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Anaplastic Oligodendroglioma  

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Although uncommon, anaplastic oligodendrogliomas (AODs) are important to recognize, as they have unique molecular, histologic, and clinical features. Patients with new seizures or new focal neurologic deficits should be referred for brain MRI with contrast. If the MRI suggests a malignant glioma, maximal feasible tumor resection is advised for accurate diagnosis and for relief of tumor-related neurologic symptoms. Radiation therapy (XRT) is the most commonly prescribed postsurgical therapy fo...

Blakeley, Jaishri; Grossman, Stuart

2008-01-01

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Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers.  

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Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA. PMID:24162810

Minniti, Giuseppe; Arcella, Antonella; Scaringi, Claudia; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Pace, Andrea; Giangaspero, Felice; Osti, Mattia Falchetto; Enrici, Riccardo Maurizi

2014-01-01

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MicroRNA expression profiling in recurrent anaplastic oligodendroglioma treated with postoperative radiotherapy  

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Full Text Available In anaplastic oligodendroglioma (AO, genetic alternation was associated with clinical outcome. We explored radiation-associated up or downregulation of microRNAs (miRNAs in AO by comparing miRNA expression profiles in newly-diagnosed AO to recurrent AO treated with postoperative radiotherapy. We identified that 23 miRNAs were upregulated and 42 miRNAs were downregulated in recurrent AO compared with newly-diagnosed AO. Especially, the expression of MiR-124, miR-128, miR-139-5p, miR-153, miR-210, miR-582-5p, and miR-96 were highly increased in the patient with recurrent AO. In contrast, MiR-1, miR-1180, miR-133b, miR-135b, miR-1539, miR-193a-5p, miR-196a, miR-196b, miR-200b, miR-21*, miR-221*, miR-224, miR-24-1*, miR-31, miR-32*, miR-34a*, miR-34c-5p, miR-455-5p, miR-503, and miR-631 showed extremely decreased expression in the patient with recurrent AO. Our results provide meaningful data for miRNAs as molecular diagnosis and novel therapeutic targets in recurrent AO treated with radiotherapy.

Giwon Kim

2011-08-01

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A Novel, Diffusely Infiltrative Xenograft Model of Human Anaplastic Oligodendroglioma with Mutations in FUBP1, CIC, and IDH1  

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Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment. PMID:23527265

Valenzuela, Jaime Alberto Campos; Balss, Jörg; Wang, Jian; Schubert, Manja; Sakariassen, Per Øystein; Sundstrøm, Terje; Torsvik, Anja; Aarhus, Mads; Mahesparan, Rupavathana; von Deimling, Andreas; Kaderali, Lars; Niclou, Simone P.; Schröck, Evelin; Bjerkvig, Rolf; Nigro, Janice M.

2013-01-01

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Bone marrow involvement in systemic alk+ anaplastic large cell lymphoma: morphological resemblance with hodgkin's lymphoma  

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A 21 years old male presented with enlarged cervical lymph nodes. Diagnosis of anaplastic large cell lymphoma was made on lymph node biopsy and confirmed by immunohistochemistry using a panel of monoclonal antibodies including ALK-1. Bone marrow aspiration revealed the presence of large lymphoma cells and trephine biopsy showed interstitial involvement. In addition, there was presence of binucleate cells, lymphocytes, plasma cells and eosinophils. All these features resulted in a strong resemblance of the morphology with Hodgkin's lymphoma. (author)

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Polymorphous oligodendroglioma of Zülch revisited: a genetically heterogeneous group of anaplastic gliomas including tumors of bona fide oligodendroglial differentiation.  

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A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available. From a current perspective, the term polymorphous oligodendroglioma (pO) may appear as contradictory in terms, as nuclear monotony is a histomorphological hallmark of oligodendrogliomas. For the purpose of this study, we defined pO as diffusely infiltrating gliomas felt to be of oligodendroglial rather than astrocytic differentiation and characterized by the presence of multinucleate tumor giant cells and/or nuclear pleomorphism. In a total of nine patients, we identified tumors consistent with this working definition. All tumors were high-grade. We characterized these with respect to clinical, histomorphological and genetic features. Despite clinical and genetic heterogeneity, we identified a subset of tumors of bona fide oligodendroglial differentiation as characterized by combined loss of heterozygosity of chromosome arms 1p and 19q (LOH 1p19q). Those tumors that lacked LOH 1p19q showed a high frequency of IDH1 mutations and loss of alpha thalassemia/mental retardation syndrome X-linked gene (ATRX) immunoreactivity, indicating a possible phenotypic convergence of true oligodendrogliomas and gliomas of the alternative lengthening of telomeres (ALT) pathway. p53 alterations were common irrespective of the 1p19q status. Histomorphologically, the tumors featured interspersed bizarre multinucleate giant tumor cells, while the background population varied from monotonous to significantly pleomorphic. Our findings indicate, that a rare polymorphous - or "giant cell" - variant of oligodendroglioma does indeed exist. PMID:24444336

Hewer, Ekkehard; Beck, Jürgen; Murek, Michael; Kappeler, Andreas; Vassella, Erik; Vajtai, Istvan

2014-08-01

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Pitfalls of conservative treatments of multiple probable cerebral cavernous malformations (CCMs): clinicopathological features of CCMs coexisting with vasculogenic mimicry in an anaplastic oligodendroglioma.  

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Developments in magnetic resonance imaging (MRI) techniques have dramatically increased the detection of cerebral cavernous malformations (CCMs). Conservative treatment is often recommended for asymptomatic cases. However, CCMs occasionally harbor malignant gliomas. Here, we describe a rare case of multiple probable CCMs and an anaplastic oligodendroglioma (AO) showing vasculogenic mimicry (VM) and discuss the potential pitfalls of conservative treatments. A 42-year-old otherwise healthy woman presented with generalized seizures. Magnetic resonance imaging (MRI) revealed multiple parenchymal hypointensities, particularly in the right frontal lobe, with hyperintensity on fluid-attenuated inversion recovery (FLAIR) images. The patient was diagnosed with multiple probable CCMs, and conservative treatment was administered. However, follow-up MRI showed a slightly enlarged hyperintense area in the right frontal lobe. The patient then underwent surgery; histological diagnosis was CCMs and AO with VM. The patient subsequently underwent radiotherapy and chemotherapy. No neurological deficits or tumor recurrence were evident 21 months after surgery. We present this rare case and emphasize the possibility of the coexistence of malignant gliomas with CCMs. Close observation with MRI is essential in cases of multiple probable CCMs, and a histological confirmation should be considered in cases showing any enlargement of hyperintensity on FLAIR images. PMID:24337536

Yamamoto, Junkoh; Shimajiri, Shohei; Miyaoka, Ryo; Nishizawa, Shigeru

2014-07-01

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Cognition and Quality of Life After Chemotherapy Plus Radiotherapy (RT) vs. RT for Pure and Mixed Anaplastic Oligodendrogliomas: Radiation Therapy Oncology Group Trial 9402  

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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-QOthere 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.

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Retrospective review of pediatric oligodendrogliomas  

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PURPOSE: Identify prognostic parameters and treatment outcomes in patients diagnosed with pediatric oligodendrogliomas. MATERIALS and METHODS: Between 1985 and 1995 thirty children presented with cerebral oligodendrogliomas. Ages ranged from 2 months to 18 years (median 9 yrs). Anatomical sites included temporal (n=17), frontal (n=6), occipital (n=2), parietal (n=2), and 1 each in midbrain, thalamus and cerebellum. The histopathology included oligodendrogliomas (OD, n=18) and oligoastrocytomas (OA, n=6) and anaplastic oligodendrogliomas (AO, n=6). The extent of initial surgical resection ranged from biopsy (BX, 3 pts) only to subtotal resection (STR, 10 pts) and gross-total resection (GTR, 17 pts) based on the intraoperative surgical impression. Standard approach included surgery only or the addition of radiotherapy for selected incompletely resected or anaplastic oligodendrogliomas. RESULTS: 23 patients are alive with a 3 yr overall survival (OS) of 68% standard error (SE) ± 10%. The median followup for the 23 patients is 3.1 yrs (min 2.4 months and max of 10.2 yrs). The 3 yr disease free survival (DFS) is 52% SE ± 11%. 3 yr DFS by surgical extent is 77% for GTR, 42% for STR and 0% for BX. The 3 yr OS by histology is 74% for OD, 83% for OA and 44% for AO. CONCLUSIONS: Extent of surgical resection and histological subtypes are strong predictors for local control and survival. The role of RT is difficult to assess. The most effective treatment for pediatric well diffective treatment for pediatric well differentiated oligodendrogliomas is GTR with adjuvant radiotherapy reserved for incompletely resected and unfavorable histologies

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Chromosome 1p and 19q deletions in malignant glioneuronal tumors with oligodendroglioma-like component.  

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Malignant glioneuronal tumors (MGNT) are suggested to be a new entity of glioma defined morphologically as any malignant glioma showing immunohistoichemical evidence of neuronal differentiation. We encountered seven cases of MGNT with oligodendroglioma-like component and investigated alternations of chromosome 1p and 19q in these tumors. Seven patients ranged from 33 to 62 years of age, four females and three males. Immunohistochemical study of these tumors was performed using neuronal markers (synaptophysin, neurofilament, beta-tubulin, chromogranin A and NeuN), astrocytic marker (GFAP) and Ki-67. We undertook a molecular cytogenetic study of tumor specimens obtained from seven patients using fluorescence in situ hybridization (FISH) with DNA probes mapping to chromosome 1p36, 1q25, 19p13 and 19q13. Histologically, these tumors resembled anaplastic oligodendroglioma. Immunohistochemically, tumor cells were immunoreactive for synaptophysin (7/7), neurofilament (6/7), beta-tubulin (5/7), chromogranin A (4/7), NeuN (2/7) and GFAP (7/7). The Ki-67 labeling index ranged from 4.5% to 20.7%. FISH analysis demonstrated either 1p or 19q deletion in all seven cases (100%) and both 1p and 19q deletions in five cases (71%). The 1p deletion was detected in six of seven cases (86%) and 19q deletion was also detected in six (86%). 1p and 19q deletions were present in MGNT, especially those with oligodendroglial components. We suggest that the oligodendroglial-like feature was associated with not only 1p or 19q loss but also differentiation along neuronal cell lines as a factor of favorable prognosis in glial tumors. It is inappropriate to make a diagnosis of oligodendroglioma based only on morphological resemblance to oligodendroglia. PMID:18781279

Takeuchi, Hiroaki; Kubota, Toshihiko; Kitai, Ryuhei; Matsuda, Ken; Hashimoto, Norichika; Sato, Kazufumi

2009-01-01

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Low-grade oligodendroglioma of the pineal gland: a case report and review of the literature  

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Abstract Background Gliomas are a very rare subtype of pineal region tumours, whereas oligodendrogliomas of the pineal region are exceedingly rare, since there have been only 3 cases of anaplastic oligodedrogliomas reported this far. Methods-Results We present a case of a low-grade oligodendroglioma arising in the pineal gland of a 37 year-old woman. The patient presented with diplopia associated with a cystic pineal region mass demonstrated on MRI. Total resect...

Levidou Georgia; Korkolopoulou Penelope; Agrogiannis George; Paidakakos Nikolaos; Bouramas Dimos; Patsouris Efstratios

2010-01-01

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Age-related differences in 1p and 19q deletions in oligodendrogliomas  

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Full Text Available Abstract Background Recent reports indicate that anaplastic oligodendrogliomas frequently show allelic losses on chromosome arms 1p and 19q, and that these deletions are associated with better chemotherapeutic response and overall patient survival. Because of the diversified genetic makeup of the population and the centralized provincial referral system for brain tumor patients in Manitoba, the epidemiological features of such tumors sometimes differ from the published data acquired from non-community based settings. In this study, we assessed the prevalence of allelic deletions for chromosome arms 1p and 19q in anaplastic and in low-grade oligodendrogliomas in the Manitoba population. Methods Loss of heterozygosity (LOH analysis of brain tumors was carried out using 4 microsatellite markers (D1S508, D1S2734, D19S219 and D19S412 and a PCR based assay. The tumors were consecutively acquired during the period September 1999–March 2001 and a total of 63 tumors were assessed. Results We found that allelic loss of chromosome 1p and 19q was higher in oligodendrogliomas than in other diffuse gliomas and that for anaplastic oligodendrogliomas, younger patients exhibited significantly more deletions than older patients (>60 years of age. Conclusions These studies suggest that age may be a factor in the genetic alterations of oligodendrogliomas. In addition, these studies demonstrate that this assay can easily be carried out in a cost-effective manner in a small tertiary center.

Del Bigio Marc R

2003-12-01

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Calcification in oligodendroglioma.  

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Forty-four previously diagnosed surgical biopsy specimens of oligodendroglioma with calcification from the file of Veterans General Hospital-Taipei between 1977-1985 form the base of this study. Thirty-two patients (72.8%) had varied degree of calcification deposits in tumor parenchyma related to blood vessels while 12 patients (27.2%) in tumor parenchyma unrelated to blood vessels. Ten patients (22.7%) disclosed calcification at the vicinity of tumor tissue. Histochemical studies of the calcified deposits revealed no trace minerals other than calcium and iron. Electron microscopic examination of the calculi showed membrane-bound vesicles and radially precipitated crystals that simulated hydroxyapatite of psammoma body in meningioma. There was no statistically significant correlation between the demise or recurrence of patients and the calcification of tumor when Chi-squared test was applied. PMID:2168257

Chen, W Y; Liu, H C; Lam, P C

1990-03-01

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Post-operative radiation and chemoradiation therapy with Temozolamide in patients with grade III anaplastic gliomas of the brain  

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Post-operative radiation (RT) or chemoradiation therapy (CRT) with Temozolamide promotes 5-year survival in 52.4% of cases of anaplastic oligodendroglioma and oligoastrocytoma and in 39.3% of cases of anaplastic astrocytoma. CRT (vs.RT) increases 5-year survival of the patients with anaplastic astrocytoma from 28.4±9.5% to 56.2 ±15.7% (p=0.042)

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Characteristic CT signs in oligodendrogliomas  

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Computed tomography offers valuable aid for improving the diagnostic capabilities for oligodendrogliomas. The authors have attempted to determine more precisely the CT characteristic signs for this type of tumor and to establish criteria for predicting malignancy grade. They can conclude that calcifications are the main signs which lead to the diagnosis of oligodendroglioma, as the most usual calcifying glioma. This finding was known before the CT era, but with the CT one can be more exact with regard to form, growth, number and density of the calcifications and especially the smallest of them, which are not to be seen on the conventional X-ray examination. The cyst formation is another feature of oligodendroglioma. The occurrence of contrast enhancement and cyst formation are the most characteristic signs of malignancy. (C.F.)

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Low-grade oligodendroglioma of the pineal gland: a case report and review of the literature  

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Full Text Available Abstract Background Gliomas are a very rare subtype of pineal region tumours, whereas oligodendrogliomas of the pineal region are exceedingly rare, since there have been only 3 cases of anaplastic oligodedrogliomas reported this far. Methods-Results We present a case of a low-grade oligodendroglioma arising in the pineal gland of a 37 year-old woman. The patient presented with diplopia associated with a cystic pineal region mass demonstrated on MRI. Total resection was performed and histological examination showed that the cystic wall consisted of tumour cells with a central nucleus a perinuclear halo and minimal pleomorphism. Immnunohistochemical analysis showed that these cells were diffusely positive for CD57, and negative for GFAP, CD10, CD99, cytokeratins, neurofilaments and synaptophysin. FISH analysis was performed in a small number of neoplastic cells, which were not exhausted after immunohistochemistry and did not reveal deletion of 1p and 19q chromosome arms. However, the diagnosis of a low grade oligodendroglioma of the pineal gland was assigned. Conclusion Although the spectrum of tumours arising in the pineal gland is broad, the reports of oligodendrogliomas confined to this location are exceedingly rare, and to the best of our knowledge there is no report of a low-grade oligodendroglioma. However, they should be added in the long list of tumours arising in the pineal gland.

Levidou Georgia

2010-09-01

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Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas  

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Introduction: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. Materials and Methods: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. Results: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). Conclusion: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy ± chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma

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Osteoclastoma-like anaplastic carcinoma of the thyroid  

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Anaplastic carcinoma is a highly malignant tumor that is partially or totally undifferentiated. The use of fine needle aspiration cytology (FNAC) to diagnose anaplastic carcinoma with osteoclast-like giant cells, has been rarely reported. We report here a case of osteoclastoma - anaplastic carcinoma - that was diagnosed on cytology in a 58 year-old female patient, who presented with a progressively increasing swelling over the anterior aspect of the neck. Multinucleated giant cells resembling...

Joseph Leena; Ravi A; Rekha A; Rao Shalinee; Aarthi Rajkumar; Panicker Vinod

2008-01-01

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Oligodendroglioma  

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... and size of the tumor. Tumors of the frontal lobe may cause weakness on one side of the body, personality or behavior changes, and difficulty with short-term memory. Temporal lobe tumors are usually “silent,” causing few symptoms other than ...

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Osteoclastoma-like anaplastic carcinoma of the thyroid  

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Full Text Available Anaplastic carcinoma is a highly malignant tumor that is partially or totally undifferentiated. The use of fine needle aspiration cytology (FNAC to diagnose anaplastic carcinoma with osteoclast-like giant cells, has been rarely reported. We report here a case of osteoclastoma - anaplastic carcinoma - that was diagnosed on cytology in a 58 year-old female patient, who presented with a progressively increasing swelling over the anterior aspect of the neck. Multinucleated giant cells resembling osteoclasts are rarely seen in the giant cell variant of anaplastic carcinoma.

Joseph Leena

2008-01-01

 
 
 
 
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Anaplastic thyroid cancer  

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... carcinoma is a rare and aggressive form of cancer of the thyroid gland. ... Anaplastic thyroid cancer grows very rapidly and is an invasive type of thyroid cancer . It occurs most often in people ...

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Sarcomatous evolution of oligodendroglioma ("oligosarcoma"): confirmatory report of an uncommon pattern of malignant progression in oligodendroglial tumors.  

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By analogy to gliosarcoma, the neologism "oligosarcoma" is to describe an uncommon form of biphasic central nervous system tumor composed of contiguous neuroepithelial and mesenchymal elements, each of which individually meet the criteria of oligodendroglioma and sarcoma, respectively. By virtue of its distinctive genotype (codeletion 1p/19q), oligodendroglioma is a particularly inviting paradigm to test the assumption that such mixed tumors are clonally derived from a glial primary. We observed this constellation in a 41-year-old male who underwent two resection procedures for a recurring right frontal tumor at five years' interval. On imaging, both lesions were contrast-enhancing, and measured 7 cm × 7 cm × 6.8 cm and 7 cm × 6.5 cm × 4cm, respectively. Following the first operation, temozolomide monotherapy was administered. Whereas initial histology showed conventional anaplastic oligodendroglioma, the recurrence consisted mostly of a fibrosarcoma-like, fascicular neoplasm that was immunoreactive for vimentin, smooth muscle actin, S100 protein, and focally epithelial membrane antigen. In between, a subset of otherwise indistinguishable spindle cells expressed GFAP, and focally merged with residues of oligodendroglioma. Molecular testing for loss of heterozygosity confirmed codeletion of 1p/19q in both the primary tumor and the sarcomatous recurrence. Similarly, generalized immunoreactivity for the mutant R132H form of isocitrate dehydrogenase in both lesions indicated an identical mutation of the IDH1 gene. By the above standards, biologically consistent "oligosarcomas" are felt to be exceedingly rare, and possibly participate of a nosologically heterogeneous group of combined glial/mesenchymal lesions that may also include iatrogenically induced second malignancies as well as true collision tumors. PMID:23102810

Vajtai, Istvan; Vassella, Erik; Hewer, Ekkehard; Kappeler, Andreas; Reinert, Michael M

2012-12-15

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Treatment of anaplastic glioma.  

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Anaplastic gliomas have received increasing attention over the past years. As opposed to glioblastoma, where the focus has been on the evaluation of novel compounds (with mainly disappointing results), in anaplastic gliomas relevant progress was generated with genotoxic therapies and translational work on biomarkers. Anaplastic gliomas are classified using single biomarkers, namely isocitrate dehydrogenase (IDH) or the related CpG island methylator phenotype (CIMP), alpha-thalassemia/mental retardation syndrome X-linked (ATRX), telomerase reverse transcriptase (TERT), p53, 1p/19q, and O(6)-methylguanine DNA-methyltransferase (MGMT). With these molecular biomarkers, three main prognostically distinct groups have been defined: (i) CIMP-negative anaplastic gliomas, which have a similar prognosis as glioblastoma, (ii) CIMP-positive 1p/19q intact, and (iii) CIMP-positive 1p/19q codeleted gliomas. In the CIMP-negative, mainly IDH wild-type group, MGMT promoter methylation may be used to identify patients who benefit from alkylating chemotherapy. The mutually exclusive ATRX losses and 1p/19q codeletions are used to subcategorize anaplastic tumors with a mixed histology according to microscopic features. This eliminates the biological basis and clinical necessity for the diagnosis of mixed gliomas (anaplastic oligoastrocytomas). Retrospective long-term analysis of the EORTC 26951 and RTOG 9402 trials revealed that patients with tumors harboring 1p/19q codeletions benefit from addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to primary radiotherapy. RTOG 9402 suggests that this may be the case also for patients with 1p/19q intact tumors, but IDH mutation. Future developments in addition to the ongoing CATNON and CODEL trials, will focus on further refinement of the molecular predictors and development of treatments that not only increase survival but also maintain neurological function, cognition, and health-related quality of life. PMID:25468227

Wick, Wolfgang; Wiestler, Benedikt; Platten, Michael

2015-01-01

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KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas.  

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The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p=0.005). KPNA2 expression (? 5% versus histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well. PMID:24929863

Gousias, Konstantinos; Niehusmann, Pitt; Gielen, Gerrit; Simon, Matthias; Boström, Jan

2014-10-01

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Molecular Diagnosis of Metastasizing Oligodendroglioma : A Case Report  

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We report the case of a suspicious parotid mass in which molecular determination of loss of heterozygosity (LOH) of chromosome arms 1p and 19q in combination with cytologic and immunohistochemical analysis defined the tumor to be metastatic oligodendroglioma. The patient was a 41-year-old woman who developed a World Health Organization grade II oligodendroglioma in her right frontal lobe at age 32, for which no adjuvant chemo- or radiotherapy was administered. Five years following this diagno...

Wang, Min; Murphy, Kathleen M.; Kulesza, Piotr; Hatanpaa, Kimmo J.; Olivi, Alessandro; Tufaro, Anthony; Erozan, Yener; Westra, William H.; Burger, Peter C.; Berg, Karin D.

2004-01-01

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The Characteristics of Astrocytomas and Oligodendrogliomas Are Caused by Two Distinct and Interchangeable Signaling Formats  

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Full Text Available Chronic platelet-derived growth factor (PDGF signaling in glial progenitors leads to the formation of oligodendrogliomas in mice, whereas chronic combined Ras and Akt signaling leads to astrocytomas. Different histologies of these tumors imply that the pathways activated by these two oncogenic stimulations are different, and that the apparent lineage of the tumor cells may result from specific signaling activity. Therefore, we have investigated the signaling effects of PDGF in culture and in gliomas in vivo. In culture, PDGF transiently activates ERK1/2 and Akt, and subsequently elevates p21 and PCNA expression similar to chronic PDGF autocrine signaling in cultured astrocytes and PDGF-induced oligodendrogliomas in vivo. Culture experiments show that autocrine PDGF stimulation, and combined active Ras and Akt generate signaling patterns that are in some ways mutually exclusive. Furthermore, forced Akt activity in the context of chronic PDGF stimulation results in cells with an astrocytic differentiation pattern both in culture and in vivo. These data imply that these two interconvertible signaling motifs are distinct in mice and lead to gliomas resembling the two major glioma histologies found in humans. The ability of signaling activity to convert tumor cells from one lineage to another presents a mechanism for the development of tumors apparently comprised of cells from multiple lineages.

Chengkai Dai

2005-04-01

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Anaplastic pleomorphic xanthoastrocytoma.  

Science.gov (United States)

A case of anaplastic pleomorphic xanthoastrocytoma (PXA) in a 9-year-old girl is reported. Histological features of PXAs are cellular pleomorphism of GFAP-positive cells, with intracytoplasmic lipidic vacuoles and a reticulin network, bizarre giant cells, low mitotic activity, and lack of necrosis and of endothelial vascular proliferations. These tumors are generally reported to have a favorable postoperative course. In our case, a poor clinical prognosis and spread of the illness through the CSF was observed. Immunohistochemical features of the tumor, which were histologically anaplastic in nature, were analyzed. There were small foci of necrosis in the sections of the material obtained at the first operation and extensive necrosis in that from the second operation, although the patient had not received radiotherapy between the operations. The presence of necrosis in PXA is an uncommon and significant feature. It predicts the poor prognosis seen in this case, and therefore this report strongly supports the notion that necrosis should automatically exclude a tumor from the PXA category. The histological grade was evaluated as grade 3 (according to the WHO classification). PMID:9083703

Bayindir, C; Balak, N; Karasu, A; Kasaro?lu, D

1997-01-01

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Anaplastic meningioma: case report  

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Full Text Available Intracranial meningiomas continue to challenge our best clinical efforts to eliminate them once discovered and deemed appropriate for treatment. Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment. The external whole brain irradiation is recommended. Traditional chemotherapy has proven ineffective; thus, new chemotherapeutic agents and new methods of delivery should be developed. Immunotherapy may be considered for patients with malignant meningiomas when all others previous treatment have failed. We report a case of anaplastic papillary meningioma. A 67-year-old man presented with partial complex seizures, headache and aggressiveness. A computerized tomography and magnetic resonance image demonstrated a large left temporo-occipital mass with difuse contrast enhancement and extensive surrounding edema. A left temporo-occipital flap was performed. The tumor and the infiltrated dura were radically removed. Postoperatively, the patient remained neurologically intact. The treatment was complemented by external whole brain radiation.

Falavigna Asdrubal

2001-01-01

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Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas  

International Nuclear Information System (INIS)

Purpose: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. Methods and Materials: Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m2 carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. Results: Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age (p=0.026), Karnofsky performance score (KPS; p=0.009), and brain necrosis (p=0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance (p=0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anapnths and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. Conclusion: When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18-33 months)

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Oligodendrogliomas en el Instituto Nacional de Neurología y Neurocirugía: comportamiento biológico en una población definida / Oligodebdrogliomas the National Institute of Neurology and neurosurgery mvs: biologic behavior in a defined population  

Scientific Electronic Library Online (English)

Full Text Available SciELO Mexico | Language: Spanish Abstract in spanish Los oligodendrogliomas corresponden entre el 2 y 5% de los tumores intracranerales siendo diagnosticados en la 4º ó 5º décadas de la vida. La localización más frecuente es el lóbulo frontal. La cirugía es la piedra angular del tratamiento utilizado. Material y métodos: entre enero de 1990 y enero de [...] l 2000, 28 pacientes tuvieron diagnóstico de oligodendroglioma. Se revisaron los expedientes en busca de localización, signos y síntomas de presentación, diagnóstico preoperatorio, estirpe histológica, tipo de tratamiento recibido y complicaciones. Resultados: el sitio de localización más frecuente fue el lóbulo frontal (43%), mientras que el síntoma de presentación principal fue epilepsia (61%). El diagnóstico preoperatorio fue glioma de bajo grado en 39% de los casos. Se realizó resección parcial en 36% de los casos. La cirugía fue realizada por un neurocirujano recibido en la mitad de los casos y por un residente de último año en la otra mitad. Recibió radioterapia fraccionada el 71% de los pacientes, mientras que 21% recibieron quimioterapia. El diagnóstico histopatológico fue oligodendroglioma en 71% de los casos y oligodendroglioma anaplásico en el 29%. La mortalidad operatoria fue del 8%. Conclusiones: los resultados obtenidos en el estudio son similares a los descritos en la literatura. Abstract in english Oligodendrogliomas represent 2 to 5% of the intracraneal tumors. Usually these tumors are diagnosed between the 4th and the 5th decades of life. The most commonly site is the frontal lobe. Surgery is the milestone of the treatment approach. Material and methods: between January 1990 and January 2000 [...] , 28 patients had a diagnosis of oligodendroglioma. We looked for localization, signs and symtoms of presentation, peroperative diagnosis, histopathology, type of treatment received and complications. Results: the most frecuent site was the frontal lobe (43%), while the main symptom of presentation were seizures (61%). The preoperative diagnosis with clinical data and imaging was low-grade glioma in 39% of the cases. Partial resection was performed in 36% of the cases being the most prevalent of all treatments. The surgery was performed by neurosurgeons in half the cases and by residents of the last year in the other half. Seventy one porcent of patients were treated with radiotherapy, and 21% with chemotherapy. The hystopathologic diagnosis was oligodendroglioma in 71% and anaplastic oligodendroglioma in 29%. The operative mortality was 8%. Conclusion: our results are similar to the ones described

Sergio, Moreno-Jiménez; Mario Alonso, Vanegas; Antonio, Bramasco Aviléz; Cuauhtémoc, García-Pastor; Javier, Terrazo-Lluch; Martha, Tena; Lucinda, Aguirre.

2005-07-01

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Anaplastic Transformation of Differentiated Thyroid Carcinoma  

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Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies that arise from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. We describe a case for huge goiter diagnosed as papillary thyroid carcinoma, which underwent thyroidectomy. The final histology showed anaplastic transformation. The clinical and possible etiological aspects are discussed.

Khairy, Gamal

2009-01-01

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Infratentorial oligodendroglioma in a child: a case report and review of the literature.  

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Oligodendrogliomas are the tumors of normal glial cells of brain called oligodendrocytes. They represent a small proportion of childhood brain tumors and are infrequently encountered in the posterior fossa. CT scan and MRI are very helpful for the preoperative management of oligodendrogliomas. However, due to the rarity and non-specific imaging features, it may be difficult to differentiate oligodendroglioma from astrocytoma especially in an infratentorial location. The short- and long-term outcome and the exact treatment protocol of posterior fossa oligodendroglioma is yet to be established. We report a rare case of an oligodendroglioma of the vermis in an 8-year-old female with a brief review of the literature. PMID:22843466

Ouni, Fatma El; Gaha, Mehdi; Moulahi, Hassen; Daadoucha, Abderrahmen; Krifa, Hedi; Tlili, Kalthoum

2012-01-01

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Gene expression profiles associated with treatment response in oligodendrogliomas.  

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Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy. In this study, we made use of expression profiling to identify chemosensitive oligodendroglial tumors. Correlation of expression profiles to loss of heterozygosity on 1p and 19q, common chromosomal aberrations associated with response to treatment, identified 376, 64, and 60 differentially expressed probe sets associated with loss of 1p, 19q or 1p, and 19q, respectively. Correlation of expression profiles to the tumors' response to treatment identified 16 differentially expressed probe sets. Because transcripts associated with chemotherapeutic response were identified independent of common chromosomal aberrations, expression profiling may be used as an alternative approach to the tumors' 1p status to identify chemosensitive oligodendroglial tumors. Finally, we correlated expression profiles to survival of the patient after diagnosis and identified 103 differentially expressed probe sets. The observation that many genes are differentially expressed between long and short survivors indicates that the genetic background of the tumor is an important factor in determining the prognosis of the patient. Furthermore, these transcripts can help identify patient subgroups that are associated with favorable prognosis. Our study is the first to correlate gene expression with chromosomal aberrations and clinical performance (response to treatment and survival) in oligodendrogliomas. The differentially expressed transcripts can help identify patient subgroups with good prognosis and those that will benefit from chemotherapeutic treatments. PMID:16357140

French, Pim J; Swagemakers, Sigrid M A; Nagel, Jord H A; Kouwenhoven, Mathilde C M; Brouwer, Eric; van der Spek, Peter; Luider, Theo M; Kros, Johan M; van den Bent, Martin J; Sillevis Smitt, Peter A

2005-12-15

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Surgical treatment for anaplastic thyroid cancer  

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Full Text Available Background: Anaplastic thyroid cancer is relatively rare but extremely aggressive neoplasm. The aim of the present paper was to study the possibility of surgery for anaplastic thyroid cancer. Methods: During 5-year period (from 1998 to 2002 in the Center for endocrine surgery, we found anaplastic thyroid cancer in 65 patients (44 female and 21 male patients of median age 63 years (range: 37-88 years. Diagnosis was determined on the basis of histological analysis in operated patients or on cytology findings in case of patients who were not operated. Histological analysis confirmed anaplastic transformation of papillary thyroid cancer in 18 cases. Results In 50% patients we performed only fine needle biopsy, and in 37% patients operative biopsy or tumor reduction. We performed radical surgery hemithyroidectomy or total thyroidectomy, in 13% patients with anaplastic thyroid cancer. Thyroid goiter was present in 35% patients longer than a year before diagnosis of anaplastic cancer was made. Conclusion: Possibility of surgery for anaplastic thyroid cancer is very limited. In about one third of patients there were longstanding goiter or histological verified dedifferentiation of papillary thyroid cancer. These patients should have been operated before anaplastic transformation.

Živaljevi? Vladan R.

2003-01-01

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Classical and anaplastic seminoma: Difference in survival  

International Nuclear Information System (INIS)

The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

36

Modeling anaplastic thyroid carcinoma in the mouse.  

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Anaplastic thyroid carcinoma is the least common form of thyroid cancer; however, it accounts for the majority of deaths associated with this family of malignancies. A number of genetically engineered immunocompetent mouse models recapitulating the genetic and histological features of anaplastic thyroid cancer have been very recently generated and represent an invaluable tool to dissect the mechanisms involved in the progression from indolent, well-differentiated tumors to aggressive, undifferentiated carcinomas and to identify novel therapeutic targets. In this review, we focus on the relevant characteristics associated with these models and on what we have learned in terms of anaplastic thyroid cancer biology, genetics, and response to targeted therapy. PMID:25420535

Champa, Devora; Di Cristofano, Antonio

2015-02-01

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Concurrent CIC mutations, IDH mutations and 1p/19q loss distinguish oligodendrogliomas from other cancers  

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Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all ...

Yip, Stephen; Butterfield, Yaron S.; Morozova, Olena; Chittaranjan, Suganthi; Blough, Michael D.; An, Jianghong; Birol, Inanc; Chesnelong, Charles; Chiu, Readman; Chuah, Eric; Corbett, Richard; Docking, Rod; Firme, Marlo; Hirst, Martin; Jackman, Shaun

2012-01-01

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

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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.

Kashima, Tsuyoshi; Vinters, H.V.; Campagnoni, A.T. [Univ. of California, Los Angeles, CA (United States)

1995-01-01

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Anaplastic seminoma: an analysis of 77 patients  

International Nuclear Information System (INIS)

Over a 28 year period, 77 patients with early stage anaplastic seminoma of the testis were treated by orchiectomy and lymphatic irradiation at three Army medical centers. With a median follow-up period of 97 months, the 10 year actuarial survival is 96% for Stage I patients and 87% for Stage II patients. For patients with Stage I anaplastic seminoma no survival advantage can be demonstrated for adding mediastinal and supraclavicular irradiation versus para-aortic and pelvic irradiation alone. The addition of retroperitoneal lymphadenectomy to lymphatic irradiation increased the frequency of major gastrointestinal complications without significantly improving survival. Patients with anaplastic seminoma and elevated serum beta-subunit human chorionic gonadotrophin levels have a poor prognosis and should be considered for adjuvant combination chemotherapy. Anaplastic seminoma of the testis has a similar clinical presentation, response to therapy and prognosis compared to typical seminoma and should be managed in the same way

40

Anaplastic thyroid cancer, tumorigenesis and therapy.  

LENUS (Irish Health Repository)

Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

O'Neill, J P

2010-03-01

 
 
 
 
41

Olig2 is useful in the differential diagnosis of oligodendrogliomas and extraventricular neurocytomas.  

Science.gov (United States)

A 42-year-old woman had suffered from headaches since April 2009. Computed tomography revealed a tumor with marked calcification in the left frontal lobe adjacent to the left anterior horn of the lateral ventricle. T1-weighted gadolinium-enhanced magnetic resonance imaging showed a well-enhanced tumor at the lesion. Dynamic methionine positron emission tomography showed no delayed methionine attenuation. Initial preoperative diagnosis was extraventricular neurocytoma (EVN). However, oligodendroglioma was determined upon a second diagnosis. The patient underwent total tumor removal. Hematoxylin and eosin staining showed the characteristic fried egg-like cells, round nuclei, and immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein, synaptophysin, neuronal nuclear antigen, microtubule-associated protein 2 and Olig2. The MIB-1 labeling index was 20%, which suggested malignancy. Although these findings demonstrated that the tumor had glioneuronal character, it was difficult to differentiate between EVN and oligodendroglioma. There have been reports that Olig2 immunohistochemistry is generally positive in cases of oligodendroglioma, but not in cases of neurocytoma. We completed the diagnosis as oligodendroglioma. Subsequent electron microscopy results presented oligodendroglial but not neuronal characteristics. We concluded that Olig2 is useful in the differential diagnosis of oligodendrogliomas and EVNs. PMID:21312066

Okada, Makoto; Yano, Hirohito; Hirose, Yoshinobu; Nakayama, Noriyuki; Ohe, Naoyuki; Shinoda, Jun; Iwama, Toru

2011-04-01

42

Anaplastic thyroid carcinoma presenting as bilateral pleural effusion  

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Anaplastic thyroid cancer presenting as bilateral malignant pleural effusion is rarely reported. We present a case who presented solely with respiratory symptoms and subsequently found to be having bilateral malignant pleural effusion secondary to anaplastic thyroid cancer.

Sodhi, R.; Sindhwani, G.; Chandra, S.; Anand, D.

2014-01-01

43

Caveolin 1 expression independently predicts shorter survival in oligodendrogliomas.  

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Caveolin 1 (cav-1) is the basic component of the flask-shaped membrane microdomains known as caveolae that are involved in various cell functions. Caveolin 1 can be overexpressed in tumors,suggesting a proneoplastic role, or it can be downregulated. We previously reported that cav-1 expression increases with tumor grade in astrocytomas. Here, we studied cav-1 immunoreactivity in brain umors with an oligodendroglial component to determine the prognostic value of cav-1 expression and to correlate it with 1p/19q deletions. Fifty-four oligodendrogliomas, 26 mixed oligoastrocytomas,and 7 glioblastomas with an oligodendroglial component were assessed for cav-1 expression by immunohistochemistry and for 1p/19q status by fluorescence in situ hybridization. Caveolin-1 was detected in a minority of cases (22%) and was associated mostly with Grade III mixed oligoastrocytomas and glioblastomas with anoligodendroglial component; cav-1 expression was significantly correlated with the absence of a 1p/19q deletion (p = 0.0002). In the 63 cases in which survival data were available, cav-1 expression was also significantly associated with shorter survivals, whereas 1p/19q deletion was associated with longer survivals. Among high-grade tumors, cav-1 expression was the only factor that retained a statistical significance after multivariate analysis for the prediction ofa short survival (p G 0.015). These data are the first evidence that cav-1 immunohistochemistry is an independent prognostic marker in tumors with an oligodendroglial component regardless of the 1p/19q status. PMID:19287309

Senetta, Rebecca; Trevisan, Elisa; Rudà, Roberta; Maldi, Elena; Molinaro, Luca; Lefranc, Florence; Chiusa, Luigi; Lanotte, Michele; Soffietti, Riccardo; Cassoni, Paola

2009-04-01

44

[High grade (B) oligodendroglioma. Concerns and pitfalls in the intraoperative examination of smears].  

Science.gov (United States)

According to the Ste Anne hospital classification and grading system of oligodendrogliomas the presence of contrast enhancement on MRI and/or the presence of an histological endothelial hyperplasia are correlated with a pejorative prognosis (high grade or grade B). Surgical tumoral exerese and adjuvant chemo or radiotherapy are indicated. When clinical and radiological aspects are typical the extemporaneous diagnosis of oligodendroglioma on smear is usually easy (1). In case of atypical forms: unusual localization or cytological appearance, especially with a small cell hyperchromatic undifferenciated tumor few diagnostic hypothesismay be considered. Four cerebellar tumors are presented with relevant and differential cytological diagnostic criteria. A comparative study between clinical and radiological aspects of medulloblastoma, primitive lymphoma, undifferenciated small cell lung carcinoma, and grade B oligodendroglioma is presented. PMID:10812434

Beuvon, F; Varlet, P; Fallet, C; Trystram, D; Daumas-Duport, C

1999-01-01

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Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma  

Science.gov (United States)

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

2013-02-27

46

Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers.  

Science.gov (United States)

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion. PMID:22072542

Yip, Stephen; Butterfield, Yaron S; Morozova, Olena; Chittaranjan, Suganthi; Blough, Michael D; An, Jianghong; Birol, Inanc; Chesnelong, Charles; Chiu, Readman; Chuah, Eric; Corbett, Richard; Docking, Rod; Firme, Marlo; Hirst, Martin; Jackman, Shaun; Karsan, Aly; Li, Haiyan; Louis, David N; Maslova, Alexandra; Moore, Richard; Moradian, Annie; Mungall, Karen L; Perizzolo, Marco; Qian, Jenny; Roldan, Gloria; Smith, Eric E; Tamura-Wells, Jessica; Thiessen, Nina; Varhol, Richard; Weiss, Samuel; Wu, Wei; Young, Sean; Zhao, Yongjun; Mungall, Andrew J; Jones, Steven J M; Morin, Gregg B; Chan, Jennifer A; Cairncross, J Gregory; Marra, Marco A

2012-01-01

47

Incidental anaplastic thyroid carcinoma: A case report  

Directory of Open Access Journals (Sweden)

Full Text Available Anaplastic thyroid carcinoma is one of the most aggressive of all human malignant diseases. It has an unfavorable prognosis and responsible for most of the mortality and morbidity rates due to thyroid carcinomas. We present a case of incidental anaplastic thyroid carcinoma and discuss the epidemiology, biology, risk factors, prognostic factors of the disease and the approach to treatment, in the light of the current medical literature. The prognosis is much better in cases with incidental carcinoma compared to the classical type and surgical excision of the tumor has a favorable effect on the results. Our case was followed-up for 1.5 years with no evidence of recurrence or metastasis.

Pembegül GÜNE?

2008-01-01

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Extensive Growth of an Anaplastic Meningioma  

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We present the case of a 30-year-old male patient with an almost complete destruction of the calvarial bone through an anaplastic meningioma diagnosed in line with dizziness. Neuroimaging revealed an extensive growing, contrast enhancing lesion expanding at the supra- and infratentorial convexity, infiltrating and destroying large parts of the skull, and infiltrating the skin. Due to progressive ataxia and dysarthria with proven tumor growth in the posterior fossa in the continuing course, pa...

Mehdorn, H. M.; Harald Barth; Mehran Mahvash; Alexandros Doukas; Petridis, Athanasios K.; Homajoun Maslehaty; Hajrullah Ahmeti

2013-01-01

49

Extensive growth of an anaplastic meningioma.  

Science.gov (United States)

We present the case of a 30-year-old male patient with an almost complete destruction of the calvarial bone through an anaplastic meningioma diagnosed in line with dizziness. Neuroimaging revealed an extensive growing, contrast enhancing lesion expanding at the supra- and infratentorial convexity, infiltrating and destroying large parts of the skull, and infiltrating the skin. Due to progressive ataxia and dysarthria with proven tumor growth in the posterior fossa in the continuing course, parts of the tumor were resected. A surgical procedure with the aim of complete tumor resection in a curative manner was not possible. Six months after the first operation, due to a new tumor progression, most extensive tumor resection was performed. Due to the aggressive and destructive growth with a high rate of recurrence and tendency of metastases, anaplastic meningiomas can be termed as malignant tumors. The extrinsic growth masks the tumor until they reach a size, which makes these tumors almost unresectable. In the best case scenarios, the five-year survival is about 50%. With the presented case, we would like to show the aggressive behavior of anaplastic meningiomas in a very illustrative way. Chemotherapy, radiotherapy, and surgery reach their limits in this tumor entity. PMID:24288634

Ahmeti, Hajrullah; Maslehaty, Homajoun; Petridis, Athanasios K; Doukas, Alexandros; Mahvash, Mehran; Barth, Harald; Mehdorn, H M

2013-01-01

50

Primary multicentric anaplastic pleomorphic xanthoastrocytoma with atypical features.  

Science.gov (United States)

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor with good prognosis after surgery. Few cases of anaplastic PXA (either de novo or secondary to transformation of a recurrent low grade PXA) have been reported. Moreover, primary anaplastic PXA with dissemination at diagnosis has been described only in two patients, to our knowledge. We report the first case of primary multicentric anaplastic PXA and discuss its atypical features and the pertinent literature. PMID:23827171

Montano, Nicola; Papacci, Fabio; Cioni, Beatrice; Gaudino, Simona; Della Pepa, Giuseppe Maria; Conforti, Giulio; Di Bonaventura, Rina; Novello, Mariangela; Lauriola, Libero; Meglio, Mario

2013-11-01

51

Cutaneous anaplastic large cell lymphoma - A case report  

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Full Text Available Cutaneous involvement in anaplastic large cell lymphoma may be in the form of primary cutaneous disease (primary cutaneous anaplastic large cell lymphoma or secondary to involvement by systemic disease (systemic anaplastic large cell lymphoma. This case report, an example of the latter, describes a solitary cutaneous lesion as the first evidence of disseminated neoplastic disease. The histology of the lesion was identical to its primary cutaneous counterpart.

Mahalingam Meera

2004-05-01

52

Histone 3 Lysine 9 Trimethylation Is Differentially Associated with Isocitrate Dehydrogenase Mutations in Oligodendrogliomas and High-Grade Astrocytomas  

Science.gov (United States)

Trimethylation of histone 3 lysine 9 (H3K9me3) is a marker of repressed transcription. Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, due to inhibition of histone demethylases by 2-hydroxyglutarate. Here, we evaluated H3K9me3 and its association with IDH mutations in 284 gliomas. H3K9me3 was significantly associated with IDH mutations in oligodendrogliomas. Moreover, 72% of World Health Organization grade II and 65% of grade III oligodendrogliomas showed combined H3K9me3 positivity and 1p19q co-deletion. In astrocytic tumors, H3K9me3 positivity was found in all grades of tumors; it showed a significant relationship with IDH mutational status in grade II astrocytomas but not in grade III astrocytomas or glioblastomas. Finally, H3K9me3-positive grade II oligodendrogliomas but not other tumor subtypes showed improved overall survival compared to H3K9me3-negative cases. These results suggest that repressive trimethylation of H3K9 in gliomas may occur in a context-dependent manner and is associated with IDH mutations in oligodendrogliomas, but may be differently regulated in high-grade astrocytic tumors. Further, H3K9me3 may define a subset of grade II oligodendrogliomas with better overall survival. Our results suggest variable roles for IDH mutations in the pathogenesis of oligodendrogliomas vs. astrocytic tumors. PMID:23481705

Venneti, Sriram; Felicella, Michelle Madden; Coyne, Thomas; Phillips, Joanna J.; Gorovets, Daniel; Huse, Jason T.; Kofler, Julia; Lu, Chao; Tihan, Tarik; Sullivan, Lisa M.; Santi, Mariarita; Judkins, Alexander R.; Perry, Arie; Thompson, Craig B.

2013-01-01

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Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss  

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Full Text Available Abstract Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73, DNA Fragmentation Factor subunits alpha (DFFA and beta (DFFB, and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25. We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.

Fuller Gregory N

2005-09-01

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Intraparenchymal clear cell ependymoma  

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Clear cell ependymoma (CCE) is an uncommon variant of ependymoma having a predilection for the supratentorial region. Histologically, it bears an uncanny resemblance to oligodendroglioma, central neurocytoma, hemangioblastoma and metastasis from clear cell carcinoma. Here, we report a rare case of clear cell ependymoma in a 45-year-old male, which histomorphologically resembled anaplastic oligodendroglioma on intraoperative smears, frozen section and routine light microscopy. Immunohistochemi...

Deb, Prabal; Manu, V.; Pradeep, H.; Bhatoe, Harjinder Singh

2011-01-01

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The Characteristics of Astrocytomas and Oligodendrogliomas Are Caused by Two Distinct and Interchangeable Signaling Formats1  

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Chronic platelet-derived growth factor (PDGF) signaling in glial progenitors leads to the formation of oligodendrogliomas in mice, whereas chronic combined Ras and Akt signaling leads to astrocytomas. Different histologies of these tumors imply that the pathways activated by these two oncogenic stimulations are different, and that the apparent lineage of the tumor cells may result from specific signaling activity. Therefore, we have investigated the signaling effects of PDGF in culture and in...

Dai, Chengkai; Lyustikman, Yelena; Shih, Alan; Hu, Xiaoyi; Fuller, Gregory N.; Rosenblum, Marc; Holland, Eric C.

2005-01-01

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Synchronous meningioma and anaplastic large cell lymphoma.  

Science.gov (United States)

Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy. PMID:19751246

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

2010-06-01

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Anaplastic thyroid carcinoma: outcome and prognostic factors  

International Nuclear Information System (INIS)

Purpose: Anaplastic carcinoma of the thyroid has been described as a rapidly progressive disease. We assessed the outcome and prognostic factors in patients with anaplastic thyroid carcinoma at our institution. Materials and Methods: Between 1975 and 1995, 37 patients were seen and treated at our institution with pathologically proven anaplastic carcinoma of the thyroid gland. Patients ranged in age from 49 to 97 years old (median 73 years) and females were represented in a 2:1 ratio. Many patients had history of prior benign thyroid disease (17) or low grade malignancy (6). Other medical illnesses were frequently present in these patients, including 5 with diabetes, 1 scleroderma, 1 sarcoidosis and 1 polycythemia vera. 12 patients had metastatic disease at presentation. 26 patients had locally advanced (T4) disease. The time from diagnosis to treatment was never longer than 1 month. Management was most often with biopsy only (22 patients) and local irradiation (34 patients, median dose 52.5 Gy). 15 patients had primary surgical resection, one of which had negative surgical margins. 11 patients received chemotherapy, 9 with Adriamycin-based regimens. Follow-up ranged from 4 months to 11 years, with a mean of 11 months. Results: 26 patients had a local response, either partial or complete, to their treatment regimen. However, systemic disease was an important cause of failure. 9 patients (24%) survived at least one year from diagnosis; 3 (8%) survived beyond two years.agnosis; 3 (8%) survived beyond two years. The development of metastases occurred quickly in originally localized disease, at a median of 2 months. Metastases occurred most commonly in the lung (11 of 14 cases), but also occured in brain (2), liver (1), bone (1) and pericardium (1). Performance status, sex, metastatic disease, hyperfractionation, treatment modalities, RT dose, age and response to treatment were assessed as prognostic factors for survival. On univariate analysis, age over 70 (p=.004) and failure to attain a complete response to therapy (p=.013) were significant predictors of poor survival. There was also a trend (p=.07) to worse outcome with dose of 50 Gy or less. Treatments incorporating chemotherapy offered the best median survival (18 months) when compared to no chemotherapy (4 months). There was no significant survival difference between patients treated with primary vs. postoperative chemoirradiation. The only long term survivor (>5 years) was treated with radical surgery with attainment of negative surgical margins followed by radiation and chemotherapy. Conclusions: Anaplastic carcinoma of the thyroid tends to present in a locally advanced or metastatic state in patients who are elderly and have concurrent illness. Its natural history is one of rapid systemic dissemination and short median survivals. Patients who are younger and have better performance status at presentation have a marginally longer median survival, as do those attaining a clinical complete response. Our experience with this disease suggests that adjuvant chemotherapy may confer a survival benefit in these patients. Our current approach in these patients is preoperative chemo-radiation (60 Gy/30 fractions/6 weeks) and surgery

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Novel approaches in anaplastic thyroid cancer therapy.  

Science.gov (United States)

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 ?B, 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

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

2014-11-01

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

Science.gov (United States)

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

2013-01-15

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Oligodendroglioma in a patient with AIDS: case report and review of the literature / Oligodendroglioma en un paciente con sida: reporte de caso y revisión de la literatura  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in spanish En los últimos años, las nuevas técnicas de neuroimágenes y diversos métodos de diagnóstico histopatológico se han agregado al manejo clínico de las lesiones de masa cerebral ocupante en los pacientes con sida. La biopsia estereotáxica es necesaria cuando, luego de dos semanas de tratamiento empíric [...] o para toxoplasmosis cerebral, no se comprueba mejoría clínica ni neurorradiológica. Presentamos una paciente con sida que desarrolló una lesión cerebral a nivel del lóbulo frontal derecho. Como antecedente refirió una larga historia de cefalea y convulsiones. La resonancia nuclear magnética con espectroscopia de voxel único ubicado a nivel de la lesión mostró un patrón de lesión tumoral con pico de colina, déficit de N-acetil-aspartato y presencia de ácido láctico. La biopsia estereotáxica y el estudio histopatológico permitieron arribar al diagnóstico de oligodendroglioma difuso de tipo A. Se le efectuó resección por microcirugía y tratamiento antirretroviral de alta eficacia. Actualmente la paciente se encuentra en buen estado clínico, con carga viral indetectable y recuento de linfocitos T CD4 + > de 200 cél/uL. Abstract in english In the last years, new techniques of neuroimages and histopathological methods have been added to the management of cerebral mass lesions in patients with AIDS. Stereotactic biopsy is necessary when after 14 days of empirical treatment for Toxoplasma gondii encephalitis there is no clinical or neuro [...] radiologic improvement. We report a woman with AIDS who developed a single focal brain lesion on the right frontal lobe. She presented a long history of headache and seizures. After two weeks of empirical treatment for toxoplasma encephalitis without response, a magnetic resonance image with spectroscopy was performed and showed a tumoral pattern with a choline peak, diminished of N-acetyl-aspartate and presence of lactate. A stereotactic biopsy was performed. Histopathological diagnosis was a diffuse oligodendroglioma type A. A microsurgical resection of the tumor was carried out and antiretroviral treatment was started. To date she is in good clinical condition, with undetectable plasma viral load and CD4 T cell count > 200 cell/uL.

Marcelo E., Corti; Claudio, Yampolsky; Humberto, Metta; Mario, Valerga; Gustavo, Sevlever; Andrés, Capizzano.

2004-08-01

 
 
 
 
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Oligodendroglioma in a patient with AIDS: case report and review of the literature Oligodendroglioma en un paciente con sida: reporte de caso y revisión de la literatura  

Directory of Open Access Journals (Sweden)

Full Text Available In the last years, new techniques of neuroimages and histopathological methods have been added to the management of cerebral mass lesions in patients with AIDS. Stereotactic biopsy is necessary when after 14 days of empirical treatment for Toxoplasma gondii encephalitis there is no clinical or neuroradiologic improvement. We report a woman with AIDS who developed a single focal brain lesion on the right frontal lobe. She presented a long history of headache and seizures. After two weeks of empirical treatment for toxoplasma encephalitis without response, a magnetic resonance image with spectroscopy was performed and showed a tumoral pattern with a choline peak, diminished of N-acetyl-aspartate and presence of lactate. A stereotactic biopsy was performed. Histopathological diagnosis was a diffuse oligodendroglioma type A. A microsurgical resection of the tumor was carried out and antiretroviral treatment was started. To date she is in good clinical condition, with undetectable plasma viral load and CD4 T cell count > 200 cell/uL.En los últimos años, las nuevas técnicas de neuroimágenes y diversos métodos de diagnóstico histopatológico se han agregado al manejo clínico de las lesiones de masa cerebral ocupante en los pacientes con sida. La biopsia estereotáxica es necesaria cuando, luego de dos semanas de tratamiento empírico para toxoplasmosis cerebral, no se comprueba mejoría clínica ni neurorradiológica. Presentamos una paciente con sida que desarrolló una lesión cerebral a nivel del lóbulo frontal derecho. Como antecedente refirió una larga historia de cefalea y convulsiones. La resonancia nuclear magnética con espectroscopia de voxel único ubicado a nivel de la lesión mostró un patrón de lesión tumoral con pico de colina, déficit de N-acetil-aspartato y presencia de ácido láctico. La biopsia estereotáxica y el estudio histopatológico permitieron arribar al diagnóstico de oligodendroglioma difuso de tipo A. Se le efectuó resección por microcirugía y tratamiento antirretroviral de alta eficacia. Actualmente la paciente se encuentra en buen estado clínico, con carga viral indetectable y recuento de linfocitos T CD4 + > de 200 cél/uL.

Marcelo E. Corti

2004-08-01

62

Intraventricular pleomorphic xanthoastrocytoma with anaplastic features.  

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Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor that usually occurs in the superficial cerebral hemispheres of children and young adults and has a relatively favorable prognosis. We report an unusual case of supratentorial, intraventricular tumor in a 52-year-old man. The tumor was composed of pleomorphic cells, including giant cells, most of which were multinucleated, and small cells. In addition, frequent xanthic changes in the cytoplasm of the tumor cells, and widespread reticulin deposits and lymphocytic infiltrates in the stroma were characteristic features. Large areas of necrosis were also evident. However, mitotic figures were rare (1-2 mitoses per 10 high-power fields). Many tumor cells were positive for GFAP, and a number were positive for neurofilament protein and synaptophysin, indicating their neuronal differentiation. In addition, occasional tumor cells were positive for CD34. p53 protein was entirely negative in the tumor cells. In diagnosing this tumor histopathologically, differentiation between PXA and giant cell glioblastoma (GCG), a rare variant of glioblastoma, was problematic. However, considering the overall histopathological picture, a final diagnosis of PXA with anaplastic features was made. The present case indicates that PXA can occur as an intraventricular tumor, and suggests that in some instances, it would be very difficult to differentiate PXA and GCG histopathologically. PMID:20051018

Fu, Yong-Juan; Miyahara, Hiroaki; Uzuka, Takeo; Natsumeda, Manabu; Okamoto, Kouichirou; Hirose, Takanori; Fujii, Yukihiko; Takahashi, Hitoshi

2010-08-01

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Primary cutaneous multifocal CD 30+ anaplastic large cell lymphoma  

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Full Text Available A 45-year-old male presented with asymptomatic tumors all over the body. The tumors showed no signs of ulceration or regression. There were generalized, nontender, firm to hard enlarged lymph nodes without hepatosplenomegaly. Biopsy and immunophenotyping revealed CD 30+ anaplastic primary cutaneous large cell lymphoma. Primary cutaneous anaplastic large cell lymphoma is characterized by single or grouped reddish-brown tumor nodules, which frequently tend to ulcerate. Secondary involvement of lymph nodes is seen in only 25%. The lesions responded dramatically to chemotherapy, but recurred.

Asha L

2006-01-01

64

Anaplastic carcinoma arising from median ectopic thyroid (thyroglossal duct remnant).  

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The first case of anaplastic carcinoma arising in median ectopic thyroid (thyroglossal duct remnants) in an 84-year-old woman is presented. This expands the spectrum of histologic types of thyroid malignancies reported in this location and supports the theory that these carcinomas arise from thyroid rests associated with thyroglossal ducts. The presence of a histologically benign follicular neoplasm adjacent to the carcinoma suggests the possibility that the anaplastic carcinoma resulted from the transformation of an underlying well-differentiated tumor. Some unusual features of this case are discussed as well as the criteria for establishing the diagnosis of carcinoma arising in a thyroglossal duct remnant. PMID:7306927

Nussbaum, M; Buchwald, R P; Ribner, A; Mori, K; Litwins, J

1981-12-15

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Identificación de alteraciones genéticas en oligodendrogliomas mediante amplificación dependiente de ligasa de múltiples sondas (MLPA) (multiple ligation-dependent probe amplification) / Identification of genetic alterations by multiple ligation-dependent probe amplification (MLPA) analysis in oligodendrogliomas  

Scientific Electronic Library Online (English)

Full Text Available SciELO Spain | Language: Spanish Abstract in spanish La alteración genética más frecuente en oligodendro gliomas es la pérdida conjunta de lp/19q. Este evento ya acontece en etapas primarias del desarrollo de estos tumores. Es de gran valor clínico conocer si dichos tumores poseen esta deleción ya que se ha correlacionado con un mejor pronóstico de lo [...] s pacientes. Además de esta alteración. también se ha observado la deleción de CDKN2A y PTEN y la amplificación de EGFR; estos cambios parecen asociarse a una mayor agresividad tumoral. Mediante la técnica de MLPA en una misma reacción podemos determinar si existe pérdida de lp/19q y deleciones/amplificaciones de los genes anteriormente mencionados en el ADN procedente de muestras tumorales. En este trabajo hemos analizado 40 oligodendrogliomas y el kit MLPA P088 para determinar el estado alélico de lp/19q, así como el kit MLPA P105 para observar la amplificación/ deleción de los genes CDKN2A, PTEN, ERBB2, TP53 y EGFR. Mostraron pérdida de 1p el 45% de los tumores (18/40) y el 65% (26/40) de los oligodendrogliomas presentaron deleción de las sondas que hibridan en las regiones de 19q. Para el kit MLPA P105, mostraron duplicación/deleción de EGFR en el 7,5% (3/41) y 35% (14/40) de las muestras, respectivamente. El 60% de los casos (24/40) mostraron deleción de CDKN2 y ninguna muestra presentó duplicación de las sondas para este gen. El gen ERBB2 se presentó duplicado en el 12,5% de los tumores (5/40) y un único tumor mostró pérdidas de dicho gen. El 30% (12/40) de las muestras presentó deleción para PTEN y el 12,5% (5/40) mostró duplicación de dicho gen y, por último, 12,5% de los casos (5/40) presentaron duplicaciones de TP53. Estos resultados indican que la técnica de MLPA es idónea para la identificación de las alteraciones moleculares características de oligodendrogliomas. Estas alteraciones estarían contribuyendo a la formación del tumor, siendo la anomalía más significativa en oligodendrogliomas la pérdida de 1p/19q. Abstract in english Concurrent deletion at 1p/19q is a common signature of oligodendrogliomas, and it may be identified in low-grade tumours (grade II) suggesting it represents an early event in the development of these brain neoplasms. Additional non-random changes primarily involve CDKN2A, PTEN and EGFR. Identificati [...] on of all of these genetic changes has become an additional parameter in the evaluation of the clinical patients' prognosis, including good response to conventional che motherapy. Multiple ligation-dependent probe amplification (MLPA) analysis is a new methodology that allows an easy identification of the oligodendrogliomas' abnormalities in a single step. No need of the respective constitutional DNA from each patient is another advantage of this method. We used MLPA kits P088 and P105 to determine the molecular characteristics of a series of 40 oligodendrogliomas. Deletions at l p and 19q were identified in 45% and 65% of cases, respectively. Alterations of EGFR, CDKN2A, ERBB2, PTEN and TP53 were also identified in variable frequencies among 7% to 35% of tumours. These findings demonstrate that MLPA is a reliable technique to the detection of molecular genetic changes in oligodendrogliomas.

C., Franco-Hernández; V., Martínez-Glez; M., Torres-Martín; J.M. de, Campos; A., Isla; J., Vaquero; C., Casartelli; J.A., Rey.

2009-04-01

66

Long-term Temozolomide Treatment Induces Marked Amino Metabolism Modifications and an Increase in TMZ Sensitivity in Hs683 Oligodendroglioma Cells  

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Full Text Available Gliomas account for more than 50% of all primary brain tumors. The worst prognosis is associated with gliomas of astrocytic origin, whereas gliomas with an oligodendroglial origin offer higher sensitivity to chemotherapy, especially when oligodendroglioma cells display 1p19q deletions. Temozolomide (TMZ provides therapeutic benefits and is commonly used with radiotherapy in highly malignant astrocytic tumors, including glioblastomas. The actual benefits of TMZ during long-term treatment in oligodendroglioma patients have not yet been clearly defined. In this study, we have investigated the effects of such a long-term TMZ treatment in the unique Hs683 oligodendroglioma model. We have observed increased TMZ sensitivity of Hs683 orthotopic tumors that were previously treated in vitro with months of progressive exposure to increasing TMZ concentrations before being xenografted into the brains of immunocompromised mice. Whole-genome and proteomic analyses have revealed that this increased TMZ sensitivity of Hs683 oligodendroglioma cells previously treated for long periods with TMZ can be explained, at least partly, by a TMZ-induced p38-dependant dormancy state, which in turn resulted in changes in amino acid metabolism balance, in growth delay, and in a decrease in Hs683 oligodendroglioma cell-invasive properties. Thus, long-term TMZ treatment seems beneficial in this Hs683 oligodendroglioma model, which revealed itself unable to develop resistance against TMZ.

Delphine Lamoral-Theys

2010-01-01

67

Successful radiopeptide targeting of metastatic anaplastic meningioma: case report.  

Science.gov (United States)

A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition. PMID:21835043

Sabet, Amir; Ahmadzadehfar, Hojjat; Herrlinger, Ulrich; Wilinek, Winfried; Biersack, Hans-Jürgen; Ezziddin, Samer

2011-01-01

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Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report  

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Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

Biersack Hans-Jürgen

2011-08-01

69

BRAF V600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas.  

Science.gov (United States)

Frequency of a BRAF V600E mutation in anaplastic thyroid carcinoma, which is thought to be derived mainly from papillary carcinoma by multi-step carcinogenesis, is much lower than that in papillary carcinomas. To clarify this phenomenon, we analysed BRAF V600E mutation in 20 cases of anaplastic carcinoma and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic carcinomas, nine and four accompanied papillary and follicular carcinomas, respectively. BRAF V600E mutation was found in four (20%) cases. BRAF V600E mutation was found in three of nine (33.3%), none of four and one of seven (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and without differentiated components, respectively. All three papillary carcinomas accompanied by anaplastic carcinoma with a BRAF V600E mutation were also shown to have a BRAF V600E mutation. In summary, BRAF V600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAF V600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma. These findings raise a question about the classical model of anaplastic transformation and suggest some roles of thyroid cancer stem cells in the generation of anaplastic carcinoma. PMID:17453004

Takano, T; Ito, Y; Hirokawa, M; Yoshida, H; Miyauchi, A

2007-05-21

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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  

Science.gov (United States)

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

2013-10-17

71

Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas  

Science.gov (United States)

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

2014-05-15

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Anaplastic Ependymoma of the Fourth Ventricle Causing Obstrictive Hydrocephalus  

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Ependymomas are relatively uncommon and present with a spectrum of biological and clinical characteristics that make specific recommendations regarding their treatment difficult and assignment of prognostic factors controversial. The case of fourth ventricular anaplastic epednymoma in a four-year-old child is reported in which the initial presentation was deterioration of the level of consciousness secondary to acute obstructive hydrocephalus. An initial insertion of a ventriculo-peritoneal s...

Iddrissu, Mi; Dakurah, Tk; Wepeba, Gk

2005-01-01

73

Intradural extramedullary anaplastic ependymoma with presumed drop metastasis  

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INTRADURAL EXTRAMEDULLARY ANAPLASTIC EPENDYMOMA WITH PRESUMED DROP METASTASIS M. Schuurmans, J. A. L. Vanneste, M. J. T. Verstegen, W. R. van Furth.Department of Neurology, Sint Lucas Andreas Ziekenhuis, Amsterdam, The Netherlands; Department of Neurosurgery, Academic Medical Centre, University of Amsterdam, The Netherlands The authors describe a 29 year old woman who presented with progressive neck pain and weakness in both arms. Magnetic resonance imaging (MRI) of the cervical spine...

Schuurmans, M.; Vanneste, J. A. L.; Verstegen, M. J. T.; Furth, W. R.

2007-01-01

74

WEE1 Inhibitor MK-1775 and Local Radiation Therapy in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas  

Science.gov (United States)

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

2015-02-05

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Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells  

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Abstract Introduction Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we per...

Emoto Mie; Yuki Kazue; Takahashi Akihisa; Yane Katsunari; Ota Ichiro; Ohnishi Ken; Hosoi Hiroshi; Ohnishi Takeo

2002-01-01

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Giant sublingual epidermoid cyst resembling plunging ranula  

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Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. We describe a rare case of large epidermoid cyst in floor of mouth, with an oral as well as submental component resembling plunging ranula reported in the literature from India. We present a case of a 16-year-old girl with complaints of a mass in sublingual region, difficulty chewing, and dysphagia for about 5 months. Fine-needle aspiration cytology showed keratin flakes and proteinaceous material. Contrast-enhan...

Verma, Sandeep; Kushwaha, Jitendra Kumar; Sonkar, A. A.; Kumar, Rahul; Gupta, Rajni

2012-01-01

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Expression of hedgehog signalling pathway in anaplastic thyroid cancer.  

Science.gov (United States)

The purpose of this work is to study the activation of the hedgehog signalling pathway is associated with tumour progression in various types of cancer, hence the development of specific antagonists raises hope for new therapeutic strategies. Therefore, the expression of hedgehog pathway components in anaplastic thyroid cancer (ATC) and effects of the hedgehog inhibitor Cyclopamine on ATC cells were investigated in this study. Expression of the ligand Sonic Hedgehog (SHh), the transmembrane protein Smoothened (Smo), the receptor Patched (Ptc) and the target gene Gli-1 was evaluated in two ATC cell lines (Hth 74, C643) by RT-PCR and in tumour specimens by immunohistochemistry. The corresponding gene products were examined by western blotting analysis. After treatment with different concentrations of Cyclopamine the time-dependent course of cell viability in ATC cell lines was evaluated by MTT assay. SHh, Smo, Ptc and Gli were clearly expressed on mRNA and protein levels in both cell lines and in tumour samples (41 %SHh, 65 %Smo, 65 %Ptc and 65 %Gli). Treatment with Cyclopamine showed a time- and dose-dependent inhibition of cell numbers with IC50 values between 1 and 4 ?M in both cell lines, comparable to other types of cancer. In conclusion, we believe that the hedgehog pathway is expressed in anaplastic thyroid carcinoma specimens and proliferation of ATC cell lines can be influenced by the Hh inhibitor Cyclopamine. Aberrant activation of this pathway might be involved in the aggressive biology of anaplastic cancer and further evaluation regarding a possible clinical impact of pathway inhibition is warranted. PMID:23860623

Hinterseher, Ulrike; Wunderlich, Annette; Roth, Silvia; Ramaswamy, Annette; Bartsch, Detlef K; Hauptmann, Stefan; Greene, Brandon H; Fendrich, Volker; Hoffmann, Sebastian

2014-04-01

78

Primary anaplastic large-cell lymphoma associated with breast implants  

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Primary T-cell anaplastic large cell lymphoma (ALCL) of the breast is a rare entity, which has been reported in association with breast implants. In a retrospective analysis of the City of Hope pathology database, we uncovered nine such patients, eight of whom had breast implants proximal to primary ALCL. The diagnosis of ALCL in the implant capsule occurred at a median of 7 years (range 5–30) following implant surgery, and median patient age was 45.5 years (range 32–62). Malignancy was e...

Popplewell, Leslie; Thomas, Sandra H.; Huang, Qin; Chang, Karen L.; Forman, Stephen J.

2011-01-01

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Phenotypic Characterization of Metastatic Anaplastic Thyroid Cancer Stem Cells  

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Emerging evidence suggests cancer stem cells (CSCs) may initiate new tumors in anaplastic thyroid carcinoma (ATC), one of the most aggressive solid tumors in humans. However, the involvement of CSCs in human tumorigenesis has not been previously studied in authenticated ATC cell lines. Here we demonstrate a functional role of CSCs in four new validated human ATC cell lines (THJ-11T, THJ-16T, THJ-21T and THJ-29T). We identified and enriched CSCs using a spheroid-forming assay. About 3 to 9% of...

Li, Wen; Reeb, Ashley N.; Sewell, William A.; Elhomsy, George; Lin, Reigh-yi

2013-01-01

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A Large Nonmetastatic Anaplastic Thyroid Cancer with Complete Thyroidal Confinement  

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Anaplastic thyroid cancer (ATC) is rare but extremely aggressive, which accounts for about 2% of all thyroid cancers yet nearly 50% of thyroid-cancer-associated deaths in the United States. The median survival time from diagnosis is 5 months, with a 1-year survival rate of only 20%. We report here a case of ATC in a 56-year-old man who survived a large ATC. Preoperative fine-needle aspiration biopsy study to a large right thyroid mass suggested ATC. Total thyroidectomy with rad...

Tufano, Ralph P.; Nishant Agrawal; Nestoras Mathioudakis; Bishop, Justin A.; Xing, Jeffrey C.

2011-01-01

 
 
 
 
81

Pleomorphic xanthoastrocytoma with anaplastic features: a case report.  

Science.gov (United States)

Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm. Recently, several patterns with relatively poor prognosis have been recorded and a new concept of "PXA with anaplastic features" has been proposed. The present case is about a 9-year-old girl who presented with symptoms of recurrent headache, seizures and poor academic performance. MRI revealed left fronto-parietal irregular enhancing mass lesion with callosal involvement and right mid-brain arteriovenous malformation. Clinical and radiological examination was suggestive of a high grade glial neoplasm/PNET. A diagnosis of high grade glial neoplasm was rendered on the squash smears submitted for frozen sections based on the presence of spindle cells, admixed with pleomorphic bizarre, giant cells with multilobated nuclei showing few atypical mitosis and abundant eosinophilic cytoplasm. Frontal craniotomy with debulking of the tumor was performed and permanent sections revealed a biphasic glial neoplasm with spindle cells arranged in fascicles admixed with bizarre multinucleated giant cells showing abundant vacuolated and lipidized cytoplasm, nuclear hyperchromasia with intranuclear inclusions. Eosinophilic granular bodies, mitosis of 7/10 HPF, micro vascular proliferation, necrosis and invasion into the underlying brain parenchyma were noted. With these histomorphological findings a diagnosis of pleomorphic xanthoastrocytoma with anaplastic features was rendered. PMID:24739844

Niamathullah, Sadiya; Sivaselvam, S; Ghosh, Mitra; Ghosh, Siddhartha

2014-01-01

82

Primary glioblastomas and anaplastic astrocytoma in a glioma family.  

Science.gov (United States)

A 72-year-old man presented with a short duration of symptoms relating to a right fronto-parietal glioblastoma and a family history of children with brain tumours. Analysis of the patient's family tree revealed that out of seven children, he had a living son with anaplastic astrocytoma, a daughter who had died with a glioblastoma, and a son who had died with a histologically undiagnosed intrinsic brain tumour. One niece was also thought to have died from a brain tumour. All of the other affected family members had onset in their third or fourth decades. Tissue was only available from two of the affected individuals, precluding familial genetic analysis at this stage. There is no clinical evidence to support a diagnosis of a multiple cancer or neurocutaneous syndrome in this family. In view of what is known about the genetics of familial glioma, it is interesting to note the clinical evidence of both 'primary' glioblastoma and anaplastic astrocytoma in the same kindred. PMID:16678736

Fountaine, Timothy; Lind, Christopher R P; Law, Andrew J J

2006-05-01

83

Bowen's disease with features resembling myrmecia wart.  

Science.gov (United States)

We report the clinical and pathological findings of two cases of Bowen's disease (BD) with features resembling myrmecia wart, and tried to find evidence of human papillomavirus (HPV) infection in such lesions by immunohistological staining, genotyping systems, polymerase chain reaction (PCR) and electron microscopy. Both cases manifested unique barnacle-like hyperkeratotic nodules or plaques clinically, and microscopically proliferation of atypical keratinocytes involving the entire thickness of the epidermis, hypergranulosis with eosinophilic and/or basophilic inclusion bodies, features that mimicked myrmecia wart. Electron microscopy revealed myrmecia inclusion-like large intranuclear and cytoplasmic electron-dense bodies. Immunohistological staining with anti-HPV antibody, genotyping systems for HPV infection and specific PCR designed to detect HPV-1 L1 sequences failed to detect evidence of HPV infection. P16(INK4a) was overexpressed in the atypical keratinocytes of both cases. This finding suggests that the pathogenesis of these two BD may involve certain unknown or undetectable HPV, or reflect disturbances of the Rb signaling pathway unrelated to HPV infection. The unique "myrmecioid" clinicopathological features in our cases suggest that this type of lesion may be a new variant of BD. PMID:25387725

Hsu, Chao-Kai; Chen, Yu-Chia; Yang, Wei-Li; Hsu, Keng-Fu; Chao, Sheau-Chiou; Lee, Julia Yu-Yun

2015-01-01

84

Giant sublingual epidermoid cyst resembling plunging ranula.  

Science.gov (United States)

Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. We describe a rare case of large epidermoid cyst in floor of mouth, with an oral as well as submental component resembling plunging ranula reported in the literature from India. We present a case of a 16-year-old girl with complaints of a mass in sublingual region, difficulty chewing, and dysphagia for about 5 months. Fine-needle aspiration cytology showed keratin flakes and proteinaceous material. Contrast-enhanced CT oral cavity was done and showed 7.0 × 5 × 4.5 cm well-circumscribed non-enhancing cystic mass extending into the floor of the mouth. On examination, a firm swelling was noticed in the submental area, extending down to the thyroid notch. The patient underwent surgical removal of the mass. On histopathology, acidophilic stratum corneum and basophilic dot like staining of stratum granulosum, which is the hallmark of an epidermoid cyst, were seen. PMID:23833501

Verma, Sandeep; Kushwaha, Jitendra Kumar; Sonkar, A A; Kumar, Rahul; Gupta, Rajni

2012-07-01

85

Expression pattern and prognostic significance of IGFBP isoforms in anaplastic astrocytoma.  

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The role of insulin-like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in recent years. There is paucity of literature on their expression and impact on clinical outcome in anaplastic astrocytomas. To evaluate the expression patterns of IGFBP isoforms in anaplastic astrocytoma and correlate with clinical outcome, a retrospective study of 53 adult patients operated for supratentorial lobar anaplastic astrocytoma was performed. The protein expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7), was studied by immunohistochemistry on all samples. The patients were followed up and outcome was documented. The median age at presentation in the present study was 35 years. The pattern of staining was intra cytoplasmic, homogenous and diffuse for IGFBP-2, -3 and -5 and granular for IGFBP-7. IGFBP-2 expression was significantly low in anaplastic astrocytoma as compared to other isoforms (P < 0.001). IGFBP-3 expression was higher than the other isoforms. However, its' expression correlated with favorable overall survival and demonstrated a trend towards significance on univariate analysis. The present study is the first of its kind to describe comprehensively the pattern of expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7) in anaplastic astrocytomas. IGFBP-2 and IGFBP-3 expression patterns and correlation to prognosis were distinct in anaplastic astrocytoma patients, contradictory to what has been reported in glioblastoma, thus giving further evidence that anaplastic astrocytomas are molecularly distinct from glioblastoma. PMID:22547392

Kulkarni, A; Thota, B; Srividya, M R; Thennarasu, K; Arivazhagan, A; Santosh, V; Chandramouli, B A

2012-10-01

86

Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy  

International Nuclear Information System (INIS)

Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author)

87

Synchronous occurrence of anaplastic, follicular and papillary carcinomas with follicular adenoma in thyroid gland  

Directory of Open Access Journals (Sweden)

Full Text Available Various combinations of thyroid carcinomas have been reported including those between different cancers of follicular cell origin and those between follicular and C-cell histogenesis. Accordingly, anaplastic carcinomas have been seen to coincide with simultaneous papillary and follicular cancers. We report a case of composite anaplastic and papillary cancer on one thyroid lobe with a follicular carcinoma in the other lobe in a female patient aged 64 years. The patient also had a separate and independent follicular adenoma in the same lobe as the composite anaplastic and papillary carcinoma. The papillary carcinoma was continuous with the anaplastic carcinoma. The findings were supported by immunohistochemistry. The patient was managed by a total thyroidectomy with bilateral modified radical neck dissection followed by chemotherapy. However, she died two months after surgery. The common follicular cell origin will explain the concurrent presence of all these cancers. This could result from the dedifferentiation of a pre-existing differentiated carcinoma.

Ganguly R

2010-04-01

88

Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma.  

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CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. We have developed a PCT methodology which has enabled the detection of the...

Waggott, W.; Lo, Ym; Bastard, C.; Gatter, Kc; Leroux, D.; Mason, Dy; Boultwood, J.; Wainscoat, Js

1995-01-01

89

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  

Science.gov (United States)

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

2014-10-09

90

Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma  

Science.gov (United States)

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

2014-08-01

91

Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma  

Science.gov (United States)

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

2015-01-29

92

Pulmonary Anaplastic Large Cell Lymphoma - a Rare Case  

Directory of Open Access Journals (Sweden)

Full Text Available Anaplastic large cell lymphoma (ALCL is a rare NHL, representing only 2-3% of all lymphomas. Pulmonary involvement is rare (5-15%. A thirty one year old female was admitted to a center with purulent fistulized lesions on the neck and axilla and enlargement of the breasts. There was no improvement with antibiotics and she had a fever. Pyogenic granulation was detected in the soft tissue biopsy of the axillary and breast. All the cultures were negative. Antituberculosis therapy was given for three months. This patient was admitted to our clinic due to clinical progression. Bilaterally painful, purulent flowing lesions on the neck and axilla, tension and sensitive breasts and high fever were found. Anemia, thrombocytosis, neutrophilic leukocytosis, low iron level and iron binding capacity and high CRP levels were detected in the laboratory tests. Anaerobic, actinomycosis, mycobacteria, nocardia and tularemia cultures were negative. Thorax CT showed a mediastinal conglomerate LN, left upper apicoposterior cavitary lesion and millimetric nodules. Abdominal CT was normal. Neck CT showed masses which erased the fat plain and submandibular LN. LN biopsy diagnosed an inflammatory variant of CD30(+ ALCL. It was considered to be stage IV due to pulmonary parenchyma, mediastinum, neck, axilla and breast involvement. After five chemotherapy sessions, there was a significant improvement in the lesions.

Züleyha Bingöl

2009-03-01

93

[Anaplastic carcinoma of the thyroid: long-term survival].  

Science.gov (United States)

Anaplastic carcinoma of the thyroid is a highly aggressive neoplasm with quickly total course. It is characterized by an average survival of 4-12 months. It infiltrates precociously into the windpipe, oesophagus, vessels of the neck and gives distant metastases in 10-48% of cases. In 30.8 to 80% of cases, this carcinoma originates in an old multinodular goiter. The hypothesis has been also advanced that this neoplasm could derive from a pre-existent well-differentiated carcinoma. The improvement in diagnostic techniques (especially immunohistochemistry) allows a more correct definition of this neoplasm, permitting a differential diagnosis with other tumours (lymphoma, medullary carcinoma, hemangioblastoma) with which in the past it has been erroneously identified. The results reported in the literature are controversial as regards long-term survival, but usually it is less than one year. Longer survival must lead to the suspicion of wrong diagnosis. A relatively better prognosis is observable in intraglandular forms, "minimi" neoplastic focus and young patients. The presence of regional metastatic lymph nodes doesn't seem to modify the prognosis. Instead, a factor which can condition the prognosis is the type of therapy. Now a days the most efficacious curative treatment is the multinodal one (surgery, radio- and chemotherapy). The best results about survival and quality of life have been obtained using chemo-radiotherapy before operation and chemotherapy after it. PMID:8152560

Cannizzaro, M A; De Maria, A; Fazzi, C; Mazzone, G; Terminella, A; Fiorenza, G; Veroux, P F

1993-11-01

94

A case of anaplastic pleomorphic xanthoastrocytoma presenting with tumor bleeding and cerebrospinal fluid dissemination.  

Science.gov (United States)

Pleomorphic xanthoastrocytoma (PXA) has been considered an astrocytic tumor with a relatively favorable prognosis. However, PXA cases having several recurrent patterns with poor prognosis have been reported in recent years, and a new concept of anaplastic PXA has been proposed. The present case was a 59-year-old woman who presented with tumor bleeding onset and cerebrospinal fluid dissemination. The patient had sudden-onset right hemiparesis, aphasia, and consciousness disturbance and was admitted to a local area hospital. After emergency surgery had removed the hematoma, postoperative contrast-enhanced CT scan revealed a left temporal tumor. A second surgery was therefore performed for initial tumor removal 2 months later. Histopathological findings showed that the tumor was typical PXA with strong pleomorphism and xanthomatous changes and contained an ependymoma-like component in the center area. However, endothelial proliferation and mitosis were more remarkable compared to ordinary PXA. The MIB-1 labeling index was 9.8% high. From these findings, the histopathological diagnosis was anaplastic PXA. The patient underwent surgery to remove recurrent tumors 5 and 16 months later. The patient died 36 months after the first onset, and CT revealed glioblastoma-like findings and cerebrospinal fluid dissemination. This case report is the first case in which PXA presented with tumor bleeding onset. Histopathological findings suggested anaplastic PXA from the first surgical specimens, and PXA recurred many times. We thus believe that the patient displayed primary anaplastic PXA rather than secondary anaplastic PXA that results in malignant transformation. PMID:18095120

Asano, Kenichiro; Miyamoto, Seiichi; Kubo, Osami; Kikkukawa, Tomoshige; Yagihashi, Akinori; Ohkuma, Hiroki

2006-04-01

95

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus  

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Full Text Available Abstract Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT, and 8 supratentorial primitive neuroectodermal tumors (sPNET using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3 was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.

Shah Keerti V

2005-02-01

96

miRNA Expression in Anaplastic Thyroid Carcinomas  

Science.gov (United States)

Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents an end stage of thyroid tumor progression. No effective treatment exists so far. In this study, we analyzed the miRNA expression profiles of 11 ATC by microarrays and their relationship with the mRNA expression profiles of the same 11 ATC samples. ATC show distinct miRNA expression profiles compared to other less aggressive thyroid tumor types. ATC show 18 commonly deregulated miRNA compared to normal thyroid tissue (17 downregulated and 1 upregulated miRNA). First, the analysis of a combined approach of the mRNA gene expression and of the bioinformatically predicted mRNA targets of the deregulated miRNA suggested a role for these regulations in the epithelial to mesenchymal transition (EMT) process in ATC. Second, the direct interaction between one of the upregulated mRNA target, the LOX gene which is an EMT key player, and a downregulated miRNA, the miR-29a, was experimentally validated by a luciferase assay in HEK cell. Third, we confirmed that the ATC tissue is composed of about 50% of tumor associated macrophages (TAM) and suggested, by taking into account our data and published data, their most likely direct or paracrine intercommunication between them and the thyroid tumor cells, amplifying the tumor aggressiveness. Finally, we demonstrated by in situ hybridization a specific thyrocyte localization of 3 of the deregulated miRNA: let-7g, miR-29a and miR-30e and we pointed out the importance of identifying the cell type localization before drawing any conclusion on the physiopathological role of a given gene. PMID:25153510

Hébrant, Aline; Floor, Sébastien; Saiselet, Manuel; Antoniou, Aline; Desbuleux, Alice; Snyers, Bérengère; La, Caroline; de Saint Aubain, Nicolas; Leteurtre, Emmanuelle; Andry, Guy; Maenhaut, Carine

2014-01-01

97

Combined chemotherapy and irradiation in anaplastic thyroid carcinoma  

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Full Text Available Background: Anaplastic thyroid carcinoma (ATC is a very rare and extremely aggressive cancer; patient's death usually occurs rapidly after diagnosis with a mean survival of six months in the majority of individual research series. Treatment of ATC ranges from surgery, radiotherapy, chemotherapy, or a combination of these regimes. Yet, the optimal sequence of treatment modalities has not been established. Methods: From 1997 to 2002 six consecutive patients with a histological diagnosis of ATC were treated with combined chemotherapy and irradiation at our Clinic for Oncology, Clinical Center Ni¹. Five of these patients were females and 1 male, aged between 28 and 71 years (mean age: 57 years. None of them had distant metastases at the time of diagnosis. Extrathyroidal extension was present in 3 patients with invasion into skin and hypoderm. Treatment consisted of doxorubicin 60 mg/m 2 plus cisplatin 60 mg/m 2 every three weeks. Total doses ranged between 158-375 mg/m 2 for doxorubicin and 183-380 mg/m 2 for cisplatin. External beam radiation to the neck was administered, at a daily dose of 1.2 Gy, up to total doses ranging between 45-60 Gy. Results: One patient achieved a complete response (CR and one patient achieved a partial response (PR. Three patients had stable disease. One patient with CR progressed during follow-up and died 18 months from bone and brain metastases. The treatment was moderately well tolerated, although all patients experienced some mild form of toxicity; neutropenia occurred in all patients, but none of them required hospital admission. Median survival was 8 months (range: 4-18 months. Conclusion: We concluded that the present regimen produces meaningful responses for patients with localized ATC. A randomized study is needed to determine the effect on survival.

Pej?i? Ivica

2003-01-01

98

Anaplastic pleomorphic xanthoastrocytomas. Review of the literature with reference to malignancy potential.  

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Malignancy potential of pleomorphic xanthoastrocytomas (PXAs) has rather been an underestimated reality. We report the case of a 13-year-old boy who presented with signs of increased intracranial pressure. The child had been epileptic since the age of 2. Computed tomography and magnetic resonance scans revealed a huge left frontal mass. At surgery, a subtotal excision was accomplished. Histopathological diagnosis was anaplastic PXA (grade III; WHO, 2000). The tumor showed an increased mitotic index and minimal endothelial proliferation. The patient died 3.5 months later due to a fatal intracranial hemorrhage. A review of the entire PXA literature revealed 15 well-documented cases of PXA with subsequent malignant transformation and 11 cases of primary anaplastic PXA. The prognosis was grim for both subsets of patients. Anaplastic PXAs clearly represent the transition between the original PXA concept and lipidized giant-cell glioblastoma. PMID:15608490

Tekkök, Ismail H; Sav, Aydin

2004-01-01

99

ALK negative anaplastic large cell lymphoma of the oral cavity showing spontaneous regression  

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Full Text Available Anaplastic large cell lymphoma is a subset of T-cell lymphoma which is rarely seen in the oral cavity. This entity may be either primary cutaneous or systemic and the prognosis varies significantly by subtype. In addition, several similar entities have been reported which may mimic this lesion both clinically and histologically. We present a case of anaplastic large cell lymphoma, ALK negative, on the mucosal aspect of the upper lip of an 88 year-old female with a history of cutaneous T-cell lymphoma which demonstrated spontaneous regression after biopsy. A brief review of the literature along with an overview of clinical behavior, histologic presentation, immunohistochemical analysis, genetics, and differential diagnosis of this subtype of anaplastic large cell lymphoma are presented.

Sarah G Fitzpatrick

2012-06-01

100

ALK negative anaplastic large cell lymphoma of the oral cavity showing spontaneous regression  

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Anaplastic large cell lymphoma is a subset of T-cell lymphoma which is rarely seen in the oral cavity. This entity may be either primary cutaneous or systemic and the prognosis varies significantly by subtype. In addition, several similar entities have been reported which may mimic this lesion both clinically and histologically. We present a case of anaplastic large cell lymphoma, ALK negative, on the mucosal aspect of the upper lip of an 88 year-old female with a history of cuta...

Fitzpatrick, Sarah G.; Bowers, Leah M.; Al-quran, Samer Z.; Fox, Eric G.; Cohen, Donald M.; Indraneel Bhattacharyya

2012-01-01

 
 
 
 
101

Long-term survival in a young patient with anaplastic glioma.  

Science.gov (United States)

A 26-year-old man with anaplastic glioma in the left frontoparietal lobe survived for 9 years and 9 months after combined therapy, including subtotal resection, postoperative irradiation, and chemotherapy. The tumor recurred and he received immunotherapy using lymphokine-activated killer (LAK) cells. At the last LAK cell infusion, infection of the Ommaya reservoir occurred, but subsided after antibiotics were administered. Follow-up neuroimaging showed no recurrence of the tumor. Review of the surgical specimens found that the original diagnosis of glioblastoma was inconclusive, although the tumor is considered to be a type of anaplastic glioma. PMID:9384806

Naganuma, H; Sasaki, A; Satoh, E; Nagasaka, M; Isoe, S; Nakano, S; Nukui, H

1997-01-01

102

Anaplastic meningioma: case report / Meningioma anaplásico: relato de caso  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese O tratamento adequado para os pacientes com meningiomas intracranianos continua sendo um desafio, principalmente o de sua variante maligna, a qual tem incidência de 10% a 15%, sem uma certeza do melhor tratamento adjuvante. É indicado o uso da radioterapia externa holocraniana. O uso da quimioterapi [...] a tradicional se mostra ineficaz, havendo necessidade de estudos para desenvolver outros agentes quimioterápicos e novos métodos de administração desses agentes no tumor cerebral. A imunoterapia pode ser considerada para os casos de refratariedade aos outros tratamentos adjuvantes. Relatamos o caso de um paciente de 67 anos, com história progressiva de cefaléia, crises convulsivas parciais complexas e agressividade. A investigação radiológica com tomografia computadorizada e ressonância magnética evidenciaram um processo expansivo na região temporoccipital esquerda com contrastação difusa e edema peritumoral importante. Foi realizada craniotomia frontoparietotemporal esquerda com remoção radical da dura-máter infiltrada e do tumor. O paciente evoluiu sem déficit neurológico no pós-operatório. O exame anatomopatológico foi compatível com meningioma maligno do tipo papilar. Foi instituído tratamento complementar com radioterapia externa holocraniana. Abstract in english Intracranial meningiomas continue to challenge our best clinical efforts to eliminate them once discovered and deemed appropriate for treatment. Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment. The external whole brain irradi [...] ation is recommended. Traditional chemotherapy has proven ineffective; thus, new chemotherapeutic agents and new methods of delivery should be developed. Immunotherapy may be considered for patients with malignant meningiomas when all others previous treatment have failed. We report a case of anaplastic papillary meningioma. A 67-year-old man presented with partial complex seizures, headache and aggressiveness. A computerized tomography and magnetic resonance image demonstrated a large left temporo-occipital mass with difuse contrast enhancement and extensive surrounding edema. A left temporo-occipital flap was performed. The tumor and the infiltrated dura were radically removed. Postoperatively, the patient remained neurologically intact. The treatment was complemented by external whole brain radiation.

Asdrubal, Falavigna; José Augusto Nasser dos, Santos; Leila, Chimelli; Fernando Antonio Patriani, Ferraz; Antonio de Padua Furquim, Bonatelli.

2001-12-01

103

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

Science.gov (United States)

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

2014-11-11

104

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  

Science.gov (United States)

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

2014-11-13

105

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

Science.gov (United States)

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

2015-01-30

106

Uterine neoplasm resembling an ovarian sex cord tumor.  

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Uterine neoplasm resembling an ovarian sex cord tumor is a rare neoplasm. Patients are generally of reproductive age, although a few may be perimenopausal or post menopausal. This neoplasm produces abnormal vaginal bleeding and uterine enlargement, suggesting leiomyoma or polyps. Based on the histology and clinical outcome, this tumor can be classified into 2 groups, namely one with focal areas resembling sex cord elements with a tendency to recur or metastasize and another with exclusive sex cord elements which runs a benign course. Immunohistochemical stains of the sex cord elements may show positively for vimentin, cytokeratin, actin and desmin in variable proportions. Inhibin is a more specific marker for these cells. Our case was a 50-year- old Omani lady with menorrhagia. Histology revealed features consistent with uterine neoplasm resembling an ovarian sex cord tumor.

Sarah Kuruvila

2003-02-01

107

Cerebral dynamic studies for early detection of recurrent anaplastic intracranial gliomas  

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The authors compared radionuclide cerebral dynamic studies, brain scans, and clinical evaluation as indicators of recurrence of intracranial anaplastic gliomas and found cerebral dynamic studies more sensitive to tumor growth than static brain scans. The former may show changes prior to clinical evidence of tumor progression

108

[Small bowel intussusception caused by metastasis from anaplastic thyroid carcinoma: case report and literature review].  

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Symptomatic involvement of the small bowel by metastasis from an extra-abdominal primary malignancy is rare, most commonly resulting from malignant melanoma and lung cancer; very rarely is small bowel involvement as first metastatic site. The Authors report a case of anaplastic thyroid carcinoma with lung metastasis, brain metastasis and an isolated metastasis to the small bowel leading intestinal obstruction due to small bowel intussusception. The Authors review the international literature about frequency, etiopathogenesis, clinical and diagnostic features and therapy of small bowel metastasis by extra-abdominal malignancies, especially by primary anaplastic thyroid carcinoma. Small bowel metastasis from extra-abdominal malignancies are very unusual, especially from anaplastic thyroid carcinoma, and the etiopathogenesis is still unknown. Clinical findings are typical for abdominal urgency, especially by small bowel obstruction from anaplastic thyroid carcinoma. Computed Tomography has an important role in detecting the type of intestinal obstruction despite it is often unable to diagnose an isolated metastasis. Best therapy is surgical resection, that allows the assessment of metastasis and the definitive staging. The prognosis is poor, despite long-term survival has been occasionally reported for isolated small bowel metastasis PMID:16910363

Ricciardelli, Luigi; Rapicano, Gaetano; Pinto, Antonio; Napolitano, Giuseppe; Feleppa, Cosimo; Martino, Giovanni; Martino, Antonio

2006-01-01

109

How does conformational flexibility influence key structural features involved in activation of anaplastic lymphoma kinase?  

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Anaplastic Lymphoma Kinase (ALK) plays a major role in developing tumor processes and therefore has emerged as a validated therapeutic target. Applying atomistic molecular dynamics simulations on the wild type enzyme and the nine most frequently occurring and clinically important activation mutants we revealed important conformational effects on key interactions responsible for the activation of the enzyme. PMID:24675991

Karabencheva, Tatyana G; Lee, Christian C; Black, Gary W; Donev, Rossen; Christov, Christo Z

2014-06-01

110

Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells  

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Abstract Background Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. Methods In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to r...

Rotiroti Domenicoantonio; Arturi Franco; Paolino Donatella; Bulotta Stefania; Calvagno Maria; Celano Marilena; Filetti Sebastiano; Fresta Massimo; Russo Diego

2004-01-01

111

Kaposi Sarcoma of the Adrenal Gland Resembling Epithelioid Angiosarcoma: A Case Report  

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Patients with human immunodeficiency virus infection are known to have increased risk of various neoplasms, including Kaposi sarcoma, which classically involves the skin and mucosal locations. The anaplastic variant of Kaposi sarcoma is rare and poorly documented in the literature. It is characterised clinically by a more aggressive behaviour and increased metastatic potential, and histologically by increased cellularity, mitotic rate, and rarely by epithelioid angiosarcoma-like morphology. We report herein a 64-year-old man with a long-standing history of human immunodeficiency virus infection who developed a right adrenal tumor with a high-grade anaplastic angiosarcoma-like morphology. Immunohistochemistry for human herpes virus-8 was strongly positive in the tumor cells. To the best of our knowledge, this is the first report of an anaplastic Kaposi sarcoma in the adrenal gland. PMID:21845069

Huwait, Hassan; Meneghetti, Adam; Nielsen, Torsten O.

2011-01-01

112

Anaplastic and Atypical Meningiomas Express High Levels of Fas and Undergo Apoptosis in Response to Fas Ligation  

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In this study we characterized the expression of Fas and Fas ligand in different types of meningiomas and examined the effect of Fas ligation on the death of meningioma cells in culture. Using Western blot analysis, we found that extracts derived from anaplastic and atypical meningiomas expressed high levels of Fas, whereas benign meningiomas did not express detectable levels of this protein. All of the meningiomas examined expressed low levels of Fas ligand. Cultures of anaplastic meningioma...

Weisberg, Shira; Ashkenazi, Ely; Israel, Zvi; Attia, Moshe; Shoshan, Yigal; Umansky, Felix; Brodie, Chaya

2001-01-01

113

Sunitinib in Treating Patients With Recurrent Malignant Gliomas  

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Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

2013-03-18

114

Breast Cancer Metastasis to the Stomach Resembling Early Gastric Cancer  

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Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infi...

Eo, Wan Kyu

2008-01-01

115

Giant lymph node hyperplasia resembling abdominal abscess on gallium scan  

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A case of giant lymph node hyperplasia with systemic symptoms resembling chronic infection is described which showed intense gallium uptake and indistinguishable from uptake seen in an abscess. This rare syndrome may mimic an abdominal abscess and should be considered in the differential diagnosis of patients without prior history of abdominal surgery and in whom an abdominal abscess is suspected. The condition is relatively benign

116

Effect of boron neutron capture therapy for recurrent anaplastic meningioma: an autopsy case report.  

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A 70-year-old woman died of systemic metastasis from anaplastic meningioma and underwent autopsy. The patient underwent twice total removal of the right sphenoid ridge meningioma 2 years ago. The tumor recurred 3 times, and then stereotactic radiotherapy was employed. Boron neutron capture therapy (BNCT) was performed for the fourth local recurrence and an additional new lesion. Proliferative activity of the newly developed meningioma, which had been treated with BNCT only, was significantly lower than that of untreated metastatic liver tumor, as well as that of the meningioma specimen obtained at the second surgery. Our pathological findings demonstrated, for the first time, the therapeutic effect of BNCT on anaplastic meningioma at an early stage (2.5 months). PMID:24807102

Kawaji, Hiroshi; Miyatake, Shin-Ichi; Shinmura, Kazuya; Kawabata, Shinji; Tokuyama, Tsutomu; Namba, Hiroki

2014-05-01

117

Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma.  

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CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35) ALCL cases based on a long-range PCR of genomic DNA. The rapidity and robustness of this method may have diagnostic applications for ALCL. PMID:7772531

Waggott, W; Lo, Y M; Bastard, C; Gatter, K C; Leroux, D; Mason, D Y; Boultwood, J; Wainscoat, J S

1995-04-01

118

Acute pyelonephritis with anaplastic thyroid carcinoma producing granulocyte colony-stimulating factor  

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Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8?...

Kang, Keunhee; Park, Joo Hee; Ryu, Ja Young; Lee, Sang Yup; Ko, Gang Jee; Kwon, Young Joo

2013-01-01

119

Tumor Stroma in Anaplastic Thyroid Carcinoma : Interstitial Collagen and Tumor Interstitial Fluid Pressure  

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Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy in man with stromal fibrosis as one of the main features. Carcinoma cells synthesized no or little collagen I protein. Pro-?1(I) collagen mRNA was expressed by stromal cells throughout the tumor, but expression of procollagen type I protein was restricted to stromal cells situated close to nests of carcinoma cells. These data suggest that the carcinoma cells stimulated collagen type I deposition by increasing pro-?1(1) collagen ...

Lammerts, Ellen

2001-01-01

120

Anaplastic thyroid carcinoma: A comprehensive review of current and future therapeutic options  

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Anaplastic thyroid carcinoma (ATC) is the rarest, but deadliest histologic type among thyroid malignancies, with a dismal median survival of 3-9 mo. Even though ATC accounts for less than 2% of all thyroid tumors, it is responsible for 14%-39% of thyroid carcinoma-related deaths. ATC clinically presents as a rapidly growing mass in the neck, associated with dyspnoea, dysphagia and vocal cord paralysis. It is usually locally advanced and often metastatic at initial presentation. For operable d...

Francesco Perri, Giuseppe Di Lorenzo

2011-01-01

 
 
 
 
121

Systemic Capillary Leak Syndrome as an Initial Presentation of ALK-Negative Anaplastic Large Cell Lymphoma  

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Systemic capillary leak syndrome (SCLS) is a rare disease characterized by third spacing of plasma into the extravascular compartment, leading to anasarca, hemoconcentration, and hypovolemic shock. It has been rarely associated with lymphomas, and reports usually indicate that it occurs after antineoplastic treatment. We present the case of a patient with ALK-negative anaplastic large cell lymphoma who presented with SCLS as the initial manifestation of her lymphoma. The SCLS resolved with tr...

Merry-Jennifer Markham; Dang, Nam H.; Lourdes, Laura S.; Al-quran, Samer Z.

2012-01-01

122

Systemic Capillary Leak Syndrome as an Initial Presentation of ALK-Negative Anaplastic Large Cell Lymphoma.  

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Systemic capillary leak syndrome (SCLS) is a rare disease characterized by third spacing of plasma into the extravascular compartment, leading to anasarca, hemoconcentration, and hypovolemic shock. It has been rarely associated with lymphomas, and reports usually indicate that it occurs after antineoplastic treatment. We present the case of a patient with ALK-negative anaplastic large cell lymphoma who presented with SCLS as the initial manifestation of her lymphoma. The SCLS resolved with treatment of the malignancy with steroids and chemotherapy. PMID:22953081

Lourdes, Laura S; Al-Quran, Samer Z; Dang, Nam H; Markham, Merry-Jennifer

2012-01-01

123

A time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) activity.  

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A novel time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) was developed. We used a straightforward strategy to modify a known ALK substrate into a peptide biosensor that can accommodate terbium luminescence sensitization upon its phosphorylation by ALK. Since this strategy is generalizable, this high-throughput screening compatible assay serves as an example for development of other kinase assays that employ terbium luminescence as a read-out. PMID:25406835

Cui, Wei; Parker, Laurie L

2015-01-01

124

FDG PET staging compared to C.T. in children with Hodgkin's disease or anaplastic lymphoma  

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The accuracy of initial staging in Hodgkin's disease and anaplastic lymphoma is very important since treatment depends on the initial staging disease. An error of assessment can have serious consequences on evolution and survival. To judge PET scan performances initial staging was done on our patients by both conventional imaging and PET scan. Methods: 21 children (10 girls, 11 boys), median age 14,9 years (8 to 22) had a PET scan for the initial staging (17 Hodgkin's disease, 4 anaplastic lymphomas). Conventional staging for imaging included: Thorax x-ray, thorax and abdomen C.T., abdominal echography, and also two bone marrow biopsies. Others exams were done in accordance with special clinical data. PET scan was done on a C PET scan ADAC one hour after IV injection of 2 MBq/Kg of 18 FDG. C.T. and PET scan images were revised blindly and separately by radiologist and nuclearist with no knowledge of clinical data. Results: the staging by C.I. and PET scan were concordant in 84% of cases. In 16% of cases PET scan displayed localisation not seen by C.I., particularly bone lesions. The staging changed grading status from stage III to stage IV. The clinical cases will be presented. PET scan upgrading were confirmed by resonance imaging or bone scintigraphy. The change of stage led in each child an intensification of chemotherapy (6 courses instead of 4). Conclusion: FDG PET is a useful diagnostic tool in children with Hodgkin's disease or anaplastic lymphoma to achieve wisease or anaplastic lymphoma to achieve with a single exam an accurate staging allowing to choose the best treatment

125

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

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Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: 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...

Chen X.; La, Soma; Jr, Fromm

2013-01-01

126

Anaplastic large-cell lymphoma with florid granulomatous reaction: A case report and review of literature  

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Granulomatous reactions have been reported in association with lymphomas, more often with Hodgkins disease than with Non-Hodgkins Lymphoma. Not many reports are available on the association of anaplastic large-cell lymphoma with sarcoid-type granuloma. Herein, we report a case of an elderly female with generalized lymphadenopathy who had a florid granulomatous reaction almost masking the lymphoma cells in the lymph node biopsy. A detailed clinical history, careful histological examination and...

Balamurugan S; Rajasekar B; Rao R

2009-01-01

127

Emergency total thyroidectomy for bleeding anaplastic thyroid carcinoma: A viable option for palliation  

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Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive thyroid neoplasm. Bleeding from tumor is an uncommon, but potentially life-threatening complication requiring sophisticated intervention facilities which are not usually available at odd hours in emergency. We report the case of a 45-year-old woman who presented with exsanguinating hemorrhage from ATC and was treated by emergency total thyroidectomy. The patient is well three months postoperatively. Emergency total thyroidecto...

Kumar Sunil; Joshi Mohit

2011-01-01

128

Immunohistochemical detection of epithelialmesenchymal transition associated with stemness phenotype in anaplastic thyroid carcinoma  

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Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm resistant to radiation and chemotherapy. Epithelial-mesenchymal transition (EMT) generating cells with stem cell characteristics have been reported to be associated with chemoradioresistance in cultured cells. However, EMT and stem cell properties in ATC have not been fully investigated. In this study, we retrieved 2 thyroidectomy specimens of ATC with coexisting well differentiated thyroid carcinomas (DTCs) including one papi...

Liu, Jing; Brown, Robert E.

2010-01-01

129

Combined chemical and radiotherapy of the small cell anaplastic carcinoma of the lung  

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In this thesis the therapeutic regimens for small cell anaplastic carcinoma of the lung (SCL) are reviewed. In addition, the results of a course of combined chemotherapy and radiotherapy in a series of patients with SCL are presented. The purpose of this study was to investigate, whether this regimen of combination therapy inproves survival and subjective well-being of the patients as compared both with previously used therapeutic regimens for SCL in the Department of Pulmonology, Academic Hospital, Groningen and elsewhere. (Auth.)

130

Imprint cytology facilitating the diagnosis of primary cutaneous anaplastic large cell lymphoma of iliac fossa  

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Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a form of cutaneous T-cell lymphoma that is characterized by solitary nodules and plaques. In this report, the authors present an unusual case of a 59-year-old male with a solitary ulcerofungative mass in the left iliac fossa clinically masquerading as sqaumous cell carcinoma. The imprint smears of the lesion had characterstic morphological features which helped in the diagnosis. Subsequently, the imprint cytology correlated well wi...

Singh, Suman; Gupta, Neelam; Tekta, Geeta R.

2012-01-01

131

Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma  

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Neuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the ident...

Chand, Damini; Yamazaki, Yasuo; Ruuth, Kristina; Scho?nherr, Christina; Martinsson, Tommy; Kogner, Per; Attiyeh, Edward F.; Maris, John; Morozova, Olena; Marra, Marco A.; Ohira, Miki; Nakagawara, Akira; Sandstro?m, Per-erik; Palmer, Ruth H.; Hallberg, Bengt

2013-01-01

132

Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma.  

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Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage characterized by uniform CD30 expression. The 2008 World Health Organization classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK)-positive (established entity) and ALK-negative (proposed new entity) ALCL. The genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly understood. In this study, we used microRNA microarray analysis to identify differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed significantly higher expression of miR-155 (0.888 ± 0.228) compared with ALK+ ALCL (0.0565 ± 0.009) on microarray and by quantitative real-time polymerase chain reaction in ALK- ALCL compared with ALK+ ALCL (P miR-155 (mean score, 2.3 versus 1.3; P = .01) for the first time in tissue sections of ALCL. Among computationally predicted targets of miR-155, we identified ZNF652 (r = -0.57, P = .05), BACH1 (r = 0.88, P = .02), RBAK (r = 0.81, P = .05), TRIM32 (r = 0.92, P = .01), E2F2 (r = 0.81, P = .05), and TP53INP1 (r = -0.31, P = .03) as genes whose expression by quantitative real-time polymerase chain reaction correlated significantly with the level of miR-155 in ALCL tumor tissue. PMID:25128227

Mehrotra, Meenakshi; Medeiros, L Jeffrey; Luthra, Rajyalakshmi; Sargent, Rachel L; Yao, Hui; Barkoh, Bedia A; Singh, Rajesh; Patel, Keyur P

2014-10-01

133

The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer  

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Full Text Available Nerina Denaro,1,2 Cristiana Lo Nigro,3 Elvio G Russi,4 Marco C Merlano1 1Oncology Department, AO S Croce e Carle, 2Human Pathology Department, Messina University, 3Cancer Genetics and Translational Oncology Department, 4Radiation Oncology Department, AO S Croce e Carle, Messina, Italy Abstract: Anaplastic thyroid cancer represents 1%–2% of thyroid cancers. For its aggressiveness, it is considered a systemic disease at the time of diagnosis. Surgery remains the cornerstone of therapy in resectable tumor. Traditional chemotherapy has little effect on metastatic disease. A multimodality approach, incorporating cytoreductive surgical resection, chemoradiation, either concurrently or sequentially, and new promising target therapies is advisable. Doxorubicin is the most commonly used agent, with a response rate of 22%. Recently, other chemotherapy agents have been used, such as paclitaxel and gemcitabine, with superimposable activity and response rates of 10%–20%. However, survival of patients with anaplastic thyroid cancer has changed little in the past 50 years, despite more aggressive systemic and radiotherapies. Several new agents are currently under investigation. Some of them, such as sorafenib, imatinib, and axitinib have been tested in small clinical trials, showing promising disease control rates ranging from 35%–75%. Referral of patients for participation in clinical trials is needed. Keywords: thyroid cancer, emerging therapies, anaplastic thyroid carcinoma, chemotherapy, radiotherapy

Denaro N

2013-09-01

134

A case of anaplastic transformation of papillary thyroid carcinoma in recurrent disease after radioiodine therapy  

International Nuclear Information System (INIS)

Anaplastic thyroid carcinoma is a rare and lethal human malignancy. In this paper, we report on a case of a 55-year-old man who had undergone radiation therapy on the cervical region for malignant lymphoma at 14 years of age, and had been consulting our hospital for 19 years. He underwent a left hemithyroidectomy for papillary thyroid carcinoma at the age of 35, and 11 years after that a total thyroidectomy was performed for cervical nodal disease. After the operation he underwent radioiodine therapy twice. Five years after radiotherapy, anaplastic carcinomas arose in the left cervix and the cranium. Soon after complete resections of the tumors, systemic metastases were detected with fluorodexyglucose positron emission tomography (FDG-PET). Finally, 11 months after the operation, he died in our palliative care unit at the age of 55 due to frequent bleeding from a palatal carcinoma. A review of the literature showed that the age at which the tumor arose, namely the peak of the patient's life, was earlier than was usually reported. The survival time of 11 months observed in our patient was more than that generally observed in patients with anaplastic carcinoma. (author)

135

Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells  

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Full Text Available Abstract Introduction Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells. To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. Results Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. Conclusion These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas.

Emoto Mie

2002-10-01

136

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

Science.gov (United States)

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

2014-07-09

137

Yoga Therapy in Treating Patients With Malignant Brain Tumors  

Science.gov (United States)

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

2012-09-28

138

ALK-positive anaplastic large cell lymphoma presenting as intradural spinal mass: first reported case and review of literature.  

Science.gov (United States)

Anaplastic large cell lymphoma (ALCL) is characterized by large anaplastic cells of T-cell or null-cell phenotype expressing CD30 (Ki-1 antigen). In most cases this neoplasm expresses the anaplastic lymphoma kinase (ALK), a chimeric protein resulting from the t(2;5)(p23;q35) translocation. ALK-positive anaplastic large cell lymphoma is most frequent in the first three decades of life and shows a male predominance, involving both nodal and extranodal sites, but rarely the CNS. We report a 21-year-old patient with a previous history of nodal ALK-positive ALCL, lymphohistiocytic subtype, who was admitted for recent occurrence of left-sided anesthesia with pain and progressive motor weakness of both legs. An MRI of the spine documented an intradural extramedullary mass dislocating the thoracic cord, suggesting a meningioma and the patient underwent surgical decompression. Histological examination revealed a lymphoproliferative neoplasm with morphology and immunophenotype of ALK-positive anaplastic large cell lymphoma. After surgery, all preoperative symptoms disappeared. To our knowledge, no cases of ALCL presenting as secondary localization with an intradural extramedullary spinal mass have been reported in the literature. PMID:23082771

Novello, Mariangela; Lauriola, Libero; Della Pepa, Giuseppe Maria; Giuseppe, La Rocca; Coli, Antonella; Visocchi, Massimiliano

2013-08-01

139

Differentiated human stem cells resemble fetal, not adult, ? cells  

Science.gov (United States)

Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic ? cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS+) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS+ cells and (ii) hPSC-derived INS+ (hPSC-INS+) cells more closely resemble human fetal ? cells than adult ? cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS+ cells and true ? cells and provides a catalog of genes whose manipulation may convert hPSC-INS+ cells into functional ? cells. PMID:24516164

Hrvatin, Sinisa; O’Donnell, Charles W.; Deng, Francis; Millman, Jeffrey R.; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K.; Melton, Douglas A.

2014-01-01

140

Differentiated human stem cells resemble fetal, not adult, ? cells.  

Science.gov (United States)

Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic ? cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal ? cells than adult ? cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true ? cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional ? cells. PMID:24516164

Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

2014-02-25

 
 
 
 
141

PERCEPTUAL RESEMBLANCE OF FACIAL IMAGES: A NEAR SET APPROACH  

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Full Text Available In this paper, we introduce a near set approach to image analysis. Near sets result from generalization of rough settheory. One set X is near another set Y to the extent that the description of at least one of the objects in X matches thedescription of at least one of the objects in Y. Near set Evaluation And Recognition (NEAR system is used to measure thedegree of resemblance between facial images. The goal of the NEAR system is to extract perceptual information fromimages using near set theory, which provides a framework for measuring the perceptual nearness of objects. In this work,we have used images from Japanese Female Facial Expression (JAFFE database. The images were first converted intoLocal Binary Patterns (LBP images and then divided into non-overlapping blocks. The degree of nearness of histogramsof all the blocks of one image is measured with the corresponding blocks of another image by using NEAR system

A.MUSTAFI

142

Paraspinal Gossypiboma Resembling an Abscess: A Case Report  

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Full Text Available A 45-year-old man presented with complaints of low back pain, sciatalgia on the  left persisting for five months and fluid leakage from the wound. He had been operated for L4-5 disc herniation before seven months. Computed tomography (CT and magnetic resonance imaging (MRI detected a contrasted mass lesion resembling abscess formation localized in the left posterior paravertebral region. Paravertebral abscess was diagnosed and aspiration was planned under local anesthesia with ultrasonography guidance. During intervention, a needle was inserted into cavity but enough material was not aspirated. Thus, surgery was plannedand a retained sponge material was found within the left paraspinal region  and removed totally. The patient healed without complication.

Süleyman Coþkun

2013-05-01

143

The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.  

LENUS (Irish Health Repository)

The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic possibilities.

Kelleher, Fergal C

2012-02-01

144

Investigation of the results of therapy of anaplastic thyroid gland carcinomas  

International Nuclear Information System (INIS)

The results of the treatment of 28 patients with an anaplastic thyroid gland carcinoma are investigated, to see whether an optimal therapy is indicated. The execution of an operation before radiotherapy does not appear to improve the prognosis (statistically this conclusion is not wholly justified). The presence of metastases at the beginning of the therapy gave rise to a worse prognosis than the absence of metastases. The combination treatment of chemotherapy and either surgery or radiotherapy was only applied to two patients so no conclusions can be made about its benefit. (C.F.)

145

Anaplastic large-cell lymphoma with florid granulomatous reaction: A case report and review of literature  

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Full Text Available Granulomatous reactions have been reported in association with lymphomas, more often with Hodgkins disease than with Non-Hodgkins Lymphoma. Not many reports are available on the association of anaplastic large-cell lymphoma with sarcoid-type granuloma. Herein, we report a case of an elderly female with generalized lymphadenopathy who had a florid granulomatous reaction almost masking the lymphoma cells in the lymph node biopsy. A detailed clinical history, careful histological examination and immunohistochemistry helped in attaining the correct diagnosis.

Balamurugan S

2009-01-01

146

Primary Cutaneous CD 30+ Anaplastic Large Cell Lymphoma. A Case Report and Literature Review  

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Primary cutaneous CD 30+ anaplastic large cell lymphoma is part of the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, together with lymphomatoid papulosis. Its frequency is less than 0.5 x 100 000 inhabitants per year. It accounts for a very small proportion of non-Hodgkins lymphomas. The case of an 80-year-old female patient whose diagnosis was established in 2006 because of lesions on the face and neck is presented. The lesions continued to grow in an exaggerated fashio...

Miguel Ángel Serra Valdés; Julian Manzur Katrib; Yordanka Aleaga Hernández

2014-01-01

147

Clinical evaluation of 67Ga scanning in the diagnosis of anaplastic carcinoma and malignant lymphoma of the thyroid  

International Nuclear Information System (INIS)

While 67Ga uptake has been reported to be highly variable and nonspecific in the diagnosis of malignant tumors of the thyroid, it has also been observed to depend on the histological nature of the lesion. For this reason, the behavior of 67Ga in various types of thyroid cancer was investigated in a prospective study of 86 patients with thyroid masses compatible with anaplastic carcinoma or malignant lymphoma. The study demonstrated a distinct difference in uptake between well-differentiated adenocarcinoma of the thyroid and the more undifferentiated anaplastic carcinoma and malignant lymphoma

148

Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates  

International Nuclear Information System (INIS)

The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by [3H]thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with [3H]thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific [3H]thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebratesfor other invertebrates

149

Breast cancer metastasis to the stomach resembling early gastric cancer.  

Science.gov (United States)

Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast. PMID:19688132

Eo, Wan Kyu

2008-12-01

150

[Pleomorphic xanthoastrocytoma with intraventricular extension and anaplastic transformation in an adult patient: Case report].  

Science.gov (United States)

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumour that usually occurs in the superficial cerebral hemispheres of children and young adults. Although it has a relatively favourable prognosis, malignant progression of these tumours has been described. Therefore, we present an unusual case of a 54-year-old male with a right, multicystic, parietooccipital tumour extending through the ipsilateral ventricle. After surgical resection, histological examination revealed a lesion with pleomorphic cells, cytoplasmic lipidisation, intensely eosinophilic granular bodies, well-delimitated unique nuclei and focal, positive immunoreactivity for synaptophysin, glial fibrillary acidic protein (GFAP), S-100 protein, vimentin and CD56. Once other tumours, such as giant cell metastatic carcinoma or primary lesion like subependymal giant cell astrocytoma, were ruled out, a final diagnosis of XAP was established. After a follow-up period of 9 months, the patient suffered an extensive and local tumour relapse considered inoperable, with progressive neurological deterioration and radiological findings of malignant progression. The brain biopsy procedure revealed anaplastic changes, including necrosis foci, higher mitotic activity (5×10 high-power fields) and a 10% proliferation index measured by Ki67 labelling. The present case showed intraventricular extension and a more aggressive behaviour, both uncommon in these tumours (similar to anaplastic astrocytoma or glioblastoma multiforme), thus demanding an initial, optimal surgical treatment with close clinical and radiological follow-up, due to the high potential for malignant transformation of XAPs. PMID:22867919

Rodríguez-Mena, Ruben; Joanes-Alepuz, Vicente; Barbella-Aponte, Rosa; Pérez-Valles, Ana

2012-09-01

151

High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma  

DEFF Research Database (Denmark)

AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pre-therapeutic parameters and outcome in a cohort of treatment-naive ALCL patients. METHODS AND RESULTS: Pre-therapeutic tumour specimens from 52 patients with ALCL were included in a tissue microarray. The intratumoral macrophage content was assessed by immunohistochemical staining for CD68 and CD163, and quantified using digital image analysis. Anaplastic lymphoma kinase (ALK)-positive patients were significantly younger and had a favourable outcome compared with ALK-negative ALCL patients (median age: 42 versus 59 years; P = 0.008). However, ALK expression was not a significant predictor when adjusting for age. Although classical risk factors were distributed evenly between the compared groups, high intratumoral content of CD68 and/or CD163 correlated with poor outcome, in both univariate and multivariate analyses. High intratumoral CD163 content showed the strongest adverse association with both overall and progression-free survival in ALK-negative patients (P < 0.001). CONCLUSIONS: A high content of intratumoral CD68- and/or CD163-positive macrophages correlates with an adverse outcome in ALK-negative ALCL.

Pedersen, Martin B; Danielsen, Allan V

2014-01-01

152

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

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Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: 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 (CD30 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.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

Chen X

2013-12-01

153

Carcinoma anaplásico. Presentación de un caso / Anaplastic carcinoma. A case report  

Scientific Electronic Library Online (English)

Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish A la consulta especializada de cirugía del tiroides acude un paciente joven por presentar en el breve tiempo de una semana aumento de volumen del lateral izquierdo del cuello acompañado de tos, disfonía y disfagia, sintomatología común en el carcinoma anaplásico. Con el propósito de exponer las cara [...] cterísticas del carcinoma anaplásico en una edad poco usual, su evolución y pronóstico, así como el tratamiento aplicado en este caso se efectuó una tiroidectomía total y tratamiento oncológico con radioquimio-terapia .Se realiza un análisis de las características clínicas, anatomopatológicas y tratamiento en relación con este caso, y se compara con lo reportado en la literatura consultada. Abstract in english A patient who attended to the specialized medical office for the surgery of thyroid gland presented, in a short period of time (a week), an enlargement in the left part of the neck associated with other common symptoms in the presence of anaplastic carcinoma: cough, dysphonia and dysphagia. This pap [...] er was aimed at explaining the characteristics of the anaplastic carcinoma in an uncommon age, its natural history, prognosis and the treatment in this case: a total Thyroidectomy and Radiotherapy. An analysis of the clinical and pathological features, as well as the treatment applied was carried out. This case was compared with other cases reported in the medical literature.

Gladys, Iglesias Díaz.

2008-06-01

154

Disseminated struma ovarii containing focal anaplastic carcinoma in peritoneal implants: a case report.  

Science.gov (United States)

Malignant changes in struma ovarii have been defined using histopathologic criteria for carcinomas of the cervical thyroid gland. We report a case of struma ovarii with extensive extraovarian spread containing a small focus of anaplastic carcinoma (AC) in peritoneal implants. AC arising in benign-looking struma ovarii with peritoneal implants has not been reported. Multiple pelvic masses were identified on abdominopelvic computed tomography in a 38-yr-old woman. An exploratory laparotomy revealed multiple, variable-sized masses on the omentum, and colonic and uterine serosa. A microscopic but grossly unidentifiable lesion in the right ovary had a histologic appearance that mimicked hyperplastic follicular epithelium of nodular thyroid goiter. Multiple peritoneal implants showed histology similar to the ovarian lesions except a focal area of AC in the omental mass. Anaplastic cells demonstrated characteristic immunoreactivity for p53, cyclin D1, and a high Ki-67 index of about 30%, with loss of expression of thyroid transcription factor-1 and thyroglobulin, whereas the remaining goitrous background showed opposite expression patterns in all aspects. Furthermore, the areas of AC showed p53 mutation by molecular analysis. The AC harboring p53 mutation within extraovarian spread suggests that disseminated struma ovarii mimicking nodular goiter has potential for histologic progression through similar pathogenetic mechanism with cervical thyroid carcinoma despite the innocuous appearance. PMID:25272300

Kim, Wook Youn; Kim, Sehun; Hyun, Jee; Song, Kee-Ho

2014-11-01

155

Anaplastic thyroid cancer – an overview of genetic variations and treatment modalities  

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Full Text Available Honey V Reddi,1 Anirudh Kumar,2 Roger Kulstad3 1Transgenomic, Inc., New Haven, CT, USA; 2University of Toronto, Toronto, ON, Canada; 3Division of Endocrinology, Marshfield Clinic, Marshfield, WI, USA Abstract: Anaplastic thyroid carcinoma (ATC is a rare but highly aggressive malignancy that accounts for about 1%–2% of all thyroid cancer diagnoses but is responsible for up to 30%–40% of thyroid cancer deaths. ATCs are poorly differentiated tumors that develop on the background of preexisting, often undiagnosed, papillary thyroid carcinoma or follicular thyroid carcinoma, through progressive accumulation of changes in several oncogenic and tumor suppressor pathways, including p53, RAS, RAF, Wnt-?-catenin and the PTEN-AKT pathways. Consequently, the 1-year survival rate after diagnosis ranges from 5% to 15%. Current therapeutic approaches are aimed at common late oncogenic changes and involve inhibition of MAPK and PI3K cell proliferation pathways or restoration of p53 and PTEN tumor suppressor pathways. Since single-modality therapy has limited effect on anaplastic thyroid cancer, aggressive multimodal treatments are now the treatment of choice, in spite of which, the mean survival time from diagnosis to death continues to remain at about 6 months. The current review attempts to summarize the genetics involved in the development and progression of ATC and provides some insight into the therapeutic options being evaluated for this aggressive cancer. Keywords: genetic alterations, treatment strategies, diagnostic testing

Reddi HV

2015-01-01

156

Anaplastic large cell lymphoma (ALCL) and breast implants: breaking down the evidence.  

Science.gov (United States)

Systemic anaplastic large cell lymphoma (ALCL) is a distinct disease classification provisionally sub-divided into ALCL, Anaplastic Lymphoma Kinase (ALK)(+) and ALCL, ALK(-) entities. More recently, another category of ALCL has been increasingly reported in the literature and is associated with the presence of breast implants. A comprehensive review of the 71 reported cases of breast implant associated ALCL (iALCL) is presented indicating the apparent risk factors and main characteristics of this rare cancer. The average patient is 50 years of age and most cases present in the capsule surrounding the implant as part of the periprosthetic fluid or the capsule itself on average at 10 years post-surgery suggesting that iALCL is a late complication. The absolute risk is low ranging from 1:500,000 to 1:3,000,000 patients with breast implants per year. The majority of cases are ALK-negative, yet are associated with silicone-coated implants suggestive of the mechanism of tumorigenesis which is discussed in relation to chronic inflammation, immunogenicity of the implants and sub-clinical infection. In particular, capsulotomy alone seems to be sufficient for the treatment of many cases suggesting the implants provide the biological stimulus whereas others require further treatment including chemo- and radiotherapy although reported cases remain too low to recommend a therapeutic approach. However, CD30-based therapeutics might be a future option. PMID:25475421

Ye, Xuan; Shokrollahi, Kayvan; Rozen, Warren M; Conyers, Rachel; Wright, Penny; Kenner, Lukas; Turner, Suzanne D; Whitaker, Iain S

2014-01-01

157

Anaplastic Large Cell Lymphomas: ALK Positive, ALK Negative, and Primary Cutaneous.  

Science.gov (United States)

Anaplastic large cell lymphomas (ALCLs) comprise a group of CD30-positive non-Hodgkin lymphomas that generally are of T-cell origin and share common morphologic and phenotypic characteristics. The World Health Organization recognizes 3 entities: primary cutaneous ALCL (pcALCL), anaplastic lymphoma kinase (ALK)-positive ALCL, and, provisionally, ALK-negative ALCL. Despite overlapping pathologic features, these tumors differ in clinical behavior and genetics. pcALCL presents in the skin and, while it may involve locoregional lymph nodes, rarely disseminates. Outcomes typically are excellent. ALK-positive ALCL and ALK-negative ALCL are systemic diseases. ALK-positive ALCLs consistently have chromosomal rearrangements involving the ALK gene with varied gene partners, and generally have a favorable prognosis. ALK-negative ALCLs lack ALK rearrangements and their genetic and clinical features are more variable. A subset of ALK-negative ALCLs has rearrangements in or near the DUSP22 gene and has a favorable prognosis similar to that of ALK-positive ALCL. DUSP22 rearrangements also are seen in a subset of pcALCLs. In this review, we discuss the clinical, morphologic, phenotypic, genetic, and biological features of ALCLs. PMID:25461779

Xing, Xiaoming; Feldman, Andrew L

2015-01-01

158

{sup 18}F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase  

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Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) findings in primary systemic ALCL according to ALK expression. Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peak SUV, and interim and post-therapy PETs were visually analyzed. All cases were {sup 18}F-FDG-avid on baseline PET. The peak SUV of ALK-positive ALCL (n =16, 18.7±10.5) was higher than that of ALK-negative ALCL (n =21, 10.0±4.9) (P =0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P=0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P =0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P =0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P =0.06) and post-therapy PET patients (70.0%vs 20.0 %, P =0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results. On baseline PET, all cases showed {sup 18}F-FDG avidity, and ALK expression was related to higher {sup 18}F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.

Lee, Dong Yun; Lee, Jong Jin; Park, Seol Hoon; Chae, Sunyoung; Kim, Shin; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung; Ryu, Jinsook [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

2013-12-15

159

18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase  

International Nuclear Information System (INIS)

Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in primary systemic ALCL according to ALK expression. Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peak SUV, and interim and post-therapy PETs were visually analyzed. All cases were 18F-FDG-avid on baseline PET. The peak SUV of ALK-positive ALCL (n =16, 18.7±10.5) was higher than that of ALK-negative ALCL (n =21, 10.0±4.9) (P =0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P=0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P =0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P =0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P =0.06) and post-therapy PET patients (70.0%vs 20.0 %, P =0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results. On baseline PET, all cases showed 18F-FDG avidity, and ALK expression was related to higher 18F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group

160

Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma: Case report  

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Full Text Available Introduction. Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN. It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. Case report. We presented a 20-year-old patient with abdominal and retroperitoneal malignancy - anaplastic carcinoma combined with choriocarcinoma metastases in. Tumor developed three months after left adnexectomy which had been done because of adnexal tumor. Choriocarcinoma was immunohistochemicaly confirmed in adnexal masses. Two courses of chemotherapy, metotrexate + folic acid (MTX+FA regimen, were administrated. The initial serum beta human chorionic gonadotropin level stayed unknown as well as the last one after the treatment. The patient came from the other country and was hospitalized because of pelvic and abdominal pain and palpable abdominal masses in hypogastrium with progressive anemia. The human chorionic gonadotropin level was 38 mIU/L. Tumor biopsy was done and choriocarcinoma metastases were immunohistochemicaly confirmed with predominant anaplastic carcinoma. Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment. Relaparotomy was perforemed and tumor completely exceeded. Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon. Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination. Immunohistochemical examination excluded choriocarcinoma in tumor mass. After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day. The patient rejected chemotherapy which was recommended according to the protocol and died one month after the operation. Conclusion. Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiriness to chemotherapy has poor prognosis and leads to lethal outocome. [Acknowledgment. Projekat Ministarstva nauke Republike Srbije, br. 41021 and 175082

Nikoli? Branka

2012-01-01

 
 
 
 
161

Cáncer anaplásico de tiroides de manejo quirúrgico / Anaplastic thyroid carcinoma, review of six patients  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish Introducción: El Cáncer Anaplásico de Tiroides corresponde al 2 a 5% del total de cánceres tiroideos. Afecta a mujeres en la sexta o séptima década de la vida, presentándose como masa cervical pétrea de crecimiento rápido, adherida a planos profundos. El tratamiento incluye cirugía, quimioterapia y [...] radioterapia, siendo de elección el tratamiento multimodal. Objetivo: Conocer los resultados de una serie de casos manejados quirúrgicamente en el Hospital Dr. Gustavo Fricke de Viña del Mar. Pacientes y Método: Estudio de serie de casos de Cáncer Anaplásico de Tiroides tratados exclusivamente con cirugía entre los años 2002 y 2008. Se registraron características generales, técnica operatoria, complicaciones, uso de otras terapias y sobrevida. Resultados: Se manejaron 6 pacientes, cuatro hombres y dos mujeres. El promedio de edad fue de 59 años. La estadía hospitalaria promedio fue de 6 días. Se realizó tiroidectomía total bilateral en 4 pacientes. Dos pacientes requirieron traqueostomía durante el postoperatorio. En ninguno de ellos se realizó radioquimioterapia neoadyuvante o adyuvante. La sobrevida promedio fue de 108 días. Discusión: Destaca en esta serie el diagnóstico en etapas avanzadas de la enfermedad, lo cual determina la imposibilidad de realizar terapia multimodal y la sobrevida observada. Por lo anterior, es de importancia la sospecha y la derivación inmediata para el manejo especializado, aumentando así la posibilidad del uso de terapia multimodal con mejores resultados en términos de sobrevida. Se observó una sobrevida menor a la reportada en la literatura. Abstract in english Background: Anaplastic Thyroid Carcinoma corresponds 2 to 5% of all thyroid cancers. It affects mainly women in the sixth or seventh decade of life, appearing as a hard, fast growing cervical mass that is adhered to surrounding structures. Treatment includes surgery, chemotherapy and radiotherapy. A [...] im: to report a series of patients with anaplastic thyroid carcinoma. Patients and Methods: Review of medical records of patients with anaplastic thyroid cancer operated between 2002 and 2008. Results: The records of six patients aged 46 to 82 years (four males), were retrieved. A bilateral total thyroidectomy was performed in four patients. Two patients required tracheostomy during the postoperative period. Mean hospital stay was six days. None received neoadjuvant or adjuvant radio-chemotherapy. Three patients died within one month of the operation. The rest died at 115, 184 and 283 days after surgery. Conclusions: All these patients were diagnosed in advanced stages of the disease, a fact that can explain the dismal evolution observed.

ADRIANA, LOBOS M; DIEGO, VILLAGRÁN R; CAROLINA, OPAZO T; FELIPE, CARDEMIL M.

2009-10-01

162

Cáncer anaplásico de tiroides de manejo quirúrgico Anaplastic thyroid carcinoma, review of six patients  

Directory of Open Access Journals (Sweden)

Full Text Available Introducción: El Cáncer Anaplásico de Tiroides corresponde al 2 a 5% del total de cánceres tiroideos. Afecta a mujeres en la sexta o séptima década de la vida, presentándose como masa cervical pétrea de crecimiento rápido, adherida a planos profundos. El tratamiento incluye cirugía, quimioterapia y radioterapia, siendo de elección el tratamiento multimodal. Objetivo: Conocer los resultados de una serie de casos manejados quirúrgicamente en el Hospital Dr. Gustavo Fricke de Viña del Mar. Pacientes y Método: Estudio de serie de casos de Cáncer Anaplásico de Tiroides tratados exclusivamente con cirugía entre los años 2002 y 2008. Se registraron características generales, técnica operatoria, complicaciones, uso de otras terapias y sobrevida. Resultados: Se manejaron 6 pacientes, cuatro hombres y dos mujeres. El promedio de edad fue de 59 años. La estadía hospitalaria promedio fue de 6 días. Se realizó tiroidectomía total bilateral en 4 pacientes. Dos pacientes requirieron traqueostomía durante el postoperatorio. En ninguno de ellos se realizó radioquimioterapia neoadyuvante o adyuvante. La sobrevida promedio fue de 108 días. Discusión: Destaca en esta serie el diagnóstico en etapas avanzadas de la enfermedad, lo cual determina la imposibilidad de realizar terapia multimodal y la sobrevida observada. Por lo anterior, es de importancia la sospecha y la derivación inmediata para el manejo especializado, aumentando así la posibilidad del uso de terapia multimodal con mejores resultados en términos de sobrevida. Se observó una sobrevida menor a la reportada en la literatura.Background: Anaplastic Thyroid Carcinoma corresponds 2 to 5% of all thyroid cancers. It affects mainly women in the sixth or seventh decade of life, appearing as a hard, fast growing cervical mass that is adhered to surrounding structures. Treatment includes surgery, chemotherapy and radiotherapy. Aim: to report a series of patients with anaplastic thyroid carcinoma. Patients and Methods: Review of medical records of patients with anaplastic thyroid cancer operated between 2002 and 2008. Results: The records of six patients aged 46 to 82 years (four males, were retrieved. A bilateral total thyroidectomy was performed in four patients. Two patients required tracheostomy during the postoperative period. Mean hospital stay was six days. None received neoadjuvant or adjuvant radio-chemotherapy. Three patients died within one month of the operation. The rest died at 115, 184 and 283 days after surgery. Conclusions: All these patients were diagnosed in advanced stages of the disease, a fact that can explain the dismal evolution observed.

ADRIANA LOBOS M

2009-10-01

163

Familial resemblance of plasma apolipoprotein B: the Nancy study.  

Science.gov (United States)

The familial resemblance of plasma apolipoprotein B (apo B) was investigated in a sample of 102 families including 419 members who volunteered for a free health checkup in the Preventive Center of Vandoeuvre-lès-Nancy, France. The mean levels (+/- SD) of apo B were 141.0 (+/- 32.6), 121.8 (+/- 27.7), and 98.6 (+/- 22.6) mg/dl in fathers, mothers, and offspring, respectively. The familial correlations were 0.04, 0.13, 0.21 (P less than .01), and 0.47 (P less than .001) between spouses, father-offspring, mother-offspring, and siblings, respectively, after adjustment on age, body mass index, and sex. A genetic analysis was performed using the approach proposed by Bonney, which indicated that a recessive and a dominant major-locus model appeared nearly equally supported by the data. Under the recessive model, the frequency q of the most common allele was estimated as 0.825, with a mean difference of 60.4 mg/dl between high and low homozygotes. Under the dominant model, q was estimated as 0.875, with a mean increase of 34.2 mg/dl in heterozygotes and high homozygotes. However, the hypothesis of Mendelian transmission and the environmental hypothesis could not be formally tested because of great numeric difficulties encountered in the estimation of the three transmission probabilities. Given these analytical restrictions, we cannot conclude in favor of a major locus influencing apo B level in our population, even though the evidence is suggestive. The genetic heterogeneity underlying the familial aggregation of apo B level, suggested by several recent publications, might explain the difficulty in discerning a single major locus in a population sample of small nuclear families, not ascertained through patients enriching the sample in high values of apo B. These findings call into question the relevance of the approach through "healthy" populations in the search for major loci influencing biological traits. PMID:2369998

Tiret, L; Steinmetz, J; Herbeth, B; Visvikis, S; Rakotovao, R; Ducimetiere, P; Cambien, F

1990-01-01

164

Clinical Response with Sunitinib Therapy in the Treatment of Anaplastic Thyroid Cancer  

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Full Text Available Background: Anaplastic thyroid cancer (ATC, while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in the process of clinical testing, and promising agents include those in the tyrosine kinase inhibitor family. Our patient represents a novel case of ATC treated with sunitinib, one such tyrosine kinase inhibitor. Methods/Results: We utilized the experimental sunitinib in conjunction with radiation therapy to treat a patient with aggressive ATC in whom curative resection was unable to be achieved due to carotid sheath and tracheal involvement. The patient had marked clinical response and sustained stable disease for 8 months, which coincides with reported data regarding sunitinib to treat other thyroid malignancies. Conclusion: Our case illustrates the efficacy of sunitinib therapy as a possible adjunct in the treatment of ATC.

Jan Geliebter

2012-04-01

165

Conduction Aphasia as a Result of Left Parietal-Temporal-Occipital Anaplastic Astrocytoma: A Case Study  

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Full Text Available Conduction aphasia is a language disorder characterized by an impaired ability to repeat verbal material associated with phonological paraphasias but a relatively fluent spontaneous speech and preserved comprehension. It has been attributed to lesions of the arcuate fasciculus by disconnection between posterior temporal lobe and frontal lobe, however, this idea has been debated, because the integrity and function of the arcuate fasciculus does not seem to be essential in verbal repetition. We report a case of a 23 year old male, with conduction aphasia as a result of a recurrent anaplastic astrocytoma in parietal and temporo-occipital areas. We propose a reconceptualization of the aphasia, analyzing it in terms of clinical neuropsychological and neural networks between ipsilateral and contralateral posterior brain areas

Oscar Mauricio Aguilar Mejía

2011-01-01

166

Brentuximab vedotin: treatment role for relapsed refractory systemic anaplastic large-cell lymphoma.  

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The identification of CD30 has been known since 1985. Trials exploring the targeted therapy focusing on this antigen have led to the successful development and approval of brentuximab vedotin (Adcetris®) for treatment of relapsed refractory systemic anaplastic large-cell lymphoma. Brentuximab vedotin has a high-level of response with generally durable remission. Common side effects of brentuximab vedotin include peripheral neuropathy, fatigue, nausea, arthralgia, and pyrexia. Grade 3-4 neutropenia, thrombocytopenia, and hyperglycemia have also been reported. Development of progressive multifocal leukoencephalopathy from John Cunningham virus is a very rare occurrence, but its seriousness has prompted the US FDA to mandate a black box warning. Brentuximab vedotin is currently being evaluated to be used in conjunction with other chemotherapy regimens, including in frontline therapies to induce potentially higher complete remission rate than chemotherapy alone and thus achieve potentially higher progression-free survival rates that might translate ultimately to improve overall survival. PMID:23991923

Lai, Chao-Ming; Horowitz, Sandra

2013-08-01

167

Primary Cutaneous CD 30+ Anaplastic Large Cell Lymphoma. A Case Report and Literature Review  

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Full Text Available Primary cutaneous CD 30+ anaplastic large cell lymphoma is part of the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, together with lymphomatoid papulosis. Its frequency is less than 0.5 x 100 000 inhabitants per year. It accounts for a very small proportion of non-Hodgkins lymphomas. The case of an 80-year-old female patient whose diagnosis was established in 2006 because of lesions on the face and neck is presented. The lesions continued to grow in an exaggerated fashion lately leading to deformity of her face. She was admitted due to neurological manifestations unrelated to the lesions. The presentation of this case is necessary because it requires performing differential diagnosis in clinical practice. Given its rarity, it is of interest to the medical community, especially trainees.

Miguel Ángel Serra Valdés

2014-03-01

168

Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.  

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The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm. PMID:25531848

Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-Ichi

2014-12-01

169

Value of sequential postoperative brain scans in patients with anaplastic gliomas  

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The authors analyze the postoperative course of 30 patients with anaplastic supratentorial gliomas to evaluate the usefulness of sequential brain scanning as an adjunct to clinical neurological examinations in the early detection of tumor recurrence. The correlation between sequential scanning and clinical evaluation was excellent; no examples of divergent results were seen. With the exception of scans made very early in the postoperative period or when postoperative scalp flap infections were present, initial postoperative scans were easily interpreted in terms of both the superficial (postcraniotomy) and parenchymal changes. The specific type of postoperative therapy (radiation therapy, chemotherapy, or both) could not be correlated with whether scan or examination ultimately changed first. However, analysis of original tumor location revealed that while sequential postoperative scanning offered no advantage over repetitive neurological examinations in the detection of recurrent tumor in the neurologically dominant left hemisphere, scan changes preceded examination changes in eight of 17 cases involving tumors of the neurologically nondominant right hemisphere

170

Ki-1-positive large cell anaplastic lymphoma diagnosed by urinary cytology. A case report.  

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Cytomorphologic and immunocytochemical findings in urinary cytology in a case of Ki-1-positive large cell anaplastic lymphoma in the left cervical region in a 42-year-old man are reported. Smears stained with Papanicolaou or Wright-Giemsa stain showed a cytomorphologic spectrum that varied from immunoblastlike cells to large neoplastic cells with pleomorphic nuclei and vacuolated cytoplasm. Neoplastic cells with multilobulated, bizarre nuclei and mitosis were also observed. Immunocytochemistry on urinary sediments showed that the tumor cells were of a "null" phenotype and strongly expressed the Ki-1 antigen and "activation" markers of HLA-DR, Tac (CD25) and OKT9 (CD71). Histology and immunohistochemistry confirmed these findings. PMID:8392254

Tanaka, T; Yoshimi, N; Sawada, K; Takami, T; Sugie, S; Etori, F; Kachi, H; Mori, H

1993-01-01

171

Differential expression of cyclin D3 in ALK+ and ALK- anaplastic large cell lymphoma.  

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As defined in the World Health Organization classification, anaplastic large cell lymphoma (ALCL) is a distinct type of non-Hodgkin lymphoma of T/null cell lineage, a subset of which is associated with translocations involving 2p23 resulting in expression of anaplastic lymphoma kinase (ALK). The most common translocation, the t(2;5)(p23;q35), results in expression of nucleophosmin (NPM)-ALK. NPM-ALK has been shown to activate signal transducer and activator of transcription (STAT) 3, a transcriptional regulator of cyclin D3. In this study, we assessed cyclin D3 expression in 2 ALK+ ALCL cell lines (Karpas 299 and SU-DHL1) and 1 ALK- ALCL cell line (Mac2A) by Western blot analysis. We also assessed cyclin D3 expression in 52 ALCL tumors (32 ALK+, 20 ALK-) by immunohistochemistry using tissue microarrays. These results were compared with phosphorylated (activated) STAT3 (pSTAT3) expression. Both ALK+ ALCL cell lines, but not the ALK- ALCL cell line, expressed cyclin D3 and pSTAT3. Cyclin D3 was expressed in 25 (78%) of 32 ALK+ ALCL tumors and in 4 (20%) of 20 ALK- ALCL tumors (P < .001, Fisher exact test ). In ALK+ ALCL tumors, the mean percentage of cyclin D3-positive tumor cells was 40.6% compared with 5.1% in ALK- ALCL tumors (P < .001, Mann-Whitney U test). The percentages of cyclin D3-positive and pSTAT3-positive tumor cells were positively correlated (Spearman R = 0.35, P = .036). We conclude that cyclin D3 is differentially expressed in ALK+ and ALK- ALCL and that high expression levels of cyclin D3 in ALK+ ALCL may be attributable to STAT3 activation. PMID:16084951

Dalton, Rory R; Rassidakis, George Z; Atwell, Coralyn; Wang, Sarah; Oyarzo, Mauricio P; Medeiros, L Jeffrey

2005-07-01

172

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer  

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Pleiotrophin (PTN, Ptn) is an 18 kDa cytokine expressed in human breast cancers. Since inappropriate expression of Ptn stimulates progression of breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive breast cancer phenotype. Pleiotrophin signals by inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP)?/?, and, recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTP?/? signaling pathway in PTN-stimulated cells, not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant cancers and activated ALK is a potent oncogenic protein, we examined human breast cancers to test the possibility that ALK may be expressed in breast cancers and potentially activated through the PTN/RPTP?/? signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the 'dotted' pattern characteristic of ALK fusion proteins in anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast ca may be important in human breast cancers and potentially activated either through the PTN/RPTP?/? signaling pathway, or, alternatively, as an activated fusion protein to stimulate progression of breast cancer in humans

173

Cáncer anaplásico de tiroides: Reporte de caso / Anaplastic thyroid cancer: A case report  

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Full Text Available SciELO Peru | Language: Spanish Abstract in spanish Mujer de 40 años, sin antecedente de patología tiroidea, con historia de enfermedad de cuatro semanas caracterizado por baja de peso, aumento rápido del tamaño de la glándula tiroides y dolor óseo generalizado. El examen físico mostró bocio multinodular no doloroso con múltiples ganglios cervicales. [...] Los análisis de laboratorio mostraron anemia y niveles elevados de transaminasas, fosfatasa alcalina y deshidrogenasa láctica. El perfil tiroideo fue normal y los anticuerpos antiperoxidasa tiroidea fueron negativos. La biopsia por aspiración mostró carcinoma de tiroides. Se realizó una tiroidectomía total con disección amplia de los ganglios del cuello y en el estudio de anatomía patológica resultó un carcinoma anaplásico de tiroides. La evolución de la paciente fue desfavorable, falleciendo por insuficiencia respiratoria, secundaria a embolismo pulmonar. El carcinoma anaplásico de tiroides es poco frecuente, pero tiene una alta mortalidad. Las metástasis a distancia están asociadas a mal pronóstico. Abstract in english A 40-year-old woman presented with a four weeks history of weight loss, rapid thyroid enlargement, and generalized bone pain. Her previous medical history was unremarkable. Physical examination showed a painless multinodular goiter with multiple cervical lymph nodes. Laboratory tests showed anemia, [...] elevated levels of transaminases, alkaline phosphatase, and lactic dehydrogenase. Thyroid profile was normal and thyroid autoantibodies were negative. Fine-needle aspiration biopsy showed a malignant carcinoma of thyroid. A total thyroidectomy and extensive neck dissection for lymph nodes were performed. Pathology examination showed an anaplastic thyroid carcinoma. The clinical evolution was torpid, and patient died because of respiratory insufficiency, secondary to pulmonary embolism. Anaplastic thyroid carcinoma is an uncommon and lethal malignancy. Distant metastases are associated with a low survival rate.

Miguel, Pinto-Valdivia; Milagros, Ortiz-Torres; Jaime, Villena-Chávez; César, Chian-García.

2012-04-01

174

MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma  

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Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17?92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.

Liu, Cuiling; Iqbal, Javeed

2013-01-01

175

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

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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/m2) and cisplatin (120 mg/m2) 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 significaic 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

176

Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma.  

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Hypoxia is an important factor mediating tumor progression and therapeutic resistance, in part through proteome changes mediated by the transcription factor hypoxia-inducible factor (HIF)-1. Since glioblastoma multiforme is the epitome of a highly aggressive tumor entity, while lower-grade astrocytomas often show a prolonged clinical course, a profound difference in the extent of hypoxic tissue areas and corresponding magnitude of HIF-1 activity may exist between these entities. In this study, to address this question, serial sections of 11 glioblastomas and 10 anaplastic astrocytomas were immunostained for HIF-1?, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX (i.e., hypoxia-related markers), Ki67 (proliferation), phosphorylated ribosomal protein S6 [p-rpS6; mammalian target of rapamycin (mTOR) activity] and CD34 (microvascular endothelium). Digital scans of whole tumor sections were registered to achieve geometric correspondence for subsequent morphometric operations. HIF-1?-, GLUT-1- and CA IX-positive staining was found in all 11 glioblastomas, showing a preferential expression in tissue areas adjacent to necroses. A considerable spatial overlap between GLUT-1 and CA IX, and a colocalization of these proteins with areas of enlarged mean diffusion distances were observed. Conversely, 8 of the 10 anaplastic astrocytomas were completely negative for hypoxia-related markers. The glioblastomas also showed significantly greater heterogeneity of intercapillary distances, larger diffusion-limited tissue fractions, significantly higher mTOR activity and a trend for higher proliferation rates. Microregionally, mTOR and proliferation showed a significant spatial overlap with areas of shorter mean diffusion distances. In conclusion, diffusion-limited hypoxia, leading to the expression of hypoxia-related markers is a pivotal element of the glioblastoma phenotype and may be driven by dysregulated growth and proliferation in normoxic subregions. PMID:22825389

Mayer, Arnulf; Schneider, Fabienne; Vaupel, Peter; Sommer, Clemens; Schmidberger, Heinz

2012-10-01

177

Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: Regulatory roles of cell surface glycans  

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Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic ac...

Suzuki, Osamu; Abe, Masafumi

2014-01-01

178

IL-21 Contributes to JAK3/STAT3 Activation and Promotes Cell Growth in ALK-Positive Anaplastic Large Cell Lymphoma  

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Interleukin (IL)-21 has been reported to both stimulate cell growth and promote survival in benign lymphoid cells and several types of hematopoietic neoplasms. It induces JAK3/STAT3 signaling, a biologically important cellular pathway activated in most cases of anaplastic lymphoma kinase (ALK)-expressing anaplastic large cell lymphoma (ALK+ALCL). Therefore, we hypothesize that IL-21 may contribute to JAK3/STAT3 activation and cell growth in ALK+ALCL. By reverse transcription-PCR, we found con...

Dien Bard, Jennifer; Gelebart, Pascal; Anand, Mona; Zak, Zoulika; Hegazy, Samar A.; Amin, Hesham M.; Lai, Raymond

2009-01-01

179

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report  

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Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice...

Daneshbod Yahya; Omidvari Shapour; Daneshbod Khosrow; Negahban Shahrzad; Dehghani Mehdi

2006-01-01

180

Anaplastic spindle cell carcinoma, arising in a background of an ovarian mucinous cystic tumor: a case report with clinical follow up, review of the literature  

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Anaplastic carcinoma (AC) of spindle cell type is an exceedingly rare ovarian malignant neoplasm. The histo-genesis of these tumors is still controversial. Although it was first thought to carry an invariably unfavorable prognosis, recent data indicates that this does not apply to stage Ia tumors. To date, there have been less than ten cases of anaplastic spindle cell carcinoma reported in the medical literature. Furthermore, our case is the first time this tumor has been described in a 40-ye...

Hillesheim, Paul B.; Farghaly, Hanan

2010-01-01

 
 
 
 
181

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*  

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Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective coho...

Kempf, W.; Pfaltz, K.; Vermeer, M. H.; Cozzio, A.; Ortiz-romero, P. L.; Bagot, M.; Olsen, E.; Kim, Y. H.; Dummer, R.; Pimpinelli, N.; Whittaker, S.; Hodak, E.; Cerroni, L.; Berti, E.; Horwitz, S.

2011-01-01

182

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  

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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

2013-01-15

183

Feasibility and limitations of radioiodine therapy in oncocytic (oxyphilic), medullary (C-cell) and anaplastic (undifferentiated) thyroid carcinoma  

International Nuclear Information System (INIS)

Oncocytic, medullary and anaplastic thyroid cancers are not supposed to take up radioiodine because of their cellular differentiation. Therefore, I-131 therapy should not be feasible in these special types of thyroid carcinoma. Literature reports concerning successful I-131 treatment in patients with those cancers may be explained by the occurrence of rare 'mixed tumor types' or 'collision tumors', which consist of oncocytic, medullary or anaplastic parts as well as of sections with follicular or papillary differentiation which may take up I-131. Moreover, in the region of the thyroid gland, tumor tissue which is not able to take up radioiodine may be surrounded by normal thyrocytes taking up I-131. Radioiodine treatment therefore may be indicated in proven mixed tumor types and in collision tumors as well as in cases of residual tumor tissue in the neighbourhood of normal thyrocytes. (orig.)

184

Remission of the Lambert-Eaton Syndrome and small cell anaplastic carcinoma of the lung induced by chemotherapy and radiotherapy  

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A patient presented with the Lambert-Eaton syndrome and small cell anaplastic carcinoma of the lung was subsequently diagnosed. Treatment with cytotoxic chemotherapy and radiotherapy resulted in remission of both the cancer and the neuromuscular disorder. This case represents the first documented remission of the Lambert-Eaton syndrome following nonoperative treatment of the primary malignancy and emphasizes the therapeutic value of early diagnosis of this disorder

185

A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma  

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Abstract Background Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy. Results In this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic...

Zu Youli; Wong Michael S; Bagaria Hitesh G; Zhao Nianxi

2011-01-01

186

Meta-analysis of glioblastoma multiforme versus anaplastic astrocytoma identifies robust gene markers  

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Abstract Background Anaplastic astrocytoma (AA) and its more aggressive counterpart, glioblastoma multiforme (GBM), are the most common intrinsic brain tumors in adults and are almost universally fatal. A deeper understanding of the molecular relationship of these tumor types is necessary to derive insights into the diagnosis, prognosis, and treatment of gliomas. Although genomewide profiling of expression levels with microarrays can be used to identify differentially express...

Park Peter J; Johnson Mark D; Dreyfuss Jonathan M

2009-01-01

187

Complete response to weekly carboplatin-docetaxel chemotherapy in a 91-year-old woman with anaplastic thyroid cancer.  

Science.gov (United States)

Anaplastic thyroid cancer (ATC) is an unusual tumor with the worst prognosis among thyroid malignancies. Treatment of the patients diagnosed with ATC is not standardized and the feasible options include surgery, radiotherapy and chemotherapy. ATC cannot be regarded as a very chemo-sensitive tumor. Herein, we reported a case of a 91-year-old woman with complete response after induction chemotherapy (weekly carboplatin and docetaxel) that underwent subsequent radiotherapy. PMID:25681954

Koussis, Haralabos; Giorgi, Carlo Alberto; Di Liso, Elisabetta; Carlucci, Maria Concetta; Fassina, Ambrogio; Marioni, Gino; Conte, Pier Franco

2015-01-01

188

Malignant trigeminal nerve sheath tumor and anaplastic astrocytoma collision tumor with high proliferative activity and tumor suppressor p53 expression.  

Science.gov (United States)

Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53) gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST) and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa. PMID:25386378

Kurdi, Maher; Al-Ardati, Hosam; Baeesa, Saleh S

2014-01-01

189

Clinical and laboratory characteristics of systemic anaplastic large cell lymphoma in Chinese patients  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Systemic anaplastic large cell lymphoma (S-ALCL is a rare disease with a highly variable prognosis and no standard chemotherapy regimen. Anaplastic lymphoma kinase (ALK has been reported as an important prognostic factor correlated with S-ALCL in many but not all studies. In our study, we retrospectively analyzed 92 patients with S-ALCL from the Peking University Lymphoma Center for clinical and molecular prognostic factors to make clear the role of ALK and other prognostic factors in Han Chinese S-ALCL. Results The majority of Chinese S-ALCL patients were young male patients (median age 26, male/female ratio 1.7 and the median age was younger than previous reports regardless of ALK expression status. The only statistically significant different clinical characteristic in S-ALCL between ALK positive (ALK+ and ALK negative (ALK- was age, with a younger median age of 22 for ALK+ compared with 30 for ALK-. However, when pediatric patients (?18 were excluded, there was no age difference between ALK+ and ALK-. The groups did not differ in the proportion of males, those with clinical stage III/IV (49 vs 51% or those with extranodal disease (53 vs 59%. Of 73 evaluable patients, the 3-year and 5-year survival rates were 60% and 47%, respectively. Univariate analysis showed that three factors: advanced stage III/IV, lack of expression of ALK, and high Ki-67 expression, were associated with treatment failure in patients with S-ALCL. However, ALK expression correlated with improved survival only in patients younger than 14?years, while not in adult patients. In multivariate analysis, only clinical stage was an independent prognostic factor for survival. Expressions of Wilms tumor 1 (WT1 and B-cell lymphoma 2 protein (BCL-2 correlated with the expression of ALK, but they did not have prognostic significance. High Ki-67 expression was also a poor prognostic factor. Conclusions Our results show that ALK expression alone is not sufficient to determine the outcome of ALCL and other prognostic factors must be considered. Clinical stage is an independent prognostic factor. Ki-67 expression is a promising prognostic factor.

Wang Yan-Fang

2012-07-01

190

Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations.  

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Context: Anaplastic thyroid cancer (ATC) is the most lethal of all thyroid cancers and one of the most aggressive human carcinomas. In the search for effective treatment options, research towards targeted, personalized therapies is proving to be a path with great potential. As we gain a deeper understanding of the genetic (e.g. BRAF(V600E), PIK3CA, TP53 mutations, hTERT mutations, etc.) and epigenetic alterations (e.g. microRNAs) driving ATC, we are able to find targets when developing novel therapies to improve the lives of patients. Beyond development, we can look into the effectiveness of already approved targeted therapies (e.g. anti-BRAF(V600E) selective inhibitors, tyrosine kinase inhibitors, histone deacetylase inhibitors, inhibitors of DNA methylation, etc.) to potentially test in ATC after learning the molecular mechanisms that aid in tumor progression. Design: We performed a literature analysis in Medline through the PubMed website for studies published between 2003 and 2014, using the main key-words: anaplastic thyroid cancer, genetic and epigenetic alterations. Objective: Here, we outline the common pathways that are altered in ATC, including the BRAF(V600E)/ERK1/2-MEK1/2 and PI3K-AKT pathways. We then examined the current research looking into personalized, potential targeted therapies in ATC, mentioning those that have been tentatively advanced into clinical trials and those with the potential to reach that stage. We also reviewed side effects of the current and potential targeted therapies used in patients with advanced thyroid cancer. Conclusions: DNA and RNA next generation sequencing analysis will be fundamental to unravel a precise medicine and therapy in patients with ATC. Indeed, given the deep biological heterogeneity/complexity and high histological grade of this malignancy and its tumor microenvironment, personalized therapeutic approaches possibly based on the use of combinatorial targeted therapy will provide a rational approach when finding the optimal way to improve treatments for patients with ATC. PMID:25347569

Smith, Neal; Nucera, Carmelo

2014-10-27

191

Survival and Compliance with the Use of Radiation Therapy for Anaplastic Thyroid Carcinoma  

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The purpose of this study was to evaluate the impact of the use of external radiation therapy (ERT) in terms of survival and compliance in patients with anaplastic thyroid carcinoma. Materials and Methods: The medical records of 17 patients with anaplastic thyroid carcinoma treated with ERT between 1993 and 2002 were retrospectively reviewed. ERT was administered after surgery in 14 patients and after a biopsy in three patients. Among the 14 patients who had undergone surgery, nine underwent a curative resection and five underwent a palliative resection. Six patients had associated well-differentiated thyroid carcinomas and 14 patients were diagnosed with a tumor size exceeding 5 cm. The radiation dose ranged from 6-70 Gy (median dose, 37.5 Gy). Eleven patients completed the planned course of ERT, whereas six patients did not. The follow-up period ranged from 1-104 months (median, 5 months; mean, 20 months). Results: Five patients started the ERT without the presence of a gross mass and all of the patients completed ERT without a re-growth of tumor. Twelve patients (four patients after a curative resection, five patients after a palliative resection and three patients after a biopsy) started ERT with a gross mass present and only six patients were able to complete the planned course of ERT. Among the six patients who completed ERT, two patients showed a marked regression of the tumor mass, whereas two patients showed slight regression and two patients showed no response. The median survival was five months (range, 1-104 months) and the mean survival was 21 months. The overall survival was 41% at 1-year, 24% at 2-years and 12% at 5-years. Significant prognostic factors included the number of primary tumors present, tumor size, whether surgery was performed and completion of ERT as planned. Long-term survivors showed a tendency of having smaller sized initial tumors and smaller sized pre-ERT tumors than the short-term survivors. Conclusion: This study suggests that patients with a small initial tumor ({<=}5 cm), which was treated by surgery (curative resection or palliative resection) before ERT, and without rapid re-growth of the mass seen at the surgical site at the beginning of the ERT course, would be the best candidates for postoperative ERT. In contrast, patients with a large initial tumor (>5 cm) and did not undergo surgery before ERT or that rapid re-growth of the mass was observed at the surgical site are likely to have a short survival time, along with the interruption of ERT. In these cases, the role of ERT is very limited and the omission of ERT could be considered.

Oh, Yoon Kyeong; Jang, Ji Young [Chosun University College of Medicine, Seoul (Korea, Republic of); Chung, Woong Ki [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

2008-12-15

192

Anaplastic thyroid carcinoma: A comprehensive review of current and future therapeutic options  

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Full Text Available Anaplastic thyroid carcinoma (ATC is the rarest, but deadliest histologic type among thyroid malignancies, with a dismal median survival of 3-9 mo. Even though ATC accounts for less than 2% of all thyroid tumors, it is responsible for 14%-39% of thyroid carcinoma-related deaths. ATC clinically presents as a rapidly growing mass in the neck, associated with dyspnoea, dysphagia and vocal cord paralysis. It is usually locally advanced and often metastatic at initial presentation. For operable diseases, the combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin and cisplatin, is the best treatment strategy. Cytotoxic drugs for advanced/metastatic ATC are poorly effective. On the other hand, targeted agents might represent a viable therapeutic option. Axitinib, combretastatin A4, sorafenib and imatinib have been tested in small clinical trials of ATC, with a promising disease control rate ranging from 33% to 75%. Other clinical trials of targeted therapy for thyroid carcinoma are currently ongoing. Biological agents that are under investigation include pazopanib, gefitinib and everolimus. With the very limited therapeutic armamentarium available at the present time, targeted therapy constitutes an exciting new horizon for ATC. In future, biological agents will probably represent the standard of care for this aggressive malignancy, in the same fashion as it has recently occurred for other chemo-refractory tumors, such as kidney and hepatic cancer.

Francesco Perri, Giuseppe Di Lorenzo, Giuseppina Della Vittoria Scarpati, Carlo Buonerba

2011-03-01

193

Anaplastic Lymphoma Kinase (ALK and p53 Are Potentially Useful Markers to Distinguish Inflammatory Myofibroblastic Tumor  

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Full Text Available Aims: Inflammatory myofibroblastic tumor (IMT of the urinary bladder is a clinically and histologically uncommon benign tumor that can be easily mistaken for a malignant neoplasm. We sought to determine whether immunohistochemical staining would be evaluated IMT of the urinary bladder. We have also shown the literatures that imminohistochemical staining of IMT was investigated to distinguish malignant lesions using PubMed data base. Methods: Immunohistochemical staining, including anaplastic lymphoma kinase (ALK, p53, cytokeratin, vimentin, desmin, alpha-smooth muscle actin, myoglobin, smooth muscle myosin and S100, was carried out on serial sections from archival specimens of three patients who underwent transurethral resection and partial cystectomy. Results: Immunohistchemical staining in all patients was positive for ALK and weak positive for p53 protein. In the literatures, positive rates of ALK and p53 inthe IMT of the urinary bladder were 60.9% and 53.1%, respectively. Sarcoma and carcinosarcoma were shown in the pathological specimens with negative ALK and strongly positive p53 inthe same data base. Conclusions: Both ALK and p53 were potentially useful protein markers to distinguish between IMT and sarcoma. However, this study was small sample size. Further study was warranted an investigation of the availability of these proteins in IMT.

Masatsugu Iwamura

2013-05-01

194

Breast implants and anaplastic large cell lymphoma : A Danish population-based cohort study  

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Background:A potential link between breast implants and anaplastic large cell lymphoma (ALCL) has been suggested. Methods:We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973-2010. Standardized incidence ratios, with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated. Results:: During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs for ALCL and lymphoma overall were 0 (95% CI, 0-10.3) and 1.20 (95% CI, 0.82-1.70), respectively. Conclusions:In our nationwide cohort study, we did not find an increased risk of lymphoma in general, or ALCL in particular, among Danish women who underwent breast implantation. However, our evaluation of ALCL risk was limited by the rarity of the disease. Impact:Our results do not support an association between breast implants and ALCL and are consistent with other studies on cancer-risk and breast implants.

Vase, Maja Ølholm; Friis, SØren

2013-01-01

195

Anaplastic lymphoma kinase: a glimmer of hope in lung cancer treatment?  

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Anaplastic lymphoma kinase (ALK) rearrangements (ALK-Rs) have been identified in 3-7% of all non-small-cell lung cancers (NSCLCs) and represent an important molecular target for NSCLC treatment. The authors discuss the role of ALK-Rs in the prediction of clinical-pathological features of NSCLCs and the technical problems related to their determination in specimens. The authors also describe the preclinical and clinical results derived from the use of ALK inhibitors. ALK-R is generally detected in patients with specific clinical-pathological features: never-smokers, young males, adenocarcinoma histotype and EGF receptor/KRAS wild-type. The diagnosis of ALK-R remains a challenge, implicating the need of a careful filtering of patients. NSCLC patients harboring ALK-R have shown sensitivity to ALK inhibitors even if their activity is limited at the time by the occurrence of mechanisms of resistance. The authors summarize the strategies that in the future could overcome these mechanisms of escape. PMID:23560836

Franco, Renato; Rocco, Gaetano; Marino, Federica Zito; Pirozzi, Giuseppe; Normanno, Nicola; Morabito, Alessandro; Sperlongano, Pasquale; Stiuso, Paola; Luce, Amalia; Botti, Gerardo; Caraglia, Michele

2013-04-01

196

Trofosfamide as salvage therapy for anaplastic large cell lymphoma relapsing after high-dose chemotherapy.  

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Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK + anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was hot possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL. PMID:12613523

Andersson, P O; Braide, I; Nilsson-Ehle, H

2002-12-01

197

Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer.  

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The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies. PMID:25135623

Vijayvergia, Namrata; Mehra, Ranee

2014-09-01

198

Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma tyrosine kinase ALK.  

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Anaplastic lymphoma kinase (ALK) is a member of the receptor tyrosine kinase superfamily. The ALK gene is a site of frequent mutation and chromosomal rearrangement in various types of human cancers. A novel chromosomal translocation was recently identified in human colorectal cancer between the ALK gene and chromosome 2, open reading frame 44 (C2orf44), a gene of unknown function. As a first step in understanding the oncogenic properties of this fusion protein, C2orf44 cDNA was cloned and the encoded protein was characterized, which was designated as WD repeat and coiled coil containing protein (WDCP). A C-terminal proline-rich segment in WDCP was shown to mediate binding to the Src homology 3 domain of the Src family kinase hematopoietic cell kinase (Hck). Co-expression with Hck lead to tyrosine phosphorylation of WDCP. Chromatographic fractionation of WDCP-containing lysates indicates that the protein exists as an oligomer in mammalian cells. These results suggest that, in the context of the ALK-C2orf44 gene fusion, WDCP imposes an oligomeric structure on ALK that results in constitutive kinase activation and signaling. PMID:25469238

Yokoyama, Noriko; Miller, W Todd

2015-01-01

199

A rare case of anaplastic thyroid carcinoma in a young woman with prolonged survival  

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Full Text Available Anaplastic thyroid cancer (ATC is one of the most aggressive tumors in human medicine. Despite the multimodal therapy, the average survival of patients is just several months. Fortunately, it is an extremely rare tumor. Most frequently, ATC occurs in the elderly, with the average age of the patients being almost 70 years. It is extremely rare that ATC occurs in people under the age of 40. We report a case of a 33 year old woman with ATC, with the diameter of the tumor being 8x7cm, confirmed by histopathology and imunohistochemistry. In January 2001, a total thyroidectomy was performed, and the tumor was completely resected. Postoperatively, the patient received radiation therapy. Ten years after the surgery, on regular check-ups, the patient is still living and there is no evidence of a recurrent tumor or metastases. This case is instructive for two reasons, as it shows that ATC can occur in younger people and that there is a possibility of long term survival.

Tauaanovi? Katarina

2013-01-01

200

Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer  

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Full Text Available The rate of the anaplastic lymphoma kinase (ALK gene rearrangements in non-small cell lung cancer (NSCLC tissues is 3%-5%. The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802, and AP26113, and new agents shock protein 90 inhibitors. This review aims to present the current knowledge on this fusion gene, the treatment advances, and novel drug clinical trials in ALK rearranged NSCLC.

Li MA

2014-12-01

 
 
 
 
201

Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma  

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Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

Arai Hajime

2007-08-01

202

Primary Ki-1 (anaplastic large cell) lymphoma of the brain and spinal cord.  

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The authors report a case of primary Ki-1 lymphoma of the brain. The patient was a 4 1/2-year-old black girl who presented with a 4- and 5-day history of headaches, nausea, vomiting, neck stiffness, and difficulty in walking. Computed tomography (CT) scan of the brain showed two discrete densities in the left occipital lobe and in the brain stem. Magnetic resonance imaging (MRI) showed multiple densities scattered over the brain surface and brain stem. Microscopically, the tumor was an anaplastic neoplasm that diffusely infiltrated brain parenchyma. The neoplastic cells were large with amphophilic cytoplasm, large nuclei with irregular nuclear contours and prominent nucleoli. A high mitotic rate including atypical mitotic figures was noted. Immunohistochemical stains showed diffuse strong positivity for CD30 and moderate focal staining for epithelial membrane antigen. Leukocyte common antigen, cytokeratin, neuron specific enolase, monocyte/macrophage and B- and T-marker stains were negative. The histology was characteristic for Ki-1 large cell lymphoma. Cytologic examination of cerebrospinal fluid (CSF) demonstrated similar neoplastic cells. This is one of the first reports of this variant in the pediatric population. PMID:7726150

Havlioglu, N; Manepalli, A; Galindo, L; Sotelo-Avila, C; Grosso, L

1995-04-01

203

Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases.  

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This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10(9) /l, with 12-90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed. PMID:24666317

Spiegel, Alexandra; Paillard, Catherine; Ducassou, Stephane; Perel, Yves; Plantaz, Dominique; Strullu, Marion; Eischen, Alice; Lutz, Patrick; Lamant, Laurence; Le Deley, Marie-Cécile; Brugières, Laurence

2014-05-01

204

miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression.  

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Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelial-mesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC. Cancer Res; 75(2); 367-77. ©2014 AACR. PMID:25488748

Boufraqech, Myriem; Nilubol, Naris; Zhang, Lisa; Gara, Sudheer Kumar; Sadowski, Samira M; Mehta, Amit; He, Mei; Davis, Sean; Dreiling, Jennifer; Copland, John A; Smallridge, Robert C; Quezado, Martha M; Kebebew, Electron

2015-01-15

205

Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer.  

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The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)-ALK fusions, which were identified by 5' RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer. PMID:25527510

Park, Gahee; Kim, Tae Hyuk; Lee, Hae-Ock; Lim, Jung Ah; Won, Jae-Kyung; Min, Hye Sook; Lee, Kyu Eun; Park, Do Joon; Park, Young Joo; Park, Woong-Yang

2015-02-01

206

Ionizing radiation enhances dl922-947-mediated cell death of anaplastic thyroid carcinoma cells.  

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dl922-947 is an oncolytic adenovirus potentially suitable for the treatment of aggressive localized tumors, such as anaplastic thyroid carcinoma (ATC). In this study, we have analyzed the effects of dl922-947 in combination with ionizing radiations, testing different schedules of administration and observing synergistic effects only when ATC cells were irradiated 24 h prior to viral infection. Cells undergoing combined treatment exhibited a marked increase in cell death and viral replication, suggesting that irradiation blocks cells in a more permissive state for viral life cycle. We also show that dl922-947 triggers a DNA damage response, characterized by mobilization of the MRN complex (composed by Mre11-Rad50-Nbs1), accumulation of ?H2AX, and activation of the checkpoint kinases ataxia telangiectasia mutated (ATM) and Chk1. Based on these observations, we speculate that the DNA damage response acts as a cellular protective mechanism to hinder viral infection and replication. To confirm this hypothesis, we demonstrate that the ATM inhibitor KU55933 increased the oncolytic activity of dl922-947 and its replication. Finally, we validate the potential therapeutic use of this approach by showing in vivo that the combined treatment slows tumor xenograft growth more potently than either irradiation or infection alone. PMID:23839822

Passaro, Carmela; Abagnale, Antonella; Libertini, Silvana; Volpe, Massimiliano; Botta, Ginevra; Cella, Laura; Pacelli, Roberto; Halldèn, Gunnel; Gillespie, David; Portella, Giuseppe

2013-10-01

207

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report  

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Full Text Available Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

Dehghani Mehdi

2006-01-01

208

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report  

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Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease. PMID:17052355

Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-01-01

209

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

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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 Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

2014-12-12

210

Survival and Compliance with the Use of Radiation Therapy for Anaplastic Thyroid Carcinoma  

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The purpose of this study was to evaluate the impact of the use of external radiation therapy (ERT) in terms of survival and compliance in patients with anaplastic thyroid carcinoma. Materials and Methods: The medical records of 17 patients with anaplastic thyroid carcinoma treated with ERT between 1993 and 2002 were retrospectively reviewed. ERT was administered after surgery in 14 patients and after a biopsy in three patients. Among the 14 patients who had undergone surgery, nine underwent a curative resection and five underwent a palliative resection. Six patients had associated well-differentiated thyroid carcinomas and 14 patients were diagnosed with a tumor size exceeding 5 cm. The radiation dose ranged from 6-70 Gy (median dose, 37.5 Gy). Eleven patients completed the planned course of ERT, whereas six patients did not. The follow-up period ranged from 1-104 months (median, 5 months; mean, 20 months). Results: Five patients started the ERT without the presence of a gross mass and all of the patients completed ERT without a re-growth of tumor. Twelve patients (four patients after a curative resection, five patients after a palliative resection and three patients after a biopsy) started ERT with a gross mass present and only six patients were able to complete the planned course of ERT. Among the six patients who completed ERT, two patients showed a marked regression of the tumor mass, whereas two patients showed slight regression and two patients showed no respongression and two patients showed no response. The median survival was five months (range, 1-104 months) and the mean survival was 21 months. The overall survival was 41% at 1-year, 24% at 2-years and 12% at 5-years. Significant prognostic factors included the number of primary tumors present, tumor size, whether surgery was performed and completion of ERT as planned. Long-term survivors showed a tendency of having smaller sized initial tumors and smaller sized pre-ERT tumors than the short-term survivors. Conclusion: This study suggests that patients with a small initial tumor (?5 cm), which was treated by surgery (curative resection or palliative resection) before ERT, and without rapid re-growth of the mass seen at the surgical site at the beginning of the ERT course, would be the best candidates for postoperative ERT. In contrast, patients with a large initial tumor (>5 cm) and did not undergo surgery before ERT or that rapid re-growth of the mass was observed at the surgical site are likely to have a short survival time, along with the interruption of ERT. In these cases, the role of ERT is very limited and the omission of ERT could be considered

211

Breast Implant–associated Anaplastic Large Cell Lymphoma: Updated Results from a Structured Expert Consultation Process  

Science.gov (United States)

Background: Despite increased cases published on breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), important clinical issues remain unanswered. We conducted a second structured expert consultation process to rate statements related to the diagnosis, management, and surveillance of this disease, based on their interpretation of published evidence. Methods: A multidisciplinary panel of 12 experts was selected based on nominations from national specialty societies, academic department heads, and recognized researchers in the United States. Results: Panelists agreed that (1) this disease should be called “BIA-ALCL”; (2) late seromas occurring >1 year after breast implantation should be evaluated via ultrasound, and if a seroma is present, the fluid should be aspirated and sent for culture, cytology, flow cytometry, and cell block to an experienced hematopathologist; (3) surgical removal of the affected implant and capsule (as completely as possible) should occur, which is sufficient to eradicate capsule-confined BIA-ALCL; (4) surveillance should consist of clinical follow-up at least every 6 months for at least 5 years and breast ultrasound yearly for at least 2 years; and (5) BIA-ALCL is generally a biologically indolent disease with a good prognosis, unless it extends beyond the capsule and/or presents as a mass. They firmly disagreed with statements that chemotherapy and radiation therapy should be given to all patients with BIA-ALCL. Conclusions: Our assessment yielded consistent results on a number of key, incompletely addressed issues regarding BIA-ALCL, but additional research is needed to support these statement ratings and enhance our understanding of the biology, treatment, and outcomes associated with this disease. PMID:25674377

Predmore, Zachary S.; Mattke, Soeren; van Busum, Kristin; Gidengil, Courtney A.

2015-01-01

212

Anaplastic lymphoma kinase rearrangement in lung cancer: its biological and clinical significance.  

Science.gov (United States)

Anaplastic lymphoma kinase (ALK) has been found to fuse with other partners, such as echinoderm microtubule-associated protein-like 4 (EML4), leading to potent malignant transformation in lung cancer, specifically non-small-cell lung cancer (NSCLC). The frequency of the ALK rearrangement in patients with NSCLC is reported to be 4-7%, and the rearrangement is frequently observed in relatively younger patients, non- or light smokers and those with adenocarcinoma histology without other genetic disorders, such as mutations of the epidermal growth factor receptor gene. Crizotinib, which is a first-in-class ALK tyrosine kinase inhibitor (TKI), was shown to be effective and well tolerated in ALK-positive NSCLC patients by a single-arm phase I study. Furthermore, a phase III randomized study demonstrated the superiority of crizotinib to standard chemotherapy (pemetrexed or docetaxel) in the treatment of NSCLC patients harboring the ALK rearrangement who had received one prior platinum-based chemotherapy. However, the mechanisms of resistance to crizotinib are major concerns when administering crizotinib to ALK-positive NSCLC patients, and they include second mutations and a gain in the copy number of the ALK gene, activation of other oncogenes, etc. Treatment strategies to overcome these mechanisms of resistance have been developed, including the use of second-generation ALK inhibitors, such as alectinib and ceritinib, heat shock protein 90 inhibitors and so on. In this article, we review the pre-clinical and clinical data regarding the biologal and clinical significance of the ALK rearrangement in lung cancer. PMID:25453376

Toyokawa, Gouji; Seto, Takashi

2014-11-01

213

Cytomorphology of non-small cell lung carcinoma with anaplastic lymphoma kinase gene rearrangement.  

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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase demonstrating activating mutations in several malignancies including a subset (1-5%) of non-small cell lung carcinomas (NSCLC). Prior work examining, the histologic features of these tumors found a spectrum of findings, notably a solid/acinar pattern, as well as a mucinous cribriform pattern. We present the first study to date describing the cytomorphology of NSCLC harboring ALK rearrangements. A retrospective database search was conducted to identify cytologic specimens of NSCLC demonstrating ALK rearrangement. Cytogenetic analysis was performed with fluorescence in situ hybridization. A total of 12 patients were identified, 10 with available material. Cellular morphology and smear background was evaluated in the study group, as well as control cases lacking ALK rearrangement. A total of 25 specimens from 10 patients were obtained. Five patients never smoked, and four patients had a remote smoking history. ALK rearrangements were identified in cells with unique cytologic characteristics. All cases demonstrated moderate to poor differentiation with a predominance of single cells showing anisonucleosis and frequent intracytoplasmic neutrophils. The control cases showed cells with smaller, less pleomorphic nuclei, and smaller nucleoli with more clusters/tissue fragments. Several unique cytomorphologic features were consistently identified in the study population relative to the control population and include a prominence of single, markedly enlarged tumor cells with plasmacytoid features and anisonucleosis, as well as intracytoplasmic neutrophils. Larger studies are warranted to confirm our preliminary findings, as these features may help establish a more cost-effective means to select patients being tested for ALK mutational analysis. PMID:24723496

Toll, Adam D; Maleki, Zahra

2015-01-01

214

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

Science.gov (United States)

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. PMID:25074669

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

215

Immunohistochemical detection of epithelialmesenchymal transition associated with stemness phenotype in anaplastic thyroid carcinoma.  

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Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm resistant to radiation and chemotherapy. Epithelial-mesenchymal transition (EMT) generating cells with stem cell characteristics have been reported to be associated with chemoradioresistance in cultured cells. However, EMT and stem cell properties in ATC have not been fully investigated. In this study, we retrieved 2 thyroidectomy specimens of ATC with coexisting well differentiated thyroid carcinomas (DTCs) including one papillary carcinoma (PTC) and one follicular carcinoma (FTC). We used im-munohistochemistry to examine the expression of stem cell markers (nestin, CD133 and CD44) and a marker for EMT (E-cadherin). Intense expressions of nestin, CD133 and CD44, and no expression of E-cadherin were observed in both ATCs. In contrast, the PTC and FTC, and non-neoplastic thyroid tissue in both cases were negative for nestin and positive for E-cadherin. The expressions of CD133 and CD44 were variable in the PTC, FTC, and non-neoplastic thyroid tissue and were at a lower level of expression of these markers in the overall pattern. The results confirmed EMT, demonstrated the stem cell phenotype in ATC, and revealed the difference in expression of these markers between ATC and DTCs/non-neoplastic thyroid tissue. Nestin may be the most specific marker for stemness in ATC by immuno-histochemial staining. The results warrant future studies on a large series of cases in order to gain the understanding of the tumor biology and to provide molecular basis for restoring the sensitivities to clinical therapies. PMID:21151388

Liu, Jing; Brown, Robert E

2010-01-01

216

S100A8 is a novel therapeutic target for anaplastic thyroid carcinoma.  

Science.gov (United States)

Context: Anaplastic thyroid carcinoma (ATC) is one of the most deadly human malignancies. It is 99 percent lethal, and patients have a median survival of only 6 months after diagnosis. Despite these grim statistics, the mechanism underlying the tumorigenic capability of ATC cells is unclear. Objective: S100A8 and S100A9 proteins have emerged as critical mediators in cancer. The aim was to investigate the expression and function of S100A8 and S100A9 in ATC and the mechanisms involved. Design: We determined the expression of S100A8 and S100A9 in human ATC by gene array analysis and immunohistochemistry. Using RNAi-mediated stable gene knockdown in human ATC cell lines and bioluminescent imaging of orthotopic and lung metastasis mouse models of human ATC, we investigated the effects of S100A8 and S100A9 on tumorigenesis and metastasis. Results: We demonstrated that S100A8 and S100A9 were overexpressed in ATC but not in other types of thyroid carcinomas. In vivo analysis in mice using ATC cells that had S100A8 knocked down revealed reduced tumor growth and lung metastasis, as well as significantly prolonged animal survival. Mechanistic investigations showed that S100A8 promotes ATC cell proliferation through an interaction with RAGE, which activates the p38, ERK1/2 and JNK signaling pathways in the tumor cells. Conclusions: These findings establish a novel role for S100A8 in the promoting and enhancing of ATC progression. They further suggest that the inhibition of S100A8 could represent a relevant therapeutic target, with the potential of enabling a more effective treatment path for this deadly disease. PMID:25423568

Reeb, Ashley N; Li, Wen; Sewell, Will; Marlow, Laura A; Tun, Han W; Smallridge, Robert C; Copland, John A; Spradling, Kyle; Chernock, Rebecca; Lin, Reigh-Yi

2014-11-25

217

Clinical study of 10 cases of anaplastic carcinoma of the thyroid  

International Nuclear Information System (INIS)

Ten cases (5 males and 5 females) of anaplastic carcinoma of the thyroid treated at Hyogo Cancer Center between February 1994 and October 2006 were reviewed. Patient ages ranged from 47 to 84 years with a median of 65.5 years. Only one case is alive after 12 years and 8 months; 8 cases died of the disease and one died of a different disease. The 8 cases who died from the carcinoma consisted of 4 cases of suffocation by primary tumor invasion and 4 cases of distant metastasis. All 9 cases died within one year after their treatment. The 6 cases were treated by surgery with postoperative radiotherapy and the 2 cases of them underwent chemotherapy. The local tumor was resected radically in the 3 cases and was not resected radically but debulked in the 3 cases. Only 1 long-time survivor whose preoperative pathological diagnosis was squamous cell carcinoma was treated by induction chemotherapy, radical operation with pharyngolaryngoesophagectomy, and postoperative radiotherapy. Half of the 6 surgical cases died of suffocation. The 4 non-surgical cases were treated by combination therapy with chemotherapy and radiotherapy. The 3 cases of the 4 non-surgical cases died of distant metastasis. The rate of life at home during survival time was higher in the cases treated surgically than in the non-surgery cases. The possibility is suggested that the rate of life at home during survival time was higher with surgical treatment even the debulking operation and the improvement of qualking operation and the improvement of quality of life (QOL) was achieved. But the debulking operation was not more effective for the improvement of the survival time and the local control, compared with the cases treated without surgery. (author)

218

Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.  

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Neuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and R1464STOP), which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression, we have employed cell culture-based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I) generates a gain-of-function receptor capable of activating intracellular targets such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand-independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These classes are: (i) gain-of-function ligand-independent mutations such as ALK(F1174l), (ii) kinase-dead ALK mutants, e.g. ALK(I1250T) (Schönherr et al., 2011a) and (iii) ALK mutations that are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity. PMID:23104988

Chand, Damini; Yamazaki, Yasuo; Ruuth, Kristina; Schönherr, Christina; Martinsson, Tommy; Kogner, Per; Attiyeh, Edward F; Maris, John; Morozova, Olena; Marra, Marco A; Ohira, Miki; Nakagawara, Akira; Sandström, Per-Erik; Palmer, Ruth H; Hallberg, Bengt

2013-03-01

219

Dosimetric comparison between helical tomotherapy and volumetric modulated arc-therapy for non-anaplastic thyroid cancer treatment.  

Science.gov (United States)

BackgroundTo evaluate and compare dosimetric parameters of volumetric modulated arctherapy (VMAT) and helical tomotherapy (HT) for non-anaplastic thyroid cancer adjuvant radiotherapy.MethodsTwelve patients with non-anaplastic thyroid cancer at high risk of local relapse received adjuvant external beam radiotherapy with curative intent in our institution, using a two-dose level prescription with a simultaneous integrated boost approach. Each patient was re-planned by the same physicist twice using both VMAT and HT. Several dosimetric quality indexes were used: target coverage index (proportion of the target volume covered by the reference isodose), healthy tissue conformity index (proportion of the reference isodose volume including the target volume), conformation number (combining both previous indexes), Dice Similarity Coefficient (DSC), and homogeneity index ((D2%-D98%)/prescribed dose). Dose-volume histogram statistics were also compared.ResultsHT provided statistically better target coverage index and homogeneity index for low risk PTV in comparison with VMAT (respectively 0.99 vs. 0.97 (p¿=¿0.008) and 0.22 vs. 0.25 (p¿=¿0.016)). However, HT provided poorer results for healthy tissue conformity index, conformation number and DSC with low risk and high risk PTV. As regards organs at risk sparing, by comparison with VMAT, HT statistically decreased the D2% to medullary canal (25.3 Gy vs. 32.6 Gy (p¿=¿0.003)). Besides, HT allowed a slight sparing dose for the controlateral parotid (Dmean: 4.3 Gy vs. 6.6 Gy (p¿=¿0.032)) and for the controlateral sub-maxillary gland (Dmean: 29.1 Gy vs. 33.1 Gy (p¿=¿0.041)).ConclusionsBoth VMAT and HT techniques for adjuvant treatment of non-anaplastic thyroid cancer provide globally attractive treatment plans with slight dosimetric differences. However, helical tomotherapy clearly provides a benefit in term of medullary canal sparing. PMID:25424320

Khalifa, Jonathan; Vieillevigne, Laure; Boyrie, Sabrina; Ouali, Monia; Filleron, Thomas; Rives, Michel; Laprie, Anne

2014-11-26

220

Primary cutaneous anaplastic large-cell lymphoma - case report / Linfoma cutâneo primário de grandes células anaplásicas - relato de caso  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Linfoma cutâneo primário de grandes células T anaplásicas faz parte do espectro de processos linfoproliferativos cutâneos CD30+ e caracteriza-se por nódulos únicos ou multifocais, ulcerados, autorregressivos e recidivantes. Pode haver disseminação extracutânea, principalmente para linfonodos regiona [...] is. O histológico mostra infiltrado difuso, não-epidermotrópico, grandes células linfóides anaplásicas de imunohistoquímica CD30+, CD4+, EMA-/+, ALK-, CD15- e TIA1-/+. O prognóstico é bom e independe da invasão ganglionar. Radioterapia, retirada da lesão e/ou metotrexato em baixas doses são os tratamentos de escolha. Este estudo relata o caso de uma mulher, 57 anos, com Linfoma cutâneo primário de grandes células T com lesões multifocais e que, após 7 anos, evoluiu com acometimento pulmonar. Apresentou boa resposta ao tratamento com metotrexato em baixas doses semanais. Abstract in english Primary cutaneous anaplastic large-cell lymphoma is part of the spectrum of CD30+ lymphoproliferative cutaneous processes, characterized by single or multifocal nodules that ulcerate, are autoregressive and recurrent. Extracutaneous dissemination may occur, especially to regional lymph nodes. Histol [...] ogy shows a diffuse, non-epidermotropic infiltrate , anaplastic large lymphoid cells of immunohistochemistry CD30+, CD4+, EMA-/+, ALK-, CD15- and TIA1-/+. Prognosis is good and does not depend on lymphatic invasion. Radiotherapy, removal of the lesion and/or low-dose methotrexate are the treatments of choice. The present study reports the case of a 57-year-old-woman presenting Primary cutaneous anaplastic large-cell lymphoma with multifocal lesions. The pacient evolved with pulmonary involvement 7 years later. She showed a good response to the treatment with low-dose methotrexate prescribed weekly.

Luciana Silveira Rabello de, Oliveira; Madeleyne Palhano, Nobrega; Maira Gomes, Monteiro; Wagner Leite de, Almeida.

2013-12-01

 
 
 
 
221

Autocrine release of interleukin-9 promotes Jak3-dependent survival of ALK+ anaplastic large-cell lymphoma cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The aberrant fusion protein NPM-ALK plays an important pathogenetic role in ALK+ anaplastic large-cell lymphoma (ALCL). We previously demonstrated that Jak3 potentiates the activity of NPM-ALK. Jak3 activation is restricted to interleukins that recruit the common ? chain (?c) receptor, including IL-9. NPM-ALK was previously shown to promote widespread lymphomas in IL-9 transgenic mice by unknown mechanisms. We hypothesized that IL-9 plays an important role in ALK+ ALCL via Jak3 activation. ...

Qiu, Lin; Lai, Raymond; Lin, Quan; Lau, Esther; Thomazy, David M.; Calame, Daniel; Ford, Richard J.; Kwak, Larry W.; Kirken, Robert A.; Amin, Hesham M.

2006-01-01

222

Kawasaki disease, Mycoplasma pneumoniae infection and anaplastic large cell lymphoma: An uncommon association  

Directory of Open Access Journals (Sweden)

Full Text Available Kawasaki disease (KD is an acute febrile systemic vasculitis occurring predominantly in young children less than 5 years of age. Although imperfectly known, the aetiopathogenesis of KD would be secondary to immunological abnormalities that could constitute a favourable terrain for neoplasms. We report on a case in a 2-year-old girl who presented clinical manifestations compatible with Kawasaki disease complicated by coronary aneurysm. Aetiopathological investigations revealed M. pneumoniae infection as specific IgM were present in the serum (Elisa. The patient was initially treated by intravenous immunoglobulins (IVIG and aspirin to anti-inflammatory dose. Following a few days of desquamation, resolution of the symptomatology occurred. Four weeks later she developed disseminated tumorous syndrome. Lymph node biopsy revealed massive infiltration by large cells lymphomatous proliferation. Histologic and immunophenotypic findings were characteristic of ALK-1+ anaplastic large cell lymphoma. Four weeks later, the patient died from a severe nosocomial infection complicated by septic shock. Our observation is the first cases describing the association between anaplastic large cell lymphoma, KD and M. pneumoniae. Immunologic disorder due to KD and M. pneumoniae infection may play probably a central role for malignancy.

Jalel Chemli

2012-09-01

223

Talis pater, talis filius: perceived resemblance and the belief in genetic relatedness.  

Science.gov (United States)

People hardly ever realize that their belief in their high rate of success in detecting family resemblances is affected by their knowledge of the actual genetic link between individuals. In the three studies reported here, 100 men and 100 women were requested to estimate the facial resemblance of photographically portrayed child-adult pairs, while being given either truthful or deceitful information, or no information, about their relatedness. Believing that the members of a pair were parent and offspring was the main predictor of the perceived similarity between them. Men and women agreed in judging children as more similar to female than to male adults, except when the pair members were believed to be related; in this case, men judged the child as resembling the alleged parents equally. Common remarks on family resemblance thus appear to ensue less from a conscious desire to please or reassure the parents than from general hypothesis-testing biases in human reasoning, made perhaps more specific in men by a concern with the problem of uncertain paternity. PMID:12009040

Bressan, Paola; Martello, Maria F Dal

2002-05-01

224

Human Coinfection with Bartonella henselae and Two Hemotropic Mycoplasma Variants Resembling Mycoplasma ovis?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Two variants of an organism resembling the ovine hemoplasma, Mycoplasma ovis, were detected by PCR in blood samples from a veterinarian in Texas. Coinfection with similar variants has been described in sheep. This represents the first report of human infection with this organism. The veterinarian was coinfected with Bartonella henselae.

Sykes, Jane E.; Lindsay, Leann L.; Maggi, Ricardo G.; Breitschwerdt, Edward B.

2010-01-01

225

18F-DOPA-PET in Planning Surgery in Patients With Gliomas  

Science.gov (United States)

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; 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; Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebellar Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Choroid Plexus Neoplasm; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Supratentorial Ependymoma; Malignant Adult Intracranial Hemangiopericytoma; Medulloepithelioma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Neoplasm; 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 Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Pleomorphic Xanthoastrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; 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 Medulloblastoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilocytic Astrocytoma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Pineoblastoma; Untreated Childhood Pleomorphic Xanthoastrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor; Untreated Childhood Visual Pathway Glioma

2014-12-17

226

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

Science.gov (United States)

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 Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

2014-02-14

227

Anaplastic lymphoma kinase-positive large B-cell lymphoma: description of a case with an unexpected clinical outcome.  

Science.gov (United States)

Anaplastic lymphoma kinase-positive (ALK-positive) large B-cell lymphoma is a rare and aggressive variant of large B-cell lymphoma (LBCL), first reported by Delsol et al in 1997, showing distinctive morphologic, immunophenotypic and cytogenetic features. The latest 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid tissues recognizes ALK-positive LBCL as a separate entity. Here, we report a case of ALK-positive large B-cell lymphoma in a 53-year-old man with diffuse abdominal and mediastinal lymph-nodes involvement. According to the Ann Arbor staging system, the patient had a stage IIIB lymphoma. The age-adjusted International Prognostic Index was 2 (stage III and elevated lactate dehydrogenase), so the disease was considered high risk. The patient underwent chemotherapy, radiotherapy, and an autologous stem cell transplantation. The patient is alive and free of disease 35 months after diagnosis. PMID:24868005

Zanelli, Magda; Valli, Riccardo; Capodanno, Isabella; Ragazzi, Moira; Ascani, Stefano

2015-02-01

228

Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma  

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Full Text Available Nicolas Graf,1 Zhoulei Li,2 Ken Herrmann,2,4 Daniel Weh,2 Michaela Aichler,3 Jolanta Slawska,2 Axel Walch,3 Christian Peschel,1 Markus Schwaiger,2 Andreas K Buck,2,4 Tobias Dechow,1,* Ulrich Keller1,* 1III Medical Department, 2Department of Nuclear Medicine, Technische Universität München, Munich, Germany; 3Research Unit Analytical Pathology, Helmholtz Zentrum München, Munich, Germany; 4Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany *These authors contributed equally to this work Background: Dual phosphatidylinositol-3-kinase (PI3K/mammalian target of rapamycin (mTOR inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226, in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET imaging using the standard tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG and the thymidine analog, 3'-deoxy-3'-[18F]fluorothymidine (FLT. Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy. Keywords: lymphoma, phosphatidylinositol-3-kinase, mammalian target of rapamycin, inhibition, positron emission tomography

Graf N

2014-05-01

229

Particular features of cell-mediated immunity in patients with anaplastic gliomas. A comparison with kidney and bladder cancer patients.  

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The authors studied 24 patients affected by anaplastic gliomas in regard to the killer (Antibody-Dependent Cellular Cytotoxicity) and natural killer (Spontaneous Lymphocyte-Mediated Cytotoxicity) immunological functions, by counting the Cr51 release in Change liver and K 562 cell cultures, respectively. These parameters were also evaluated in 24 healthy donors as control, in 24 patients affected by bladder cancer and in nine cases of kidney cancer. Our data show, pre-operatively, a statistically significant impairment of ADCC and SLMC activity in glioma patients as compared both with controls, bladder and kidney cancer patients. The particular impairment of K and NK functions in gliomas is discussed with regard to the specific features of Central Nervous System malignancies. An improvement of ADCC activity was also found in the post-operative samples. This finding confirms other reports about partial restoring of altered immunocompetence after surgery, suggesting a link between extention of tumor mass and impaired immunological reactions. PMID:6088720

Servadei, F; Parente, R; Bucci, M; Beltrandi, E; Tognetti, F; Gaist, G

1983-01-01

230

A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy. Results In this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK gene in lymphoma cells. The nanocomplexes were formulated by incorporating both ALK siRNA and a RNA-based CD30 aptamer probe onto nano-sized polyethyleneimine-citrate carriers. To minimize potential cytotoxicity, the individual components of the nanocomplexes were used at sub-cytotoxic concentrations. Dynamic light scattering showed that formed nanocomplexes were ~140 nm in diameter and remained stable for more than 24 hours in culture medium. Cell binding assays revealed that CD30 aptamer probes selectively targeted nanocomplexes to ALCL cells, and confocal fluorescence microscopy confirmed intracellular delivery of the nanocomplex. Cell transfection analysis showed that nanocomplexes silenced genes in an ALCL cell type-selective fashion. Moreover, exposure of ALCL cells to nanocomplexes carrying both ALK siRNAs and CD30 RNA aptamers specifically silenced ALK gene expression, leading to growth arrest and apoptosis. Conclusions Taken together, our findings indicate that this functional RNA nanocomplex is both tumor cell type-selective and cancer gene-specific for ALCL cells.

Zu Youli

2011-01-01

231

The oncogenic JUNB/CD30 axis contributes to cell cycle deregulation in ALK+ anaplastic large cell lymphoma.  

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Anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) resulting in expression of NPM1(NPM)-ALK oncogenic kinase. The latter is capable of activating ERK kinase, which upregulates JUNB expression through ETS1. JUNB, in turn, interacts with the TNFRSF8 (CD30) gene promoter and induces CD30 (TNFRSF8) overexpression. However, the role of CD30 overexpression in ALK+ ALCL oncogenesis remains unknown. Here we show that the JUNB gene is frequently amplified in ALK+ ALCL, suggesting gene amplification as an additional underlying mechanism for JUNB overexpression. Silencing of JUNB resulted in reduced cell growth and colony formation associated with decreased activator protein-1 activity and G1/S and G2/M cell cycle arrest. These effects were linked to decreased CD30 levels, downregulation of CCNA2 (Cyclin A), CCND2 (Cyclin D2) and CCND3 (Cyclin D3) and upregulation of cyclin-dependent kinase inhibitors CDKN2A (p14) and CDKN1A (p21), but not CDKN1B (p27). Similar cell cycle changes were observed following the knock-down of TNFRSF8 gene or blockade of its function using anti-CD30 antibodies, which were associated with upregulation of CDKN2A and CDKN1A, but not CDKN1B. These findings indicate that JUNB may partly operate through CD30 signalling. Silencing of JUNB also sensitized NPM1-ALCL+ cells to standard chemotherapeutic agents. Our findings uncover the oncogenic role of the JUNB/CD30 axis and its potential as therapeutic target in ALK+ ALCL. PMID:25145835

Atsaves, Vassilis; Lekakis, Lazaros; Drakos, Elias; Leventaki, Vasiliki; Ghaderi, Mehran; Baltatzis, George E; Chioureas, Dimitris; Jones, Dan; Feretzaki, Marianna; Liakou, Chryssoula; Panayiotidis, Panayiotis; Gorgoulis, Vassilis; Patsouris, Efstratios; Medeiros, L Jeffrey; Claret, Francois X; Rassidakis, George Z

2014-11-01

232

Anaplastic sarcoma of the kidney: a clinicopathologic study of 20 cases of a new entity with polyphenotypic features.  

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We report 20 cases of a distinct, previously unrecognized renal neoplasm, anaplastic sarcoma of the kidney with polyphenotypic features. The tumors were identified by re-reviewing tumors with unusual anaplastic features from the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group trials. Patients ranged in age from 10 months to 41 years (median age 5 y, mean age 12 y) and females predominated (1.5:1). Twelve tumors presented in the right kidney, and 5 in the left (laterality was unknown in 3 cases). The most common presentation was a renal mass. Grossly, most tumors were large, measured 4 to 21 cm (mean 12.7 cm) and weighed 115 to 1820 g (mean 835 g). Seven out of 12 tumors suitable for assessment had a distinct cystic component. The tumors involved the pelvi-calyceal system in 5 of the cases. Histologically, all tumors showed a spindle cell component which contained either multiple foci or diffuse, widespread anaplastic changes with bizarre pleomorphic cells and very atypical mitotic figures. Chondroid differentiation was seen in 16 cases, usually in the form of islands of hyaline cartilage (13 cases) or chondroid matrix (3 cases). The nodules of cartilage showed both benign and malignant features, often within the same tumor. In 2 cases small foci of osteoid were found whereas osteoclast-like giant cells were seen in 4 cases. Only 3 of the tumors exhibited a primitive blastema-like area. No neoplastic epithelial structures were identified. No nephrogenic rests were found. Limited immunohistochemical studies showed vimentin positivity in 5/5 cases, desmin was positive in 4/6 cases, MYF4 showed focal weak nuclear positivity in 1/4 cases, but MyoD1 was negative in all cases (0/5). PGP9.5 was focally, strongly positive in 4/5 cases and p53 was strongly positive in 3/6 cases. Cytokeratin, using the antibody CAM5.2, was uniformly negative within the tumor cells. Finally, CD56 was focally positive in 1/6 tumors, whereas all other markers were negative including NB84a (4/4), CD34 (5/6), CD99 (5/5), and WT1 (6/6 cases). In 4 tumors reverse transcriptase-polymerase chain reaction was performed to detect the SYT-SSX fusion transcript produced by the t(x;18), and the ETV6-NTRK3 fusion transcript using RNA extracted from archived paraffin blocks-results were negative in all 4 specimens. Tumor stage was known in 15 patients including 7 stage I, 4 stage II, 3 stage III, and 1 stage IV tumors. They were usually diagnosed as anaplastic Wilms tumors and treated accordingly. Of the 13 patients with a minimum of 2 years follow-up, 4 patients developed distant metastases and 1 had local recurrence including 1 patient with stage IV, 2 with stage III, and 2 with stage I at presentation. Three of them died and 2 were lost to follow-up. One patient with stage I tumor developed widespread metastases and died. Another stage I patient developed local recurrence after 3 months of diagnosis, but was lost to follow-up. Five stage I patients were alive and free of tumor at last follow-up. The most common sites of metastases were lung (3 cases), and liver and bones (2 cases each). These tumors showed pathologic features similar to the pleuropulmonary blastoma of childhood and undifferentiated (embryonal) sarcoma of the liver. In the differential diagnosis, anaplastic Wilms tumor, primary renal synovial sarcoma, malignant mesenchymoma, ectomesenchymoma, and mesenchymal chondrosarcomas have been considered but none of these tumors shared the same features as the 20 cases described here which represent a distinct clinicopathologic entity with morphologic features of a polyphenotypic anaplastic sarcoma of the kidney. Further molecular studies are needed to better understand its nature and more accurate classification. PMID:17895746

Vujani?, Gordan M; Kelsey, Anna; Perlman, Elizabeth J; Sandstedt, Bengt; Beckwith, J Bruce

2007-10-01

233

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with metastasis: clinicopathological study of two cases  

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Uterine tumors with sex cord-like elements are divided in two groups; uterine tumors resembling ovarian sex cord tumors (UTROSCT), and endometrial stromal tumors with sex cord-like elements (ESTSCLE). UTROSCT is currently defined as the neoplasm predominantly or exclusively composed of sex cord-like elements, and generally behaves in a benign fashion. We studied two unusual cases of UTROSCT with metastasis. One case was a 38-year-old multiparous woman presented with hypermenorrhea. The tumor ...

Umeda, Shigeaki; Tateno, Masatoshi; Miyagi, Etsuko; Sakurai, Koji; Tanaka, Reiko; Tateishi, Yoko; Tokinaga, Aya; Ohashi, Kenichi; Furuya, Mitsuko

2014-01-01

234

Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax.  

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We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory. PMID:24766340

Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

2014-04-01

235

Case of a palatal tic resembling palatal tremor in a patient with Tourette syndrome.  

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We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought. PMID:17266076

Schwingenschuh, Petra; Wenzel, Karoline; Katschnig, Petra; Saurugg, Ronald; Ott, Erwin

2007-04-15

236

An insulinoma with clinical and electroencephalographic features resembling complex partial seizures*  

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We described a female patient with insulinoma who experienced recurrent episodes of automatism, confusion and convulsion. Furthermore, her electroencephalography (EEG) findings resembled the pattern in complex partial seizures with secondary generalization. The interictal EEG showed spikes and sharp waves, as well as focal slowing over the left temporal lobe, and the ictal EEG revealed generalized spikes and sharp waves associated with diffused slowing. She was initially misdiagnosed as pharm...

Wang, Shuang; Hu, Hai-tao; Wen, Shu-qun; Wang, Zhong-jin; Zhang, Bao-rong; Ding, Mei-ping

2008-01-01

237

Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus  

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Abstract Staphylococcus pseudintermedius is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if S. pseudintermedius expresses surface proteins resembling those from Staphylococcus aureus and to characterise them. S. pseudintermedius strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the ?-chain of fibrinogen which, along with binding to cytokeratin 10, is the hall...

2009-01-01

238

Transformation of Sézary Syndrome Into CD30+ Anaplastic Large T-Cell Lymphoma After Alemtuzumab Therapy With Evidence of Clonal Unity.  

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: 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. PMID:25548993

Nevet, Mariela Judith; Zuckerman, Tsila; Sahar, Dvora; Bergman, Reuven

2015-01-01

239

Resembling a viper: implications of mimicry for conservation of the endangered smooth snake.  

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The phenomenon of Batesian mimicry, where a palatable animal gains protection against predation by resembling an unpalatable model, has been a core interest of evolutionary biologists for 150 years. An extensive range of studies has focused on revealing mechanistic aspects of mimicry (shared education and generalization of predators) and the evolutionary dynamics of mimicry systems (co-operation vs. conflict) and revealed that protective mimicry is widespread and is important for individual fitness. However, according to our knowledge, there are no case studies where mimicry theories have been applied to conservation of mimetic species. Theoretically, mimicry affects, for example, frequency dependency of predator avoidance learning and human induced mortality. We examined the case of the protected, endangered, nonvenomous smooth snake (Coronella austriaca) that mimics the nonprotected venomous adder (Vipera berus), both of which occur in the Åland archipelago, Finland. To quantify the added predation risk on smooth snakes caused by the rarity of vipers, we calculated risk estimates from experimental data. Resemblance of vipers enhances survival of smooth snakes against bird predation because many predators avoid touching venomous vipers. Mimetic resemblance is however disadvantageous against human predators, who kill venomous vipers and accidentally kill endangered, protected smooth snakes. We found that the effective population size of the adders in Åland is very low relative to its smooth snake mimic (28.93 and 41.35, respectively).Because Batesian mimicry is advantageous for the mimic only if model species exist in sufficiently high numbers, it is likely that the conservation program for smooth snakes will fail if adders continue to be destroyed. Understanding the population consequences of mimetic species may be crucial to the success of endangered species conservation. We suggest that when a Batesian mimic requires protection, conservation planners should not ignore the model species (or co-mimic in Mullerian mimicry rings) even if it is not itself endangered. PMID:25103364

Valkonen, Janne K; Mappes, Johanna

2014-12-01

240

ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice  

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Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer variant, accounting for 1–2% of all cases, but 33% of deaths, and exhibiting an average life expectancy of 5 months. ATC is largely unresponsive to radioactive iodine, chemotherapy, external beam radiation or surgery, underscoring the need for new and effective therapies. We evaluated the therapeutic potential of an oncolytic adenovirus, ONYX-411, that replicates selectively in and kills cells with dysfunction of the r...

Reddi, Hv; Madde, P.; Reichert-eberhardt, Aj; Galanis, Ec; Copland, Ja; Mciver, B.; Grebe, Skg; Eberhardt, Nl

2008-01-01

 
 
 
 
241

Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer  

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Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms in humans and myeloid-derived suppressor cells (MDSCs) contribute to the negative regulation of immune responses in the context of cancer and inflammation. In order to investigate the pathophysiology of thyroid cancer, peripheral blood mononuclear cells (PBMCs) were obtained from 49 patients with thyroid cancer, 18 patients with non-cancerous thyroid diseases and 22 healthy volunteers. The MDSC levels were found to be ...

Suzuki, Shinichi; Shibata, Masahiko; Gonda, Kenji; Kanke, Yasuyuki; Ashizawa, Mai; Ujiie, Daisuke; Suzushino, Seiko; Nakano, Keiichi; Fukushima, Toshihiko; Sakurai, Kenichi; Tomita, Ryouichi; Kumamoto, Kensuke; Takenoshita, Seiichi

2013-01-01

242

Combined BRAFV600E- and SRC-inhibition induces apoptosis, evokes an immune response and reduces tumor growth in an immunocompetent orthotopic mouse model of anaplastic thyroid cancer  

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Anaplastic (ATC) and refractory papillary thyroid cancer (PTC) lack effective treatments. Inhibition of either oncogenic BRAF or SRC has marked anti-tumor effects in mouse models of thyroid cancer, however, neither drug induces notable apoptosis. Here we report that the SRC-inhibitor dasatinib further sensitizes BRAFV600E-positive thyroid cancer cells to the BRAFV600E-inhibitor PLX4720. Combined treatment with PLX4720 and dasatinib synergistically inhibited proliferation and reduced migration...

Borre, Pierre Vanden; Gunda, Viswanath; Mcfadden, David G.; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Parangi, Sareh

2014-01-01

243

Gene expression after x-ray irradiation and/or glycerol in human anaplastic carcinoma cells harboring mutated p53 gene  

International Nuclear Information System (INIS)

Full text: It is well known that most patients with anaplastic thyroid carcinoma die within a year after diagnosis. Thus, it is important to improve the therapeutic effects to restore radio- and chemo-sensitivity to anaplastic thyroid carcinoma. We have reported that wild type p53 cells were radiosensitive and thermo sensitive, because the cells showed a high incidence of apoptosis after radiotherapy and hyperthermia compared with mutant p53 cancer cells. Mutation in p53 is closely related to the poor prognosis of anaplastic thyroid carcinoma in part. We have reported a new strategy using glycerol as a chemical chaperone for cancer therapy against mutant p53 cultured cancer cells. This strategy is based on a conformational change in mutant p53 molecules restoring the normal function of p53. We used the human anaplastic carcinoma strain 8305c. We analyzed the radio-sensitivity by colony formation assay, frequency of apoptosis by Hoechst staining and the expression of apoptosis-related genes by DNA array. The expressions of apoptosis-inductive genes, such as Apaf-1, PTEN were increased by the combined treatment with X-ray and glycerol. In addition, apoptosis-suppressive genes such as Survivin, IAP-1 and IAP-2 were increased with the combined them. These results suggest that X-ray sensitivity and induction of apoptosis might be controlled by the balance of apoptosis inductive and suppressive genes, when 8305c cells were treated with glycerol and then irradiated with X-raith glycerol and then irradiated with X-ray

244

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.  

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We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we deci...

Jerzy Sowinski; Maciej Gembicki; Jan Breborowicz; Marek Ruchala; El Ali Ziad; Marian Grzymislawski

2009-01-01

245

Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation  

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We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues. His parents were found to be carriers of a nonsense mutation of the PMS2 gene.

Gururangan, Sridharan; Frankel, Wendy; Broaddus, Russell; Clendenning, Mark; Senter, Leigha; Mcdonald, Marie; Eastwood, James; Reardon, David; Vredenburgh, James; Quinn, Jennifer; Friedman, Henry S.

2008-01-01

246

A xanthomatous lesion resembling balloon cell melanoma of the iris and ciliary body of a dog.  

Science.gov (United States)

A slow-growing xanthomatous tumour which diffusely infiltrated the iris and ciliary body of a dog was composed of large, pale, vacuolated cells which contained scattered fine pigment granules. Electron microscopy revealed coalescing vacuoles, lamellar membranous structures, and small groups of melanosomes in the cytoplasm, suggesting melanocytic origin. The lesion resembled balloon cell melanoma of the ciliary body of man. The behaviour of the tumour was benign. This is a clinical and pathological entity which has not been reported previously in the dog. PMID:3837792

Mays, M B; Nguyen, H T; Wolf, E D; Samuelson, D A; Bromberg, N M

1985-04-01

247

A Drosophila gene encoding a protein resembling the human ?-amyloid protein precursor  

International Nuclear Information System (INIS)

The authors have isolated genomic and cDNA clones for a Drosophila gene resembling the human ?-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human ?-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development

248

A colonization of basal cell carcinoma by malignant melanoma in situ resembling a malignant basomelanocytic tumor.  

Science.gov (United States)

We report a case of colonization of basal cell carcinoma (BCC) by malignant melanoma in situ (MIS) simulating a malignant basomelanocytic tumor. A biopsy of a pigmented lesion present on an 83-year-old man's scalp displayed intimate admixing of basaloid and melanocytic cells. This seemingly inseparable combination of BCC and neoplastic melanocytes has been referred to as a malignant basomelanocytic tumor. However, our case also displays an adjacent component of MIS, thus favoring colonization of BCC by MIS as the etiology. To our knowledge, this is the third case report of colonization of BCC by MIS resembling a malignant basomelanocytic tumor. PMID:24752214

Goeser, Megan; DiMaio, Dominick J

2014-11-01

249

Charge on luminous bodies resembling natural ball lightning produced via electrical arcs through lump silicon  

Science.gov (United States)

A phenomenon resembling natural ball lightning can be produced via electrical arcing through silicon. We use lump silicon instead of silicon wafers to achieve higher production rates and larger, longer-lived luminous balls than previously reported. The luminous balls consist of a silicon core surrounded by a porous network of loosely bound silicon dioxide nanoparticles. We find that the balls carry a small net charge on the order of 10-12 C and propose that the nanoparticles are electrostatically bound to the core due to this charge.

Porter, Christina L.; Miley, Galen P.; Griffiths, David J.; Sánchez, Erik

2014-12-01

250

HyperPeer : Searching for resemblance in a P2P network  

DEFF Research Database (Denmark)

This paper presents HyperPeer, a framework for developing peer-to-peer based hypermedia. The distribution of hypermedia structures is handled through a peer-to-peer (P2P) network, allowing for highly scalable sharing between users. A central challenge of all decentralized systems is to locate material of interest and this paper presents the HyperPeer Hierarchy of Resemblance (HR) searching algorithm, which provides an efficient search as well as partitioning of the network into groups of common interest.

Larsen, R.D.; Bouvin, N.O.

2004-01-01

251

Pleomorphic xanthoastrocytoma with anaplastic features presenting without GFAP immunoreactivity: implications for differential diagnosis.  

Science.gov (United States)

Pleomorphic xanthoastrocytoma (PXA) is an uncommon, usually low-grade, astrocytic tumor. Characteristic histological features include tumor cell pleomorphism and lipidization of tumor cells. Albeit prognosis in PXA is generally good, cases with histological signs of anaplasia have been observed. In these cases, the differential diagnosis needs to exclude other malignancies, for example, glioblastoma or malignant fibrous histiocytoma. Immunocytochemical detection of GFAP may support exclusion of non-glial neoplasms resembling PXA. However, GFAP expression in PXA may be faint or focal, although complete lack of GFAP has not been described. A 43-year-old woman was operated on for a left occipital parasagital tumor attached to the dura. Histopathology showed a pleomorphic tumor with moderate mitotic activity and necrosis, lack of GFAP immunoreactivity and ultrastructural detection of premelanosome-like structures. These features led to the tentative diagnosis of amelanotic melanoma, and the patient was irradiated. Three years later she had local tumor recurrence and underwent another operation. The recurrent tumor showed similar plain histology as the first specimen. In contrast, anti-GFAP immunoreactivity was now detectable in pleomorphic tumor cells. Anti-GFAP staining of the first biopsy was repeated using monoclonal and polyclonal antibodies in combination with prolonged tissue pretreatment. Focal GFAP staining of tumor cells was now achieved. We conclude that non-standard GFAP staining protocols may enhance sensitivity and thus lead to detection of a low level of GFAP expression in tumor specimens, in which PXA is considered in the differential diagnosis. This may avoid misleading diagnostic considerations that impact on postoperative patient management. PMID:16193842

Gelpi, Ellen; Popovic, Mara; Preusser, Matthias; Budka, Herbert; Hainfellner, Johannes

2005-09-01

252

Keratocytes Derived from Spheroid Culture of Corneal Stromal Cells Resemble Tissue Resident Keratocytes  

Science.gov (United States)

Purpose Corneal stromal cells transform to precursor cells in spheroid culture. We determined whether keratocytes derived from spheroid culture of murine corneal stromal cells resemble tissue resident keratocytes. Methods Spheroid culture was performed by seeding dissociated stromal cells onto ultra-low attachment plates containing serum-free mesenchymal stem cell culture medium. Spheroids were characterized with phenotype specific markers and stemness transcription factor genes. Spheroids and adherent cells in culture were induced to differentiate to keratocytes using keratocyte induction medium (KIM) and compared with tissue resident keratocytes. Results Stromal cells formed spheroids in ultra-low attachment plates, but not in polystyrene tissue culture dishes. Keratocan expression and abundance was significantly higher in spheroids as compared to adherent cells whereas alpha-smooth muscle actin (?-SMA) was significantly lower. As compared to adherent culture-derived cells, the expressions of keratocan, aldehyde dehydrogenase (ALDH3A1) and ?-SMA in spheroid-derived cells approximated much more closely the levels of these genes in tissue resident keratocytes. Of the stemness genes, Nanog and Oct4 were upregulated in the spheroids. Conclusion Stemness transcription factor genes are upregulated in spheroids. Keratocytes derived from spheroids resemble tissue resident keratocytes, thus increasing manifolds the quantity of these cells for in-vitro experiments. PMID:25384043

Byun, Yong-Soo; Tibrewal, Sapna; Kim, Eunjae; Yco, Lisette; Sarkar, Joy; Ivanir, Yair; Liu, Chia-Yang; Sano, Cecile M.; Jain, Sandeep

2014-01-01

253

Aneuploidy and high S-phase as biomarkers of poor clinical outcome in poorly differentiated and anaplastic thyroid carcinoma.  

Science.gov (United States)

This study aimed to investigate the prognostic influence of DNA flow cytometry and RAS gene mutations in patients with poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC). The series consisted of 26 patients with PDTC and ATC, and a median follow-up of 10 months (range 1-138). DNA ploidy and S-phase fraction (SPF) were assessed by flow cytometry on frozen samples. RAS point mutations were detected using PCR techniques. Disease staging and tumour angioinvasion were included as prognostic parameters for survival analysis. Nineteen patients (73.1%) succumbed to the disease (median time 5 months; range 1-45). Eighteen tumours (69.2%) were classified as DNA aneuploid. Median SPF was 5.6% (range 1.9-23.1), which was used as a cut-off value to distinguish between low versus high cell proliferation. Three of 20 (15%) patients presented N-RAS gene mutations in codon 61. DNA aneuploidy was most frequently found in female patients (p=0.034). Kaplan-Meier and Cox regression analyses showed that only DNA aneuploidy (p=0.044 and p=0.055, respectively) and high SPF (p=0.001 and p=0.006, respectively) significantly correlated with worse survival. The results indicate that aneuploidy and high SPF are biomarkers of poor clinical outcome in PDTC and ATC, which may provide useful prognostic information with a potentially therapeutic impact in patient management. PMID:18813835

Pinto, António E; Silva, Giovani; Banito, Ana; Leite, Valeriano; Soares, Jorge

2008-10-01

254

Phase I/II study of oral erlotinib for treatment of relapsed/refractory glioblastoma multiforme and anaplastic astrocytoma.  

Science.gov (United States)

We evaluated the safety and survival benefits of orally administered erlotinib monotherapy for patients with relapsed/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). A dose escalation schedule was administered with a starting dose of 150 mg/day for the first cycle (28 days), followed by 100 mg twice daily for 14 days, and 150 mg twice daily for another 14 days. Assuming no dose limiting toxicities were observed, dosage was maintained at 150 mg BID for 10 more cycles. Disease and tumor responses were assessed after every other cycle; toxicity assessments were conducted for a minimum of 10 weeks. Patients discontinued use of enzyme-inducing anticonvulsants (EIAED) and started non-EIAEDs. Patients with previous erlotinib exposure were ineligible. Eleven patients were enrolled: 8 (73%) GBM; 3 (27%) AA. Adverse events limited study accrual, originally intended to accrue 43 patients. Nine patients (90%) experienced rash within the first 2 cycles: 7 (64%) within cycle 1; 6 (60%) reported diarrhea within the first 2 cycles. Median progress-free survival (PFS) and overall survival (OS) was 1.9 months and 6.9 months. All patients showed disease progression while on the drug. Despite the sample size, the toxicity of erlotinib supersedes any marginal benefit it as a monotherapy for relapsed/refractory GBM/AA. PMID:22946346

Kesavabhotla, Kartik; Schlaff, Cody D; Shin, Benjamin; Mubita, Lynn; Kaplan, Rachel; Tsiouris, Apostolos J; Pannullo, Susan C; Christos, Paul; Lavi, Ehud; Scheff, Ronald; Boockvar, John A

2012-01-01

255

Herbimycin A inhibits cell growth with reversal of epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells.  

Science.gov (United States)

We aimed to elucidate the effect of herbimycin A (HMA), a heat shock protein 90 inhibitor, on cell growth and epithelial-mesenchymal transition (EMT) in anaplastic thyroid carcinoma (ATC) cells. HMA inhibited cell growth and migration concomitantly with increase of E-cadherin as well as decrease of N-cadherin and vimentin. Moreover, HMA upregulated p21 and p27, while it downregulated p53 and Akt. In HMA-treated condition, knockdown of E-cadherin and overexpression of p53 increased N-cadherin and vimentin, and mitigated the inhibitory effects of HMA on cell growth and migration. Furthermore, knockdown of p21 and p27 ameliorated inhibition of cell growth and reversal of EMT. In addition, the activation of Akt attenuated growth inhibition, cell death and EMT reversal. Therefore, we propose that HMA suppresses cell growth, and reverses EMT in conjunction with the activation of E-cadherin, p21 and p27 and the inactivation of p53 and PI3K/Akt signaling in ATC cells. PMID:25446094

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

2014-12-12

256

Immediate disappearance of hemifacial spasm after partial removal of ponto-medullary junction anaplastic astrocytoma: case report.  

Science.gov (United States)

Hemifacial spasm (HFS) is generally caused by a neurovascular conflict (NC) at the root exit zone (REZ) of the facial nerve at the brainstem. Although a direct compression to the seventh cranial nerve (CN) by the anterior inferior cerebellar artery (AICA) is generally the most frequent cause, secondary HFS may be related to other pathological conditions. HFS due to an intracranial mass lesion is exceptionally rare and it has been reported in very few cases. The online database was searched for English-language articles reporting cases of HFS due to brainstem mass lesions and the possible pathophysiological mechanisms involved in its genesis. A 47-year-old man affected by an anaplastic astrocytoma of the brainstem at the level of the ponto-medullary junction developed right HFS. He underwent a subtotal surgical removal of the tumor with complete resolution of the HFS. This is the ninth reported case of HFS caused by an intrinsic brainstem tumor. The exceptional rarity of the relationship between intra-axial tumors and peripheral HFS was analyzed. PMID:25382264

Castiglione, Melina; Broggi, Morgan; Cordella, Roberto; Acerbi, Francesco; Ferroli, Paolo

2014-11-11

257

Development of anaplastic lymphoma kinase (ALK) inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer.  

Science.gov (United States)

The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK) was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%-5% of non-small-cell lung cancer (NSCLC) cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC. PMID:24623980

Iwama, Eiji; Okamoto, Isamu; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

2014-01-01

258

Heterogeneity of epidermal growth factor receptor mutations in lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangements: A case report.  

Science.gov (United States)

Lung cancer is a heterogeneous and complex disease that remains the leading cause of cancer-related mortality worldwide. The identification of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangements has changed the treatment of non-small cell lung cancer, creating a personalized treatment era that is based on the appropriate molecular selection of patients. In spite of the efficacy of tyrosine kinase inhibitors (TKIs), acquired resistance remains inevitable due to various mechanisms. The present study reports the case of a 30-year-old patient with stage IV lung adenocarcinoma initially harboring an EGFR mutation. However, following disease progression and a series of treatments, the wild-type EGFR gene was observed and the ALK rearrangements were revealed. Erlotinib administration resulted in a good response in the patient initially, but crizotinib did not. This indicated an association between the secondary mutations in kinases and the drug resistance to TKIs. This case should also highlight the clinical significance of repeat biopsies for the subsequent therapeutic choices at the onset of clinical progression. PMID:25295096

Sun, Qiong; Wu, Jian-Yu; Jiao, Shun-Chang

2014-11-01

259

Evaluation of immunohistochemistry using two different antibodies and procedures for primary lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangement.  

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Rearrangements of anaplastic lymphoma kinase (ALK) have been recently identified in non-small cell lung carcinomas. Previous studies have revealed characteristic features, including adenocarcinoma histology and mucin production, in ALK-positive lung carcinoma. The present study evaluated immunohistochemistry (IHC) in ALK-positive lung carcinoma using two different antibodies, clone 5A4 and D5F3, and compared the results. On the basis of the aforementioned characteristic features, out of 359 primary lung carcinomas, the ALK status of 14 adenocarcinomas was screened using the intercalated antibody-enhanced polymer (iAEP) method with antibody 5A4, and this was compared with the ALK status obtained using rabbit monoclonal antibody D5F3 and fluorescence in situ hybridization for ALK. Eight cases were demonstrated to be ALK-positive by IHC. Seven cases exhibited ALK rearrangement, which was demonstrated by fluorescence in situ hybridization. The IHC for ALK obtained using D5F3 was comparable with that of the iAEP and exhibited low heterogeneity. This finding suggests that IHC for ALK could be useful in limited tissue samples, such as biopsy specimens or cytology, for the screening of ALK-positive lung carcinoma. In the present study, it was demonstrated that IHC with ALK monoclonal antibody D5F3 was useful for screening lung adenocarcinoma harboring ALK rearrangement. PMID:25295103

Akiba, Jun; Kawahara, Akihiko; Abe, Hideyuki; Azuma, Koichi; Yamaguchi, Tomohiko; Taira, Tomoki; Fukumitsu, Chihiro; Takase, Yorihiko; Yasumoto, Makiko; Umeno, Yumi; Todoroki, Keita; Kurita, Takashi; Yamaguchi, Rin; Kage, Masayoshi; Yano, Hirohisa

2014-11-01

260

Pediatric radical abdominal trachelectomy for anaplastic embryonal rhabdomyosarcoma of the uterine cervix: an alternative to radical hysterectomy.  

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Rhabdomyosarcoma arising in the female genital tract carries 5-year survival in excess of 80%, but lifelong infertility may be a consequence of local control strategies. We present the technique and outcome for a fertility-sparing, radical abdominal trachelectomy in a 12-year-old girl with anaplastic, embryonal rhabdomyosarcoma involving the uterine cervix. The patient had presented to our center after the piecemeal resection of a uterine cervical mass; because of concern about microscopic residual disease, we classified her as group II-A according to the Intergroup Rhabdomyosarcoma Study system. Staging studies excluded the presence of distant disease. The patient received 4 cycles of multiagent chemotherapy and then underwent radical abdominal trachelectomy, with removal of the uterine cervix, parametria, vaginal cuff, and regional lymph nodes. Microscopically, the specimen showed treatment effect and no residual tumor. Regional nodes were negative. Radical abdominal trachelectomy, which has not been previously reported for rhabdomyosarcoma, has appeared to secure local disease control in this case while preserving the patient's future fertility potential. In properly selected cases of rhabdomyosarcoma of the uterine cervix, where involvement of the uterus proper is not present, radical abdominal trachelectomy may be an attractive fertility-sparing alternative to radical hysterectomy. PMID:19361657

Kayton, Mark L; Wexler, Leonard H; Lewin, Sharyn N; Park, Kay J; La Quaglia, Michael P; Abu-Rustum, Nadeem R

2009-04-01

 
 
 
 
261

Potential nosocomial acquisition of epidemic Listeria monocytogenes presenting as multiple brain abscesses resembling nocardiosis.  

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Listerial brain abscesses are rare, and are found mostly in patients with underlying hematological malignancies or solid-organ transplants. A case of a patient with Crohn's disease and multiple brain abscesses involving the left cerebellum and right sylvian fissure is described. The Gram stain and histopathology of the cerebellar abscess revealed Gram-positive, beaded rods suggestive of Nocardia. However, on culture, Listeria monocytogenes was identified. Listeria may appear Gram-variable and has been misidentified as streptococci, enterococci and diphtheroids. The present case is the first reported case of L monocytogenes resembling Nocardia on both microbiological and histopathological assessment. Reported cases of listerial brain abscesses are sporadic, while the current case was part of a nationwide listerial outbreak linked to consumption of contaminated deli meats. Broad antimicrobial therapy (including antilisterial coverage) in immunosuppressed patients presenting with brain abscess is crucial, until cultures confirm the identification of the organism. PMID:21358887

Stefanovic, Aleksandra; Reid, James; Nadon, A Celine; Grant, Jennifer

2010-01-01

262

A universal, easy-to-apply light-quality index based on natural light spectrum resemblance  

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Light-quality is extremely crucial for any light source to be used for illumination. However, a proper light-quality index is still missing although numerous electricity-driven lighting measures have been introduced since past 150 yr. We present in this communication a universal and easy-to-apply index for quantifying the quality of any given lighting source, which is based on direct comparison of its lumen spectrum with the natural light counterpart having the same color temperature. A general principle for creating high quality pseudo-natural light is accordingly derived. By using organic light-emitting diode technology, for example, daylight-style emission with a 96% natural light resemblance is obtained as a high number of organic emitters with diffused colors spanning throughout the entire visible range are employed. The same principle can be extended to other lighting technology such as light-emitting diode to generate natural light-style emission.

Jou, Jwo-Huei; Chou, Kun-Yi; Yang, Fu-Chin; Agrawal, Abhishek; Chen, Sun-Zen; Tseng, Jing-Ru; Lin, Ching-Chiao; Chen, Po-Wei; Wong, Ken-Tsung; Chi, Yun

2014-05-01

263

Focal defect resembling a subchondral bone cyst of the ulnar trochlear notch in a dog.  

Science.gov (United States)

A 13 mo old spayed female golden retriever/standard poodle mixed-breed dog was presented for intermittent right forelimb lameness. Physical examination revealed marked effusion and decreased flexion in the right elbow joint, radiography showed mild osteophytosis of the right elbow joint, and computed tomography showed a focal defect in the subchondral bone in the trochlear notch of the ulna resembling a subchondral bone cyst. Arthroscopy of the affected elbow revealed a focal defect in the articular cartilage on the trochlear notch with vascular ingrowth covering a defect in the subchondral bone plate. The synovium surrounding the defect was inflamed. To the authors' knowledge, this is the first published report of a subchondral bone cyst in the ulna of a dog. PMID:25415218

Makielski, Kelly; Muir, Peter; Bleedorn, Jason

2015-01-01

264

Exophytic Colon Cancer: Resemblance to a Gastrointestinal Stromal Tumor of the Stomach: A Case Report  

International Nuclear Information System (INIS)

An exophytic adenocarcinoma of the colon is very rare with only a few reports to date. To the best of our knowledge, the CT appearance of colon cancer, which simulated the classic appearance of a GIST has only been reported once in the world's literature. We recently evaluated a patient with a large lobulated mass involving the stomach, pancreas and colon. The CT appearance of the case was consistent with the diagnosis of an exophytic gastric GIST. However, at surgery, the patient was found to have a large ulcerated carcinoma of the colon near the splenic flexure that had invaded the stomach and pancreas. We report a case of an exophytic adenocarcinoma of the colon that resembled the classic appearance of a gastrointestinal stromal tumor of the stomach

265

Evidence for a class of supernova remnants resembling the Crab Nebula  

International Nuclear Information System (INIS)

This paper suggests that there is evidence for the existence of another group of supernova remnants which resemble, at least in their radio properties, the Crab Nebula - an object previously considered unique. The general signatures of these objects are of a) being Galactic and radiating non-thermal radio emission but b) having relatively flat radio spectra and c) exhibiting 'filled-centre' rather than 'shell-like' radio structures. In addition, these objects show strong linear polarization and rather uniform magnetic field organization in their central regions. Finally, there is some indication that they may deviate from the well-known Surface Brightness-Linear Diameter (?-D) relation (which describes the evolution of the 'shell-like' remnants) in the sense of being too small or greatly under luminous. (Auth.)

266

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer  

DEFF Research Database (Denmark)

INTRODUCTION:Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population.METHODS:Texture patterns were recorded in digitalized pre-diagnosis (3.7years) film mammograms of a nested case-control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case-control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1+S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormone usage.RESULTS:The mean ages of S1 and S2 were 58.0+/-5.7years and 55.2+/-10.5years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC)=0.63+/-0.02, P

Nielsen, Mads; Vachon, Celine M.

2014-01-01

267

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer  

Science.gov (United States)

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

268

Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis.  

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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. PMID:23923082

George, Eva V; Pharm, John; Houston, Courtney; Al-Quran, Semar; Brian, Grey; Dong, Huijia; Hai, Wang; Reeves, Westley; Yang, Li-Jun

2013-01-01

269

Intragenic anaplastic lymphoma kinase (ALK) rearrangements: Translocations as a novel mechanism of ALK activation in neuroblastoma tumors.  

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Anaplastic lymphoma kinase (ALK) has been demonstrated to be deregulated in sporadic as well as in familiar cases of neuroblastoma (NB). Whereas ALK-fusion proteins are common in lymphoma and lung cancer, there are few reports of ALK rearrangements in NB indicating that ALK mainly exerts its oncogenic capacity via activating mutations and/or overexpression in this tumor type. In this study, 332 NB tumors and 13 cell lines were screened by high resolution single nucleotide polymorphism microarray. Gain of 2p was detected in 23% (60/332) of primary tumors and 46% (6/13) of cell lines, while breakpoints at the ALK locus were detected in four primary tumors and two cell lines. These were further analyzed by next generation sequencing and a targeted enrichment approach. Samples with both ALK and MYCN amplification displayed complex genomic rearrangements with multiple breakpoints within the amplicon. None of the translocations characterized in primary NB tumors are likely to result in a chimeric protein. However, immunohistochemical analysis reveals high levels of phosphorylated ALK in these samples despite lack of initial exons, possibly due to alternative transcription initiation sites. Both ALK proteins predicted to arise from such alterations and from the abnormal ALK exon 4-11 deletion observed in the CLB-BAR cell line show strong activation of downstream targets STAT3 and extracellular signal-regulated kinase (ERK) when expressed in PC12 cells. Taken together, our data indicate a novel, although rare, mechanism of ALK activation with implications for NB tumorigenesis. © 2014 Wiley Periodicals, Inc. PMID:25251827

Fransson, Susanne; Hansson, Magnus; Ruuth, Kristina; Djos, Anna; Berbegall, Ana; Javanmardi, Niloufar; Abrahamsson, Jonas; Palmer, Ruth H; Noguera, Rosa; Hallberg, Bengt; Kogner, Per; Martinsson, Tommy

2015-02-01

270

Lobatin B inhibits NPM/ALK and NF-?B attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation.  

Science.gov (United States)

An apolar extract of the traditional medicinal plant Neurolaena lobata inhibited the expression of the NPM/ALK chimera, which is causal for the majority of anaplastic large cell lymphomas (ALCLs). Therefore, an active principle of the extract, the furanoheliangolide sesquiterpene lactone lobatin B, was isolated and tested regarding the inhibition of ALCL expansion and tumour cell intravasation through the lymphendothelium. ALCL cell lines, HL-60 cells and PBMCs were treated with plant compounds and the ALK inhibitor TAE-684 to measure mitochondrial activity, proliferation and cell cycle progression and to correlate the results with protein- and mRNA-expression of selected gene products. Several endpoints indicative for cell death were analysed after lobatin B treatment. Tumour cell intravasation through lymphendothelial monolayers was measured and potential causal mechanisms were investigated analysing NF-?B- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-R?, and attenuated proliferation of ALCL cells by arresting them in late M phase. Mitochondrial activity remained largely unaffected upon lobatin B treatment. Nevertheless, caspase 3 became activated in ALCL cells. Also HL-60 cell proliferation was attenuated whereas PBMCs of healthy donors were not affected by lobatin B. Additionally, tumour cell intravasation, which partly depends on NF-?B, was significantly suppressed by lobatin B most likely due to its NF-?B-inhibitory property. Lobatin B, which was isolated from a plant used in ethnomedicine, targets malignant cells by at least two properties: I) inhibition of NPM/ALK, thereby providing high specificity in combating this most prevalent fusion protein occurring in ALCL; II) inhibition of NF-?B, thereby not affecting normal cells with low constitutive NF-?B activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this early step of metastatic progression. PMID:25444930

Kiss, Izabella; Unger, Christine; Huu, Chi Nguyen; Atanasov, Atanas Georgiev; Kramer, Nina; Chatruphonprasert, Waranya; Brenner, Stefan; McKinnon, Ruxandra; Peschel, Andrea; Vasas, Andrea; Lajter, Ildiko; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

2015-01-28

271

Extrinsic apoptotic pathways: A new potential "Target" for more sufficient therapy in a case of cutaneous anaplastic large CD30+ ALK-T--cell lymphoma  

Directory of Open Access Journals (Sweden)

Full Text Available 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(lon. 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-?, 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.

Georgi Tchernev

2011-01-01

272

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.  

Directory of Open Access Journals (Sweden)

Full Text Available We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1 and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5% in the comparison with the follicular areas (2 +/- 1%. The evaluation of the thyroid transcription factor 1 (TTF-1 expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.

Jerzy Sowinski

2009-01-01

273

Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis.  

Science.gov (United States)

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures. PMID:11401889

Borzone, G; Moreno, R; Urrea, R; Meneses, M; Oyarzún, M; Lisboa, C

2001-06-01

274

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with metastasis: clinicopathological study of two cases.  

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Uterine tumors with sex cord-like elements are divided in two groups; uterine tumors resembling ovarian sex cord tumors (UTROSCT), and endometrial stromal tumors with sex cord-like elements (ESTSCLE). UTROSCT is currently defined as the neoplasm predominantly or exclusively composed of sex cord-like elements, and generally behaves in a benign fashion. We studied two unusual cases of UTROSCT with metastasis. One case was a 38-year-old multiparous woman presented with hypermenorrhea. The tumor grew as an intramural mass, and metastasized to a pelvic lymph node. Another case was a 57-year-old woman presented with genital bleeding. The tumor grew as a submucosal exophytic mass, and metastasized to the epiploic appendix. Microscopic examination of the 2 cases revealed that they were composed of sex cord-like cells, epithelioid cells and spindle cells. They exhibited solid pattern in predominance. Both solid and sex cord-like elements showed similar immunoreactivities for more than 3 sex cord markers, but simultaneously showed different staining patterns for some other markers. Characteristic features of endometrial stroma such as tongue-like infiltration and spiral arteries-like arterioles were not observed. RT-PCR analysis confirmed the absence of JAZF1-SUZ12 gene fusion, supporting the histopathological diagnosis of UTROSCT rather than ESTSCLE. The current cases warned the potential risk of UTROSCT whose biological behavior is still uncertain. We discuss histopathological, immunohistochemical and molecular findings of UTROSCT with metastasis. PMID:24696722

Umeda, Shigeaki; Tateno, Masatoshi; Miyagi, Etsuko; Sakurai, Koji; Tanaka, Reiko; Tateishi, Yoko; Tokinaga, Aya; Ohashi, Kenichi; Furuya, Mitsuko

2014-01-01

275

Ad-hoc KEEN-type Waves and their Occasional Resemblance to KdV Waveforms  

Science.gov (United States)

Nonlinear kinetic waves of the KEEN type [1] but constructed with two BGK recipes are tested with 1D Vlasov-Poisson simulation (1DVPS). One is that of Allis [2] as modified by Johnston (unpublished), the other is that of Eliasson and Shukla [3]. Strong kinetic waves survive well, but not weaker ones. The potential wave trains resemble those from the Korteweg-deVries equation. This proves to be natural when charge density variation with electrostatic potential is like a quadratic polynomial. For expositions on the physics of ponderomotively driven KEEN waves, consult presentations by Afeyan and Savchenko, this conference. (Part of this work was performed under the auspices of the U.S. Department of Energy under grant number DE-FG03-NA00059.) [1] B. Afeyan et al., ``Kinetic Electrostatic Electron Nonlinear (KEEN) Waves and their interactions driven by the ponderomotive force of crossing laser beams'', Proc. IFSA (Inertial Fusion Sciences and Applications 2003, Monterey, CA), 213, B. Hammel, D. Meyerhofer, J. Meyer-ter-Vehn and H. Azechi, editors, American Nuclear Society, 2004. [2] W.P. Allis, paper 3 (pp.21-42), in ``In Honor of Philip M. Morse'', ed. H. Feshbach and K. Ingard, MIT Press (1969). [3] B. Eliasson and P.K. Shukla, Phys. Rev. E 71, 046402 (2005)

Tyshetskiy, Yuriy; Afeyan, Bedros

2005-10-01

276

Primary uterine cervix melanoma resembling malignant peripheral nerve sheath tumor: a case report.  

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A rare variant of malignant melanoma (MM) of the uterine cervix that mimics a malignant peripheral nerve sheath tumor (MPNST) is described. A 43-year-old white woman was admitted to the hospital complaining of genital discharge and vaginal bleeding. Neoadjuvant chemotherapy and total abdominal hysterectomy and bilateral salpingo-ovariectomy plus pelvic lymphadenectomy were performed, and the diagnosis was MPNST, FIGO IIB. Pathological examination showed a diffuse proliferation of amelanotic spindle cells and large, highly atypical, frequently multinucleated, bizarre, and S100-, HMB-45-, vimentin-positive cells. The patient remained disease-free for 43 months, when an abdominal computed tomographic scan showed local polypoid vaginal lesions, with histological features of typical MM. A pathological review was obtained in our institution by a gynecological pathologist, who defined the primary neoplasm in the cervix as an MM, with a pattern of growth histologically simulating an MPNST, metastatic to the vagina. To our knowledge, this is the first report in literature of MM of the uterine cervix resembling MPNST. Despite its rarity, this variant of MM should be considered when a diagnosis of cervix MPNST is made. The histological and immunohistochemical features of these different entities should be considered in the differential diagnosis. PMID:18753958

Pusceddu, Sara; Bajetta, Emilio; Buzzoni, Roberto; Carcangiu, Maria Luisa; Platania, Marco; Del Vecchio, Michele; Ditto, Antonino

2008-10-01

277

Non-resonant damped transitions resembling continuous resonance scattering in coupled oscillators with essential nonlinearities  

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We study a peculiar damped nonlinear transition of a system of two coupled oscillators into a state of sustained nonlinear resonance scattering. This system consists of a grounded, weakly damped linear oscillator attached to a light, weakly damped oscillator with essential (nonlinearizable) stiffness nonlinearity of the third degree, and linear or nonlinear damping. We find that under specific forcing conditions the damped response of this system locks into a damped, non-resonant transition resembling continuous resonance scattering, whereby the transient damped dynamics closely follows an impulsive orbit manifold of the dynamics in the frequency-energy plane. This manifold is formed by a countable infinity of periodic orbits and an uncountable infinity of quasi-periodic orbits of the underlying Hamiltonian system, with each of these orbits representing the response of the Hamiltonian system being initially at rest and forced by an impulse applied to the linear oscillator. Hence, the damped transitions reported here appear to lock in sustained resonance scattering from a countable infinity of periodic orbits along the impulsive orbit manifold. Such transitions represent an anti-resonance state, where the dynamics is farthest away from resonance. We conjecture that such transitions are only made possible by the essential (nonlinearizable) stiffness nonlinearity of the nonlinear attachment and cannot be realized in linearizable nonlinear dynamics where resonance captures prevent sustained resonance scattering. Our findings are supported by numerical, analytical and experimental results.

Andersen, David; Starosvetsky, Yuli; Mane, Mercedes; Hubbard, Sean; Remick, Kevin; Wang, Xingyuan; Vakakis, Alexander; Bergman, Lawrence

2012-05-01

278

Early venous return in hepatic angiomyolipoma due to an intratumoral structure resembling an arteriovenous fistula.  

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Early venous return (EVR) is an important radiological feature of hepatic angiomyolipoma (HAML) that can aid in differential diagnosis, but the pathogenic mechanisms of EVR have yet to be elucidated. We present the first HAML case for which a probable mechanism for EVR is described. The patient was a 46-year-old woman, who had a growing 6-cm tumor with EVR in segment 3 of the liver as revealed by dynamic contrast-enhanced computed tomography. Left hepatic lobectomy was performed to prevent tumor rupture. Histopathological and immunohistochemical analyses of the excised tumor indicated HAML. Successive microsections of the tumor were stained with hematoxylin-eosin and Victoria blue to visualize the vascular structure within and around the tumor. These analyses led to three major findings. First, many well-defined thick-walled vessels, such as arteries, were found entering the tumor. Second, many thick-walled vessels within the tumor were connected directly to thin-walled vessels, resembling arteriovenous fistulae. Finally, thin-walled intratumoral vessels were connected directly to the hepatic vein. These histological findings suggested that the rich arterial flow into the tumor was being rapidly drained into the hepatic vein through intratumoral arteriovenous connections. We also detected these same anomalous circulatory pathways in tissue sections from three of four additional HAML cases with EVR. Aberrant arteriovenous fistulae within the tumor may account for many cases of EVR in HAML patients. PMID:23679956

Iwao, Yasuhito; Ojima, Hidenori; Onaya, Hiroaki; Sakamoto, Yoshihiro; Kishi, Yoji; Nara, Satoshi; Esaki, Minoru; Mizuguchi, Yasunori; Ushigome, Masahiko; Asahina, Daisuke; Hiraoka, Nobuyoshi; Shimada, Kazuaki; Kosuge, Tomoo; Kanai, Yae

2014-06-01

279

Mutations in human lymphocytes commonly involve gene duplication and resemble those seen in cancer cells  

International Nuclear Information System (INIS)

Mutations in human lymphocytes are commonly due to gene deletion. To investigate the mechanism of deletion for autosomal genes, the authors immunoselected lymphocytes mutated at the HLA-A locus and clones them for molecular analysis. Of 36 mutant clones that showed deletion of the selected HLA-A allele, 8 had resulted from a simple gene deletion, whereas 28 had resulted from a more complex mutational event involving reduplication of the nonselected HLA-A allele as indicated by hybridization intensity on Southern blots. In 3 of the 28 clones, retention of heterozygosity at the HLA-B locus indicated that the reduplication was due to recombination between the two chromosomes 6; but in the remaining 25 clones, distinction could not be made between recombination and chromosome reduplication. The results indicate that mutations in normal somatic cells frequently result in hemizygosity or homozygosity at gene loci and, thereby, resemble the mutations thought to be important in the etiology of various forms of cancer

280

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17  

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Full Text Available OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17. BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD, the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

Nitrini Ricardo

2001-01-01

 
 
 
 
281

Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation  

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Abstract Background Primary non-Hodgkin lymphoma (NHL) of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of...

Sur Monalisa; Ross Cathy; Ry, Bishara Mona

2009-01-01

282

Late Intervention with anti-BRAFV600E Therapy Induces Tumor Regression in an Orthotopic Mouse Model of Human Anaplastic Thyroid Cancer  

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Human anaplastic thyroid cancer (ATC) is a lethal disease with an advanced clinical presentation and median survival of 3 months. The BRAFV600E oncoprotein is a potent transforming factor that causes human thyroid cancer cell progression in vitro and in vivo; therefore, we sought to target this oncoprotein in a late intervention model of ATC in vivo. We used the human ATC cell line 8505c, which harbors the BRAFV600E and TP53R248G mutations. Immunocompromised mice were randomized to receive th...

Nehs, Matthew A.; Nucera, Carmelo; Nagarkatti, Sushruta S.; Sadow, Peter M.; Morales-garcia, Dieter; Hodin, Richard A.; Parangi, Sareh

2011-01-01

283

Alterations of the Tumor Suppressor Genes CDKN2A (p16INK4a), p14ARF, CDKN2B (p15INK4b), and CDKN2C (p18INK4c) in Atypical and Anaplastic Meningiomas  

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We investigated 67 meningothelial tumors (20 benign meningiomas, 34 atypical meningiomas, and 13 anaplastic meningiomas) for losses of genetic information from chromosome arms 1p and 9p, as well as for deletion, mutation, and expression of the tumor suppressor genes CDKN2A (p16INKa/MTS1), p14ARF, CDKN2B (p15INK4b/MTS2) (all located at 9p21) and CDKN2C (1p32). Comparative genomic hybridization and microsatellite analysis showed losses on 1p in 11 anaplastic meningiomas (85%), 23 atypical menin...

Bostro?m, Jan; Meyer-puttlitz, Birgit; Wolter, Marietta; Blaschke, Britta; Weber, Ruthild G.; Lichter, Peter; Ichimura, Koichi; Collins, V. Peter; Reifenberger, Guido

2001-01-01

284

Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy  

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Abstract Background We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas. Methods A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the stud...

Kim Dong; Paek Sun; Kim Dong-Wan; Kim Chae-Yong; Han Jung; Lee Se-Hoon; Park Chul-Kee; Heo Dae; Kim Il; Jung Hee-Won

2009-01-01

285

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

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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

2014-12-08

286

Status dystonicus resembling the intrathecal baclofen withdrawal syndrome: a case report and review of the literature  

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Full Text Available Abstract Introduction Status dystonicus is a rare but life-threatening disorder characterized by increasingly frequent and severe episodes of generalized dystonia that may occur in patients with primary or secondary dystonia. Painful and repetitive spasms interfere with respiration and may cause metabolic disturbances such as hyperpyrexia, dehydration, respiratory insufficiency, and acute renal failure secondary to rhabdomyolysis. Intrathecally administered baclofen, delivered by an implantable pump system, is widely used for the treatment of refractory spasticity. Abrupt cessation of intrathecal baclofen infusion has been associated with a severe withdrawal syndrome comprised of dystonia, autonomic dysfunction, hyperthermia, end-organ failure and sometimes death. The aetiology of this syndrome is not well understood. Status dystonicus describes the episodes of acute and life-threatening generalized dystonia, which occasionally manifest themselves in patients with dystonic syndromes. Case presentation We present the case of a nine-year-old Caucasian boy who experienced a severe episode of status dystonicus with no known cause and clinical features resembling those described in intrathecal baclofen withdrawal. Our patient subsequently underwent the placement of an intrathecal baclofen pump without incident. Conclusion The similarity between the clinical features of the case we present and those reported in connection to abrupt withdrawal of intrathecal baclofen is emphasized. Several drugs, although not intrathecal baclofen withdrawal, have previously been associated with status dystonicus. The similarity between the life-threatening dystonic episode experienced by our patient, and those reported in intrathecal baclofen withdrawal, highlights the possibility that, rather than representing a true physiological withdrawal syndrome, abrupt withdrawal of intrathecal baclofen may simply precipitate an episode of status dystonicus in susceptible individuals. The clinical similarities between the intrathecal baclofen withdrawal syndrome and status dystonicus have not previously been highlighted.

Muirhead William

2010-08-01

287

Metabolism of a lipid nanoemulsion resembling low-density lipoprotein in patients with grade III obesity  

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Full Text Available SciELO Brazil | Language: English Abstract in english INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein meta [...] bolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h-1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

Simone Alves, Dantas; Elisabeth Salvatori, Ficker; Carmen G. C., Vinagre; Barbara Maria, Ianni; Raul Cavalcante, Maranhão; Charles, Mady.

288

Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus.  

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Staphylococcus pseudintermedius is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if S. pseudintermedius expresses surface proteins resembling those from Staphylococcus aureus and to characterise them. S. pseudintermedius strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the alpha-chain of fibrinogen which, along with binding to cytokeratin 10, is the hallmark of clumping factor B of S. aureus, a surface protein that is in part responsible for colonisation of the human nares. Ligand-affinity blotting with cell-wall extracts demonstrated that S. pseudintermedius 326 expressed a cell-wall anchored fibronectin binding protein which recognised the N-terminal 29kDa fragment. The ability to bind fibronectin is an important attribute of pathogenic S. aureus and is associated with the ability of S. aureus to colonise skin of human atopic dermatitis patients. S. pseudintermedius genomic DNA was probed with labelled DNA amplified from the serine-aspartate repeat encoding region of clfA of S. aureus. This probe hybridised to a single SpeI fragment of S. pseudintermedius DNA. In the cell-wall extract of S. pseudintermedius 326, a 180kDa protein was discovered which bound to fibrinogen by ligand-affinity blotting and reacted in a Western blot with antibodies raised against the serine-aspartate repeat region of ClfA and the B-repeats of SdrD of S. aureus. It is proposed that this is an Sdr protein with B-repeats that has an A domain that binds to fibrinogen. Whether it is the same protein that binds cytokeratin 10 is not clear. PMID:19372010

Geoghegan, Joan A; Smith, Emma J; Speziale, Pietro; Foster, Timothy J

2009-09-18

289

Distinctive features and resemblances between VVER and PWR fuels tested in the Halden Reactor  

International Nuclear Information System (INIS)

The PWR types of fuel have been tested in the Halden reactor (HBWR) since 1970’s when the first Instrumented Fuel Assembly (IFA) was loaded. Since that time hundreds of PWR fuel rods have been tested under different conditions towards high fuel burnup. The VVER types of fuel have been tested in HBWR since 1995 when first VVER and PWR fuels have been loaded in IFA-503. Since that time a few fuel assemblies with several VVER fuel rods have been tested. In this paper general characterization of VVER and PWR fuels as well as VVER and PWR fuel and material investigations in the Halden reactor (comparison of in-pile performances - differences and resemblances) are presented. Conclusions: 1) Fuel temperatures of VVER hollow fuel pellets and PWR solid pellets can be compared for different diameter rods (also for the same as VVER design) to analyse effect of hollow. 2) The conductivity degradation (and reference functions used for modeling) are very similar for both fuels up to a burnup of 60 MWd/kg U. 3) Original VVER fuel densification was larger than PWR fuel but modified fuel exhibited improved dimensional behaviour, which is dependent on initial fuel microstructure. Analysis shows similar correlations of in-pile densification against re-sintering test, garin size and fission density at BOL. 4) The higher internal gas pressure at power was in the rods with hollow pellets (with the same outer diameter rods), whereas the temperature FGR threshold is identical to the PWR fuel. 5) The fuel and cladding mechanical behaviour was not enough investigated to make some conclusions (cladding creep test is going on, PCMI was done at different conditions, lift- off test was done at low coolant temperature (VVER-440), fuel creep test was not performed). 6) Corrosion behaviour of modern VVER and PWR claddings is under investigation. 7) The VVER fuel rods behaviour under LOCA conditions vs. PWR fuel is going to be analysed

290

Molecular Pathology: SC18-1 INTERESTING CASE - ACTIONABLE MUTATION IN A CASE WITH A RECURRENT PLEOMORPHIC XANTHOASTROCYTOMA WITH ANAPLASTIC FEATURES.  

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Pleomorphic xanthoastrocytoma (PXA) is an uncommon low grade astrocytic tumor and molecular alterations commonly observed in other WHO grade II gliomas, such as TP53 mutation, EGFR amplification, 1p19q deletion, are rarely seen. A 25-year-old woman experienced generalized seizures; a left temporal lesion in was identified in 2001. Resections were performed in 2004 and 2011 with a diagnosis of PXA, WHO grade II. The patient was treated with radiation and chemotherapy, but recurrence was found in 2013. The pathology of the craniotomy resection showed tumor necrosis and increased proliferation index (25% by Ki-67), and the diagnosis of PXA with anaplastic features exhibiting leptomeningeal infiltration was rendered, which likely represented malignant transformation. Targeted next-generation sequencing analysis was performed at Genomic Pathology Service (Washington University). A potentially actionable BRAF gene mutation (p.V600E) as well as potentially relevant TP53 gene p.R158H mutation was identified. The patient is on Vemurafenib and the lesion is stable on MRI. PXA has been shown to have BRAF mutations in 60-70% of cases. PXA with anaplastic features is a rare entity and has significantly worse prognosis. Vemurafenib is suggested to cross the blood-brain barrier and the patients with BRAF mutated brain tumors would benefit from BRAF targeted therapies. PMID:25188122

Harada, Shuko; Fallon, Kenneth B; Reddy, Alyssa; Nabors, Louis Burt

2014-10-01

291

Anaplastic spindle cell carcinoma, arising in a background of an ovarian mucinous cystic tumor: a case report with clinical follow up, review of the literature.  

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Anaplastic carcinoma (AC) of spindle cell type is an exceedingly rare ovarian malignant neoplasm. The histo-genesis of these tumors is still controversial. Although it was first thought to carry an invariably unfavorable prognosis, recent data indicates that this does not apply to stage Ia tumors. To date, there have been less than ten cases of anaplastic spindle cell carcinoma reported in the medical literature. Furthermore, our case is the first time this tumor has been described in a 40-year-old female with malignant spindle cells merging with conventional high grade adeno-carcinoma. The differential diagnosis of spindle cell proliferation in the ovary will be discussed and their distinction using a panel of immunohistochemical stains. This report demonstrated that the findings of malignant spindle cell proliferation does not imply this entity to be carcinosarcoma. The distinction of AC from true sarcomas is important because of the poorer prognosis of the later compared with the quite favorable behavior of AC. However, such existence necessitates a careful tissue sampling for the logical distinction between AC and carcinosarcoma, which is critical for planning further management and ultimately the predictor of prognosis. PMID:21151395

Hillesheim, Paul B; Farghaly, Hanan

2010-01-01

292

The expression of myeloid antigens CD13 and/or CD33 is a marker of ALK+ anaplastic large cell lymphomas.  

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We retrospectively studied the immunophenotype by flow cytometry of 20 anaplastic large cell lymphomas (ALCLs) (9 anaplastic lymphoma kinase [ALK]+ and 11 ALK-) with a particular emphasis on the aberrant expression of the myeloid associated antigens CD13 and/or CD33. All ALCLs expressed CD45, HLA-DR, and CD30. Most (8/9) ALK+ ALCLs expressed at least 1 surface T-cell antigen (CD4, 6/9 [67%]; CD7, 6/9 [67%]; CD2, 5/9 [56%]; CD5, 2/9 [22%]; CD8, 2/9 [22%]; CD3, 1/9 [11%]). All ALK-ALCLs expressed at least 1 surface T-cell antigen (CD3, 7/11 [64%]; CD4, 6/11 [55%]; CD2, 6/11 [55%]; CD7, 2/11 [18%]; CD5, 1/11 [9%]; CD8, 1/11 [9%]). CD13 and/or CD33 were expressed in all (9/9) ALK+ ALCLs compared with 1 of 11 ALK-ALCLs (9%) (P Surface CD3 was more likely expressed in ALK-ALCLs (7/11) compared with ALK+ ALCLs (1/9) (P .03). The myeloid-associated antigens CD13 and/or CD33 are sensitive but not entirely specific markers of ALK+ ALCLs and should not be misinterpreted as indicating myeloid sarcoma. PMID:18794057

Bovio, Ian M; Allan, Robert W

2008-10-01

293

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility  

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Full Text Available Huan-yong Che, Hang-yuan Guo, Xu-wei Si, Qiao-ying You, Wei-ying Lou Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, People's Republic of China Abstract: The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206 and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296 in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy. Keywords: anaplastic thyroid carcinoma, Akt inhibitor, PDGFR inhibitor, synergy, additive effect, viability, motility

Che HY

2014-03-01

294

PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma.  

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PARP inhibitors are mostly effective as anticancer drugs in association with DNA damaging agents. We have previously shown that the oncolytic adenovirus dl922-947 induces extensive DNA damage, therefore we hypothesized a synergistic antitumoral effect of the PARP inhibitor olaparib in association with dl922-947. Anaplastic thyroid carcinoma was chosen as model since it is a particularly aggressive tumor and, because of its localized growth, it is suitable for intratumoral treatment with oncolytic viruses. Here, we show that dl922-947 infection induces PARP activation, and we confirm in vitro and in vivo that PARP inhibition increases dl922-947 replication and oncolytic activity. In vitro, the combination with olaparib exacerbates the appearance of cell death markers, such as Annexin V positivity, caspase 3 cleavage, cytochrome C release and propidium iodide permeability. In vivo, we also observed a better viral distribution upon PARP inhibition. Changes in CD31 levels suggest a direct effect of olaparib on tumor vascularization and on the viral distribution within the tumor mass. The observation that PARP inhibition enhances the effects of dl922-947 is highly promising not only for the treatment of anaplastic thyroid carcinoma but, in general, for the treatment of other tumors that could benefit from the use of oncolytic viruses. PMID:25139258

Passaro, Carmela; Volpe, Massimiliano; Botta, Ginevra; Scamardella, Eloise; Perruolo, Giuseppe; Gillespie, David; Libertini, Silvana; Portella, Giuseppe

2015-01-01

295

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.  

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Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs. PMID:21841159

Kempf, Werner; Pfaltz, Katrin; Vermeer, Maarten H; Cozzio, Antonio; Ortiz-Romero, Pablo L; Bagot, Martine; Olsen, Elise; Kim, Youn H; Dummer, Reinhard; Pimpinelli, Nicola; Whittaker, Sean; Hodak, Emmilia; Cerroni, Lorenzo; Berti, Emilio; Horwitz, Steve; Prince, H Miles; Guitart, Joan; Estrach, Teresa; Sanches, José A; Duvic, Madeleine; Ranki, Annamari; Dreno, Brigitte; Ostheeren-Michaelis, Sonja; Knobler, Robert; Wood, Gary; Willemze, Rein

2011-10-13

296

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*  

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Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs. PMID:21841159

Pfaltz, Katrin; Vermeer, Maarten H.; Cozzio, Antonio; Ortiz-Romero, Pablo L.; Bagot, Martine; Olsen, Elise; Kim, Youn H.; Dummer, Reinhard; Pimpinelli, Nicola; Whittaker, Sean; Hodak, Emmilia; Cerroni, Lorenzo; Berti, Emilio; Horwitz, Steve; Prince, H. Miles; Guitart, Joan; Estrach, Teresa; Sanches, José A.; Duvic, Madeleine; Ranki, Annamari; Dreno, Brigitte; Ostheeren-Michaelis, Sonja; Knobler, Robert; Wood, Gary; Willemze, Rein

2011-01-01

297

Immunocytochemical analysis of glucose transporter protein-1 (GLUT-1) in typical, brain invasive, atypical and anaplastic meningioma.  

Science.gov (United States)

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 network embedded within the pattern of GLUT-1 staining. Taken together, GLUT-1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with "spontaneous" necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma. PMID:25168354

van de Nes, Johannes A P; Griewank, Klaus G; Schmid, Kurt-Werner; Grabellus, Florian

2015-02-01

298

Intraoperative cytology of central neurocytoma mimicking oligodendroglioma  

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Central neurocytomas (CNs) are uncommon tumors of the central nervous system. These tumors have a predilection for the lateral ventricles of young adults and are known to display characteristic neuroimaging and histomorphologic features. Typically, CNs are associated with a favorable outcome, although cases with more aggressive clinical course with recurrences are not unknown. Most descriptions of this tumor are available in the form of isolated histopathology-based case reports and small ser...

Deb, Prabal; Kinra, Prateek; Bhatoe, Harjinder Singh

2011-01-01

299

NALCN Ion Channels Have Alternative Selectivity Filters Resembling Calcium Channels or Sodium Channels  

Science.gov (United States)

NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE) or sodium channels (EKEE or EEKE). NALCN channels with alternative calcium, (EEEE) and sodium, (EKEE or EEKE) -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K)-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG+ impermeant and blockable with 10 µM Gd3+ ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2):371-83. PMID:23383067

Senatore, Adriano; Monteil, Arnaud; van Minnen, Jan; Smit, August B.; Spafford, J. David

2013-01-01

300

NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels.  

Science.gov (United States)

NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE) or sodium channels (EKEE or EEKE). NALCN channels with alternative calcium, (EEEE) and sodium, (EKEE or EEKE) -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K)-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG(+) impermeant and blockable with 10 µM Gd(3+) ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2):371-83. PMID:23383067

Senatore, Adriano; Monteil, Arnaud; van Minnen, Jan; Smit, August B; Spafford, J David

2013-01-01

 
 
 
 
301

Combining Different Views of Mammographic Texture Resemblance (MTR) Marker of Breast Cancer Risk  

DEFF Research Database (Denmark)

PURPOSE Mammographic density is a well established breast cancer risk factor. Texture analysis in terms of the Mammographoc Texture Resemblance (MTR) marker has recently shown to add to risk segregation. Hitherto only single view MTR analysis has been performed. Standard mammography examinations include RMLO, RCC, LMLO, LCC views. Thus here we investigated the interrelation and combination of MTR scoring from several views. METHOD AND MATERIALS The study included mammograms of 495 women (aged 58.0±5.7 years) from the Dutch screening program of which 250 controls were without diagnosis the subsequent 4 years whereas 245 cases had a diagnosis 2-4 years post mammography. We employed the MTR supervised texture learning framework to perform risk evaluation from a single mammography view. In the framework 20,000 pixels were sampled and classified by a kNN pixel classifier. A feature selection step is included to reduce input space dimensionality. Weak local decision scores for pixels were fused into an overall risk score. The dataset was randomly separated into a training data set (60%) and a test data set (40%). Risk scores for combinations of views were obtained by linear and quadratic discriminant analysis (LDA, QDA) where respectively Fisher criterion and Likelihood ratio were used as combination scores. LDA and QDA parameters were obtained from the training set. Performance was evaluated by AUC statistics. Correlations were analyses as Pearson’s linear correlation coefficient. RESULTS No significant difference in age was found between cases and controls. The AUC values for RMLO, LMLO, RCC and LCC views are respectively 0.604, 0.579, 0.602 and 0.605. Combination of views yielded RMLO & LMLO: 0.600; RCC & LCC: 0.612; RMLO & RCC: 0.632; LMLO & LCC: 0.623. The correlation of scores from contralateral views was 0.72-0.75. Scatter plots are shown below. CONCLUSION The MTR AUCs are a little lower than earlier reported probably due to the smaller training set. MTR scores obtained from two contralateral views correlated well, but not as highly as previously reported on density (>0.85). We conclude that view combination may reduce some of the risk

Sun, S; Karemore, Gopal Raghunath

302

A Taxonomic Study on the Burrowing Cricket Genus Velarifictorus with Morphologically Resembled Genus Lepidogryllus (Orthoptera: Gryllidae: Gryllinae in Korea  

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Full Text Available The burrowing-cricket genus Velarifictorus Randell, 1964 is reviewed in Korea, comparing with morphologically resembled genus Lepidogryllus Otte and Alexander, 1983 for the first time. First, Velarifictorus aspersus borealis Gorochov, 1985 is confirmed from only restricted area of southern regions in Gyeongsangnam- do and Jeollanam-do. Second, Velarifictorus micado (Saussure, 1877 is confirmed from nearly all around the Korean peninsula including North Korea. Third, the previously not recorded Velarifictorus ornatus (Shiraki, 1911 is newly recognized from South Korea. Relating to the genus Velarifictorus, the resembled genus Lepidogryllus Otte and Alexander, 1983 and its species Lepidogryllus siamensis (Chopard, 1961 com. & stat. nov. is studied and compared with Velarifictorus members. A key, descriptions, tables, photographs, figures, oscillograms and spectrograms of calling sounds are provided to aid identification between the four similar species.

Tae-Woo Kim

2013-10-01

303

Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response  

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Abstract Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of t...

Muñoz-de-Toro Mónica; Ramos Jorge G; Ortega Hugo H; Rodríguez Horacio A; Luque Enrique H

2003-01-01

304

A Taxonomic Study on the Burrowing Cricket Genus Velarifictorus with Morphologically Resembled Genus Lepidogryllus (Orthoptera: Gryllidae: Gryllinae) in Korea  

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The burrowing-cricket genus Velarifictorus Randell, 1964 is reviewed in Korea, comparing with morphologically resembled genus Lepidogryllus Otte and Alexander, 1983 for the first time. First, Velarifictorus aspersus borealis Gorochov, 1985 is confirmed from only restricted area of southern regions in Gyeongsangnam- do and Jeollanam-do. Second, Velarifictorus micado (Saussure, 1877) is confirmed from nearly all around the Korean peninsula including North Korea. Third, the previously not record...

Tae-Woo Kim

2013-01-01

305

Martian alkaline basites chemically resemble basic rocks of the Lovozero alkaline massif, Kola peninsula  

Science.gov (United States)

The comparative wave planetology [1, 5] successfully overcomes the most principal martian test having now analyses of alkaline rocks from Columbia Hills [2, 3, 4]. This kind of rocks was predicted earlier on basis of the wave paradigm having stated that "the higher planetary relief range - the higher density difference between lithologies composing hypsometrically (tectonically) contrasting blocks [5]. This paradigm declares that "celestial bodies are dichotomic"(Theorem 1), "celestial bodies are sectoral" (Theorem 2), "celestial bodies are granular"(Theorem 3), "angular momenta of different level blocks tend to be equal" (Theorem 4)[1, 5]. Mars is a typical terrestrial planet but the farthest from Sun and thus with the smallest tide effects. Nevertheless it has the highest relief range and seems to be most distorted (ellipsoid in shape) and broken by deep fissures. The wave approach explains this by a warping action of standing waves of 4 ortho- and diagonal directions - they are the longest and highest in the martian case. These interfering warping waves caused by the elliptic keplerian orbits implying periodically changing accelerations and inertia-gravity forces produce inevitable tectonic dichotomy (the fundamental wave 1 long 2?R), sectoring (wave 2, ?R, and other overtones), granulation. A granule size depends on an orbital frequency: the higher frequency the smaller granule. The Earth's granule, as a scale, is ?R/4 (see it in NASA's PIA04159), Venus ` ?R/6, Mercury's ?R/16, Mars' ?R/2 (the sizes are strictly tied to orb. fr.). Along with the granule sizes increase relief ranges ( Mercury ˜5 km, Venus 14, Earth 20, Mars ˜30) and compositional (density) difference between lowland and highland lithologies [5]. The lowland compositions become Fericher and denser: enstatite (Mercury), Mg-basalt (Venus), tholeiite (Earth), Fe-basalt (Mars). The highland compositions get less dense, lighter: anorthosite, alkaline basalt, andesite and conditional "albitite" (syenite, granite) for Mars [5]. Actually the martian missions successively discovered andesite, dacite, low-Fe highlands. Now "Spirit" has found on a small outlier of highlands -Columbia Hills -a batch of thinly layered gently dipping light rocks that surely are not impact melts as at very short distance there is a sharp transition from light Fe-poor to ultrabasic rocks (on opposite slopes of this small hill) [6]. This layered sequence of more or less altered and weathered rocks resembles differentiated sequences of Lovozero and other alkaline and UB-alkaline massifs of Kola Peninsula (though fresh and much richer in alkalis). Here we compare compositions of alkaline basic rocks of Columbia Hills (dyke or sill [4]) with that of basic volcanics and a later dyke at Lovozero. 5 analyses in wt.%: 1-Backstay (tra1 chybasalt) & 2-Irvine (basalt) of CH, 3-augiteporphyrite, 4-essexite-porphyrite, 5- alkali- lamprophyre dyke of Lovozero. SiO2 -49.9, 47.7, 45.78, 48.09, 41.57; TiO2 - 0.93, 1.07, 7.80, 2.35, 2.92; Al2 O3 -13.2; 10.8, 8.08; 13.74; 11.77; Fe2 O3 -3.40, 7.79 (4.99), 5.90, 6.00, 4.53; FeO -10.6, 12.5 (15.0), 8.65, 7.60, 8.28; MnO -0.25, 0.37, 0.12, 0.17, 0.28; MgO -8.36, 10.8, 7.61, 7.19, 10.59; CaO -6.09, 6.12, 10.73, 8.77, 11.24; Na2 O -4.02, 2.72, 2.80, 2.84, 3.63; K2 O -1.02, 0.69, 1.97, 2.09, 1.38. Compositional similarities between basites occurring in alkaline conditions on both planets can be found. References: [1] Kochemasov G.G. (1999) Theorems of wave planetary tectonics // Geophys. Res. Abstr., v. 1, # 3, 700; [2] Gellert R. et al. (2006) JGR Planets, v. 111, #E2, EO2505; [3] Squyres S.W. et al. (2006) JGR Planets, v.111, #E2, EO2511; [4] McSween H.Y. et al. (2006) JGR Planets, submitted ; [5] Kochemasov G. G. (1995) Golombek M.P., Edgett K.S., Rice J.W. Jr. (Eds). Mars Pathfinder Landing Site Workshop II: Characteristics of the Ares Vallis Region and Field trips to the Channeled Scabland, Washington. LPI Tech. Rpt. 95-01. Pt.1.LPI, Houston, 1995, 63 pp.; [6] Mittlefehldt D.W.

Kochemasov, G.

306

Long-Term Remission in a Case of Anaplastic Thyroid Carcinoma Following Local Irradiation and High-Dose Chemotherapy With Autologous Peripheral Blood Stem Cell Transplantation  

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Full Text Available Anaplastic thyroid carcinoma (ATC is a tumor with bad prognosis and long-term survival is very low. However, appropriate combinations of chemotherapy, surgery, and radition have been reported to potentially improve the treatment results for ATC. We describe a case of refractory ATC successfully treated with high-dose chemotherapy (HDC followed by autologous peripheral blood stem cell transplantation (auto-PBSCT. There has not been any evidence of recurrence for 10 years after auto-PBSCT. To the best of our knowledge, this is the first case of ATC that has been followed up for a longterm period after HDC with auto-PBSCT. This case suggests that intensive therapeutic approach such as HDC with auto- PBSCT may be useful.

Koji Kato

307

The effect of multifraction X-irradiation on a fast growing anaplastic murine tumour and their modification by hypoxic cell radiosensitisers  

International Nuclear Information System (INIS)

The anaplastic MT tumour is very radio-resistant and the optimum X-ray regime for treating this tumour with respect to the corresponding normal tissue damage was found to be many fractions in a short overall time, i.e. 20F/4 + 3/4D. All x-ray regimes, whether therapeutically poor or good, were improved by the hypoxic cell radiosensitiser and cytotoxin, misonidazole. Although the fewer the fractions the greater the sensitiser enhancement ratio, the therapeutic gain with misonidazole was greatest after many fractions. Furthermore, misonidazole rendered multiple fractionated regimes therapeutically superior to the best X-ray only regime. This, and the fact that significant sensitisation was observed at tumour levels of only 4 ?g/g with single doses of x-rays and 35 ?g/g with 20 fractions, augurs well for the clinical trials now in progress with this drug. (author)

308

Papillary and mucoepidermoid carcinoma of the thyroid with anaplastic transformation: a case report with histologic and immunohistochemical findings that support a provocative histogenetic hypothesis.  

Science.gov (United States)

A unique thyroid tumor in a 62-year-old woman is reported. Foci of papillary carcinoma (PC), mucoepidermoid carcinoma (MEC) and undifferentiated carcinoma (UC) were found in the surgical specimen. Acid mucosubstances were observed in the two histologically differentiated areas of the neoplasia. The PC showed immunoreactivity for thyroglobulin, and both PC and MEC foci were positive for high-molecular-weight keratins. Papillary carcinoma, MEC and UC were stained with antibodies against keratin CAM 5.2, vimentin, S-100 protein and neuron-specific enolase. No immunoreactivity was found for calcitonin, calcitonin-gene-related peptide, chromogranin, keratin 1, carcinoembryonic antigen and p53 suppressor gene. The diagnosis of this peculiar carcinoma of the thyroid exhibiting papillary and mucoepidermoid features together with undifferentiated (anaplastic) areas, reinforces the existence of a close relationship between papillary carcinoma and mucoepidermoid carcinoma, and supports the importance that ultimobranchial multipotential stem cells may have in the histogenesis of thyroid carcinomas. PMID:8927569

Cameselle-Teijeiro, J; Febles-Pérez, C; Sobrinho-Simões, M

1995-12-01

309

Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung  

International Nuclear Information System (INIS)

The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p>0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight).There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment. (orig.)

310

Resveratrol enhances the expression of death receptor Fas/CD95 and induces differentiation and apoptosis in anaplastic large-cell lymphoma cells.  

Science.gov (United States)

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin found in grapes and other plants, plays a protective role in human atherosclerosis and carcinogenesis. We examined the effects of resveratrol on the anaplastic large-cell lymphoma (ALCL) cell line SR-786. Resveratrol inhibited growth and induced cellular differentiation, as demonstrated by morphological changes and elevated expression of T cell differentiation markers CD2, CD3, and CD8. Resveratrol also triggered cellular apoptosis, as demonstrated by morphological observations, DNA fragmentation, and cell cycle analyses. Further, the surface expression of the death receptor Fas/CD95 was increased by resveratrol treatment. Our data suggest that resveratrol may have potential therapeutic value for ALCL. PMID:21683516

Ko, Ya-Chen; Chang, Chia-Ling; Chien, Hsiung-Fei; Wu, Ching-Hsiang; Lin, Liang-In

2011-10-01

311

Opposite-sex siblings decrease attraction, but not prosocial attributions, to self-resembling opposite-sex faces  

Science.gov (United States)

Contextual cues of genetic relatedness to familiar individuals, such as cosocialization and maternal–perinatal association, modulate prosocial and inbreeding-avoidance behaviors toward specific potential siblings. These findings have been interpreted as evidence that contextual cues of kinship indirectly influence social behavior by affecting the perceived probability of genetic relatedness to familiar individuals. Here, we test a more general alternative model in which contextual cues of kinship can influence the kin-recognition system more directly, changing how the mechanisms that regulate social behavior respond to cues of kinship, even in unfamiliar individuals for whom contextual cues of kinship are absent. We show that having opposite-sex siblings influences inbreeding-relevant perceptions of facial resemblance but not prosocial perceptions. Women with brothers were less attracted to self-resembling, unfamiliar male faces than were women without brothers, and both groups found self-resemblance to be equally trustworthy for the same faces. Further analyses suggest that this effect is driven by younger, rather than older, brothers, consistent with the proposal that only younger siblings exhibit the strong kinship cue of maternal–perinatal association. Our findings provide evidence that experience with opposite-sex siblings can directly influence inbreeding-avoidance mechanisms and demonstrate a striking functional dissociation between the mechanisms that regulate inbreeding and the mechanisms that regulate prosocial behavior toward kin. PMID:21709272

DeBruine, Lisa M.; Jones, Benedict C.; Watkins, Christopher D.; Roberts, S. Craig; Little, Anthony C.; Smith, Finlay G.; Quist, Michelle C.

2011-01-01

312

TREATMENT EFFICACY AND RESISTANCE MECHANISMS USING THE SECOND-GENERATION ALK INHIBITOR AP26113 IN HUMAN NPM-ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA.  

Science.gov (United States)

ALK is a tyrosine kinase receptor involved in a broad range of solid and hematological tumors. Among 70-80% of ALK+ Anaplastic Large Cell Lymphoma (ALCL) are caused by the aberrant oncogenic fusion protein NPM-ALK. Crizotinib was the first clinically relevant ALK inhibitor, now approved for the treatment of late stage and metastatic cases of lung cancer. However, patients frequently develop drug resistance to Crizotinib, mainly due to the appearance of point mutations located in the ALK kinase domain. Fortunately, other inhibitors are available and in clinical trial, suggesting the potential for second line therapies to overcome Crizotinib resistance. This study focuses on the ongoing Phase I/II trial small-molecule tyrosine kinase inhibitor (TKI) AP26113, by Ariad Pharmaceuticals, which targets both ALK and EGFR. Two NPM-ALK+ human cell lines, KARPAS-299 and SUP-M2, were grown in the presence of increasing concentrations of AP26113 and eight lines were selected that demonstrated resistance. All lines show inhibitory concentration (IC50) values higher (130 to 1000-fold) than the parental line. Mechanistically, KARPAS-299 populations resistant to AP26113 show NPM-ALK overexpression, while SUP-M2 resistant cells harbor several point mutations spanning the entire ALK kinase domain. In particular, amino acid substitutions: L1196M, S1206C, the double F1174V+L1198F and L1122V+L1196M mutations were identified. The knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI resistant cases. Implications: This work defines reliable anaplastic large cell lymphoma model systems of AP26113 resistance and provides a valuable tool in the management of all cases of relapse upon NPM-ALK targeted therapy. PMID:25421750

Ceccon, M; Mologni, L; Giudici, G; Piazza, R; Pirola, A; Fontana, D; Gambacorti-Passerini, C

2014-11-24

313

Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged nonsmall cell lung cancer and beyond  

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Full Text Available Sai-Hong Ignatius OuChao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CAAbstract: Epidermal growth factor receptor (EGFR tyrosine inhibitors were first approved for the treatment of non-small cell lung cancer (NSCLC in 2003 in the US. Activating EGFR mutations were subsequently discovered in 2004, and heralded the era of molecular targeted therapy in NSCLC. The discovery of anaplastic lymphoma kinase (ALK rearrangement in NSCLC in 2007 by two independent groups not only represents the first time ALK rearrangement has been discovered in common solid tumors but also represents another important milestone in the era of molecular targeted therapy in NSCLC. Crizotinib, a mesenchymal-epithelial transition (MET/ALK multi-targeted receptor tyrosine kinase inhibitor went into early Phase I clinical development in 2007. Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites. It cumulated in the conditional approval of crizotinib by the US Food and Drug Administration on August 26, 2011 for the treatment of ALK-rearranged NSCLC. The conditional approval was based on response rates of 50% and 61% from 255 ALK-rearranged NSCLC patients enrolled in two single-arm trials. Common adverse events of crizotinib include mild transient visual disorders, mild gastrointestinal toxicities, fatigue, rare alanine transaminase elevations, and even rarer pneumonitis (1.6%. Confirmatory trials comparing crizotinib with standard chemotherapy are ongoing. It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALK-rearranged NSCLC.Keywords: crizotinib, PF-02341066, anaplastic lymphoma kinase (ALK, rearrangement, non-small cell lung cancer

Ou SH

2011-11-01

314

Pseudo-Kaposi's sarcoma: The association of arterio-venous malformations with skin lesions resembling Kaposi's sarcoma  

International Nuclear Information System (INIS)

A patient is described with skin lesions resembling Kaposi's sarcoma (KS). Arteriography revealed multiple arteriovenous malformations in the affected limb. This condition has been termed pseudo-Kaposi's sarcoma. Although reports of this condition have appeared in dermatological journals, as yet we are unaware of any account in the radiological literature. This paper presents a case and reviews the literature. In suspected cases of KS in which the history or clinical features are atypical, this unusual condition should be considered and a search made for the diagnostic vascular lesions. Copyright (2001) Blackwell Science Pty Ltd

315

Feasibility and limitations of radioiodine therapy in oncocytic (oxyphilic), medullary (C-cell) and anaplastic (undifferentiated) thyroid carcinoma. Moeglichkeiten und Grenzen der Radiojodtherapie beim onkozytaeren, medullaeren und anaplastischen Schilddruesenkarzinom  

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Oncocytic, medullary and anaplastic thyroid cancers are not supposed to take up radioiodine because of their cellular differentiation. Therefore, I-131 therapy should not be feasible in these special types of thyroid carcinoma. Literature reports concerning successful I-131 treatment in patients with those cancers may be explained by the occurrence of rare 'mixed tumor types' or 'collision tumors', which consist of oncocytic, medullary or anaplastic parts as well as of sections with follicular or papillary differentiation which may take up I-131. Moreover, in the region of the thyroid gland, tumor tissue which is not able to take up radioiodine may be surrounded by normal thyrocytes taking up I-131. Radioiodine treatment therefore may be indicated in proven mixed tumor types and in collision tumors as well as in cases of residual tumor tissue in the neighbourhood of normal thyrocytes. (orig.).

Reiners, C.; Schaeffer, R. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Klinik und Poliklinik fuer Nuklearmedizin Giessen Univ. (Germany, F.R.). Medizinisches Zentrum fuer Pathologie)

1991-02-01

316

Anaplastic Myoepithelial Carcinoma of the Sinonasal Tract: an Underrecognized Salivary-Type Tumor Among the Sinonasal Small Round Blue Cell Malignancies? Report of One Case and a Review of the Literature  

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We present a 45 year old female patient with a nasal carcinoma showing high-grade/anaplastic histomorphological features and with a distinct myoepithelial immunohistochemical phenotype including positivity for smooth muscle actin, p63, S100 protein with no sustentacular pattern, calponin, cytokeratin 14, vimentin and cytokeratins (AE1-3 and CK5/6). A minority (<5%) of the cells showed focal and variable immunoreactivity for EMA with no cuticular/canalicular pattern. Bcl-2, CD99, CD117 and CD...

Petersson, Fredrik; Chao, Siew Shuen; Ng, Siok Bian

2011-01-01

317

Phase III randomized study of radiotherapy plus PCV with or without BUdR for the treatment of anaplastic astrocytoma: RTOG 9404 interim report  

International Nuclear Information System (INIS)

Purpose/Objective: This study was an open label, randomized, phase III trial in newly diagnosed patients with anaplastic astrocytoma comparing radiotherapy plus adjuvant Procarbazine, CCNU, and Vincristine (PCV) with or without bromodeoxyuridine (BUdR) given as a 96 hour infusion each week of radiotherapy. Material/Methods: Only patients 18 years or older with newly diagnosed anaplastic astrocytoma were eligible; central pathology review was not mandated prior to registration. The study had initially opened as an Northern California Oncology Group (NCOG) trial in 1991, becoming an intergroup RTOG, SWOG and NCCTG study in July, 1994. Total accrual of 293 patients was initially planned as the sample size, using time to tumor progression and survival as the primary endpoints. The experimental arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3 year follow-up after completion of enrollment. Results: As of Feb. 1997, 268 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review and 13 were canceled. In total, 30% of patients were excluded from analysis, with additional pathology review still pending for some patients. The treatment arms remained well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July, 199nded suspension of enrollment in July, 1996 based upon a stochastic curtailment analysis which strongly suggested that the study endpoint would not be achieved in the RT/BUdR plus PCV arm. In Feb., 1997, the study was closed prior to full enrollment. At that time, the one-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one sided p=0.96). The conditional power analysis indicated that even with an additional 12 months of accrual and follow-up the probability of detecting the pre specified difference was less than 0.01%. The differences seen in the two arms seems to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. Conclusions: Despite encouraging phase II results with BUdR, it is unlikely a survival benefit will be seen. A final study analysis will be not be done until all patients have been followed for at least 3 years

318

Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: regulatory roles of cell surface glycans.  

Science.gov (United States)

Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic acid enhanced Arachis hypogaea (PNA), Helix pomatia (HPA) and Phaseolus vulgaris-L (L-PHA) lectin binding reactivity to cell surface of lymphoma cells suggesting that neuraminidase removes cell surface sialic acid. In cell adhesion and invasion assays treatment with neuraminidase markedly enhanced cell adhesion to galectin-1 and decreased cell invasive capacity through galectin-1. ?2,6-linked sialic acid may be involved in masking the effect of the interaction between galectin-1 and cell surface glycans. H-ALCL cells expressed the ?-galactoside-?2,6-sialyltransferase ST6Gal1. On resialylation assay by recombinant ST6Gal1 with CMP-Neu5Ac, ?2,6-resialylation of L-PHA reactive oligosaccharide by ST6Gal1 resulted in inhibition of H-ALCL cell adhesion to galectin-1 compared to the desialylated H-ALCL cells. On knockdown experiments, knockdown of ST6Gal1 dramatically enhanced cell adhesion to galectin-1. N-glycosylation inhibitor swainsonine treatment resulted in enhancement of cell adhesion to galectin-1. In glycomic analysis using the lectin blocking assay treatment with PNA, Artocarpus integrifolia (Jacalin), Glycine max (SBA), Helix pomatia (HPA), Vicia villosa (VVA), Ulex europaeus (UEA-1), Triticum vulgaris (WGA), Canavalia ensiformis (ConA), Phaseolus vulgaris-L (L-PHA), Phaseolus vulgaris-E4 (E-PHA), Datura stramonium (DSA) lectins resulted in modulation of lymphoma cell to galectin-1 suggesting that several types of glycans may regulate cell adhesion to galectin-1 by steric hindrance. The adhesive capacity of H-ALCL cells is regulated by phosphatidylinositol 3 phosphate kinase (PI3K) and actin cytoskeleton, and the invasive capacity of H-ALCL cells is regulated by PI3K, mitogen-activated protein kinase (MAPK), Rho and actin cytoskeleton. Furthermore, galectin-1-induced cell death in H-ALCL cells was accompanied by inhibition of CD45 protein tyrosine phosphatase (PTP) activity. In conclusion, cell adhesion and invasion to galectin-1 appeared to be regulated by cell surface sialylation and N-glycosylation, and galectin-1 regulates cell death through inhibition of CD45 PTP activity of H-ALCL. PMID:24589677

Suzuki, Osamu; Abe, Masafumi

2014-05-01

319

Wild-type p53 enhances the cytotoxic effect of radionuclide gene therapy using sodium iodide symporter in a murine anaplastic thyroid cancer model  

International Nuclear Information System (INIS)

To evaluate the role of p53 in radionuclide gene therapy, we investigated the cytotoxic effect of 131I and 188Re following cotransfection of the sodium iodide symporter (NIS) and wild-type p53 (wt-p53) genes into cancer cells. The NIS gene was transfected to human anaplastic thyroid carcinoma cells (ARO) expressing mutant p53 (mt-p53) using liposomes. The uptakes of 125I and 188Re were measured in the transfected (ARO-N) and wild-type cell lines (ARO). A recombinant adenovirus-5 vector containing a CMV promoter and wt-p53 cDNA, called Ad-p53, was established and transduced to ARO and ARO-N cells. After incubating cells with 131I and 188Re, the survival rate of each cell line was measured using a clonogenic assay. For radionuclide gene therapy in an animal model, Ad-p53 was injected directly into ARO and ARO-N tumours which were transplanted to nude mice. Two days later, 188Re or saline was injected intraperitoneally into the mice, and the tumours were measured using a calliper for 4 weeks. In ARO-N cells, the uptakes of 125I and 188Re were 505.16±21.30 pmol/106 cells and 13,875.20±504.85 cpm/106 cells at 30 min, respectively. There was no difference between the survival rates of ARO cells and ARO-N cells after incubation with 131I or 188Re. When Ad-p53 was transduced to ARO-N cells, the survival rate of wt-p53-expressing ARO- survival rate of wt-p53-expressing ARO-N cells incubated with 131I (18.5 MBq/5 ml) and 188Re (18.5 MBq/5 ml) decreased to 48.8±18.4% and 32.6±23.5%, respectively. In the nude mice experiment, ARO and ARO-N tumours gradually grew up to six to eight times larger than the initial volume. ARO and ARO-N tumours transduced with Ad-p53 continued to grow. However, the ARO-N tumours treated with Ad-p53 and 185 MBq of 188Re regressed to 20% of the initial volume. Growth of ARO-N tumour treated with 131I or 188Re was significantly inhibited by Ad-p53 transduction in vivo as well as in vitro. Transfection of the NIS gene into human anaplastic thyroid cancer induced the accumulation of beta-emitter radionuclides, and cotransfection with a wt-p53 gene enhanced the cytotoxic effect. (orig.)

320

Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls  

International Nuclear Information System (INIS)

Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [14C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

 
 
 
 
321

'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease  

Energy Technology Data Exchange (ETDEWEB)

''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

Walor, David M.; Berdon, Walter E. [Columbia University Medical Center, Department of Radiology Children' s Hospital of New York, New York, NY (United States); Westra, Sjirk J. [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

2005-07-01

322

'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease  

International Nuclear Information System (INIS)

''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

323

Meningiomas with conventional MRI findings resembling intraaxial tumors: can perfusion-weighted MRI be helpful in differentiation?  

International Nuclear Information System (INIS)

To investigate the contribution of perfusion-weighted MRI to the differentiation of meningiomas with atypical conventional MRI findings from intraaxial tumors. We retrospectively analyzed 54 meningiomas, 12 glioblastomas and 13 solitary metastases. We detected 6 meningiomas with atypical features on conventional MRI resembling intraaxial tumors. The regional cerebral blood flow (rCBV) ratios of all tumors were calculated via perfusion-weighted MRI. The signal intensity-time curves were plotted and three different curve patterns were observed. The type 1 curve resembled normal brain parenchyma or the postenhancement part was minimally below the baseline, the type 2 curve was similar to the type 1 curve but with the postenhancement part above the baseline, and the type 3 curve had the postenhancement part below the baseline accompanied by widening of the curve. Student's t-test was used for statistical analysis. On CBV images meningiomas were hypervascular and the mean rCBV ratio was 10.58±2.00. For glioblastomas and metastatic lesions, the rCBV ratios were 5.02±1.40 and 4.68±1.54, respectively. There was a statistically significant difference in rCBV ratios between meningiomas and glioblastomas and metastases (P<0.001). Only one of the meningiomas displayed a type 2 curve while five showed a type 3 curve. Glioblastomas and metastases displayed either a type 1 or a type 2 curve. None of the meningiomas showed a type 1 curve and none of the glioblastomas or metastasesnone of the glioblastomas or metastases showed a type 3 curve. (orig.)

324

mRNA expression patterns indicate CD30 mediated activation of different apoptosis pathways in anaplastic large cell lymphoma but not in Hodgkin's lymphoma.  

Science.gov (United States)

One of the main functions of the tumor necrosis factor receptor (TNFR) family is induction of apoptosis. CD30, a member of the TNFR superfamily is overexpressed in highly proliferating tumors such as anaplastic large cell lymphoma (ALCL) and Hodgkin's lymphoma (HL). CD30 stimulation leads to apoptosis and growth arrest in cultured ALCL, but not in Hodgkin-Reed-Sternberg cells. To identify changes in the transcriptional program responsible for these opposing effects, we performed gene expression analysis in CD30-stimulated ALCL (Karpas 299) and HL (KM-H2) cell lines using cDNA microarrays. Selected genes were validated by real-time PCR. Hierarchical clustering was applied to the whole dataset and separated the cell lines clearly with respect to their origin. In HL, there were only minor CD30-specific alterations, whereas ALCL unequivocally showed a pronounced CD30-specific transcriptional response. Ninety-three genes (6.6% of total) were deregulated by more than a factor of two after CD30 stimulation in ALCL cells. The majority of genes identified are involved in cell cycle regulation and apoptosis. mRNA expression patterns further indicate that in contrast to HL, CD30 stimulation in ALCL induces cell death via the CD95-CD95 ligand (CD95L) pathway and the TNF-R1/TNF-R2 crosstalk. These data provide a detailed view on the transcriptional changes upon CD30 stimulation and may explain the observed functional differences of HL and ALCL. PMID:16198418

Staber, P B; Noehammer, C; Dürkop, H; Schauer, S; Kenner, L; Linkesch, W; Hoefler, G

2006-03-01

325

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.  

Science.gov (United States)

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy. PMID:24665203

Che, Huan-Yong; Guo, Hang-Yuan; Si, Xu-Wei; You, Qiao-Ying; Lou, Wei-Ying

2014-01-01

326

Foscarnet reduces FGF2-induced proliferation of human umbilical vein endothelial cells and has antineoplastic activity against human anaplastic thyroid carcinoma cells.  

Science.gov (United States)

In contrast to many reports dealing with inhibitors of growth factor receptors like VEGF or FGFR, only few reports of low molecular weight inhibitors, which are directed against growth factors itself, are known. Here, foscarnet, an antiviral drug which inhibits several viral DNA polymerases by mimic pyrophosphate of nucleotides, was identified to interact with fibroblast growth factor 2 and stabilize the growth factor against tryptic digestion similar like the non-nitrogen containing bisphosphonates clodronate and etidronate that we have reported just recently as inhibitors of FGF-induced cell proliferation. Foscarnet competes with ATP against the binding on fibroblast growth factor 2 at the heparin/ATP-binding domain. This indicates binding of foscarnet at the heparin-binding domain of FGF2. This interaction of foscarnet with fibroblast growth factor 2 reduces FGF2-induced proliferation of human umbilical vein endothelial cells and intracellular signaling via ERK1/2 kinases in this cell line. Additionally, foscarnet reduces in a dose-dependent manner proliferation of CAL-62 cells that belong to anaplastic thyroid carcinoma, a rare but lethal type of thyroid cancer that expresses FGF2. PMID:23228448

Rose, Karsten

2013-02-01

327

Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex  

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Full Text Available 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.

Rocco Piazza

2013-05-01

328

Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to chemosensitize anaplastic thyroid carcinoma.  

Science.gov (United States)

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we investigated and correlated the expression of phosphatase and tensin homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and p53 genes in samples of patients with ATC. Furthermore, we evaluated the potential of inhibition of these pathways on chemosensitization of ATC using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results revealed a negative correlation between the activity of RAS-MAPK-ERK and PI3K-AKT-mTOR pathways in samples of patients. To be specific, the PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or high pERK expression. In vitro results suggest that the inhibition of either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity of thyroid cancer cells to classic chemotherapeutics. This may form a basis for the development of novel genetic-based therapeutic approach for this cancer type. PMID:25016932

Milosevic, Zorica; Pesic, Milica; Stankovic, Tijana; Dinic, Jelena; Milovanovic, Zorka; Stojsic, Jelena; Dzodic, Radan; Tanic, Nikola; Bankovic, Jasna

2014-11-01

329

AZD1152 negatively affects the growth of anaplastic thyroid carcinoma cells and enhances the effects of oncolytic virus dl922-947.  

Science.gov (United States)

Novel therapeutic approaches are required for the treatment of anaplastic thyroid carcinoma (ATC), an incurable disease resistant to current available therapies. Aurora B is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers including ATC and represents a potential target for chemotherapy. The effects of AZD1152, a specific Aurora B kinase inhibitor, have been evaluated against ATC, showing G(2)/M accumulation, polyploidy and subsequent cell death by mitotic catastrophe upon drug treatment. Only three administrations of AZD1152 significantly reduced the growth of ATC tumour xenogratfs. Oncolytic viruses in association with other forms of treatment have proven highly promising in preclinical and clinical reports. The oncolytic adenovirus dl922-947 is active against ATC cells, and we have evaluated the effects of the association between AZD1152 and dl922-947. In cells treated with virus and drug, we report additive/synergistic killing effects. Interestingly, the phosphorylation of histone H3 (Ser10), the main Aurora B substrate, is inhibited by dl922-947 in a dose-dependent manner, and completely abolished in association with AZD1152. The combined treatment significantly inhibited the growth of ATC tumour xenografts with respect to single treatments. Our data demonstrate that the Aurora B inhibitor AZD1152, alone or in combination with oncolytic virus dl922-947, could represent a novel therapeutic option for the treatment of ATC. PMID:21071467

Libertini, Silvana; Abagnale, Antonella; Passaro, Carmela; Botta, Ginevra; Barbato, Sara; Chieffi, Paolo; Portella, Giuseppe

2011-02-01

330

Wild-type p53 enhances the cytotoxic effect of radionuclide gene therapy using sodium iodide symporter in a murine anaplastic thyroid cancer model  

Energy Technology Data Exchange (ETDEWEB)

To evaluate the role of p53 in radionuclide gene therapy, we investigated the cytotoxic effect of {sup 131}I and {sup 188}Re following cotransfection of the sodium iodide symporter (NIS) and wild-type p53 (wt-p53) genes into cancer cells. The NIS gene was transfected to human anaplastic thyroid carcinoma cells (ARO) expressing mutant p53 (mt-p53) using liposomes. The uptakes of {sup 125}I and {sup 188}Re were measured in the transfected (ARO-N) and wild-type cell lines (ARO). A recombinant adenovirus-5 vector containing a CMV promoter and wt-p53 cDNA, called Ad-p53, was established and transduced to ARO and ARO-N cells. After incubating cells with {sup 131}I and {sup 188}Re, the survival rate of each cell line was measured using a clonogenic assay. For radionuclide gene therapy in an animal model, Ad-p53 was injected directly into ARO and ARO-N tumours which were transplanted to nude mice. Two days later, {sup 188}Re or saline was injected intraperitoneally into the mice, and the tumours were measured using a calliper for 4 weeks. In ARO-N cells, the uptakes of {sup 125}I and {sup 188}Re were 505.16{+-}21.30 pmol/10{sup 6} cells and 13,875.20{+-}504.85 cpm/10{sup 6} cells at 30 min, respectively. There was no difference between the survival rates of ARO cells and ARO-N cells after incubation with {sup 131}I or {sup 188}Re. When Ad-p53 was transduced to ARO-N cells, the survival rate of wt-p53-expressing ARO-N cells incubated with {sup 131}I (18.5 MBq/5 ml) and {sup 188}Re (18.5 MBq/5 ml) decreased to 48.8{+-}18.4% and 32.6{+-}23.5%, respectively. In the nude mice experiment, ARO and ARO-N tumours gradually grew up to six to eight times larger than the initial volume. ARO and ARO-N tumours transduced with Ad-p53 continued to grow. However, the ARO-N tumours treated with Ad-p53 and 185 MBq of {sup 188}Re regressed to 20% of the initial volume. Growth of ARO-N tumour treated with {sup 131}I or {sup 188}Re was significantly inhibited by Ad-p53 transduction in vivo as well as in vitro. Transfection of the NIS gene into human anaplastic thyroid cancer induced the accumulation of beta-emitter radionuclides, and cotransfection with a wt-p53 gene enhanced the cytotoxic effect. (orig.)

Lee, Yong Jin [Seoul National University College of Medicine, Department of Nuclear Medicine, Chongno-gu, Seoul (Korea); Seoul National University College of Medicine, Cancer Research Institute, Chongno-gu, Seoul (Korea); Seoul National University College of Medicine, Tumor Immunity Medical Research Center, Chongno-gu, Seoul (Korea); Korea Institute of Radiological and Medical Sciences, Molecular Imaging Research Center, Nowon-Gu, Seoul (Korea); Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Chongno-gu, Seoul (Korea); Seoul National University College of Medicine, Cancer Research Institute, Chongno-gu, Seoul (Korea); Seoul National University College of Medicine, Tumor Immunity Medical Research Center, Chongno-gu, Seoul (Korea); Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Molecular Imaging Research Center, Nowon-Gu, Seoul (Korea); Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, Chongno-gu, Seoul (Korea); Seoul National University College of Medicine, Cancer Research Institute, Chongno-gu, Seoul (Korea); Lee, Dong Soo; Lee, Myung Chul [Seoul National University College of Medicine, Department of Nuclear Medicine, Chongno-gu, Seoul (Korea)

2010-02-15

331

ECG phenomena: pseudopreexcitation and repolarization disturbances resembling ST-elevation myocardial infarction caused by an intraatrial rhabdomyoma in a newborn.  

Science.gov (United States)

As is known from other reports, a rhabdomyoma or tumor metastasis may alter intracardiac electrical conduction, producing electrical phenomena like pseudopreexcitation or repolarization disturbances resembling ST-elevation myocardial infarction or Brugada's syndrome. We present a newborn with a giant atrial rhabdomyoma and additionally multiple ventricular rhabdomyomas. He presented with several electrocardiogram (ECG) phenomena due to tumor-caused atrial depolarization and repolarization disturbances. Except from the cardiac tumors, the physical status was within normal range. Initial ECG showed a rapid atrial tachycardia with a ventricular rate of 230?bpm, which was terminated by electrical cardioversion. Afterwards, the ECG showed atrial rhythm with frequent atrial premature contractions and deformation of the PR interval with large, broad P waves and loss of discret PR segment, imposing as pseudopreexcitation. The following QRS complex was normal, with seemingly abnormal ventricular repolarization resembeling ST-elevation myocardial infarction. The atrial tumor was resected with consequent vast atrial reconstruction using patch plastic. The ventricular tumors were left without manipulation. After surgery, pseudopreexcitation and repolarization abnormalities vanished entirely and an alternans between sinus rhythm and ectopic atrial rhythm was present. These phenomena were supposably caused by isolated atrial depolarization disturbances due to tumor-caused heterogenous endocardial activation. The seemingly abnormal ventricular repolarization is probably due to repolarization of the atrial mass, superimposed on the ventricular repolarization. Recognizably, the QRS complex before and after surgical resection of the rhabdomyoma is identical, underlining the atrial origin of the repolarization abnormalities before surgery. PMID:23663513

Paech, Christian; Gebauer, Roman Antonin

2014-01-01

332

Extending the honey bee venome with the antimicrobial peptide apidaecin and a protein resembling wasp antigen 5.  

Science.gov (United States)

Honey bee venom is a complex mixture of toxic proteins and peptides. In the present study we tried to extend our knowledge of the venom composition using two different approaches. First, worker venom was analysed by liquid chromatography-mass spectrometry and this revealed the antimicrobial peptide apidaecin for the first time in such samples. Its expression in the venom gland was confirmed by reverse transcription PCR and by a peptidomic analysis of the venom apparatus tissue. Second, genome mining revealed a list of proteins with resemblance to known insect allergens or venom toxins, one of which showed homology to proteins of the antigen 5 (Ag5)/Sol i 3 cluster. It was demonstrated that the honey bee Ag5-like gene is expressed by venom gland tissue of winter bees but not of summer bees. Besides this seasonal variation, it shows an interesting spatial expression pattern with additional production in the hypopharyngeal glands, the brains and the midgut. Finally, our immunoblot study revealed that both synthetic apidaecin and the Ag5-like recombinant from bacteria evoke no humoral activity in beekeepers. Also, no IgG4-based cross-reactivity was detected between the honey bee Ag5-like protein and its yellow jacket paralogue Ves v 5. PMID:23350689

Van Vaerenbergh, M; Cardoen, D; Formesyn, E M; Brunain, M; Van Driessche, G; Blank, S; Spillner, E; Verleyen, P; Wenseleers, T; Schoofs, L; Devreese, B; de Graaf, D C

2013-04-01

333

2MASSJ035523.51+113337.4: A Young, Dusty, Nearby, Isolated Brown Dwarf Resembling A Giant Exoplanet  

CERN Document Server

We present parallax and proper motion measurements, near-infrared spectra, and WISE photometry for the low surface gravity L5gamma dwarf 2MASSJ035523.51+113337.4 (2M0355). We use these data to evaluate photometric, spectral, and kinematic signatures of youth. We confirm low-gravity spectral morphology and find a strong resemblance to the sharp triangular shaped H-band spectrum of the ~10 Myr planetary-mass object 2MASSJ1207b. We find that 2M0355 is underluminous compared to a normal field L5 dwarf in the optical and MKO J,H, and K bands and transitions to being overluminous from 3-12 microns indicating that enhanced photospheric dust shifts flux to longer wavelengths for young, low-gravity objects, creating a red spectral energy distribution. Investigating the near-infrared color magnitude diagram for brown dwarfs confirms that 2M0355 is redder and underluminous compared to the known brown dwarf population, similar to the peculiarities of directly imaged exoplanets 2MASSJ1207b and HR8799bcd. We calculate UVW ...

Faherty, Jacqueline K; Cruz, Kelle L; Mamajek, Eric E; Núñez, Alejandro

2012-01-01

334

Sensory afferent segregation in three-eared frogs resemble the dominance columns observed in three-eyed frogs.  

Science.gov (United States)

The formation of proper sensory afferent connections during development is essential for brain function. Activity-based competition is believed to drive ocular dominance columns (ODC) in mammals and in experimentally-generated three-eyed frogs. ODC formation is thus a compromise of activity differences between two eyes and similar molecular cues. To gauge the generality of graphical map formation in the brain, we investigated the inner ear projection, known for its well-defined and early segregation of afferents from vestibular and auditory endorgans. In analogy to three eyed-frogs, we generated three-eared frogs to assess to what extent vestibular afferents from two adjacent ears could segregate. Donor ears were transplanted either in the native orientation or rotated by 90 degrees. These manipulations should result in either similar or different induced activity between both ears, respectively. Three-eared frogs with normal orientation showed normal swimming whereas those with a rotated third ear showed aberrant behaviors. Projection studies revealed that only afferents from the rotated ears segregated from those from the native ear within the vestibular nucleus, resembling the ocular dominance columns formed in three-eyed frogs. Vestibular segregation suggests that mechanisms comparable to those operating in the ODC formation of the visual system may act on vestibular projection refinements. PMID:25661240

Elliott, Karen L; Houston, Douglas W; Fritzsch, Bernd

2015-01-01

335

Resembling breast milk: influence of polyamine-supplemented formula on neonatal BALB/cOlaHsd mouse microbiota.  

Science.gov (United States)

Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula). In addition to its nutritional value, breast milk contains bioactive substances that drive microbial colonisation and support immune system development, which are usually not present in infant formulas. Among these substances, polyamines have been described to be essential for intestinal and immune functions in newborns. However, their effect on the establishment of microbiota remains unclear. Therefore, the aim of the present study was to ascertain whether an infant formula supplemented with polyamines has an impact on microbial colonisation by modifying it to resemble that in breast-fed neonatal BALB/c mice. In a 4 d intervention, a total of sixty pups (14 d old) were randomly assigned to the following groups: (1) breast-fed group; (2) non-enriched infant formula-fed group; (3) three different groups fed an infant formula enriched with increasing concentrations of polyamines (mixture of putrescine, spermidine and spermine), following the proportions found in human milk. Microbial composition in the contents of the oral cavity, stomach and small and large intestines was analysed by quantitative PCR targeted at fourteen bacterial genera and species. Significantly different (PAkkermansia muciniphila, Lactobacillus, Bifidobacterium, Bacteroides-Prevotella and Clostridium groups to levels found in the breast-fed group. Such an effect requires further investigation in human infants, as supplementation of an infant formula with polyamines might contribute to healthy gastrointestinal tract development. PMID:24229796

Gómez-Gallego, Carlos; Collado, M Carmen; Pérez, Gaspar; Ilo, Toni; Jaakkola, Ulla-Marjut; Bernal, María J; Periago, María J; Frias, Rafael; Ros, Gaspar; Salminen, Seppo

2014-03-28

336

No signature of Y chromosomal resemblance between possible descendants of the Cimbri in Denmark and Northern Italy.  

DEFF Research Database (Denmark)

Two European populations are believed to be related to the ancient Germanic tribe Cimbri: one living in Northern Italy, the other living in Jutland, Denmark. The people called Cimbri are documented in the ancient Roman historical record. Arriving from the far north their movements can be tracked from successive battles with the Romans. The Cimbri finally entered Italy from the northeast and were defeated at Vercellae (present day Vercelli) in 101 BC by Gaius Marius and his professional legions. Classical sources from the first centuries AD relate the homeland of the Cimbri to the coasts around the Elb estuary (northern Germany) or specifically towards the north (Himmerland in northern Jutland). In the alpine parts of Veneto, northeast of the historical battlefield, local traditions dating back to late medieval time, identify a local population as Cimbri living in Terra dei Cimbri. They are considered the descendents of the Germanic combatants that fled the battlefield at Vercelli. As the defeated Cimbri that possibly fled to the mountains of Northern Italy most likely would have been male (warriors), the present study investigated the possible Y chromosomal diversity of the two present populations using microsatellite markers and single nucleotide polymorphisms. While Cimbri from Himmerland resembled their geographical neighbors from Denmark for the Y-chromosome markers, Cimbri from Italy were significantly differentiated both from Cimbri from Himmerland and from Danes. Therefore, we were not able to show any biological relationship for uniparentally transmitted markers. Udgivelsesdato: 2007-Feb

BØrglum, Anders; Vernesi, Cristiano

2007-01-01

337

Ethnic Heterogeneity and Public Support for Welfare Policies : Is the 'black' American experience resembled in Britian, Sweden and Denmark?  

DEFF Research Database (Denmark)

The link between ethnic heterogeneity and support for welfare policy is debated. The thesis of a negative relationship is supported by a large American research effort. Historically the race issue have blocked a number of US welfare schemes, across USA ethnic heterogene-ous states have less generous benefits, and citizens having negative attitudes towards blacks oppose welfare. The question is to what extend increased ethnic heterogeneity in European countries will establish the same mechanisms. Three theoretical positions are discussed; the position that the ‘black’ American experience is unique, the position that it is general, and a middle position of it being contingent on institutional settings. The latter position predicts that the ‘black’ American experience especially can be avoided in social democratic welfare regimes where the political elites have not played the race card. Em-pirically the article is based on survey data from UK, Sweden and Denmark, where a num-ber of American GSS items have been directly replicated. Despite indications of American uniqueness and welfare regime effects the findings support the position that the American in-group out-group mechanisms are resembled in Europe.

Larsen, Christian Albrekt

2010-01-01

338

Tectonic resemblance of the Indian Platform, Pakistan with the Moesian Platform, Romania and strategy for exploration of hydrocarbons  

International Nuclear Information System (INIS)

There is a remarkable tectonic resemblance between the indian Platform (Pakistan) and the Moesian Platform (Romania). As viewed in global tectonic perspective Moeslan and Indian Plates have played important role in Alpine Himalayan Orogeny; Moesian and Indian Platforms are extension of these respective plates. Characteristics features of both the platforms are block faulting which has effected not only the general tectonic framework but has also played important role in oil accumulation. Main producing rocks in the Moesian platform are Jurassic sandstones and cretaceous limestones while in the indian platform cretaceous sandstones are important reservoirs. The average geothermal gradient in the indian platform is 2.45 C/100m with the higher gradients in the central gas producing region. Geothermal gradients in the Moesian platform have an average value of 3 C/100m with higher gradients in the northern in the northern part. Some of the producing structures in both the platforms are remarkably similar, traps associated with normal faults are very important. Extensive exploration carried in the Moesian Platform makes it very important oil producing region of Romania. After the discovery of oil lower Sindh, serious exploration is being carried in the Indian platform. The paper deals with the similarities between these two important platforms. In the light of the studies of the Moesian platform, strategies or exploration of oil and gas in the Indian Platform are suggested. gas in the Indian Platform are suggested. (author)

339

Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors  

Energy Technology Data Exchange (ETDEWEB)

Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important role in the development of radiation-associated adult-onset papillary thyroid cancer. (authors)

Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y. [Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima (Japan); Hayashi, Y. [Geriatric Health Service Facility Hidamari, Hiroshima (Japan)

2012-07-01

340

Correlation of Anaplastic Lymphoma Kinase Overexpression and the EML4-ALK Fusion Gene in Non-Small Cell Lung Cancer by Immunohistochemical Study  

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Full Text Available Background: Recently the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK fusion gene with transforming activity was identified in non-small cell lung cancer (NSCLC. In addition, NSCLC patients with the EML4-ALK fusion gene had a dramatic response and longer progression free survival after ALK inhibitor treatment than those without this fusion gene. However, the incidence and clinical and molecular characteristics of the EML4-ALK fusion gene in NSCLC patients of Taiwan are still unclear.Methods:Sixty-four fresh frozen tumor specimens were obtained from the tissue bank of Chang Gung Memorial Hospital for RNA extraction and EML4-ALK fusion gene detection. Paraffin sections of lung tumors from all of these patients were available and were analyzed for ALK protein expression by immunohistochemical (IHC study. The results were correlated with clinical and molecular biomarkers.Results: Three of the 64 tumors (4.7% had the EML4-ALK fusion gene. Two were adenocarcinomas, and one was adenosquamous carcinoma. Twenty patients with non-squamous cell carcinomas had epidermal growth factor receptor (EGFR mutations, so the EML4-ALK fusion gene was found in 14.3% of EGFR wild type non-squamous cell carcinomas. Two tumors were variant 3 (3a+3b with 3b predominant and had strong staining (3+ for ALK by IHC stains. One tumor was variant 1 and had moderate staining (2+ for ALK. None of the ALK wild type tumors had strong staining for ALK. When compared with other clinical and molecular features, only the IHC stain for ALK was significantly correlated with the EML4-ALK fusion gene (p = 0.0002.Conclusions: ALK overexpression detected by IHC study could be a promising detection method for the EML4-ALK fusion gene and is worth further confirmation with more samples.

Shiu-Feng Huang

2012-08-01

 
 
 
 
341

Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines.  

Science.gov (United States)

Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem-loop-mediated reverse transcription real-time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR-138, was significantly downregulated in ATC cell lines in comparison with PTC (P cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR-138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = -0.392, P = 0.148). We demonstrated that overexpression of miR-138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR-138 and the hTERT 3'-untranslated region by luciferase reporter assay. These results suggest that loss of miR-138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma. PMID:18201269

Mitomo, Shingo; Maesawa, Chihaya; Ogasawara, Satoshi; Iwaya, Takeshi; Shibazaki, Masahiko; Yashima-Abo, Akiko; Kotani, Koji; Oikawa, Hiroki; Sakurai, Eiich; Izutsu, Naoko; Kato, Kuniyuki; Komatsu, Hideaki; Ikeda, Kenichro; Wakabayashi, Go; Masuda, Tomoyuki

2008-02-01

342

Inhibition of p21 and Akt potentiates SU6656-induced caspase-independent cell death in FRO anaplastic thyroid carcinoma cells.  

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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 ?M 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. PMID:23386415

Kim, S H; Kang, J G; Kim, C S; Ihm, S-H; Choi, M G; Yoo, H J; Lee, S J

2013-06-01

343

The selective anaplastic lymphoma receptor tyrosine kinase inhibitor ASP3026 induces tumor regression and prolongs survival in non-small cell lung cancer model mice.  

Science.gov (United States)

Activation of anaplastic lymphoma receptor tyrosine kinase (ALK) is involved in the pathogenesis of several carcinomas, including non-small cell lung cancer (NSCLC). Echinoderm microtubule-associated protein like 4 (EML4)-ALK, which is derived from the rearrangement of ALK and EML4 genes, has been validated as a therapeutic target in a subset of patients with NSCLC. Here, we investigated the effects of ASP3026, a novel small-molecule ALK inhibitor, against ALK-driven NSCLC. ASP3026 inhibited ALK activity in an ATP-competitive manner and had an inhibitory spectrum that differed from that of crizotinib, a dual ALK/MET inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, orally administered ASP3026 was well absorbed in tumor tissues, reaching concentrations >10-fold higher than those in plasma, and induced tumor regression with a wide therapeutic margin between efficacious and toxic doses. In the same mouse model, ASP3026 enhanced the antitumor activities of paclitaxel and pemetrexed without affecting body weight. ASP3026 also showed potent antitumor activities, including tumor shrinkage to a nondetectable level, in hEML4-ALK transgenic mice and prolonged survival in mice with intrapleural NCI-H2228 xenografts. In an intrahepatic xenograft model using NCI-H2228 cells, ASP3026 induced continuous tumor regression, whereas mice treated with crizotinib showed tumor relapse after an initial response. Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance. Taken together, these findings indicate that ASP3026 has potential efficacy for NSCLC and is expected to improve the therapeutic outcomes of patients with cancer with ALK abnormality. PMID:24419060

Mori, Masamichi; Ueno, Yoko; Konagai, Satoshi; Fushiki, Hiroshi; Shimada, Itsuro; Kondoh, Yutaka; Saito, Rika; Mori, Kenichi; Shindou, Nobuaki; Soga, Takatoshi; Sakagami, Hideki; Furutani, Takashi; Doihara, Hitoshi; Kudoh, Masafumi; Kuromitsu, Sadao

2014-02-01

344

Sister chromatid exchange induction in patients with anaplastic gliomas undergoing treatment with radiation plus diaziquone or 1,3-bis(2-chloroethyl)-1-nitrosourea  

International Nuclear Information System (INIS)

Diaziquone (AZQ) (NSC 182986), a lipid-soluble benzoquinone derivative, is presently being tested in a Phase III clinical trial to determine its efficacy in patients with anaplastic gliomas compared to the more standard 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment following whole-brain irradiation. These patients on single-drug chemotherapy allowed us to evaluate the effects of each agent on sister chromatid exchange (SCE) induction in vivo. Eight weeks following the final radiation treatment, patients were randomly assigned to one of two groups: (a) 200 mg BCNU/m2, i.v., every 8 weeks; of (b) 15 mg AZQ/m2/day, i.v., for 3 consecutive days, every 4 weeks. Blood (5-10 ml) was drawn by venipuncture before treatment, within 10 h after treatment, and for two BCNU-treated patients at various other times. Peripheral blood lymphocytes were cultured by standard techniques for analysis of SCE. Eight weeks after irradiation but before chemotherapy, the mean SCE frequency in the patients' peripheral blood lymphocytes was 9.6 SCEs/metaphase. Following treatment with AZQ or BCNU, the baseline SCE frequency was increased more than 2-fold or 3-fold, respectively. Two months after BCNU treatment, there was less than a 25% reduction in SCE levels compared to samples taken and cultured within 10 h after treatment. These data show that lesions leading to SCE in human peripheral blood lymphocytes are relatively longlived, and that on a mg/m2 basis, AZQ is a more potent inducer og/m2 basis, AZQ is a more potent inducer of SCE in vivo than is BCNU

345

Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome.  

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Signaling through the interleukin 2 receptor (IL-2R) involves phosphorylation of several proteins including Jak3, STAT5, and, in preactivated cells, STAT3. In the present study, we examined the functional status of the IL-2R-associated Jak/STAT pathway in malignant T lymphocytes from advanced skin-based lymphomas: anaplastic large T-cell lymphoma (ALCL) and Sezary syndrome (SzS). Proliferation of three ALCL cell lines (PB-1, 2A, and 2B) was partially inhibited by rapamycin, a blocker of some ...

Zhang, Q.; Nowak, I.; Vonderheid, E. C.; Rook, A. H.; Kadin, M. E.; Nowell, P. C.; Shaw, L. M.; Wasik, M. A.

1996-01-01

346

Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type.  

Science.gov (United States)

Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African-American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal-like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre-invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis. PMID:22669576

Zhao, Min; Sachs, Patrick C; Wang, Xu; Dumur, Catherine I; Idowu, Michael O; Robila, Valentina; Francis, Michael P; Ware, Joy; Beckman, Matthew; Rizki, Aylin; Holt, Shawn E; Elmore, Lynne W

2012-07-01

347

Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type  

Science.gov (United States)

Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African-American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal-like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre-invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis. PMID:22669576

Zhao, Min; Sachs, Patrick C.; Wang, Xu; Dumur, Catherine I.; Idowu, Michael O.; Robila, Valentina; Francis, Michael P.; Ware, Joy; Beckman, Matthew; Rizki, Aylin; Holt, Shawn E.; Elmore, Lynne W.

2012-01-01

348

Mitochondrial oxidative stress alters a pathway in Caenorhabditis elegans strongly resembling that of bile acid biosynthesis and secretion in vertebrates.  

Science.gov (United States)

Mammalian bile acids (BAs) are oxidized metabolites of cholesterol whose amphiphilic properties serve in lipid and cholesterol uptake. BAs also act as hormone-like substances that regulate metabolism. The Caenorhabditis elegans clk-1 mutants sustain elevated mitochondrial oxidative stress and display a slow defecation phenotype that is sensitive to the level of dietary cholesterol. We found that: 1) The defecation phenotype of clk-1 mutants is suppressed by mutations in tat-2 identified in a previous unbiased screen for suppressors of clk-1. TAT-2 is homologous to ATP8B1, a flippase required for normal BA secretion in mammals. 2) The phenotype is suppressed by cholestyramine, a resin that binds BAs. 3) The phenotype is suppressed by the knock-down of C. elegans homologues of BA-biosynthetic enzymes. 4) The phenotype is enhanced by treatment with BAs. 5) Lipid extracts from C. elegans contain an activity that mimics the effect of BAs on clk-1, and the activity is more abundant in clk-1 extracts. 6) clk-1 and clk-1;tat-2 double mutants show altered cholesterol content. 7) The clk-1 phenotype is enhanced by high dietary cholesterol and this requires TAT-2. 8) Suppression of clk-1 by tat-2 is rescued by BAs, and this requires dietary cholesterol. 9) The clk-1 phenotype, including the level of activity in lipid extracts, is suppressed by antioxidants and enhanced by depletion of mitochondrial superoxide dismutases. These observations suggest that C. elegans synthesizes and secretes molecules with properties and functions resembling those of BAs. These molecules act in cholesterol uptake, and their level of synthesis is up-regulated by mitochondrial oxidative stress. Future investigations should reveal whether these molecules are in fact BAs, which would suggest the unexplored possibility that the elevated oxidative stress that characterizes the metabolic syndrome might participate in disease processes by affecting the regulation of metabolism by BAs. PMID:22438816

Liu, Ju-Ling; Desjardins, David; Branicky, Robyn; Agellon, Luis B; Hekimi, Siegfried

2012-01-01

349

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

Science.gov (United States)

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 Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Pleomorphic Xanthoastrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; 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 Medulloblastoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilocytic Astrocytoma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Pineoblastoma; Untreated Childhood Pleomorphic Xanthoastrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

2014-11-13

350

{sup 131}I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma. Phase I and II study  

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Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The {sup 131}I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, and antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR+PR+NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease. (orig.)

Riva, P.; Franceschi, G.; Casi, M.; Gentile, R. [`M.Bufalini` Hospital, Cesena (Italy). Dept. of Nuclear Medicine; Frattarelli, M.; Guiducci, G.; Cremonini, A.M.; Giuliani, G. [`M.Bufalini` Hospital, Cesena (Italy). Dept. of Neurosurgery; Riva, N. [`Pierantoni` Hospital, Forli (Italy). Dept. of Medical Oncology; Jekunen, A.A.; Kairemo, J.A. [Helsinki University Central Hospital (Finland). Dept. of Oncology

1999-11-01

351

Does My Baby Really Look Like Me? Using Tests for Resemblance between Parent and Child to Teach Topics in Categorical Data Analysis  

Science.gov (United States)

In this article, we present a study to test whether neutral observers perceive a resemblance between a parent and a child. We demonstrate the general approach for two separate parent/ child pairs using survey data collected from introductory statistics students serving as neutral observers. We then present ideas for incorporating the study design…

Froelich, Amy G.; Nettleton, Dan

2013-01-01

352

Translational pharmacokinetic-pharmacodynamic modeling for an orally available novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1.  

Science.gov (United States)

An orally available macrocyclic small molecule, PF06463922 [(10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile], is a selective inhibitor of anaplastic lymphoma kinase (ALK) and c-Ros oncogene 1 (ROS1). The objectives of the present study were to characterize the pharmacokinetic-pharmacodynamic relationships of PF06463922 between its systemic exposures, pharmacodynamic biomarker (target modulation), and pharmacologic response (antitumor efficacy) in athymic mice implanted with H3122 non-small cell lung carcinomas expressing echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutation (EML4-ALK(L1196M)) and with NIH3T3 cells expressing CD74-ROS1. In these nonclinical tumor models, PF06463922 was orally administered to animals with EML4-ALK(L1196M) and CD74-ROS1 at twice daily doses of 0.3-20 and 0.01-3 mg/kg per dose, respectively. Plasma concentration-time profiles of PF06463922 were adequately described by a one-compartment pharmacokinetic model. Using the model-simulated plasma concentrations, a pharmacodynamic indirect response model with a modulator sufficiently fit the time courses of target modulation (i.e., ALK phosphorylation) in tumors of EML4-ALK(L1196M)-driven models with EC50,in vivo of 36 nM free. A drug-disease model based on an indirect response model reasonably fit individual tumor growth curves in both EML4-ALK(L1196M)- and CD74-ROS1-driven models with the estimated tumor stasis concentrations of 51 and 6.2 nM free, respectively. Thus, the EC60,in vivo (52 nM free) for ALK inhibition roughly corresponded to the tumor stasis concentration in an EML4-ALK(L1196M)-driven model, suggesting that 60% ALK inhibition would be required for tumor stasis. Accordingly, we proposed that the EC60,in vivo for ALK inhibition corresponding to the tumor stasis could be considered a minimum target efficacious concentration of PF06463922 for cancer patients in a phase I trial. PMID:25073473

Yamazaki, Shinji; Lam, Justine L; Zou, Helen Y; Wang, Hui; Smeal, Tod; Vicini, Paolo

2014-10-01

353

Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation  

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Full Text Available Abstract Background Primary non-Hodgkin lymphoma (NHL of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML, the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude sarcomatoid carcinoma, malignant melanoma and pleomorphic sarcoma by an appropriate panel of immunostains to arrive at the correct diagnosis of ALCL.

Sur Monalisa

2009-04-01

354

Sialylation by ??galactoside ??2,6?sialyltransferase and N?glycans regulate cell adhesion and invasion in human anaplastic large cell lymphoma.  

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The interaction between cell surface glycans and extracellular matrix (ECM) including galectins is known to be closely associated with tumor cell adhesion, invasion and metastasis. We analyzed the roles of cell surface sialylation or glycosylation in galectin or ECM?mediated cell adhesion and invasion of human malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU) treatment resulted in reduction of cell adhesion to galectin?8 in human anaplastic large cell lymphoma (H?ALCL) which was established in our laboratory. The knockdown of ??galactoside ??2,6?sialyltrans-ferase (ST6Gal1) by siRNA showed inhibition of ST6Gal1 expression in the cytoplasm of H?ALCL cells on immunohistochemical findings, and showed dramatic enhancement of cell adhesion to galectin?8. On the other hand, ??2,3?specific neuraminidase treatment resulted in moderate enhancement of cell adhesion to galectin?8. We performed chemically artificial modification of cell surface O?glycans by treatment of benzyl 2?acetamido?2?deoxy???D?galactopyranoside (Bz???GalNAc) in H?ALCL. Cell adhesion to galectin?8 was enhanced by treatment of Bz???GalNAc suggesting that inhibition of elongation of O?glycans may enhance cell adhesion to galectin?8 in H?ALCL cells. On the other hand inhibition of elongation of N?glycosylation by tunicamycin (TM) resulted in inhibition of Phaseolus vulgaris?L (L?PHA) lectin?binding activity and inhibited cell adhesion to galectin?8, laminin and fibronectin. Neuraminidase treatment enhanced cell adhesion to laminin, and knockdown of ST6Gal1 resulted in enhancement of cell adhesion to laminin, but not to fibronectin, collagen type 1 and 4. Galectin?8 pre?treatment dramatically enhanced cell adhesion to laminin and neuraminidase treatment also enhanced cell adhesion to laminin in combination with galectin?8. Rho inhibitor, C3?transferase pre?treatment resulted in inhibition of cell invasion to galectin?8. Phosphatidylinositol 3?phosphate kinase (PI3K) inhibitor, wortmannin inhibits the cell invasive capacity to galectin?8. Neuraminidase treatment induces growth inhibition of lymphoma cells by galectin?8. PMID:25573487

Suzuki, Osamu; Abe, Masafumi; Hashimoto, Yuko

2015-03-01

355

Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas  

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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 hion-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 published data for future treatment decision-making remains difficult when the histologic diagnosis has not been based on the new improved classification system.

356

Mechanistic understanding of translational pharmacokinetic-pharmacodynamic relationships in nonclinical tumor models: a case study of orally available novel inhibitors of anaplastic lymphoma kinase.  

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The orally available novel small molecules PF06463922 [(10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile] and PF06471402 [(10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(azeno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile] are second-generation anaplastic lymphoma kinase (ALK) inhibitors targeted to both naïve and resistant patients with non-small cell lung cancer (NSCLC) to the first-generation ALK inhibitor crizotinib. The objectives of the present study were to characterize and compare the pharmacokinetic-pharmacodynamic (PKPD) relationships of PF06463922 and PF06471402 for target modulation in tumor and antitumor efficacy in athymic mice implanted with H3122 NSCLC cells expressing a crizotinib-resistant echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutation, EML4-ALK(L1196M). Furthermore, the PKPD relationships for these ALK inhibitors were evaluated and compared between oral administration and subcutaneous constant infusion (i.e., between different pharmacokinetic [PK] profiles). Oral and subcutaneous PK profiles of these ALK inhibitors were adequately described by a one-compartment PK model. An indirect response model extended with a modulator fit the time courses of PF06463922- and PF06471402-mediated target modulation (i.e., ALK phosphorylation) with an estimated unbound EC50,in vivo of 36 and 20 nM, respectively, for oral administration, and 100 and 69 nM, respectively, for subcutaneous infusion. A drug-disease model based on the turnover concept fit tumor growth curves inhibited by PF06463922 and PF06471402 with estimated unbound tumor stasis concentrations of 51 and 27 nM, respectively, for oral administration, and 116 and 70 nM, respectively, for subcutaneous infusion. Thus, the EC50,in vivo to EC60,in vivo estimates for ALK inhibition corresponded to the concentrations required tumor stasis in all cases, suggesting that the pharmacodynamic relationships of target modulation to antitumor efficacy were consistent among the ALK inhibitors, even when the PK profiles with different administration routes were considerably different. PMID:25349124

Yamazaki, Shinji; Lam, Justine L; Zou, Helen Y; Wang, Hui; Smeal, Tod; Vicini, Paolo

2015-01-01

357

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain  

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Purpose: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were ? 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) ? 60%. Methods and Materials: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m2) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m2) given at 6-week intervals or 6-mercaptopurine (6-MP, 750 mg/m2 IV daily for 3 days every 6 weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average age 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS ? 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age ? 45 years (b) KPS < 90%; (c) GBM/Gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35)nths for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). Conclusions: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU

358

Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, phase I-II study  

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Purpose: This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are now presenting the results on the long-term follow-up of patients with AA. Methods and Materials: Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed malignant glioma. Twenty-one of 79 were AA. The study was designed to have a fixed dose of radiation consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment. Results: The last AA patient was entered in March 1991. Ninety-five percent of the AA patients were under 59 years of age and 86% had a Karnofsky score 80. Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor diameter between 5-10 cm. Seventy-six percent had partial or total tumor resection. The toxicity of this treatment was acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AA are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years. Thirty-om the Kaplan-Meier, is 3.2 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with postoperative external radiation plus chemotherapy, median survival time (MST) of 3 years, and previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone, MST of 2 years. Conclusions: Our findings in patients with AA corroborate the improved therapeutic results published recently when combining external radiation with 'long' infusion of i.v. BUdR and indicate the need to proceed with randomized Phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG no. 94-04

359

The Chineysky layered massif (Siberia, Russia) and Upper Zone of the Bushveld Complex: resemblance and difference features  

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Layered intrusions represent a small part of a large group of continental basic-ultrabasic complexes. They attract geologists' attention due to their unusual magmatic structures and associated PGE, Cr and V deposits. The outstanding example of this phenomenon is the Bushveld Complex in South Africa. The largest layered intrusion in Russia is the Chineysky massif (Transbaikalia, Siberia). It is characterized by excellent layering and accompanying titanomagnetite and sulfide mineralization. It hosts Russia's largest deposits of Fe-Ti-V ores which are also among the world's largest [1]. Origin of such huge metal concentrations in the crust is unsettled problem. Therefore the ore conditions' determination from different intrusions is very actually. We compared the structure, rock and parental magmas compositions for two plutons mentioned above. The Chineysky massif consists of gabbronorites and anorthozites and the petrography of the rocks resembles that of the Upper Zone of the Bushveld [3]. Vanadium ores from these two intrusions are very similar: they are represented by massive and disseminated varieties. However, the small size of Chineysky massiv gives an opportunity to observe the number of petrological processes in a frame of one area, as opposed to Bushveld, where this is impossible. The separateness of the bodies and the scarcity of geochemical data on their rocks precluded the development of a comprehensive model for the evolution of magmatism in this part of the Kodar- Udokan trough. So one of the tasks of our research was to study the spatial and genetic relations between the ultrabasite-basite intrusive bodies and their possible grouping within a single magmatic system, with the Chineysky massif being its part. The second tasks was to determine the phase characteristics of the parental magma of the massif . An important aspect of this study was the examination of the inner structure of the Chineysky massiv. The main features of the structure are following: 1) consecutive introduction of magmas of different composition; 2) stratification of different nature; 3) differently grade rhythmicity. The Chineysky massif is thought to have been produced by successive emplacement of magmas, which formed four rock groups. These are the pyroxenite of the first group, titanomagnetite gabbronorites and leucogabbro of the second group, gabbronorites of the third group, and lamprophyres of the fourth group The trace-element patterns of various rocks and the results of simulations by the COMAGMAT-3.5 computer program led us to believe that all four rock groups of the massif were generated by the successive emplacements of several portions of the initial magma, which was a complicatedly differentiated suspension of olivine, plagioclase, and magnetite crystals in ferroabsaltic melt at a temperature of approximately 1130°?. The gravitational separation of these phases in the melt before its emplacement into the chamber and during the subsequent emplacement of various portions of the initial magma into the modern chamber predetermined the heterogeneity of the massif (its block structure). As a result, the bulk of the Chineysky massif is composed of compositionally principally different rocks of the second and third groups, with the predominance of intratelluric plagioclase and magnetite crystals in the former case (gabbronorite and leucogabbro series in the western and southeastern blocks) and orthopyroxene in the latter one (norite series, central block). The rocks of the third group were generated later. The crystallization sequences of minerals modeled for the Chineysky massif can be classed into two major types [2]: (a) "high-Al", which is typical of the "leucogabbro" compositions and characterized by the occurrence of a magnetite-plagioclase cotectic, and (b) "high-Mg", which is typical of the noriteseries and is characterized by the early appearance of olivine on the liquidus or the concurrent crystallization of this mineral with magnetite or plagioclase. It is worth mentioning the early app

Gongalskiy, B.; Krivolutskaya, N.

2009-04-01

360

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

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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

2014-12-19

 
 
 
 
361

Review of the Article by Orlando Lourenco:Piaget and Vygotsky: Many resemblances, and a crucial difference(NewIdeasinPsychology 30 (2012) P. 281-295)  

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The article sets a goal to introduce readers to the article of Orlando Lourenco, professor of Lisbon University, who suggests totally new (and from his point of view unreasonably ignored for a long period of time) parameters of assessing resemblances and differences in approaches of two influential developmental psychologists (Piaget and Vygotsky) to several fundamental problems of psychology: 1)the origins of knowledge and motor of development; 2) influence of equal vs. those based on autho...

Alexeyeva G.V.; Yermolova T.V.

2013-01-01

362

Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso  

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One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembling Leishmania sp. were visualized by citology.Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico par...

Brito, F. L. C.; Alves, L. C.; Maia, F. C. L.; Albuquerque, A. R.; Ortiz, J. P. D.; Laus, J. L.

2007-01-01

363

Fetuin-A/Albumin-Mineral Complexes Resembling Serum Calcium Granules and Putative Nanobacteria: Demonstration of a Dual Inhibition-Seeding Concept  

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Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine wit...

Wu, Cheng-yeu; Martel, Jan; Young, David; Young, John D.

2009-01-01

364

Kuttner's tumor of salivary glands resembling marginal zone B-cell lymphoma of the MALT type: a histopathologic and immunohistochemical study of 7 cases.  

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Kuttner's tumor is a benign inflammatory process of the submandibular gland that presents as a hard mass mimicking a malignant neoplasm clinically. The histologic feature varies according to stage of evolution and severity of inflammation. We report here 7 cases of Kuttner's tumor that morphologically resemble primary salivary gland marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Histologically, the lobular architecture was distorted and the septa showed sclerosis. There was a dense lymphoplasmacytoid infiltration with lymphoid follicle formation accompanied by loss of acini and ducts. In 4 cases, a few salivary gland ducts contained the lymphoid cells within the epithelium. However, a true lymphoepithelial lesion was observed in none of the 7 cases. Immunohistochemical study demonstrated a disrupted follicular dendritic cell network, which is a characteristic finding of follicular colonization of MALT-type lymphoma. In 6 cases, there were a few small foci of lymphocytes somewhat resembling centrocyte-like cells of MALT-type lymphoma. However, immunohistological study demonstrated the mixed nature of the cells resembling centrocyte-like cells. Moreover, the polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. PMID:15494864

Kojima, Masaru; Nakamura, Shigeo; Itoh, Hideaki; Yamane, Yuko; Shimizu, Kazuhiko; Masawa, Nobuhide

2004-10-01

365

{sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT  

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A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its limitations, {sup 18}F-FDG PET-CT is used for imaging of high-grade glioma. Amino acid PET radiotracers including {sup 18}F-FDOPA display superior contrast to {sup 18}F-FDG because of low uptake of amino acids in normal brain tissue. They have particularly special value in the detection of low-grade gliomas. However, {sup 18}F-FDOPA tumour uptake cannot provide reasonable predictions about tumour grade and proliferation in recurrent tumours that have undergone treatments. Also, their difficult synthesis or need for an on-site cyclotron limits their widespread use. The present case shows the utility of {sup 18}F-FDOPA PET-CT in detection of a recurrent high-grade AA that was missed by {sup 18}F-FDG PET-CT. It highlights that {sup 18}F-FDG PET-CT can be falsely negative, even in high-grade recurrent gliomas and, therefore, in cases with strong clinical suspicion {sup 18}F-FDOPA PET-CT can be an alternative imaging modality to rule out recurrence even when {sup 18}F-FDG PET-CT is negative.

Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

2013-12-15

366

18F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by 18F-FDOPA PET-CT  

International Nuclear Information System (INIS)

A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. 18F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (18F-FDOPA) PET-CT was done, 5 days after 18F-FDG PET-CT. The study revealed an 18F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. 18F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. 18F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its limitations, 18F-FDG PET-CT is used for imaging of high-grade glioma. Amino acid PET radiotracers including 18F-FDOPA display superior contrast to 18F-FDG because of low uptake of amino acids in normal brain tissue. They have particularly special value in the detection of low-grade gliomas. However, 18F-FDOPA tumour uptake cannot provide reasonable predictions about tumour grade and proliferation in recurrent tumours that have undergone treatments. Also, their difficult synthesis or need for an on-site cyclotron limits their widespread use. The present case shows the utility of 18F-FDOPA PET-CT in detection of a recurrent high-grade AA that was missed by 18F-FDG PET-CT. It highlights that 18F-FDG PET-CT can be falsely negative, even in high-grade recurrent gliomas and, therefore, in cases with strong clinical suspicion 18F-FDOPA PET-CT can be an alternative imaging modality to rule out recurrence even when 18F-FDG PET-CT is negative

367

Matrix comparison, Part 2 : Measuring the resemblance between proximity measures or ordination results by use of the mantel and procrustes statistics  

DEFF Research Database (Denmark)

The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing such comparisons, matrix generation, and the composition of proximity measures, are introduced and discussed. In this second part, the authors introduce and thoroughly demonstrate two related matrix comparison techniques the Mantel test and Procrustes analysis, respectively. These techniques can compare and evaluate the degree of monotonicity between different proximity measures or their ordination results. In common with these techniques is the application of permutation procedures to test hypotheses about matrix resemblances. The choice of technique is related to the validation at hand. In the case of the Mantel test, the degree of resemblance between two measures forecast their potentially different affect upon ordination and clustering results. In principle, two proximity measures with a very strong resemblance most likely produce identical results, thus, choice of measure between the two becomes less important. Alternatively, or as a supplement, Procrustes analysis compares the actual ordination results without investigating the underlying proximity measures, by matching two configurations of the same objects in a multidimensional space. An advantage of the Procrustes analysis though, is the graphical solution provided by the superimposition plot and the resulting decomposition of variance components. Accordingly, the Procrustes analysis provides not only a measure of general fit between configurations, but also values for individual objects enabling more elaborate validations. As such, the Mantel test and Procrustes analysis can be used as statistical validation tools in informetric studies and thus help choosing suitable proximity measures.

Schneider, Jesper Wiborg; Borlund, Pia

2007-01-01

368

Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso  

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Full Text Available One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembling Leishmania sp. were visualized by citology.Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico parasitológico e sorológico por meio de exame do material da medula óssea e por imunofluorescência indireta, respectivamente. À citologia da úlcera corneana, visibilizaram-se formas amastigotas compatíveis com Leishmania sp.

F.L.C. Brito

2007-02-01

369

Therapeutic Intervention of Post Surgical Removal of Oligodendroglioma- Case Report  

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Aims and objectives: To describe the evaluation, management and rehabilitation of left side hemi plegia of a middle aged female in spastic stage. Background: History of tumor which was treated surgically. The reported onset was gradual with chief complaint of not being able to use her left side of the body, post surgery. Treatment: The patient was having medical, surgical and physiotherapy treatment from last 6 years. Uniqueness: This case is unique in terms that it involves a patien...

Narkeesh; Lekhni Priya

2012-01-01

370

Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: English Abstract in english 7-ketocholesterol (7-KC) differs from cholesterol by a functional ketone group at C7. It is an oxygenated cholesterol derivative (oxysterol), commonly present in oxidized low-density lipoprotein (LDL). Oxysterols are generated and participate in several physiologic and pathophysiologic processes. Fo [...] r instance, the cytotoxic effects of oxidized LDL have been widely attributed to bioactive compounds like oxysterols. The toxicity is in part due to 7-KC. Here we aimed to demonstrate the possibility of incorporating 7-KC into the synthetic nanoemulsion LDE, which resembles LDL in composition and behavior. This would provide a suitable artificial particle resembling LDL to study 7-KC metabolism. We were able to incorpórate 7-KC in several amounts into LDE. The incorporation was evaluated and confirmed by several methods, including gel filtration chromatography, using radiolabeled lipids. The incorporation did not change the main lipid composition characteristics of the new nanoparticle. Particle sizes were also evaluated and did not differ from LDE. In vivo studies were performed by injecting the nanoemulsion into mice. The plasma kinetics and the targeted organs were the same as described for LDE. Therefore, 7-KC-LDE maintains composition, size and some functional characteristics of LDE and could be used in experiments dealing with 7-ketocholesterol metabolism in lipoproteins.

Giovani M, Favero; Raul C, Maranhão; Durvanei A, Maria; Débora, Levy; Sérgio P, Bydlowski.

371

Analysis of high–dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer  

International Nuclear Information System (INIS)

The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84 Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6 mm3, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife

372

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404  

International Nuclear Information System (INIS)

Purpose: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. Methods and Materials: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. Results: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which sta stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. Conclusions: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years

373

Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report / Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico parasitológico e sorológico por meio de exame do material da medula óssea e por imunofluorescência indireta, respectivamente. À citologia da úlcera corneana, visi [...] bilizaram-se formas amastigotas compatíveis com Leishmania sp. Abstract in english One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembli [...] ng Leishmania sp. were visualized by citology.

F.L.C., Brito; L.C., Alves; F.C.L., Maia; A.R., Albuquerque; J.P.D., Ortiz; J.L., Laus.

2007-02-01

374

Secondary syphilis lesions resembling pityriasis  

International Nuclear Information System (INIS)

This case report describes a male patient who presented with generalized, centrally-ulcerated papules with crusts and hypopigmented macules. Initially, differential diagnostic considerations included pityriasis lichenoides but the serology for syphilis was positive and there was a rapid response to penicillin with clearing of the lesions at the end of three weeks treatment. (author)

375

Analysis of high–dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer  

Energy Technology Data Exchange (ETDEWEB)

The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D{sub 5%} of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D{sub 98%}, was 27.93 ± 0.84 Gy. The V{sub 100%} of the prostate target was 95.57% ± 3.47%. The V{sub 100%} of the bladder and the rectum were 717.16 and 79.6 mm{sup 3}, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D{sub 98%} to D{sub 80%}) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D{sub 10%} and D{sub 5%}. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.

Sudahar, H., E-mail: h.sudahar@gmail.com [Department of Radiotherapy, Apollo Speciality Hospital, Chennai (India); Kurup, P.G.G.; Murali, V.; Mahadev, P. [Department of Radiotherapy, Apollo Speciality Hospital, Chennai (India); Velmurugan, J. [Department of Medical Physics, Anna University, Chennai (India)

2013-01-01

376

Magnetic resonance imaging of wrist and finger joints in healthy subjects occasionally shows changes resembling erosions and synovitis as seen in rheumatoid arthritis.  

DEFF Research Database (Denmark)

OBJECTIVE: To explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings. METHODS: Twenty-eight healthy individuals were studied. Contrast-enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema. RESULTS: Conventional radiography revealed erosion-like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low-grade erosion-like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low-grade synovitis-like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C-reactive protein, and these subjects displayed 44.5% of the synovitis-like changes and 41.7% of the erosion-like changes. Bone marrow edema-like changes were not found in any joints. CONCLUSION: Changes resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion-like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints

Ejbjerg, Bo; Narvestad, Eva

2004-01-01

377

Complete nucleotide sequence of the S10-spc operon of phytoplasma: gene organization and genetic code resemble those of Bacillus subtilis.  

Science.gov (United States)

An 11.4-kbp region of genomic DNA containing the complete S10-spc operon was constructed by an integrative mapping technique with eight plasmid vectors carrying ribosomal protein sequences from onion yellows phytoplasma. Southern hybridization analysis indicated that phytoplasmal S10-spc is a single-copy operon. This is the first complete S10-spc operon of a phytoplasma to be reported, although only a part of six serial genes of the S10 operon is reported previously. The operon has a context of 5'-rps10, rpl3, rpl4, rpl23, rpl2, rps19, rpl22, rps3, rpl16, rpl29, rps17, rpl14, rpl24, rpl5, rps14, rps8, rpl6, rpl18, rps5, rpl30, rpl15, SecY-3', and is composed of 21 ribosomal protein subunit genes and a SecY protein translocase subunit gene. Resembling Bacillus, this operon contains an rpl30 gene that other mollicutes (Mycoplasma genitalium, M. pneumoniae, and M. pulmonis) lack. A phylogenetic tree based on the rps3 sequence showed that phytoplasmas are phylogenetically closer to acholeplasmas and bacillus than to mycoplasmas. In the S10-spc operon, translation may start from either a GTG codon or an ATG codon, and stop at a TGA codon, as has been reported for acholeplasmas and bacillus. However, in mycoplasmas, GTG was found as a start codon, and TGA was found not as a stop codon, but instead as a tryptophan codon. These data derived from the gene organization, and the genetic code deviation support the hypothesis that phytoplasmal genes resemble those of acholeplasmas and Bacillus more than those of other mollicutes. PMID:12162807

Miyata, Shin-Ichi; Furuki, Ken-Ichiro; Oshima, Kenro; Sawayanagi, Toshimi; Nishigawa, Hisashi; Kakizawa, Shigeyuki; Jung, Hee-Young; Ugaki, Masashi; Namba, Shigetou

2002-07-01

378

A citrus flavonoid, 6-demethoxytangeretin, suppresses production and gene expression of interleukin-6 in human mast cell-1 via anaplastic lymphoma kinase and mitogen-activated protein kinase pathways.  

Science.gov (United States)

Citrus species has been traditionally used in Korea for the treatment of coughing, sputum and dyspepsia. Of the known citrus flavonoids, 6-demethoxytangeretin was reported to exert anti-inflammatory activity. In order to determine the anti-allergic activity of 6-demethoxytangeretin, we examined whether or not 6-demethoxytangeretin was able to suppress activation of the human mast cell line, HMC-1, induced by phorbol 12-myristate 13-acetate (PMA) plus A23187. Interleukin-6 production and relevant gene expression in activated HMC-1 cells were determined by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Also, the involvement of the anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinases (MAPKs) in activated HMC-1 cells were studied. 6-Demethoxytangeretin suppresses interleukin-6 production, tumor necrosis factor-alpha gene expression, ALK and MAPKs in HMC-1 cells stimulated by PMA plus A23187. Therefore, it was evident that 6-demethoxytangeretin suppressed activation of HMC-1 cells by PMA plus A23187 by inhibiting the activity of ALK and MAPKs and subsequently suppressing gene expression, which suggest that 6-demethoxytangeretin may be involved in the regulation of mast cell-mediated inflammatory responses. PMID:24500009

Kim, Young-Mi; Chae, Hee-Sung; Lee, Eun Joo; Yang, Min Hye; Park, Jin Hee; Yoon, Kee Dong; Kim, Jinwoong; Ahn, Hee Chul; Choi, Young Hee; Chin, Young-Won

2014-01-01

379

Combined BRAF(V600E)- and SRC-inhibition induces apoptosis, evokes an immune response and reduces tumor growth in an immunocompetent orthotopic mouse model of anaplastic thyroid cancer.  

Science.gov (United States)

Anaplastic (ATC) and refractory papillary thyroid cancer (PTC) lack effective treatments. Inhibition of either oncogenic BRAF or SRC has marked anti-tumor effects in mouse models of thyroid cancer, however, neither drug induces notable apoptosis. Here we report that the SRC-inhibitor dasatinib further sensitizes BRAFV600E-positive thyroid cancer cells to the BRAFV600E-inhibitor PLX4720. Combined treatment with PLX4720 and dasatinib synergistically inhibited proliferation and reduced migration in PTC and ATC cells. Whereas PLX4720 did not induce robust apoptosis in thyroid cancer cells, combined treatment with dasatinib induced apoptosis in 4 of 6 lines. In an immunocompetent orthotopic mouse model of ATC, combined PLX4720 and dasatinib treatment significantly reduced tumor volume relative to PLX4720 treatment alone. Immune cell infiltration was increased by PLX4720 treatment and this effect was maintained in mice treated with both PLX4720 and dasatinib. Further, combined treatment significantly increased caspase 3 cleavage in vivo relative to control or either treatment alone. In conclusion, combined PLX4720 and dasatinib treatment induces apoptosis, increases immune cell infiltration and reduces tumor volume in a preclinical model of ATC, suggesting that the combination of these FDA-approved drugs may have potential for the treatment of patients with ATC or refractory PTC. PMID:24994118

Vanden Borre, Pierre; Gunda, Viswanath; McFadden, David G; Sadow, Peter M; Varmeh, Shohreh; Bernasconi, Maria; Parangi, Sareh

2014-06-30

380

Redifferentiation and induction of tumor suppressors miR-122 and miR-375 by the PAX8/PPAR? fusion protein inhibits anaplastic thyroid cancer: a novel therapeutic strategy.  

Science.gov (United States)

Anaplastic thyroid cancer (ATC) is an aggressive, fatal disease unresponsive to traditional therapies, generating a need to develop effective therapies. The PAX8/PPAR? fusion protein (PPFP) has been shown to favorably modulate tumor growth in follicular thyroid cancer, prompting our evaluation of its efficacy to inhibit ATC cell and tumor growth in vitro and in vivo. PPFP was constitutively expressed in five ATC cell lines: BHT-101, FRO, C-643, KTC-2 and KTC-3, and inhibited cell growth in four of five cell lines and xenograft tumor growth in four of four cell lines. PPFP-mediated growth inhibition involved multiple mechanisms, including upregulation of miR-122 and miR-375, associated with decreased angiogenesis and AKT pathway inactivation, respectively. Also, PPFP expression resulted in marked increase of thyroid-specific marker transcripts, including PAX8, thyroid peroxidase (TPO), sodium iodide symporter (NIS) and thyroglobulin, to varying degrees by activating their respective promoters, suggesting that PPFP induced cellular redifferentiation. Functional studies demonstrate that increased NIS messenger RNA is not associated with increased 125I uptake. However, ectopic expression of wild-type NIS-induced perchlorate-sensitive iodine uptake, suggesting that endogenous NIS in ATC cell lines is defective. As current treatment for ATC is only palliative, overexpression of PPFP may offer a novel therapeutic strategy for the treatment of ATC. PMID:23598436

Reddi, H V; Driscoll, C B; Madde, P; Milosevic, D; Hurley, R M; McDonough, S J; Hallanger-Johnson, J; McIver, B; Eberhardt, N L

2013-05-01

 
 
 
 
381

Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques.  

Science.gov (United States)

Using 3D searching techniques based on algorithms derived from graph theory, we have established two previously unreported structural similarities involving the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT). First, we report that there is a strong similarity between the 3D folds of the RNase H domain of RT and the 'ATPase folds' of hexokinase, the 70 kDa heat-shock cognate protein and actin. Like RNase H, these enzymes are involved in nucleotide binding and metal ion-catalysed cleavage of a phosphodiester bond. Similarities of the folding motif and the position of the metal-binding site in these enzymes suggest possible functional analogies and evolutionary relationships with RNase H. Second, we find there is a strong resemblance between the folds of the RNase H domain and of the p66 and p51 'connection' domains of RT. It is possible that this striking similarity within the RT structure indicates a possible ancestral gene doubling event. The similarity may also indicate that the connection domains possess functional roles in addition to those previously suggested, and they may therefore represent a further target for the design of therapeutic agents. PMID:7684987

Artymiuk, P J; Grindley, H M; Kumar, K; Rice, D W; Willett, P

1993-06-01

382

Inferior Cerebellar Hypoplasia Resembling a Dandy-Walker-Like Malformation in Purebred Eurasier Dogs with Familial Non-Progressive Ataxia: A Retrospective and Prospective Clinical Cohort Study  

Science.gov (United States)

Cerebellar malformations can be inherited or caused by insults during cerebellar development. To date, only sporadic cases of cerebellar malformations have been reported in dogs, and the genetic background has remained obscure. Therefore, this study`s objective was to describe the clinical characteristics, imaging features and pedigree data of a familial cerebellar hypoplasia in purebred Eurasier dogs. A uniform cerebellar malformation characterized by consistent absence of the caudal portions of the cerebellar vermis and, to a lesser degree, the caudal portions of the cerebellar hemispheres in association with large retrocerebellar fluid accumulations was recognized in 14 closely related Eurasier dogs. Hydrocephalus was an additional feature in some dogs. All dogs displayed non-progressive ataxia, which had already been noted when the dogs were 5 – 6 weeks old. The severity of the ataxia varied between dogs, from mild truncal sway, subtle dysmetric gait, dysequilibrium and pelvic limb ataxia to severe cerebellar ataxia in puppies and episodic falling or rolling. Follow-up examinations in adult dogs showed improvement of the cerebellar ataxia and a still absent menace response. Epileptic seizures occurred in some dogs. The association of partial vermis agenesis with an enlarged fourth ventricle and an enlarged caudal (posterior) fossa resembled a Dandy-Walker-like malformation in some dogs. Pedigree analyses were consistent with autosomal recessive inheritance. PMID:25668516

Bernardino, Filipa; Rentmeister, Kai; Schmidt, Martin J.; Bruehschwein, Andreas; Matiasek, Kaspar; Matiasek, Lara A.; Lauda, Alexander; Schoon, Heinz A.; Fischer, Andrea

2015-01-01

383

A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer  

International Nuclear Information System (INIS)

In a process seeking out a good model cell line for Epstein-Barr virus (EBV)-associated gastric cancer, we found that one previously established gastric adenocarcinoma cell line is infected with type 1 EBV. This SNU-719 cell line from a Korean patient expressed cytokeratin without CD19 or CD21 expression. In SNU-719, EBNA1 and LMP2A were expressed, while LMP1 and EBNA2 were not. None of the tested lytic EBV proteins were detected in this cell line unless stimulated with phorbol ester. EBV infection was also shown in the original carcinoma tissue of SNU-719 cell line. Our results support the possibility of a CD21-independent EBV infection of gastric epithelial cells in vivo. As the latent EBV gene expression pattern of SNU-719 closely resembles that of the EBV-associated gastric cancer, this naturally derived cell line may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis