  17. 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

  18. [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.

  19. 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

  20. ADAM 12: A Putative Marker of Oligodendrogliomas?

    PubMed Central

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours. PMID:23324579

  1. ADAM 12: a putative marker of oligodendrogliomas?

    PubMed

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours.

  2. Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma

    PubMed Central

    Doucette, Tiffany; Fuller, Gregory N.; Yang, Yuhui; Suki, Dima; Zhang, Wei; Fults, Daniel W.

    2011-01-01

    A significant subset of gliomas arises after activation of the pro-proliferative platelet-derived growth factor (PDGF) pathway. The progression of low-grade gliomas to more malignant tumors may be due to oncogenic cellular programs combining with those suppressing apoptosis. Anti-apoptotic genes are overexpressed in a variety of cancers and the anti-apoptotic gene, BCL2, is associated with treatment resistance and tumor recurrence in gliomas. However, the impact of anti-apoptotic gene expression to tumor formation and progression is unclear. We overexpressed Bcl-2 in a PDGFB-dependent mouse model of oligodendroglioma, a common glioma subtype, to assess its effect in vivo. We hypothesized that the anti-apoptotic effect would complement the pro-proliferative effect of PDGFB to promote tumor formation and progression to anaplastic oligodendroglioma (AO). Here, we show that co-expression of PDGFB and Bcl-2 results in a higher overall tumor formation rate compared to PDGFB alone. Co-expression of PDGFB and Bcl-2 promotes progression to AO with prominent foci of necrosis, a feature of high-grade gliomas. Median tumor latency was shorter in mice injected with PDGFB and Bcl-2 compared to those injected with PDGFB alone. Although independent expression of Bcl-2 was insufficient to induce tumors, suppression of apoptosis (detected by cleaved caspase-3 expression) was more pronounced in AOs induced by PDGFB and Bcl-2 compared to those induced by PDGFB alone. Tumor cell proliferation (detected by phosphohistone H3 activity) was also more robust in high-grade tumors induced by PDGFB and Bcl-2. Our results indicate that suppressed apoptosis enhances oligodendroglioma formation and engenders a more malignant phenotype. PMID:21171016

  3. IDH1 Mutations Are Early Events in the Development of Astrocytomas and Oligodendrogliomas

    PubMed Central

    Watanabe, Takuya; Nobusawa, Sumihito; Kleihues, Paul; Ohgaki, Hiroko

    2009-01-01

    IDH1 encodes isocitrate dehydrogenase 1, which participates in the citric acid cycle and was recently reported to be mutated in 12% of glioblastomas. We assessed IDH1 mutations in 321 gliomas of various histological types and biological behaviors. A total of 130 IDH1 mutations was detected, and all were located at amino acid residue 132. Of these, 91% were G→A mutations (Arg→His). IDH1 mutations were frequent in low-grade diffuse astrocytomas (88%) and in secondary glioblastomas that developed through progression from low-grade diffuse or anaplastic astrocytoma (82%). Similarly, high frequencies of IDH1 mutations were found in oligodendrogliomas (79%) and oligoastrocytomas (94%). Analyses of multiple biopsies from the same patient (51 cases) showed that there were no cases in which an IDH1 mutation occurred after the acquisition of either a TP53 mutation or loss of 1p/19q, suggesting that IDH1 mutations are very early events in gliomagenesis and may affect a common glial precursor cell population. IDH1 mutations were co-present with TP53 mutations in 63% of low-grade diffuse astrocytomas and with loss of heterozygosity 1p/19q in 64% of oligodendrogliomas; they were rare in pilocytic astrocytomas (10%) and primary glioblastomas (5%) and absent in ependymomas. The frequent presence of IDH1 mutations in secondary glioblastomas and their near-complete absence in primary glioblastomas reinforce the concept that despite their histological similarities, these subtypes are genetically and clinically distinct entities. PMID:19246647

  4. 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.

  5. 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.

  6. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

    PubMed Central

    Cairncross, G.; Swinnen, L.; Bayer, R.; Rosenfeld, S.; Salzman, D.; Paleologos, N.; Kaminer, L.; Forsyth, P.; Stewart, D.; Peterson, K.; Hu, W.; Macdonald, D.; Ramsay, D.; Smith, A.

    2000-01-01

    The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status. PMID:11303620

  7. 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.

  8. 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

  9. 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.

  10. Genetic and epigenetic stability of oligodendrogliomas at recurrence.

    PubMed

    Aihara, Koki; Mukasa, Akitake; Nagae, Genta; Nomura, Masashi; Yamamoto, Shogo; Ueda, Hiroki; Tatsuno, Kenji; Shibahara, Junji; Takahashi, Miwako; Momose, Toshimitsu; Tanaka, Shota; Takayanagi, Shunsaku; Yanagisawa, Shunsuke; Nejo, Takahide; Takahashi, Satoshi; Omata, Mayu; Otani, Ryohei; Saito, Kuniaki; Narita, Yoshitaka; Nagane, Motoo; Nishikawa, Ryo; Ueki, Keisuke; Aburatani, Hiroyuki; Saito, Nobuhito

    2017-03-07

    Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients. World Health Organization histological grade at recurrence was mostly stable; it was increased in 2, the same in 9, and decreased in 1 cases. Whole-exome sequencing demonstrated that the rate of shared mutation between the primary and recurrent tumors was relatively low, ranging from 3.2-57.9% (average, 33.3%), indicating a branched evolutionary pattern. The trunk alterations that existed throughout the course were restricted to IDH1 mutation, 1p/19q-codeletion, and TERT promoter mutation, and mutation of the known candidate tumor suppressor genes CIC and FUBP1 were not consistently observed between primary and recurrent tumors. Multiple sampling from different regions within a tumor showed marked intratumoral heterogeneity. Notably, in general, the number of mutations was not significantly different after recurrence, remaining under 100, and no hypermutator phenotype was observed. FUBP1 mutation, loss of chr. 9p21, and TCF12 mutation were among a few recurrent de novo alterations that were found at recurrence, indicating that these events were clonally selected at recurrence but were not enough to enhance malignancy. Genome-wide methylation status, measured by Illumina 450 K arrays, was stable between recurrence and the primary tumor. In summary, although oligodendroglioma displays marked mutational heterogeneity, histological malignant transformation accompanying events such as considerable increase in

  11. 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

  12. Alien limb syndrome secondary to multimodal treatment of recurrent oligodendroglioma.

    PubMed

    Gallant, Rachel E; Bonney, Phillip A; Sughrue, Michael E; Bharucha, Kersi J; Battiste, James D

    2015-10-01

    We present a 41-year-old man who experienced alien limb syndrome as a complication of treatment for recurrent Grade III oligodendroglioma of the right parietal lobe. Alien limb syndrome is a rare phenomenon in which a limb performs involuntary actions and the affected individual feels a sense of estrangement towards the limb. It occurs most commonly as a result of corticobasal syndrome, though a variety of other etiologies have been reported. It is rarely associated with focal lesions, such as stroke or tumors.

  13. [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.

  14. [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.

  15. 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.

  16. 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

  17. 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.

  18. Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: concrete premises for a new reliable diagnostic marker in gliomas.

    PubMed

    Cassoni, Paola; Senetta, Rebecca; Castellano, Isabella; Ortolan, Erika; Bosco, Martino; Magnani, Ivana; Ducati, Alessandro

    2007-05-01

    Caveolins are basic constituents of flask-shaped cell membrane microdomains (caveolae), which are involved in many cell functions, including signalling, trafficking, and cellular growth control. The distribution of caveolae within the normal brain and in brain tumors is controversial. In the present study, we describe the expression of caveolin-1 (cav-1) in 64 brain tumors of different grade, of either astroglial or oligodendroglial origin. All studied astrocitomas of any grade (from II to IV) were cav-1 positive, displaying staining patterns and intensity specifically associated to the different tumor grades. In all glioblastomas and gliosarcomas, cav-1 staining was extremely intense, typically localized at the cell membrane and recognized a variable percentage of cells, including the majority of spindle cells and palisade-oriented perinecrotic cells. In anaplastic astrocytomas, a less intense membrane staining or a cytoplasmic dotlike immunoreactivity were present, the latter being almost the exclusive pattern observed in diffuse astrocitomas grade II. In contrast to astroglial tumors, the striking totality of grade II oligodendrogliomas and the large majority of grade III were lacking cav-1 expression. Interestingly, a cav-1 distribution overlapping the pattern described in tissues was observed also in primary cell cultures of human glioblastomas and astrocytomas, and also in one established glioblastoma cell line (U251 MG), analyzed by means of confocal microscopy and flow cytometry. In conclusion, among astroglial tumors cav-1 expression varies in distribution, pattern, and intensity specifically according to tumor types and grades. The association between tumor progression and a more structured membranous pattern of cav-1 expression could suggest the hypothesis of a neoplastic shift towards a mesenchymal phenotype, whose behavioral and biologic significance worth further studies. Finally, the lack of cav-1 immunoreactivity in oligodendrogliomas suggests its

  19. World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Yoon, Sang-In; Park, Dong-Hyuk; Kang, Shin-Hyuk; Park, Jung-Yul; Chung, Yong-Gu

    2016-01-01

    When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment. PMID:27867928

  20. Secondary oligodendroglioma after postoperative irradiation for medulloblastoma: a case report and review of the literature

    PubMed Central

    He, Hong-Lin; Lee, Ying-En; Chen, Han-Jung; Hsu, Chao-Tien; Huang, Yu-Yi; Chang, I-Wei

    2014-01-01

    Medulloblastoma, a malignant, invasive embryonal tumor of the cerebellum, occurs most often in children. It has high metastatic potential and is usually treated by aggressive multimodal therapy, including surgery, chemotherapy and craniospinal irradiation. Multiple secondary tumors have been reported following craniospinal irradiation. It is rare with the occurrence of oligodendroglioma after irradiation. In this report, we described a patient with secondary oligodendroglioma after postoperative craniospinal irradiation for medulloblastoma. PMID:24817982

  1. Oligodendroglioma metastasis to the bone marrow mimicking multiple myeloma: A case report

    PubMed Central

    JIAN, YUAN; GAO, WEN; WU, YIN; LI, YANCHEN; ZHANG, YONG; YANG, GUANGZHONG; CHEN, WENMING

    2016-01-01

    The present study reports a case of a 59-year-old male suffering from oligodendroglioma that metastasized to the bone marrow (BM). The metastasis was detected 5 years after craniotomy was performed for the resection of the primary tumor; however, it manifested as multiple myeloma (MM)-like bone lesions, a small M component and myeloma cell-like morphology in the BM. A brain magnetic resonance imaging scan was performed; evidence from the previously performed oligodendroglioma resection was observed on the scan, but there were no significant findings, which made the diagnosis particularly challenging. The patient exhibited no response to the multiple combination therapies administered targeting MM and oligodendroglioma, and subsequently developed epilepsy and pneumonia, prior to succumbing to multiple organ failure. Among the various tumor types involving the central nervous system, oligodendroglioma is the least likely to metastasize; thus, distant metastases from brain oligodendrogliomas are extremely rare. To the best of our knowledge, this is the first case of metastatic oligodendroglioma presenting with typical MM-like symptoms and without any recurrence in the brain. PMID:27347150

  2. Unexpected expression of intermediate filament protein genes in human oligodendroglioma cell lines

    SciTech Connect

    Kashima, Tsuyoshi; Vinters, H.V.; Campagnoni, A.T.

    1995-01-01

    From a human oligodendroglioma cell line cDNA library, ten intermediate filament (IF) cDNA clones were isolated. Five clones corresponded to vimentin mRNA, two corresponded to cytokeratin K7 mRNA, and two corresponded to cytokeratin K8 mRNA. One clone encoded a novel IF mRNA. The expression of these and other IF protein genes was examined in five cell lines derived from human oligodendroglioma, astrocytoma and neuroblastoma tumors. Vimentin mRNA and K18 mRNA were expressed in all the cell lines. The K7 and K8 genes were expressed only in the oligodendroglioma cell lines. Surprisingly, nestin mRNA was expressed in the astrocytoma lines and the neuroblastoma line, but was not expressed in the oligodendroglioma lines. These results indicate that oligodendroglioma cell lines express Types I and II cytokeratin genes. This pattern of IF gene expression was different from that of the astrocytoma and neuroblastoma cell lines, which expressed IF genes usually associated with the mature cell types or with differentiating fetal neural precursor cells, i.e. GFAP and neurofilament-L. The results also suggest that the oligodendroglioma cell lines are more epithelial in character and do not reflect the gene expression of mature oligodendrocytes. 46 refs., 8 figs., 2 tabs.

  3. 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

  4. 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.

  5. 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

  6. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

    PubMed

    Ho, D M; Wong, T T; Guo, W Y; Chang, K P; Yen, S H

    1997-10-01

    Extramedullary myeloid cell tumors (EMCTs) are tumors consisting of immature cells of the myeloid series that occur outside the bone marrow. Most of them are associated with acute myelogenous leukemia or other myeloproliferative disorders, and a small number occur as primary lesions, i.e., are not associated with hematological disorders. Occurrence inside the cranium is rare, and there has been only one case of primary EMCT involving the cerebellum reported in the literature. The case we report here is a blastic EMCT occurring in the cerebellum of a 3-year-old boy who had no signs of leukemia or any hematological disorder throughout the entire course. The cerebellar tumor was at first misdiagnosed as an "oligodendroglioma" because of the uniformity and "fried egg" artifact of the tumor cells. The tumor disappeared during chemotherapy consisting of 12 treatments. However, it recurred and metastasized to the cerebrospinal fluid (CSF) shortly after the therapy was completed. A diagnosis of EMCT was suspected because of the presence of immature myeloid cells in the CSF, and was confirmed by anti-myeloperoxidase and anti-lysozyme immunoreactivity of the cerebellar tumor. The patient succumbed 1 year and 3 months after the first presentation of the disease.

  7. 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.

  8. 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.

  9. 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

  10. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.

    PubMed

    Tirosh, Itay; Venteicher, Andrew S; Hebert, Christine; Escalante, Leah E; Patel, Anoop P; Yizhak, Keren; Fisher, Jonathan M; Rodman, Christopher; Mount, Christopher; Filbin, Mariella G; Neftel, Cyril; Desai, Niyati; Nyman, Jackson; Izar, Benjamin; Luo, Christina C; Francis, Joshua M; Patel, Aanand A; Onozato, Maristela L; Riggi, Nicolo; Livak, Kenneth J; Gennert, Dave; Satija, Rahul; Nahed, Brian V; Curry, William T; Martuza, Robert L; Mylvaganam, Ravindra; Iafrate, A John; Frosch, Matthew P; Golub, Todd R; Rivera, Miguel N; Getz, Gad; Rozenblatt-Rosen, Orit; Cahill, Daniel P; Monje, Michelle; Bernstein, Bradley E; Louis, David N; Regev, Aviv; Suvà, Mario L

    2016-11-10

    Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.

  11. Oligodendrogliomas arising in the scar of a brain contusion. Report of two surgically verified cases.

    PubMed

    Pérez-Díaz, C; Cabello, A; Lobato, R D; Rivas, J J; Cabrera, A

    1985-11-01

    Several years after sustaining head injuries, two patients developed oligodendrogliomas in the scar of brain contusions. Both cases seem to fulfill the criteria currently established for accepting the traumatic origin of a brain tumor. The literature concerning the relationship between head injury and intracranial tumor is reviewed.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Oncolytic HSV-1716 in Treating Younger Patients With Refractory or Recurrent High Grade Glioma That Can Be Removed By Surgery

    ClinicalTrials.gov

    2016-05-26

    Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma

  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. 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.

  4. 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

  5. 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

  6. 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

  7. Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis

    PubMed Central

    2013-01-01

    Background Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective. Results Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci. Conclusions The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics. PMID:23885787

  8. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma

    SciTech Connect

    Kraus, J.A.; Koopmann, J.; Kaskel, P.

    1995-01-01

    Loss of heterozygosity (LOH) in specific chromosomal regions, which are likely to harbor tumor suppressor genes, has been associated with human gliomas. In this study we have analyzed astrocytic and oligodendroglial tumors for LOH on chromosomes 1 and 19. By microsatellite analysis LOH was found on chromosome arm 1p in 6/15 oligodendrogliomas WHO grade II and III, 12/25 oligoastrocytomas WHO grade II and III, 6/79 glioblastomas WHO grade IV, 5/44 astrocytomas WHO grade II and III and 0/23 pilocystic astrocytomas WHO grade I. The high incidence of LOH on chromosome arm 1p in oligodendrogliomas and oligoastrocytomas indicates that a putative tumor suppressor gene in this region is involved in the formation of gliomas with oligodendroglial features. Furthermore, the frequent involvement of chromosome arm 1p in oligodendrogliomas and oligoastrocytomas, but not in astrocytomas, suggests that genetically oligoastrocytoma is more similar to oligodendroglioma than to astrocytoma. In order to support this hypothesis, oligodendroglial and astrocytic areas in three mixed oligoastrocytomas were examined differentially for LOH 1p and for LOH 19q, the second genetic region believed to be affected in these tumors. All three tumors had LOH of 1p and LOH of 19q in both areas of oligodendroglial and of astrocytic differentiation. These findings show that the astrocytic and oligodendroglial portions of oligoastrocytoma share molecular genetic features and probably are of monoclonal origin. 32 refs., 2 figs., 1 tab.

  9. 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

  10. Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells.

    PubMed

    Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Moffett, John R; Namboodiri, Aryan M A; Viapiano, Mariano S; Lawler, Sean E; Jaworski, Diane M

    2013-01-01

    Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation.

  11. Valproic acid induces the glutamate transporter excitatory amino acid transporter-3 in human oligodendroglioma cells.

    PubMed

    Bianchi, M G; Franchi-Gazzola, R; Reia, L; Allegri, M; Uggeri, J; Chiu, M; Sala, R; Bussolati, O

    2012-12-27

    Glutamate transport in early, undifferentiated oligodendrocytic precursors has not been characterized thus far. Here we show that human oligodendroglioma Hs683 cells are not endowed with EAAT-dependent anionic amino acid transport. However, in these cells, but not in U373 human glioblastoma cells, valproic acid (VPA), an inhibitor of histone deacetylases, markedly induces SLC1A1 mRNA, which encodes for the glutamate transporter EAAT3. The effect is detectable after 8h and persists up to 120h of treatment. EAAT3 protein increase becomes detectable after 24h of treatment and reaches its maximum after 72-96h, when it is eightfold more abundant than control. The initial influx of d-aspartate increases in parallel, exhibiting the typical features of an EAAT3-mediated process. SLC1A1 mRNA induction is associated with the increased expression of PDGFRA mRNA (+150%), a marker of early oligodendrocyte precursor cells, while the expression of GFAP, CNP and TUBB3 remains unchanged. Short term experiments have indicated that the VPA effect is shared by trichostatin A, another inhibitor of histone deacetylases. On the contrary, EAAT3 induction is neither prevented by inhibitors of mitogen-activated protein kinases nor triggered by a prolonged incubation with lithium, thus excluding a role for the GSK3β/β-catenin pathway. Thus, the VPA-dependent induction of the glutamate transporter EAAT3 in human oligodendroglioma cells likely occurs through an epigenetic mechanism and may represent an early indicator of commitment to oligodendrocytic differentiation.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

    ClinicalTrials.gov

    2014-05-15

    Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Oligodendroglioma

  18. p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors

    ClinicalTrials.gov

    2016-10-21

    Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Brainstem Tumors; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumor, Primitive

  19. ImmunoFISH Is a Reliable Technique for the Assessment of 1p and 19q Status in Oligodendrogliomas

    PubMed Central

    Duval, Céline; de Tayrac, Marie; Sanschagrin, François; Michaud, Karine; Gould, Peter Vincent; Saikali, Stéphan

    2014-01-01

    Objective To develop a new ImmunoFISH technique for the study of oligodendrogliomas by combining a standard immunohistochemical stain using MIB-1 antibody with a standard FISH technique using commercial 1p36 and 19q13 chromosomal probes. Methods Validation was performed by two observers on a series of 36 pre-selected oligodendrogliomas and compared to the results previously determined by FISH alone. Results The ImFISH technique is easy to perform and to analyze and is no more time-consuming than the usual FISH technique. Our results show that the inter-observer reliability of ImFISH is high (κ = 0.86 and 0.95 respectively for 1p and 19q). Compared to FISH, the ImFISH exhibits a very high sensitivity (∼100%) and specificity (∼90%) for 1p and/or 19q deleted cases. The sensitivity is high for normal cases (∼85%) and imbalanced cases (∼90%) with a specificity ranging between 50 and 85%. Finally, there were no significant differences between FISH and ImFISH results calculated on 60, 40 or 20 cells. Conclusion Our study demonstrates the reliability of the ImFISH technique in oligodendrogliomas and emphasizes its advantage in poorly cellular tumoral specimen. PMID:24949947

  20. Radiological imaging features of glioblastoma with oligodendroglioma component: a comparison with conventional glioblastoma

    PubMed Central

    Kirii, Kazukuni; Toyoguchi, Yuuki; Nishihara, Masashi; Sakurai, Keita; Murayama, Kazuhiro; Noguchi, Tomoyuki; Matsuda, Kenichiro; Sakurada, Kaori; Sonoda, Yukihiko; Hosoya, Takaaki

    2016-01-01

    Background Glioblastoma with oligodendroglioma component (GBMO) is a subtype of conventional glioblastoma (cGBM), which is categorized as WHO grade IV. GBMO can be histopathologically distinguished from cGBM and the prognosis of GBMO is better than that of cGBM. However, no systematic review of GBMO imaging findings has been published to date. Purpose To clarify the radiological imaging features of GBMO compared with those of cGBM. Material and Methods The participants were 15 patients with GBMO and 32 patients with cGBM as a control group, all of whom were histopathologically diagnosed. A radiologist retrospectively reviewed the imaging findings of both computed tomography (CT) and magnetic resonance imaging (MRI) for density, signal intensity, contrast medium enhancement (CE), cortical swelling, and cortical swelling without CE. We statistically analyzed the imaging findings by Chi-squared test. Results Cortical swelling without CE in GBMO was significantly greater than that in cGBM (P = 0.004). Non-CE and heterogeneous solid enhancement were observed significantly more often in GBMO (P = 0.004). No other findings were significant. Conclusion There was significant difference in the findings of the CE, which exhibited solid heterogeneous enhancement in GBMO. Cortical swelling without CE can be considered significantly characteristic of GBMO. PMID:27900202

  1. Controversies over the diagnosis of oligodendroglioma: a report from the satellite workshop at the 4th international symposium of brain tumor pathology, Nagoya Congress Center, May 23, 2012.

    PubMed

    Komori, Takashi; Hirose, Takanori; Shibuya, Makoto; Suzuki, Hiroyoshi; Tanaka, Shinya; Sasaki, Atsushi

    2013-10-01

    With the goal of discussing how the neuropathology community should resolve the controversy over the diagnosis of oligodendroglioma, this Satellite Workshop reflects the collaboration between two invited keynote speakers: Dr. Johan M. Kros of the Erasmus Medical Center and Dr. Kenneth D. Aldape of the University of Texas MD Anderson Cancer Center and the Organizing Committee of the Japanese Society of Brain Tumor Pathology. In the first half of the workshop, the keynote speakers reviewed the current status of the pathology and genetics of oligodendroglioma. In the second half, six debatable cases that exemplify the current controversies over the diagnosis of oligodendroglioma were presented. The consensus diagnoses in these six cases, which have been reviewed by members of the Society, were opened to discussion and comments by the speakers. These cases highlight unresolved issues in the WHO 2007 classification of oligodendrogliomas, particularly the discordance between morphology and genetics. To achieve synchronization between phenotypes and genotypes, the neuropathology diagnosis should focus on the classic features of oligodendrogliomas that are highly correlated with the genetic background.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

    ClinicalTrials.gov

    2017-01-12

    Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  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. Oligodendroglial cell proliferation arising in an ovarian mature cystic teratoma. Clinicopathological, inmunohistochemical, and ultrastructural study of a case that may represent an oligodendroglioma.

    PubMed

    Serrano-Arévalo, Mónica Lizzette; Lino-Silva, Leonardo Saúl; Domínguez Malagón, Hugo Ricardo

    2017-01-01

    Ovarian mature cystic teratoma (OMCT) is an ovarian benign neoplasm with excellent prognosis presenting components of the three germinal layers. However, transformation into a malignant neoplasm is a rare event (so-called somatic transformation). In most of the cases, the malignant component expresses as epidermoid carcinoma, but occasionally central nervous system tumors occur. Some of the previously reported tumors are astrocytoma, glioblastoma, and ependymoma. Somatic transformation of OMCT into an oligodendroglioma is exceptional. We report a 19-year-old female with a left OMCT with an area of oligonedroglial cells proliferation characterized by immunohistochemical studies with positivity for GFAP and S100, with a low Ki67 index (5%). Additionally, electron microscopy revealed oligodendrocytes with parallel bundles of cytoplasmic intermediate filaments, confirming the oligodendroglial nature of the proliferation. The patient was treated only with left oophorectomy, and three and half years after surgery, there is no evidence of disease.

  9. Rare synchronous association of vestibular schwannoma and indolent insular oligodendroglioma in a patient without neurofibromatosis: controversial issue of timing for surgical treatment of asymptomatic low-grade gliomas

    PubMed Central

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Alvaro, Lorenzo; Nocchi, Niccolò; Polonara, Gabriele; Di Somma, Lucia Giovanna Maria; Zizzi, Antonio; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a “cure” and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment. PMID:23180968

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. [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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

    ClinicalTrials.gov

    2014-05-05

    Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. [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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

    ClinicalTrials.gov

    2016-11-09

    Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

  11. Adding Chemotherapy to Radiation Improves Survival for Some Patients with Rare Brain Cancer

    Cancer.gov

    Long-term results from two clinical trials confirm that certain patients with anaplastic oligodendrogliomas live substantially longer if they are treated with a combination of chemotherapy and radiation therapy rather than radiatiation alone.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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).

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas

    PubMed Central

    Ichimura, K; Vogazianou, AP.; Liu, L; Pearson, DM.; Bäcklund, LM; Plant, K; Baird, K; Langford, CF.; Gregory, SG.; Collins, VP

    2009-01-01

    Astrocytic, oligodendroglial and mixed gliomas are the commonest gliomas in adults. They have distinct phenotypes and clinical courses, but as they exist as a continuous histological spectrum differentiating them can be difficult. Co-deletions of total 1p and 19q are found in the majority of oligodendrogliomas and considered as a diagnostic marker and a prognostic indicator. The 1p status of astrocytomas has not yet been thoroughly examined. Using a chromosome 1 tile path array, we investigated 108 adult astrocytic tumours for copy number alterations. Total 1p deletions were rare (2%), however partial deletions involving 1p36 were frequently identified in anaplastic astrocytomas (22%) and glioblastomas (34%). Multivariate analysis showed that patients with total 1p deletions had significantly longer survival (p=0.005). In 9 glioblastomas homozygous deletions at 1p36 were identified. No somatic mutations were found among the 5 genes located in the homozygously deleted region. However, the CpG island of TNFRSF9 was hypermethylated in 19% of astrocytic tumours and 87% of glioma cell lines. TNFRSF9 expression was upregulated after demethylation of glioma cell lines. Akt3 amplifications were found in four glioblastomas. Our results indicate that 1p deletions are common anaplastic astrocytomas and glioblastomas but are distinct from the 1p abnormalities in oligodendrogliomas. PMID:17934521

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. “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

  13. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

    ClinicalTrials.gov

    2016-10-19

    Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; 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 Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  14. Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system.

    PubMed

    Figarella-Branger, Dominique; Bouvier, Corinne; de Paula, André Maues; Mokhtari, Karima; Colin, Carole; Loundou, Anderson; Chinot, Olivier; Metellus, Philippe

    2012-11-01

    Adult grade II low-grade gliomas (LGG) are classified according to the WHO as astrocytomas, oligodendrogliomas or mixed gliomas. TP53 mutations and 1p19q codeletion are the main molecular abnormalities recorded, respectively, in astrocytomas and oligodendrogliomas and in mixed gliomas. Although IDH mutations (IDH1 or IDH2) are recorded in up to 85 % of low-grade gliomas, IDH negative gliomas do occur. We have searched for p53 expression, 1p19q codeletion and IDH status (immunohistochemical detection of the common R132H IDH1 mutation and IDH direct sequencing). Internexin alpha (INA) expression previously recorded to be associated with 1p19q codeletion (1p19q+) gliomas was also analysed. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. In contrast to the WHO classification, this molecular classification predicts overall survival on uni- and multivariate analysis (P = 0.001 and P = 0.007, respectively). Group 4 carries the worst prognosis and group 2 the best. Interestingly, p53 +/INA- expression predicts lack of 1p19q codeletion (specificity 100 %, VPP 100 %). The combined use of these three molecular markers allow for an accurate prediction of survival in LGG. These findings could significantly modify LGG classification and may represent a new tool to guide patient-tailored therapy. Moreover, immunohistochemical detection of p53, INA and mR132H IDH1 expression could represent an interesting prescreening test to be performed before 1p19q codeletion, IDH1 minor mutation and IDH2 mutation detection.

  15. 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.

  16. 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

  17. 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 ...

  18. 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.

  19. 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.

  20. 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

  1. Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

    ClinicalTrials.gov

    2016-10-03

    Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Estrogen Receptor Negative; Estrogen Receptor Positive; Glioblastoma; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Metastatic Renal Cell Cancer; Recurrent Adult Brain Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Lung Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Carcinoma; Resectable Hepatocellular Carcinoma; Sarcoma; Stage IA Breast Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Lung Carcinoma; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Esophageal Cancer; Stage IIB Lung Carcinoma; Stage IIB Ovarian Cancer; Stage IIB Skin Melanoma; Stage IIC Ovarian Cancer; Stage IIC Skin Melanoma; Stage IIIA Breast Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Ovarian Cancer; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Esophageal Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  2. 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. ...

  3. Genetics of adult glioma.

    PubMed

    Goodenberger, McKinsey L; Jenkins, Robert B

    2012-12-01

    Gliomas make up approximately 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors. Despite the frequency of gliomas, the etiology of these tumors remains largely unknown. Diffuse gliomas, including astrocytomas and oligodendrogliomas, belong to a single pathologic class but have very different histologies and molecular etiologies. Recent genomic studies have identified separate molecular subtypes within the glioma classification that appear to correlate with biological etiology, prognosis, and response to therapy. The discovery of these subtypes suggests that molecular genetic tests are and will be useful, beyond classical histology, for the clinical classification of gliomas. While a familial susceptibility to glioma has been identified, only a small percentage of gliomas are thought to be due to single-gene hereditary cancer syndromes. Through the use of linkage studies and genome-wide association studies, multiple germline variants have been identified that are beginning to define the genetic susceptibility to glioma.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

    PubMed

    Pekmezci, Melike; Rice, Terri; Molinaro, Annette M; Walsh, Kyle M; Decker, Paul A; Hansen, Helen; Sicotte, Hugues; Kollmeyer, Thomas M; McCoy, Lucie S; Sarkar, Gobinda; Perry, Arie; Giannini, Caterina; Tihan, Tarik; Berger, Mitchel S; Wiemels, Joseph L; Bracci, Paige M; Eckel-Passow, Jeanette E; Lachance, Daniel H; Clarke, Jennifer; Taylor, Jennie W; Luks, Tracy; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2017-03-02

    The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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 ...

  12. 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.

  13. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  14. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  15. O8.04TEMOZOLOMIDE AFTER RADIOTHERAPY IN RECURRENT “LOW-GRADE” DIFFUSE BRAINSTEM GLIOMA IN ADULTS

    PubMed Central

    Reyes-Botero, G.; Laigle-Donadey, F.; Mokhtari, K.; Martin-Duverneuil, N.; Delattre, J.Y.

    2014-01-01

    INTRODUCTION: Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is frequently used as initial treatment. However, only limited data is available concerning chemotherapy efficacy at relapse after RT. Temozolomide (TMZ) is frequently used in progressive supratentorial gliomas after RT, but its efficacy in diffuse brainstem gliomas in adults has not been reported. PATIENTS AND METHODS: We conducted a retrospective analysis including patients from our database with non-enhancing diffuse brainstem glioma (histological or MRI criteria compatible with low-grade glioma) who received TMZ at relapse after RT. Tumors localized in the pons, medulla oblongata or midbrain were analyzed excluding supratentorial or infratentorial tumors secondary infiltrating the brainstem. Clinical and radiological responses were assessed and progression-free survival (PFS) and overall survival (OS) time were estimated. RESULTS: In total, 15 adult patients (median age 34 years) were selected. Histological analysis was available in 5 cases showing grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment obtaining a median PFS of 34.2 months (95% CI 24.1-44.2). Median KPS at the time of relapse after RT was 80. TMZ was administered orally at 150-200mg/m2 for 5 days every 28 days at progression disease after RT. Clinical improvement after TMZ was observed in 9 cases (60%) whereas radiological assessment detected 6 partial responses. Estimated median PFS after TMZ was 9.5 months (95% CI 7.9-11) and median OS was 14.4 months (95% CI 10.5-18.2). Grade 3 thrombocytopenia was observed in 26% of cases. CONCLUSIONS: TMZ could be useful in adult patients with progressive diffuse low-grade brainstem glioma after RT failure. Further studies are warranted to detect clinical and biological markers of response to TMZ.

  16. 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

  17. 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,…

  18. 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…

  19. 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.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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…

  4. 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

  5. KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.

    PubMed

    Badiali, Manuela; Gleize, Vincent; Paris, Sophie; Moi, Loredana; Elhouadani, Selma; Arcella, Antonietta; Morace, Roberta; Antonelli, Manila; Buttarelli, Francesca Romana; Figarella-Branger, Dominique; Kim, Young-Ho; Ohgaki, Hiroko; Mokhtari, Karima; Sanson, Marc; Giangaspero, Felice

    2012-11-01

    KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E) mutation was also screened. The KIAA1549-BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%). There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and BRAF(v600E) in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH mutations and the KIAA1549-BRAF fusion were present, as independent molecular events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15 (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with BRAF(v600E) mutation were both oligodendroglioma and one had IDH mutations and 1p/19q co-deletion. Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E) mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more frequent in oligodendroglial neoplasm and may be co-present with IDH mutations and 1p/19q loss.

  6. 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…

  7. 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 ...

  8. 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, ...

  9. 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, ...

  10. 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 ...

  11. 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

  12. [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.

  13. 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…

  14. Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Iseki, Hiroshi; Ikuta, Soko; Konishi, Yoshiyuki; Saito, Taichi; Tamura, Manabu; Chernov, Michael; Watanabe, Atsushi; Okamoto, Saori; Maebayashi, Katsuya; Mitsuhashi, Norio; Okada, Yoshikazu

    2013-01-01

    The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

  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. 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)

  17. 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…

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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 ...

  3. 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)

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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)

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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)…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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 ...

  2. 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

  3. 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.

  4. 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…

  5. 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…

  6. 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…

  7. 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 ...

  8. 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…

  9. 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,…

  10. 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…

  11. 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…

  12. 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…

  13. 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.…

  14. 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…

  15. 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…

  16. 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);…

  17. 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…

  18. 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…

  19. 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.

  20. 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

  1. 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. ( ...

  2. 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 ...

  3. 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 ...

  4. 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)

  5. 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)

  6. 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 ...

  7. 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)

  8. 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.

  9. 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.

  10. [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.

  11. 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.

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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…

  4. 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,…

  5. 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)

  6. 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,…

  7. 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…

  8. 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…

  9. 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…

  10. 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)

  11. 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…

  12. 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)

  13. 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…

  14. 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 ...

  15. 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…

  16. Immigration and Adult Transitions

    ERIC Educational Resources Information Center

    Rumbaut, Ruben G.; Komaie, Golnaz

    2010-01-01

    Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Ruben Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage…

  17. Profiles of Adult Learners.

    ERIC Educational Resources Information Center

    Illinois State Library, Springfield.

    Since January 1986, when the Illinois Secretary of State Literacy Grant Program began funding a wide variety of adult literacy programs, more than 30,000 students have sought help with reading. They have been matched with 25,000 tutors who have provided more than 2 million hours of volunteer instruction. The profiles in this booklet are stories of…

  18. Adult Literacy Perspectives.

    ERIC Educational Resources Information Center

    Taylor, Maurice C., Ed.; Draper, James A., Ed.

    This book, intended to serve as a professional reference work, proposes to define the field of Adult Basic Education in its evolution, its contribution to professional education, and the principal problems and issues. The volume contains the following treatises: "Definitions and Evolution of the Concepts" (Thomas); "Selected…

  19. Depression - older adults

    MedlinePlus

    ... slowly than in younger adults. To better manage depression at home: Exercise regularly, if the provider says it is OK. Surround yourself with caring, positive people and do fun activities. ... signs of depression, and know how to react if these occur. ...

  20. TRENDS IN ADULT READING.

    ERIC Educational Resources Information Center

    MILLER, JUSTIN H.

    TRENDS EVIDENT IN ADULT READING DURING THE 1960'S IN THE AREAS OF ADMINISTRATION, PROGRAMS, TEACHING, TECHNIQUES, RESEARCH PROJECTS, AND METHODS OF PROMOTION OF READING PROGRAMS ARE DISCUSSED. TWO INSTANCES OF COMMERCIAL EXPLOITATION BASED ON INTENSE AND OFTEN FALLACIOUS ADVERTISING AND ON PUBLIC IGNORANCE ARE CITED. A POSITIVE TREND IN THE AREA…

  1. Newly Diagnosed: Older Adults

    MedlinePlus

    ... Children Newly Diagnosed: Older Adults Related Topics on AIDS.gov Aging with HIV/AIDS National HIV/AIDS ... an Emerging Challenge Last revised: 07/10/2015 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

  2. Utah Adult Education Services. Adult Education Report 1968-69.

    ERIC Educational Resources Information Center

    Utah State Board of Education, Salt Lake City.

    Major purposes for the preparation of this report on public school adult education in Utah were: to provide the public with a description of achievements, trends, and needs, and with meaningful cost accounting information; to make comparisons and analyses of adult education by program, school district, and year; and to provide the adult education…

  3. What is Young Adult Literature? (Young Adult Literature).

    ERIC Educational Resources Information Center

    Crowe, Chris, Ed.

    1998-01-01

    Outlines some of the many confusions about young adult literature. Sheds some light on what young adult literature is (defining it as all genres of literature published since 1967 that are written for and marketed to young adults). Discusses briefly how it can be used in schools. Offers a list of the author's 20 favorite books for teenagers. (SR)

  4. Teaching Nontraditional Adult Students: Adult Learning Theories in Practice

    ERIC Educational Resources Information Center

    Chen, Joseph C.

    2014-01-01

    As the USA experiences rapid growth of nontraditional adult students in higher education, educators and institutions will increasingly need to look beyond the traditional youth-centric educational models to better address adult learning needs. To date, no research has been conducted examining the learning experiences of adult students enrolled in…

  5. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  6. Adult Education for Social Mobilization.

    ERIC Educational Resources Information Center

    Echeverria, Luis

    1981-01-01

    Suggests some ideas that could stimulate and be incentives for defining programs of adult education in the future. These involve changing priorities, developing a framework which allows adult education programs to be established, and managing decision-making processes. (CT)

  7. College-Age & Young Adults

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Age & Young Adults College Addiction Studies Programs Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ...

  8. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  9. Alcohol Use and Older Adults

    MedlinePlus

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  10. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Vaccination Recommendations Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  11. Enhancing Older Adults' Reading Comprehension.

    ERIC Educational Resources Information Center

    Kemper, Susan; And Others

    1993-01-01

    Investigates older adults' reading comprehension skills through syntactic measures and measures of sentence content. Analyzes the apparent reading difficulties of older adults. Provides guidelines for the preparation of prose materials for older readers. (HB)

  12. Adult Development and the Workplace.

    ERIC Educational Resources Information Center

    Heffernan, James M.

    Little attention has been given to how adults develop through their lifetimes and what roles their workplace environments play in that development. Research and theory regarding adult psychosocial development have confirmed the developmental life-cycle phases of adulthood. These are: leaving the family (ages 16-22), getting into the adult world…

  13. Facilitating Creativity in Adult Learners

    ERIC Educational Resources Information Center

    Tsai, Kuan Chen

    2013-01-01

    Creativity in education research has received increasing attention, although the major focus of this research has been on children. Despite pleas by several adult educators for promoting creativity, very few studies have focused on adult learners, leaving to it to be explored what approaches are useful for adult educators to facilitate creativity…

  14. Adult Learning. ARIS Information Sheet.

    ERIC Educational Resources Information Center

    National Languages and Literacy Inst. of Australia, Melbourne. Adult Education Resource and Information Service.

    This information sheet provides a summary of general observations regarding adult learners. Adults from different walks of life may seek out learning at different times in their lives, for different reasons, and for vastly different purposes. Adult learning groups may include students of different ages, cultures, and educational and socioeconomic…

  15. Assessment Tools for Adult Education.

    ERIC Educational Resources Information Center

    Shefrin, Carol; Shafer, Dehra; Forlizzi, Lori

    The Assessment Tools for Adult Education project was designed to provide training and support to staff of the Pennsylvania Bureau of Adult Basic and Literacy Education (ABLE) funded programs to help them use assessment tools and procedures to document the learning gains of the adult students they serve. The following candidate assessment…

  16. The Politics of Adult Education

    ERIC Educational Resources Information Center

    Adam, Roy

    1974-01-01

    All educational levels have been attacked by politicians and haunted by suspicion, and adult education has drawn more than its share. Interest groups have had a large effect on adult education. The construction of a theoretical model of the politics of adult education is suggested. (DS)

  17. Adult Multiple Intelligences and Math.

    ERIC Educational Resources Information Center

    Costanzo, Meg Ryback

    In the Adult Multiple Intelligences (AMI) study, 10 teachers of adults from the northeastern region of the United States explored for 18 months the ways that multiple intelligences (MI) theory could support instruction and assessment in various adult learning contexts. The results of this research were published in a book by Julie Viens called MI…

  18. New Thrusts in Adult Education.

    ERIC Educational Resources Information Center

    Worthington, Robert M.

    The Associate Commissioner of the Bureau of Adult, Vocational, and Technical Education is responsible for two broad and important programs, career education and broader and better services in adult education. Career education is a lifelong educational process beginning in kindergarten and extending through adult and continuing education. Career…

  19. Adult Education and Development, 1994.

    ERIC Educational Resources Information Center

    Adult Education and Development, 1994

    1994-01-01

    The publication is a half-yearly journal for adult education in Africa, Asia, and Latin America. Issue 42 includes the following: "Adult Education for Self-Reliance in Community Health Education Programmes" (Kweka); "Promoting Good Nutrition" (Mangvwat); "Incorporating Health-Improvement Activities in Adult Education…

  20. Adult Learning and HRD. Symposium.

    ERIC Educational Resources Information Center

    2002

    This symposium on adult learning and human resource development consists of three presentations. "Adult Learning Principles and Concepts in the Workplace: Implications for Training in HRD" (Margot B. Weinstein) reports on findings from interviews with restaurant employees who reported that training practices using adult learning…

  1. Adult Education through World Collaboration.

    ERIC Educational Resources Information Center

    Cassara, Beverly Benner, Ed.

    This book contains the following papers about development/delivery of adult education through the efforts of multinational and bilateral government donors and the International Council for Adult Education (ICAE): "Preface" (Beverly Benner Cassara); "Introduction: Adult Education and Democracy" (Francisco Vio Grossi);…

  2. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  3. CDC Vital Signs: Adults with Disabilities

    MedlinePlus

    ... Problem More adults with disabilities need to get physical activity. Adults with disabilities who get no physical activity ... Adults with disabilities are more likely to get physical activity if doctors recommend it. Only 44% of adults ...

  4. An Undergraduate Course in Adult Development: When the Virtual Adult Is an Adult

    ERIC Educational Resources Information Center

    Williams, Robert B.

    2014-01-01

    An aspect of an undergraduate psychology course on adult development was the preparation of case records on adults who consented to be studied. Participants (1) developed their abilities to observe and accurately record adult behavior across a variety of ages and contexts; (2) withheld judgments about behavior when evidence was lacking; (3)…

  5. The adult scoliosis.

    PubMed

    Aebi, Max

    2005-12-01

    Adult scoliosis is defined as a spinal deformity in a skeletally mature patient with a Cobb angle of more than 10 degrees in the coronal plain. Adult scoliosis can be separated into four major groups: Type 1: Primary degenerative scoliosis, mostly on the basis of a disc and/or facet joint arthritis, affecting those structures asymmetrically with predominantly back pain symptoms, often accompanied either by signs of spinal stenosis (central as well as lateral stenosis) or without. These curves are often classified as "de novo" scoliosis. Type 2: Idiopathic adolescent scoliosis of the thoracic and/or lumbar spine which progresses in adult life and is usually combined with secondary degeneration and/or imbalance. Some patients had either no surgical treatment or a surgical correction and fusion in adolescence in either the thoracic or thoracolumbar spine. Those patients may develop secondary degeneration and progression of the adjacent curve; in this case those curves belong to the type 3a. Type 3: Secondary adult curves: (a) In the context of an oblique pelvis, for instance, due to a leg length discrepancy or hip pathology or as a secondary curve in idiopathic, neuromuscular and congenital scoliosis, or asymmetrical anomalies at the lumbosacral junction; (b) In the context of a metabolic bone disease (mostly osteoporosis) combined with asymmetric arthritic disease and/or vertebral fractures. Sometimes it is difficult to decide, what exactly the primary cause of the curve was, once it has significantly progressed. However, once an asymmetric load or degeneration occurs, the pathomorphology and pathomechanism in adult scoliosis predominantly located in the lumbar or thoracolumbar spine is quite predictable. Asymmetric degeneration leads to increased asymmetric load and therefore to a progression of the degeneration and deformity, as either scoliosis and/or kyphosis. The progression of a curve is further supported by osteoporosis, particularly in post-menopausal female

  6. Adult respiratory distress syndrome.

    PubMed

    Cutts, S; Talboys, R; Paspula, C; Prempeh, E M; Fanous, R; Ail, D

    2017-01-01

    Adult respiratory distress syndrome (ARDS) has now been described as a sequela to such diverse conditions as burns, amniotic fluid embolism, acute pancreatitis, trauma, sepsis and damage as a result of elective surgery in general. Patients with ARDS require immediate intubation, with the average patient now being ventilated for between 8 and 11 days. While the acute management of ARDS is conducted by the critical care team, almost any surgical patient can be affected by the condition and we believe that it is important that a broader spectrum of hospital doctors gain an understanding of the nature of the pathology and its current treatment.

  7. Adult hereditary fructose intolerance.

    PubMed

    Burmeister, L A; Valdivia, T; Nuttall, F Q

    1991-04-01

    Hereditary fructose intolerance was diagnosed in a 69-year-old man on the basis of his medical history and the response to an intravenous fructose tolerance test. Three men of the same age as our patient were used as control subjects. Since the severity may vary and affected individuals self-impose fructose and sucrose restriction, they are essentially symptom free. The diagnosis can only be suspected by taking a careful dietary history. The prevalence of this condition in adults is unknown. It is rare but is likely to be more common than data in the literature would indicate.

  8. Intestinal lymphangiectasia in adults.

    PubMed

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

  9. Immigration and adult transitions.

    PubMed

    Rumbaut, Rubén G; Komaie, Golnaz

    2010-01-01

    Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Rubén Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage counterparts, including blacks and whites. The authors document the demographic changes in the United States over the past forty years and describe the ways in which generation and national origin shape the experiences of these newcomers as they become adults. Rumbaut and Komaie point out that immigrant groups experience gaps in social, economic, and legal status that are even greater than the gaps between native whites and blacks. By far the most-educated (Indians) and the least-educated (Mexicans) groups in the United States today are first-generation immigrants, as are the groups with the lowest poverty rate (Filipinos) and the highest poverty rate (Dominicans). These social and economic divides reflect three very different ways immigrants enter the country: through regular immigration channels, without legal authorization, or as state-sponsored refugees. For many ethnic groups, significant progress takes place from the first to the second generation. But, say the authors, for millions of young immigrants, a lack of legal permanent residency status blocks their prospects for social mobility. Having an undocumented status has become all the more consequential with the failure of Congress to pass comprehensive federal immigration reforms. In the coming two decades, as the U.S. native-parentage labor force continues to shrink, immigrants and their children are expected to account for most of the growth of the nation's labor force, with the fastest-growing occupations requiring college degrees. Rumbaut and Komaie stress that one key to the nation's future will be how it incorporates young adults of immigrant origin in its

  10. [Hearing loss in adults].

    PubMed

    Eshraghi, Adrien A; Frachet, Bruno; Van De Water, Tom R; Eter, Elias

    2009-05-20

    The management of hearing loss in adults depends of etiology and its severity. It can be as simple as treating an external otitis, removing an impacted cerumen or a more complex one such as a surgery for otosclerosis. The hearing loss is managed mainly by new advances in hearing aids technology and implantable hearing devices which include BAHA, middle ear implant and cochlear implants. The research is focused on developing new molecules for intracochlear drug therapy to treat noise induced hearing loss, drug ototoxicity as well as hearing loss related to cochlear implant insertion trauma. Antioxidant molecules, molecules against apoptosis are at this time the most promising molecules than need further investigations.

  11. Dehydration in the Older Adult.

    PubMed

    Miller, Hayley J

    2015-09-01

    Dehydration affects 20% to 30% of older adults. It has a greater negative outcome in this population than in younger adults and increases mortality, morbidity, and disability. Dehydration is often caused by water deprivation in older adults, although excess water loss may also be a cause. Traditional markers for dehydration do not take into consideration many of the physiological differences present in older adults. Clinical assessment of dehydration in older adults poses different findings, yet is not always diagnostic. Treatment of dehydration should focus on prevention and early diagnosis before it negatively effects health and gives rise to comorbidities. The current article discusses what has most thoroughly been studied; the best strategies and assessment tools for evaluation, diagnosis, and treatment of dehydration in older adults; and what needs to be researched further. [Journal of Gerontological Nursing, 41(9), 8-13.].

  12. Coeliac disease in adults.

    PubMed

    Corazza, G R; Gasbarrini, G

    1995-06-01

    Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

  13. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-08

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  14. Sexting among young adults

    PubMed Central

    Gordon-Messer, Deborah; Bauermeister, Jose Arturo; Grodzinski, Alison; Zimmerman, Marc

    2012-01-01

    Purpose Sexting has stirred debate over its legality and safety, but few researchers have documented the relationship between sexting and health. We describe the sexting behavior of young adults in the United States, and examine its association with sexual behavior and psychological well-being. Methods Using an adapted web version of Respondent-Driven Sampling (webRDS) we recruited a sample of U.S. young adults (ages 18 to 24; N=3447). We examined participant sexting behavior using 4 categories of sexting: 1) Non-Sexters, 2) Receivers, 3) Senders, and 4) Two-way Sexters. We then assessed the relationships between sexting categories and sociodemographic characteristics, sexual behavior and psychological well-being. Results Over half (57%) of respondents were Non-Sexters, 28.2% of the sample were Two-way Sexters, 12.6% were Receivers, and 2% were Senders. Males were more likely to be Receivers than females. Sexually active respondents were more likely to be Two-way Sexters than non-sexually active respondents. Among participants who were sexually active in the past 30 days, we found no differences across sexting groups in number of sexual partners, or number of unprotected sex partners in the past 30 days. We also found no relationship between sexting and psychological well-being. Conclusions Our results suggest that sexting is not related to sexual risk behavior or psychological well-being. We discuss the findings of this study and propose directions for further research on sexting. PMID:23299018

  15. Adult Acute Leukaemia

    PubMed Central

    Atkinson, K.; Wells, D. G.; Clink, H. McD.; Kay, H. E. M.; Powles, R.; McElwain, T. J.

    1974-01-01

    Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as “adult acute leukaemia” and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them. ImagesFig. 1Fig. 2Fig. 3 PMID:4141625

  16. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  17. Fecal incontinence in older adults.

    PubMed

    Tariq, Syed H

    2007-11-01

    Fecal incontinence is an underreported and underappreciated problem in older adults. Although fecal incontinence is more common in women than in men, this difference narrows with aging. Risk factors that lead to the development of fecal incontinence include dementia, physical disability, and fecal impaction. Treatment options include medical or conservative therapy for older adults who have mild incontinence, and surgical options can be explored in selected older adults if surgical expertise is available.

  18. Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-05-07

    Anaplastic Large Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  19. The Varieties of Adult Civic Engagement in Adult Learning

    ERIC Educational Resources Information Center

    Munoz, Linda; Wrigley, Heide Spruck

    2012-01-01

    Civic engagement, or the practice of democratic deliberation in adult education and learning, asks that adults use their experiences to cooperatively build solutions to the difficult social, economic, and political problems that affect their lives and communities now and into the future. The articles presented in this issue look at the…

  20. Responding to Young Adult Literature. Young Adult Literature Series.

    ERIC Educational Resources Information Center

    Monseau, Virginia R.

    This book focuses on how readers respond to the power of young adult literature--negating the assumption that because such literature appeals to adolescents it cannot possibly be worthy of a place in the language arts curriculum. The book serves two purposes: it describes and discusses the oral and written response of adolescents and adults to…

  1. Impact of Authentic Adult Literacy Instruction on Adult Literacy Practices.

    ERIC Educational Resources Information Center

    Purcell-Gates, Victoria; Degener, Sophie C.; Jacobson, Erik; Soler, Marta

    2002-01-01

    Investigates relationships between two dimensions of adult literacy instruction and change in the literacy practices of adult literacy students. Finds that authenticity of class literacy activities and texts had a statistically significant effect on change in student literacy practices; and increases in types of texts involved reading and writing…

  2. Young Adult Literature for Less Able Adult Readers.

    ERIC Educational Resources Information Center

    Radebaugh, Muriel Rogie

    1982-01-01

    Presents an annotated bibliography of 20 recent young adult novels that are also appropriate for use with adult readers in community college reading programs. Suggests ways of helping such students improve their reading comprehension by analyzing the novels' themes, conflicts, settings, characterization, and symbolism. (AEA)

  3. Adult Literacy and Numeracy: Assessing Change. Adult Literacy Research Network.

    ERIC Educational Resources Information Center

    Cumming, J. Joy, Ed.; van Kraayenoord, Christina E., Ed.

    This document contains eight papers from an action research program to foster good practice in adult literacy provision and policy. "Introduction" (J. Joy Cumming, Christina E. van Kraayenoord) presents an overview of the action research project and individual reports. "Assessment: Making a Difference in Adult Literacy and Numeracy…

  4. Oakland Adult Reading Lab. Building Comprehension in Adult Education Students.

    ERIC Educational Resources Information Center

    Johnston, Suzanne

    Many adult poor readers do not organize what they read in a way that best facilitates good comprehension. To help students overcome this problem, the Adult Day and Evening School in Oakland, California, organized a reading laboratory for their mostly low-income, educationally disadvantaged students with a diverse range of needs. Instruction in the…

  5. Adult Education in Australia: The Council of Adult Education.

    ERIC Educational Resources Information Center

    Randell, Shirley

    Liberal adult education in Victoria, Australia, takes its ideals, if not its form, from the pre-war university and Workers Education Association (WEA) partnerships: the university providing tutors and content, the WEA providing contact with unions and workers. Unique to Victoria is the level to which community-based adult education has been…

  6. Atomoxetine Treatment for ADHD: Younger Adults Compared with Older Adults

    ERIC Educational Resources Information Center

    Durell, Todd; Adler, Lenard; Wilens, Timothy; Paczkowski, Martin; Schuh, Kory

    2010-01-01

    Objective: Atomoxetine is a nonstimulant medication for treating child, adolescent, and adult ADHD. This meta-analysis compared the effects in younger and older adults. Method: A post hoc analysis was conducted using data from two double-blind, placebo-controlled clinical trials. Data from patients aged 18-25 years were compared with data from…

  7. Evaluation of Adult Education Programs. California Adult Education.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    To assist adult educators in finding meaningful ways to measure the effectiveness of instruction, this monograph provides selected illustrations of specific methods used by adult education instructors to verify student learning. Obtained from teachers in the field, the examples are from programs in (1) dental assisting, (2) instrument pilot ground…

  8. Building Resilience: Helping Young Adults in the Adult Education Classroom.

    ERIC Educational Resources Information Center

    Robinson, Elly

    2000-01-01

    Because of changes in welfare eligibility, the education system, and employment and training opportunities, it has become more likely that young people who have had difficulty with the mainstream schooling system and who face a lack of employment options will end up in adult education. Educators in the adult education classroom have an opportunity…

  9. [Hemolytic anemias in adults].

    PubMed

    Müller, A; Zimmermann, R; Krause, S W

    2011-11-01

    The erythrocyte lifespan in haemolytic anemia is shortened while erythropoesis is increased. Important labaratory findings are increased reticulocytes, LDH, indirect bilirubin and a decreased haptoglobin level. The most important diagnostic tool for further work up of hemolytic anemia is the direct antiglobulin test (DAT, Coombs test) to differentiate autoimmune hemolytic anemia (AIHA) from other causes. Another important group are fragmentation syndroms (hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). In these forms of haemolytic anemia fragmented red blood cells can be found in the blood smear together with thrombocytopenia. A severe problem in paroxysmal nocturnal hematuria is the incidence of thrombosis. The following review describes the most important forms of hemolytic anemia in the adult and the diagnostic and therapeutic strategies.

  10. [Cochlear implant in adults].

    PubMed

    Bouccara, D; Mosnier, I; Bernardeschi, D; Ferrary, E; Sterkers, O

    2012-03-01

    Cochlear implant in adults is a procedure, dedicated to rehabilitate severe to profound hearing loss. Because of technological progresses and their applications for signal strategies, new devices can improve hearing, even in noise conditions. Binaural stimulation, cochlear implant and hearing aid or bilateral cochlear implants are the best opportunities to access to better level of comprehension in all conditions and space localisation. By now minimally invasive surgery is possible to preserve residual hearing and use a double stimulation modality for the same ear: electrical for high frequencies and acoustic for low frequencies. In several conditions, cochlear implant is not possible due to cochlear nerve tumour or major malformations of the inner ear. In these cases, a brainstem implantation can be considered. Clinical data demonstrate that improvement in daily communication, for both cochlear and brainstem implants, is correlated with cerebral activation of auditory cortex.

  11. Adult feminine hygiene practices.

    PubMed

    Czerwinski, B S

    1996-08-01

    Adult feminine hygiene practices are the focus of this exploratory descriptive study. In a sample of 193 women, the typical respondent lived in the Southeast and was a single student who was 23 years of age, and White. Body cleansing, feminine hygiene, and menses management practices were examined. It was found that handwashing varied according to bodily involvement or specific feminine hygiene practices. Assorted menses management products were used for menses management and were used when the woman was not menstruating. The results of this study suggest that it might be possible for health care providers to teach women safe and economical health care practices, such as not douching and handwashing before and after use of menses management products to prevent infections.

  12. Secondary hypertension in adults

    PubMed Central

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-01-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. PMID:27211205

  13. [Vesicoureteral reflux in adults].

    PubMed

    Rollino, Cristiana; D'Urso, Leonardo; Beltrame, Giulietta; Ferro, Michela; Quattrocchio, Giacomo; Quarello, Francesco

    2011-01-01

    Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

  14. An overview of adult-learning processes.

    PubMed

    Russell, Sally S

    2006-10-01

    Part of being an effective instructor involves understanding how adults learn best. Theories of adult education are based on valuing the prior learning and experience of adults. Adult learners have different learning styles which must be assessed prior to initiating any educational session. Health care providers can maximize teaching moments by incorporating specific adult-learning principles and learning styles into their teaching strategies.

  15. Native American Adult Reader I.

    ERIC Educational Resources Information Center

    King, Lovern Root, Ed.

    Aspects of Native American history and culture as well as issues and concerns of American Indians are presented in the twelve short articles in this reader for adults. Intended for use in an adult basic education/GED program, the reader features simply written stories (for grades 0-3), illustrations, vocabulary lists and student study questions.…

  16. Perceived Stress among Deaf Adults

    ERIC Educational Resources Information Center

    Jones, Elaine G.; Ouellette, Sue E.; Kang, Youngmi

    2006-01-01

    The Present Article describes the effectiveness of stress management classes in decreasing perceived stress among Deaf adults. Deaf adults may experience unique stressors, in addition to circumstances associated with increased stress in the general population. The Perceived Stress Scale (S. Cohen, Kamarck, & Mermelstein, 1983) was used as a…

  17. Senior Adult Consumer Advisory Manual,

    ERIC Educational Resources Information Center

    Ater, E. Carolyn, Ed.

    This manual is intended for use by senior adult peer advisors (age 60 and over) engaged in helping relationships in providing consumer education to other senior adults. The advisory procedures are based on a problem solving approach which incorporates the development of a self-help concept. Chapter 1 provides information on consumer advising. It…

  18. Adult Academy Tutor Training Manual.

    ERIC Educational Resources Information Center

    Isserlis, Janet; And Others

    This handbook is for volunteer tutors, student interns, and VISTA volunteers working with adult basic education (ABE) and English-as-a-Second-Language (ESL) learners. The community-based handbook contains information about adult literacy and tutoring--what tutors do, who the learners are, and how the literacy learning process works. Introductory…

  19. Adult Education at a Distance.

    ERIC Educational Resources Information Center

    Gaudet, Alphonse

    This document, which examines the use of educational technologies for distance education for adults in Canada, consists of five narrative sections and a bibliography. The first section introduces the topic and the document's objectives (to describe those technologies used in Canadian adult distance education, paying particular attention to those…

  20. Segmenting the Adult Education Market.

    ERIC Educational Resources Information Center

    Aurand, Tim

    1994-01-01

    Describes market segmentation and how the principles of segmentation can be applied to the adult education market. Indicates that applying segmentation techniques to adult education programs results in programs that are educationally and financially satisfying and serve an appropriate population. (JOW)

  1. Women, Class and Adult Education.

    ERIC Educational Resources Information Center

    Southampton Univ. (England).

    This collection of working papers deals with the relationship among women, social class, and adult education. In her paper entitled "Women and University Extension," Pat Usher argues that by sustaining the dominant cultural, ideological, and social relationships of production in capitalist Britain, university adult education contributes…

  2. Book Display as Adult Service.

    ERIC Educational Resources Information Center

    Moore, Matthew S.

    1997-01-01

    Defines book display as an adult service as choosing and positioning adult books from the library collection to increase their circulation. The author contrasts bookstore arrangement for sales versus library arrangement for access, including contrasting missions, genre grouping, weeding, problems, and dimensions. (Author/LRW)

  3. Journey to International Adult Education

    ERIC Educational Resources Information Center

    Sun, Qi

    2005-01-01

    In this article, the author describes her journey to international adult education and shares some lessons learned from her journey. The author developed her interest in international adult education through the Scientific Research Institute of International and Comparative Education (SRIICE) at Beijing Normal University and discovered its…

  4. Curriculum Models in Adult Education.

    ERIC Educational Resources Information Center

    Langenbach, Michael

    This book describes several curriculum models currently used in the field of adult education in an effort to assist adult educators who develop curricula as a routine part of their jobs. The book is divided into 14 chapters that are grouped into 7 sections. Each section covers a type of educational program, and each chapter describes a specific…

  5. The Politics of Adult Education

    ERIC Educational Resources Information Center

    Ellison, Art

    2016-01-01

    Art Ellison is longtime advocate for adult education, having managed numerous advocacy campaigns over the past forty years on the state and national levels. Prior to his employment in 1980 as the NH State Director of Adult Education he worked for many years as a high school teacher and as a community organizer. In this article, Ellison offers some…

  6. Re-thinking Adult Literacy.

    ERIC Educational Resources Information Center

    Draper, James A.

    A study was conducted to examine the literature on literacy and adult basic education and to identify various issues, trends, problems, possible solutions, and basic principles that might guide programs and policies in adult literacy and basic education in Canada. More than 120 documents were examined, raising such issues as what is literacy and…

  7. ESOL and the Adult Learner.

    ERIC Educational Resources Information Center

    Regan, Timothy F.

    Problems of adult basic education in the United States, symptomatic of the connection between poverty, poor education, and unemployment, have forged for the disadvantaged adult most of the links in the unbreakable chain of deprivation, frustration, and despair. The problem of ESOL (English for Speakers of Other Languages) instruction is…

  8. Cultural Influences on Adult Learning.

    ERIC Educational Resources Information Center

    Conti, Gary J., Ed.; Fellenz, Robert A., Ed.

    Five projects are reported that examined factors related to adult learning in nontraditional environments. "Conrad, Montana: A Community of Memories" (Janice Counter, Lynn Paul, and Gary Conti) reports on a group of adults who for over 40 years have been active in building a better community for friends, relatives, and themselves. A…

  9. Adult Learning Opportunities in Nepal

    ERIC Educational Resources Information Center

    Regmi, Krishna; Regmi, Sharada

    2008-01-01

    This paper presents the initial findings from a study of education system in Nepal. This paper examines the adult learning opportunities within the educational and cultural contexts by reviewing available literature relevant to Nepal. Findings show that there are wider opportunities for adult learning than those considered from education and…

  10. Creating Adult Basic Education Programs.

    ERIC Educational Resources Information Center

    Harris, Dolores M.

    Adult basic education programs must teach the "social living skills" disadvantaged adults need, as well as basic literacy skills. In creating an ABE program, one must first assess the needs of the target population--through surveys, group meetings, an advisory council of members of the target population, demographic studies, and consideration of…

  11. Neuropsychological Assessment of Adult Offenders

    ERIC Educational Resources Information Center

    Marceau, Roger; Meghani, Rehana; Reddon, John R.

    2008-01-01

    This report is primarily concerned with reporting on the normative results obtained on a large sample of serious adult offenders. An expanded Halstead-Reitan Neuropsychological Test Battery was administered to 584 adult offenders (OF), 132 normal controls (NC), and 494 acute psychiatric patients (PP). Subjects were between 18 and 44 years of age.…

  12. Examining Controversies in Adult Education.

    ERIC Educational Resources Information Center

    Kreitlow, Burton W.; And Others

    Controversies over adult education purposes, methods, audiences, and procedures are examined. After outlining a procedure for reviewing competing positions on controversial topics, the book pairs the contrasting views of two authors on each of 10 key issues facing adult education. Chapters cover: philosophies at issue (David L. Boggs); identifying…

  13. Predictive Modeling in Adult Education

    ERIC Educational Resources Information Center

    Lindner, Charles L.

    2011-01-01

    The current economic crisis, a growing workforce, the increasing lifespan of workers, and demanding, complex jobs have made organizations highly selective in employee recruitment and retention. It is therefore important, to the adult educator, to develop models of learning that better prepare adult learners for the workplace. The purpose of…

  14. Travel and Adult Transformative Learning

    ERIC Educational Resources Information Center

    Lindstrom, Steven K.

    2011-01-01

    This phenomenological research study examines the lived experience of individual adult transformation in the context of travel. Adults throughout history have experienced profound personal and perception changes as a result of significant travel events. Transformative learning occurs through experience, crisis, and reflection, all of which are…

  15. Adult Transition Program without Walls

    ERIC Educational Resources Information Center

    Moberg, Eric

    2010-01-01

    Best practices in adult transition special education for moderate to severe students suggest student-centered planning that maximizes independence in adult life. Based on the above sources, school districts and governing boards would best serve moderate to severe transition special education students with increasing integration into the community…

  16. Assessment Models for Adult Education.

    ERIC Educational Resources Information Center

    Snow, Ellen; And Others

    This handbook was developed to provide adult educators in Texas with sufficient background in assessment models to ensure confidence in recognizing and/or selecting appropriate measurement techniques and in using evaluation results to individualize and improve instruction for adult students. The handbook is based on information derived from a…

  17. Literature for Today's Young Adults.

    ERIC Educational Resources Information Center

    Donelson, Kenneth L.; Nilsen, Alleen Pace

    Defining young adult literature to include any book freely chosen for reading by a person between the ages of 12 and 20, this book is intended to help educate professionals in related fields about the growing body of such literature. The first section of the book provides an introduction to young adult literature, including a discussion of the…

  18. The History of Adult Education.

    ERIC Educational Resources Information Center

    Hudson, J. W.

    Beginning with such movements as the eighteenth century moral reformation societies and Welsh Sunday schools, and the first adult schools for both men and women in the early 1800's, this historical review traces British adult education up to 1850. Emphasis is on the extensive and widespread programs of the Mechanics' (workingmen's) Institutes and…

  19. Adult Functional Competency: A Summary.

    ERIC Educational Resources Information Center

    Texas Univ., Austin. Div. of Extension.

    The Adult Performance Level (APL) project summary specifies the competencies which are functional to economic and educational success in society and describes devices developed for assessing those competencies. The APL theory of functional competency identifies adult needs in general knowledge areas (consumer economics, occupational knowledge,…

  20. Adult Education in India & Abroad.

    ERIC Educational Resources Information Center

    Roy, Nikhil Ranjan

    A survey is made of various aspects of adult education in India since 1947, together with comparative accounts of the origin, development, and notable features of adult education in Denmark, Great Britain, the Soviet Union, and the United States. Needs and objectives in India, largely in the eradication of illiteracy, are set forth, and pertinent…