Sample records for resembled anaplastic oligodendroglioma

  1. Low-grade and anaplastic oligodendroglioma. (United States)

    Van Den Bent, Martin J; Bromberg, Jacolien E C; Buckner, Jan


    Anaplastic oligodendrogliomas have long attracted interest because of their sensitivity to chemotherapy, in particular in the subset of 1p/19q co-deleted tumors. Recent molecular studies have shown that all 1p/19q co-deleted tumors have IDH mutations and most of them also have TERT mutations. Because of the presence of similar typical genetic alterations in astrocytoma and glioblastoma, the current trend is to diagnose these tumors on the basis of their molecular profile. Further long-term follow-up analysis of both EORTC and RTOG randomized studies on (neo)adjuvant procarbazine, lomustine, vincristine (PCV) chemotherapy have shown that adjuvant chemotherapy indeed improves outcome, and this is now standard of care. It is also equally clear that benefit to PCV chemotherapy is not limited to the 1p/19q co-deleted cases; potential other predictive factors are IDH mutations and MGMT promoter methylation. Moreover, a recent RTOG study on low-grade glioma also noted an improved outcome after adjuvant PCV chemotherapy, thus making (PCV) chemotherapy now standard of care for all 1p/19q co-deleted tumors regardless of grade. It remains unclear whether temozolomide provides the same survival benefit, as no data from well-designed clinical trials on adjuvant temozolomide in this tumor type are available. Another question that remains is whether one can safely leave out radiotherapy as part of initial treatment to avoid cognitive side-effects of radiotherapy. The current data suggest that delaying radiotherapy and treatment with chemotherapy only may be detrimental for overall survival.

  2. Arteriovenous malformation within an isocitrate dehydrogenase 1 mutated anaplastic oligodendroglioma

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    Grace Lai


    Full Text Available Background: The co-occurrence of intracranial arteriovenous malformations (AVMs and cerebral neoplasms is exceedingly rare but may harbor implications pertaining to the molecular medicine of brain cancer pathogenesis. Case Description: Here, we present a case of de novo AVM within an isocitrate dehydrogenase 1 mutated anaplastic oligodendroglioma (WHO Grade III and review the potential contribution of this mutation to aberrant angiogenesis as an interesting case study in molecular medicine. Conclusion: The co-occurrence of an IDH1 mutated neoplasm and AVM supports the hypothesis that IDH1 mutations may contribute to aberrant angiogenesis and vascular malformation.

  3. Racial disparities in anaplastic oligodendroglioma: An analysis on 1643 patients. (United States)

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


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

  4. Low-grade and anaplastic oligodendrogliomas: differences in tumour microvascular permeability evaluated with dynamic contrast-enhanced magnetic resonance imaging. (United States)

    Jia, Zhongzheng; Geng, Daoying; Liu, Ying; Chen, Xingrong; Zhang, Jun


    This study was designed to quantitatively assess the microvascular permeability of oligodendroglioma using the volume transfer constant (K(trans)) and the volume of the extravascular extracellular space per unit volume of tissue (V(e)) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We aimed to evaluate the effectiveness of K(trans) and V(e) in distinguishing between low-grade and anaplastic oligodendroglioma. The maximal values of K(trans) and V(e) for 65 patients with oligodendroglioma (27 grade II, 38 grade III) were obtained. Differences in K(trans) and V(e) between the two groups were analysed using the Mann-Whitney rank-sum test. Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for the K(trans) and Ve that could differentiate between low-grade and anaplastic oligodendrogliomas. Values for K(trans) and Ve in low-grade oligodendrogliomas were significantly lower than those in anaplastic oligodendrogliomas (p low-grade and anaplastic oligodendrogliomas in a statistically significant manner. Our results suggest that DCE-MRI can distinguish the differences in microvascular permeability between low-grade and anaplastic oligodendrogliomas.

  5. Complete Radiologic Response in an Anaplastic Oligodendroglioma Treated with Temozolomide and Bevacizumab

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    Artur Katz


    Full Text Available In this case report, we describe a rare case of a 32-year-old man who presented a highly aggressive, fast growing anaplastic oligodendroglioma five years after being treated with whole brain radiotherapy for a CNS recurrence of a lymphoblastic lymphoma. Initially, the patient was submitted to a surgical intervention and partial tumor resection, which allowed us to establish the pathologic diagnosis and the presence of a 1p deletion. Shortly after the operation the tumor grew back, exerting important mass effect. Since no radiation therapy or surgery could be used and the patient faced a critical condition, chemotherapy was started with a combination of temozolomide and bevacizumab. Immediately after the first cycle a marked clinical and radiological improvement was documented.

  6. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients. (United States)

    Shin, Jacob Y; Diaz, Aidnag Z


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

  7. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

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    Ahmed Idbaih

    Full Text Available Anaplastic oligodendrogliomas (AOD are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19(q10;p10, IDH1, IDH2, CIC and FUBP1 mutations.To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA," has been supported by the Institut National du Cancer (InCA. Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

  8. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

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    Barbara Klink

    Full Text Available 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.

  9. Prediction of anaplastic transformation in low-grade oligodendrogliomas based on magnetic resonance spectroscopy and 1p/19q codeletion status. (United States)

    Bourdillon, Pierre; Hlaihel, Chadi; Guyotat, Jacques; Guillotton, Laurent; Honnorat, Jérôme; Ducray, François; Cotton, François


    The aim of this study was to assess whether combining multimodal magnetic resonance imaging (MRI) with the determination of the 1p/19q codeletion status could improve the ability to predict anaplastic transformation in low-grade oligodendrogliomas. Twenty patients with grade II oligodendrogliomas were followed-up using multimodal MR [proton MR spectroscopy (MRS), perfusion, and conventional MR imaging]. All patients diagnoses were histologically proven, and 1p/19q codeletion status was analyzed for all patients. Median follow-up was 30.5 ± 11.4 months. Anaplastic transformation was observed in six patients. The only MRI feature that was associated with anaplastic transformation was an elevation of the choline/creatine ratio >2.4 which was observed in 4 out of 6 patients with anaplastic transformation versus 1 out of 14 patients without anaplastic transformation. In patients without 1p/19q codeletion, an elevation of the choline/creatine ratio >2.4 was associated with the occurrence of anaplastic transformation in all cases (4 out of 4 patients), with a mean time of 12 months. In contrast, in patients with a 1p/19q codeletion, no anaplastic transformation was observed in the patient who had an elevation of >2.4 of the choline/creatine ratio and two patients demonstrated an anaplastic transformation without any elevation of this ratio.Prospective validation in a larger series is needed, yet the present study suggests that combining data from in vivo proton MRS and genetic analysis could be a promising strategy to predict time to anaplastic transformation at the individual level in patients with low-grade oligodendrogliomas and may help deciding when chemotherapy and/or radiotherapy should be initiated in these tumors.

  10. Synergistic antitumor effect between gefitinib and fractionated irradiation in anaplastic oligodendrogliomas cannot be predicted by the Egfr signaling activity.

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    Sophie Pinel

    Full Text Available In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment "gefitinib + radiotherapy" and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4 harboring high levels of phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF 75 mg/kg/day x 5 days/week, for 2 weeks and/or fractionated radiotherapy (RT: 5x2Gy/week for 2 weeks. Our results showed that GEF and/or RT induced significant tumor growth delays. However, only the TCG3 xenografts were highly responsive to the combination GEF+RT, with ∼50% of tumor cure. Phosphoproteins analysis five days after treatment onset demonstrated in TCG3 xenografts, but not in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a transient beneficial therapeutic response, rapidly followed by tumor regrowth, along with a major vascular remodeling. Taken together, our data evoked an "EGFR-addictive" behavior for TCG3 tumors. This study confirms that combination of gefitinib with fractionated irradiation could be a potent therapeutic strategy for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment seems mainly beneficial for "EGFR-addictive" tumors. Unfortunately, neither the usual molecular markers (EGFR amplification, PTEN loss nor the basal overexpression of phosphoproteins were useful to distinguish this responsive tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the treatment might be more relevant, and requires further validation.

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

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


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

  12. Interventricular low-grade oligodendroglioma with multiple parenchymal relapse. (United States)

    Akhavan, Ali; Binesh, Fariba; Rakhsha, Afshin; Navabii, Hossein


    Oligodendrogliomas can be found anywhere oligodendrocytes exist; however, they mostly occur in frontal lobes. Although intra- and extra central nervous system dissemination of anaplastic oligodendroglioma is a well-known property of this tumour, low-grade oligodendroglioma with intracranial relapse is a very uncommon finding. In this case report, a 37-year-old man with grade II oligodendroglioma relapsed after 18 months with multiple parenchymal masses is presented.

  13. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: A report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial

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    H.J. Dubbink (Erik Jan); P.N. Atmodimedjo; J.M. Kros (Johan); P.J. French (Pim); M. Sanson (Marc); A. Idbaih (Ahmed); P. Wesseling (Pieter); R. Enting (Roelien); W.G.M. Spliet (Wim); C.C. Tijssen (Cees); W.N.M. Dinjens (Winand); T.S. Gorlia (Thierry); M.J. van den Bent (Martin)


    textabstractBackground Histopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic and predictive molecular abnormalities. We investigated a series of patients with locally diagnosed anaplastic oligodendroglial tumors included in

  14. Symptomatic spinal cord metastasis from cerebral oligodendroglioma. (United States)

    Elefante, A; Peca, C; Del Basso De Caro, M L; Russo, C; Formicola, F; Mariniello, G; Brunetti, A; Maiuri, F


    Spinal subarachnoid spread is not uncommon in brain oligodendrogliomas; on the other hand, symptomatic involvement of the spinal cord and cauda is very rare, with only 16 reported cases. We report the case of a 41-year-old man who underwent resection of a low-grade frontal oligodendroglioma 4 years previously. He was again observed because of bilateral sciatic pain followed by left leg paresis. A spine MRI showed an intramedullary T12-L1 tumor with root enhancement. At operation, an intramedullary anaplastic oligodendroglioma with left exophytic component was found and partially resected. Two weeks later, a large left frontoparietal anaplastic oligodendroglioma was diagnosed and completely resected. The patient was neurologically stable for 8 months and died 1 year after the spinal surgery because of diffuse brain and spinal leptomeningeal spread. The review of the reported cases shows that spinal symptomatic metastases can occur in both low-grade and anaplastic oligodendrogliomas, even many years after surgery of the primary tumor; however, they exceptionally occur as first clinical manifestation or as anaplastic progression. The spinal seeding represents a negative event leading to a short survival.

  15. Imaging of oligodendroglioma. (United States)

    Smits, Marion


    Oligodendroglioma are glial tumours, predominantly occurring in adults. Their hallmark molecular feature is codeletion of the 1p and 19q chromosome arms, which is not only of diagnostic but also of prognostic and predictive relevance. On imaging, these tumours characteristically show calcification, and they have a cortical-subcortical location, most commonly in the frontal lobe. Owing to their superficial location, there may be focal thinning or remodelling of the overlying skull. In contrast to other low-grade gliomas, minimal to moderate enhancement is commonly seen and perfusion may be moderately increased. This complicates differentiation from high-grade, anaplastic oligodendroglioma, in which enhancement and increased perfusion are also common. New enhancement in a previously non-enhancing, untreated tumour, however, is suggestive of malignant transformation, as is high growth rate. MR spectroscopy may further aid in the differentiation between low- and high-grade oligodendroglioma. A relatively common feature of recurrent disease is leptomeningeal dissemination, but extraneural spread is rare. Tumours with the 1p/19q codeletion more commonly show heterogeneous signal intensity, particularly on T2 weighted imaging; calcifications; an indistinct margin; and mildly increased perfusion and metabolism than 1p/19q intact tumours. For the initial diagnosis of oligodendroglioma, MRI and CT are complementary; MRI is superior to CT in assessing tumour extent and cortical involvement, whereas CT is most sensitive to calcification. Advanced and functional imaging techniques may aid in grading and assessing the molecular genotype as well as in differentiating between tumour recurrence and radiation necrosis, but so far no unequivocal method or combination of methods is available.

  16. Long-term stabilization by radiosurgery of a secondary focal anaplastic transformation in a surgically treated WHO grade II oligodendroglioma. A case report. (United States)

    Yordanova, Y N; Rodriguez-Arribas, M-A; Duffau, H


    We report on a young woman with a left temporal diffuse low-grade glioma treated initially by a subtotal resection. A focal anaplastic area appeared 5years later and was treated by radiosurgery. A long-time stabilization was therefore obtained and lasted even after pregnancy, which is a known factor of faster tumour progression. This report shows that radiosurgery could be an option in the multimodal treatment of a selected group of patients with focal malignant transformation of diffuse low-grade glioma. It could permit long-term stabilization of the tumour without any other adjuvant treatment and without compromising the quality of life.

  17. Clinical management of grade III oligodendroglioma

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    Simonetti G


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

  18. Pediatric brainstem oligodendroglioma

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    Sandeep Mohindra


    Full Text Available The authors present the first report of pediatric brainstem oligodendroglioma, infiltrating midbrain, and medulla oblongata. The report details clinical features, radiological findings, and surgical steps. As this entity is exceedingly uncommon, the overall epidemiology, prognosis, and long-term outcome remain far from established.

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

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    Del Bigio Marc R


    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.

  20. Hypoxia-inducible factor-1-regulated protein expression and oligodendroglioma patient outcome: comparison with established biomarkers and preoperative UCSF low-grade scoring system. (United States)

    Abraham, Shirley; Hu, Nan; Jensen, Randy


    Methods for predicting outcome for patients with oligodendrogliomas and anaplastic oligodendrogliomas (AOs) are limited. Hypoxia-inducible factor-1α (HIF-1α) controls many proteins involved in glycolysis and angiogenesis including VEGF, Glut-1, and CA-IX. We examined whether expression of HIF-1α and other hypoxia-regulated molecules (HRM) can predict overall (OS) and progression-free (PFS) survival. We correlated these data with more established biomarkers and a published preoperative scoring system. We prospectively collected tissue samples and followed outcomes of 50 patients with oligodendrogliomas and 32 with AOs. Tumor tissues were stained for measures of proliferative index, microvascular density, IDH-1 mutational status, and HRMs. We retrospectively analyzed preoperative imaging and clinical data based on the UCSF Scoring System (good prognostic indicators: Karnofsky Performance Scale (KPS) score > 80, age oligodendrogliomas. Both 1p19q codeletion and IDH-1 mutation predict outcome of patients with both oligodendroglioma and AO. The UCSF score is a strong predictor for oligodendrogliomas patient outcome and is strengthened by IDH-1 and 1p19q status. Glut-1 may be useful in predicting PFS in AOs. Proliferation index >5 for oligodendrogliomas and KPS ≤ 80 for AOs predict a worse prognosis. Immunohistochemical markers of HRMs show a significantly higher expression in anaplastic variants of oligodendrogliomas and may contribute to the prediction of survival in these patients.

  1. p53 protein alterations in adult astrocytic tumors and oligodendrogliomas

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    Nayak Anupma


    Full Text Available BACKGROUND: p53 is a tumor suppressor gene implicated in the genesis of a variety of malignancies including brain tumors. Overexpression of the p53 protein is often used as a surrogate indicator of alterations in the p53 gene. AIMS: In this study, data is presented on p53 protein expression in adult cases (>15 years of age of astrocytic (n=152 and oligodendroglial (n=28 tumors of all grades. Of the astrocytic tumors, 86% were supratentorial in location while remaining 14% were located infratentorially - 8 in the the cerebellum and 13 in the brainstem. All the oligodendrogliomas were supratentorial. MATERIALS AND METHODS: p53 protein expression was evaluated on formalin-fixed paraffin-embedded sections using streptavidin biotin immunoperoxidase technique after high temperature antigen retrieval. RESULTS: Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II, 53.8% of anaplastic astrocytomas (WHO Grade III and 50% of glioblastomas (WHO Grade IV were p53 protein positive. In contrast, all the infratentorial tumors were p53 negative except for one brainstem glioblastoma. Similarly, pilocytic astrocytomas were uniformly p53 negative irrespective of the location. Among oligodendroglial tumors, the overall frequency of p53 immunopositivity was lower (only 28%, though a trend of positive correlation with the tumor grade was noted - 25% in Grade II and 31.5% in grade III (anaplastic oligodendroglioma. Interestingly, p53 labeling index (p53 LI did not correlate with the histopathological grade in both astrocytic and oligodendroglial tumors. CONCLUSIONS: Thus, this study gives an insight into the genetic and hence biological heterogeneity of gliomas, not only between astrocytic tumors vs. oligodendrogliomas but also within astrocytic tumors with regard to their grade and location. With p53 gene therapy trials in progress, this will

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

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    Levidou Georgia


    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.

  3. Osteoclastoma-like anaplastic carcinoma of the thyroid

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    Joseph Leena


    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.

  4. Anaplastic thyroid cancer (United States)

    ... page: // Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

  5. Chromosome 1p/19q status combined with expression of protein improves the diagnostic and prognostic evaluation of oligodendrogliomas

    Institute of Scientific and Technical Information of China (English)

    XIONG Ji; LIU Ying; WANG Yin; KE Rong-hu; MAO Ying; YE Zhu-rong


    Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patients, the status of chromosome 1 p/19q deletion, the methylation of O6-methylguanine-DNA methyltransferase (MGMT), and the expression of p53 protein were evaluated and investigated in relation to patients' outcomes.Methods Methylation of MGMT in 73 cases was analyzed by nested methylation-specific PCR (MSP). The levels of MGMT and p53 protein were tested with immunohistochemistry. Pearson's chi-square test and Fisher's exact test were used. Multivariate and Kaplan-Meier analysis were performed to determine patients' outcomes.Results Both oligodendrogliomas and astrocytic gliomas exhibited frequent methylation of MGMT. However, the results of MSP did not completely correspond to that of the immunohistochemical staining for MGMT. The expression of p53 protein was more frequently observed in patients without a 1 p or 19q deletion in anaplastic oligodendrogliomas (=0.032,0.025). In low-grade oligodendrogliomas, methylation of MGMT was more frequent in patients with 1 p/19q deletion than in patients with 1p/19q intact (P=0.038). Patients with oligodendrogliomas with 1p/19q loss of heterozygosity and p53-negative showed a longer progression-free survival.Conclusion Detection of chromosome 1p/19q status combined with p53 protein immunohistochemistry might be beneficial to improve the pathological diagnosis and to determine the prognosis of patients with oligodendrogliomas.

  6. Oligodendroglioma in a French bulldog. (United States)

    Park, Chun-Ho


    A 5-year-old, male French bulldog with bradycardia, dyspnea, and decerebrate rigidity was necropsied. Macroscopic findings were restricted to the brain, and a single mass, 1.5 x 2.0 x 1.5 cm in size, was observed mainly at the right cingulum with prominently protruding into the dilated right lateral ventricle. The mass was grayish white in color, soft and gelatinous, but not clearly delineated. Microscopically, the mass consisted of diffuse proliferated neoplastic oligodendroglial cells characterized by small, round, and hyperchromatic nuclei with clear cytoplasm and the cells aggressively invaded into the adjacent parenchyma. Immunohistochemistry demonstrated that most of the neoplastic cells were positive for S-100 protein, vimentin, neuron specific enolase (NSE), and neurofilament protein (NFP). From these findings, the mass was diagnosed as oligodendroglioma.

  7. Recurrent Oligodendroglioma Treated with Acupuncture and Pharmacopuncture. (United States)

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


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

  8. Purely Cortical Anaplastic Ependymoma

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    Flávio Ramalho Romero


    Full Text Available Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma.

  9. Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma. (United States)

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


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

  10. Prognosis of Glioblastoma With Oligodendroglioma Component is Associated With the IDH1 Mutation and MGMT Methylation Status

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    Jae Kyung Myung


    Full Text Available Glioblastoma (GBM with oligodendroglioma component (GBMO is a newly described GBM subtype in the 2007 World Health Organization classification. However, its biological and genetic characteristics are largely unknown. We investigated the clinicopathological and molecular features of 34 GBMOs and compared the survival rate of these patients with those of patients with astrocytoma, oligodendroglioma, anaplastic oligoastrocytoma (AOA, and conventional GBMs in our hospital. GBMO could be divided into two groups based on the presence of an IDH1 mutation. The IDH1 mutation was more frequently found in secondary GBMO, which had lower frequencies of EGFR amplification but higher MGMT methylation than the wild type IDH1 group, and patients with mutant IDH1 GBMO were on average younger than those with wild-type IDH1. Therefore, GBMO is a clinically and molecularly heterogeneous subtype, largely belonging to a proneural and classical subtype of GBM. The survival rate of GBMO patients itself was worse than that of AOA patients but not significantly better than that of conventional GBM patients. GBMO survival was independent of the dominant histopathological subtype i.e., astrocyte-dominant or oligodendroglioma -dominant, but it was significantly associated with the IDH1 mutation and MGMT methylation status. Therefore, GBMO should be regarded as a separate entity from AOA and must be classified as a subtype of GBM. However, further study is needed to determine whether it is a pathologic variant or a pattern of GBM because GBMO has a similar prognosis to conventional GBMs.

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

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


    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.

  12. Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging

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    Sunwoo, Leonard; Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Yoo, Roh-Eul; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-hoon; Sohn, Chul-Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae Min; Lee, Se-Hoon [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Won, Jae-Kyung; Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)


    The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD). The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype. GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade. In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM. (orig.)

  13. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. (United States)

    Jenkins, Robert B; Blair, Hilary; Ballman, Karla V; Giannini, Caterina; Arusell, Robert M; Law, Mark; Flynn, Heather; Passe, Sandra; Felten, Sara; Brown, Paul D; Shaw, Edward G; Buckner, Jan C


    Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion (P low-grade oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion (P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients.

  14. Low-Grade Oligodendroglioma of the Pineal Region: Case Report. (United States)

    Lamis, Fabricio Correa; de Paiva Neto, Manoel Antonio; Stavale, João Norberto; Cavalheiro, Sergio


    Background Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes, > 17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature.

  15. Proliferating cell nuclear antigen and Ki-67 immunohistochemistry of oligodendrogliomas with special reference to prognosis

    DEFF Research Database (Denmark)

    HEEGAARD, S.; Sommer, Helle Mølgaard; BROHOLM, H.;


    Background. The biologic behavior of oligodendrogliomas is somewhat unpredictable. A supplementary prognostic factor is, therefore, desirable. Methods. Thirty-two pure supratentorial oligodendrogliomas were investigated using proliferating cell nuclear antigen (PCNA) and Ki-67 immunohistochemical...

  16. First report of oligodendroglioma in a sheep : clinical communication

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    A. Derakhshanfar


    Full Text Available Oligodendrogliomas occur most commonly in the dog, but have also been reported in cattle, horses and cats. A 1-year-old sheep with neurological disturbances, including blindness, ataxia, circling and incoordination was referred to the veterinary clinic of Shahid Bahonar University of Kerman. Following euthanasia and necropsy, a soft, relatively well-demarcated mass was observed in the white and grey matter of the right cerebral hemisphere, close to the sylvian fissure in the right cerebral hemisphere. Microscopic examination revealed a sheet of densely packed tumour cells with hyperchromatic nuclei, lightly staining cytoplasm and characteristic perinuclear halo effect which is consistent with a diagnosis of oligodendroglioma. This is the 1st report of oligodendroglioma in sheep.

  17. Infratentorial oligodendroglioma in a child: a case report and review of the literature. (United States)

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


    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.

  18. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. (United States)

    Wiestler, Benedikt; Capper, David; Holland-Letz, Tim; Korshunov, Andrey; von Deimling, Andreas; Pfister, Stefan Michael; Platten, Michael; Weller, Michael; Wick, Wolfgang


    Mutation/loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression has been described in anaplastic gliomas. The present study explored the role of ATRX status in the molecular classification of anaplastic gliomas and its impact on survival in the biomarker cohort of the NOA-04 anaplastic glioma trial. Patients (n = 133) of the NOA-04 trial were analyzed for ATRX expression using immunohistochemistry. ATRX status was correlated with age, histology, isocitrate dehydrogenase (IDH), 1p/19q, alternative lengthening of telomeres (ALT) and O6-methylguanine-DNA methyltransferase (MGMT) status, and the trial efficacy endpoints. Loss of ATRX expression was detected in 45 % of anaplastic astrocytomas (AA), 27 % of anaplastic oligoastrocytomas (AOA) and 10 % of anaplastic oligodendrogliomas (AO). It was mostly restricted to IDH mutant tumors and almost mutually exclusive with 1p/19q co-deletion. The ALT phenotype was significantly correlated with ATRX loss. ATRX and 1p/19q status were used to re-classify AOA: AOA harboring ATRX loss shared a similar clinical course with AA, whereas AOA carrying 1p/19q co-deletion shared a similar course with AO. Accordingly, in a Cox regression model including ATRX and 1p/19q status, histology was no longer significantly associated with time to treatment failure. Survival analysis showed a marked separation of IDH mutant astrocytic tumors into two groups based on ATRX status: tumors with ATRX loss had a significantly better prognosis (median time to treatment failure 55.6 vs. 31.8 months, p = 0.0168, log rank test). ATRX status helps better define the clinically and morphologically mixed group of AOA, since ATRX loss is a hallmark of astrocytic tumors. Furthermore, ATRX loss defines a subgroup of astrocytic tumors with a favorable prognosis.

  19. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas

    NARCIS (Netherlands)

    Triebels, V H J M; Taphoorn, M J B; Brandes, A A; Menten, J; Frenay, M; Tosoni, A; Kros, J M; Stege, E Biemond-ter; Enting, R H; Allgeier, A; van Heuvel, I; van den Bent, M J


    The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the

  20. Chromoblastomycosis resembling sporotrichosis

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    Nair Pradeep


    Full Text Available A 21-year old man presented with multiple noduloulcerative lesions in a linear form resembling sporotrichosis. Histopathology showed the fungal bodies suggestive of chromoblastomycosis and the patient responded to potassium iodide therapy.

  1. Extraneural metastases in anaplastic ependymoma

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    Kumar Pavan


    Full Text Available Ependymoma are rare glial neoplasm, it rarely metastasize outside the central nervous system. We present a case of anaplastic ependymoma with extraneural metastases with review of literature. A ten-year-old male child presented with anaplastic ependymoma of choroid plexus and treated with craniospinal radiotherapy in 1998. He had intracranial recurrence in 2004, confirmed by biopsy. He was given adjuvant chemotherapy in form of PCV. At 10 months after completion of chemotherapy, he developed extracranial scalp metastasis and so was treated with palliative local radiation therapy to the scalp metastasis and systemic chemotherapy with oral Etoposide. Scalp metastasis completely disappeared and ataxia improved. After five cycles of chemotherapy, the patient had progression of disease in form of scalp and cervical lymph node metastasis confirmed by fine needle aspiration cytology, biopsy and immunohistochemistry. He was given salvage chemotherapy (carboplatin + ifosfamide + etoposide at 3-weekly. He had partial response and was still on chemotherapy till May 2007.

  2. Favorable long-term outcome of low-grade oligodendrogliomas irrespective of 1p/19q status when treated without radiotherapy. (United States)

    Iwadate, Yasuo; Matsutani, Tomoo; Hasegawa, Yuzo; Shinozaki, Natsuki; Higuchi, Yoshinori; Saeki, Naokatsu


    Despite the accumulating evidences of high chemosensitivity especially in anaplastic oligodendrogliomas with loss of chromosomes 1p and 19q, the optimal management strategy for low-grade tumors using the 1p/19q information remains controversial. We have treated all low-grade oligodendrogliomas by a chemotherapy-preceding strategy without radiotherapy, and here we analyzed the survival outcomes of 36 consecutive patients in relation to 1p/19q status. The treatment protocol was as follows: (1) simple observation after gross total resection, and (2) modified PCV chemotherapy for postoperative residual tumors or recurrence after total resection. The 1p and 19q status were analyzed by fluorescence in situ hybridization. The median follow-up period was 7.5 years and no patient was lost during the follow-up periods. 1p/19q co-deletion was observed in 72% of the patients, and there was no significant association between 1p/19q co-deletion and chemotherapy response rate. The 5- and 10-year progression-free survival (PFS) rate was 75.1 and 46.9%, respectively, and the median PFS was 121 months for 1p/19q-deleted tumors and 101 months for non-deleted tumors (log-rank test: P = 0.894). Extent of surgery did not affect PFS (P = 0.685). In contrast, the elder patients (>50) had significantly shorter PFS (P = 0.0458). Recurrent tumors were well controlled by chemotherapy irrespective of 1p/19q status, and 35 out of 36 patients survived without receiving radiotherapy. The 5- and 10-year overall survival rates were 100 and 93.8%, respectively. Two of the patients in their sixties (29%) suffered from severe cognitive dysfunctions and marked brain atrophy following chemotherapy alone. These results show that low-grade oligodendrogliomas could be successfully treated by surgical resection and nitrosourea-based chemotherapy alone without radiotherapy irrespective of 1p/19q status.

  3. Oligodendroglioma occurring after radiation therapy for pituitary adenoma

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    Chuni Huang; Wenhysang Chiou; Ho, D.M.


    A 38 year old male dentist developed an oligodendroglioma of the left medial temporal lobe and parasellar region 12 years after radiotherapy with 6600 rads for acromegaly. The 30 cases of radiation-induced gliomas reported in the English literature are reviewed and analysed. The criteria for defining radiation-induced tumours of the central nervous system are proposed as follows: the tumour has a long quiescent ''latency period'', a location in the previously irradiated field, a verified histological difference from a primary condition, and does not arise from a primary condition associated with a genetic syndrome such as neurofibromatosis or tuberous sclerosis. The reported case fulfilled these criteria but appears to be the only reported radiation-induced oligodendroglioma.

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

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    Speirs, Christina K.; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd A. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tran, David D.; Linette, Gerry [Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Chicoine, Michael R.; Dacey, Ralph G.; Rich, Keith M.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Huang, Jiayi, E-mail: [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)


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

  5. Dysembryoplastic neuroepithelial tumor originally diagnosed as astrocytoma and oligodendroglioma

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    Diego Cassol Dozza


    Full Text Available Dysembryoplastic neuroepithelial tumor (DNT, described in 1988 and introduced in the WHO classification in 1993, affects predominantly children or young adults causing intractable complex partial seizures. Since it is benign and treated with surgical resection, its recognition is important. It has similarities with low-grade gliomas and gangliogliomas, which may recur and become malignant. OBJECTIVES: To investigate whether DNT was previously diagnosed as astrocytoma, oligodendroglioma, or ganglioglioma and to determine its frequency in a series of low-grade glial/glio-neuronal tumors. METHODS: Clinical, radiological, and histological aspects of 58 tumors operated from 1978 to 2008, classified as astrocytomas (32, including 8 pilocytic, oligodendrogliomas (12, gangliogliomas (7, and DNT (7, were reviewed. RESULTS: Four new DNT, one operated before 1993, previously classified as astrocytoma (3 and oligodendroglioma (1, were identified. One DNT diagnosed in 2002 was classified once more as angiocentric glioma. Therefore, 10 DNT (17.2% were identified. CONCLUSIONS: Clinical-radiological and histopathological correlations have contributed to diagnose the DNT.

  6. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P


    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.

  7. Pleomorphic xanthoastrocytoma with anaplastic features

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    Cheng ZHI


    Full Text Available Objective  To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA with anaplastic features.  Methods  HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP, vimentin (Vim, CD34, epithelial membrane antigen (EMA, progestrone receptor (PR, neurofilment protein (NF, neuronal nuclei (NeuN, synaptophysin (Syn, Nestin (Nes, S-100 protein (S-100, P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR amplification.  Results  A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and "map"-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found.  Conclusions  Classified as grade Ⅱ in the World Health Organization (WHO classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF and/or areas of

  8. Intramedullary spinal cord and leptomeningeal metastases from intracranial low-grade oligodendroglioma. (United States)

    Verma, Nipun; Nolan, Craig; Hirano, Miki; Young, Robert J


    We present an unusual case of a patient with an intracranial low-grade oligodendroglioma who developed recurrence with an intramedullary spinal cord metastasis and multiple spinal leptomeningeal metastases. The intramedullary spinal cord metastasis showed mild enhancement similar to the original intracranial primary, while the multiple spinal leptomeningeal metastases revealed no enhancement. This is the seventh reported case of symptomatic intramedullary spinal cord metastasis from a low-grade oligodendroglioma.

  9. Congenital Oligodendroglioma: Clinicopathologic and Molecular Assessment with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Hope Richard


    Full Text Available Oligodendroglioma is an infiltrating glial neoplasm frequently seen in adults. Pediatric oligodendrogliomas are rare, with very few cases presenting in infancy and only rare congenital examples. In contrast to adult oligodendrogliomas, pediatric cases typically lack 1p/19q codeletion. Herein we report a case of WHO grade II oligodendroglioma diagnosed in a 7-month-old male infant. The patient initially presented at 3 months of age with symptoms suspicious for seizure. Initial workup including electroencephalography (EEG, electrocardiogram (EKG, and computed tomography (CT of the head was negative. His symptoms persisted, and subsequent magnetic resonance imaging (MRI performed at age of 7 months revealed a 2 cm contrast-enhancing left temporal lobe mass. The mass was excised and the microscopic appearance was that of a classic low grade oligodendroglioma composed of cells with uniformly round nuclei, perinuclear halos, delicate branching capillaries, and an absence of high grade features. Mutant specific (R132H isocitrate dehydrogenase-1 (IDH1 immunohistochemistry was negative, and the tumor lacked detectable 1p or 19q deletions by fluorescent in situ hybridization (FISH. The onset of neurological symptoms in early infancy followed by the positive MRI findings suggests that this case represents a rare example of congenital oligodendroglioma.

  10. Anaplastic giant cell thyroid carcinoma. (United States)

    Wallin, G; Lundell, G; Tennvall, J


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

  11. Stars resembling the Sun (United States)

    Cayrel de Strobel, G.

    stars tightly neighbouring the Sun in mass, chemical composition and state of evolution. The surprising result is that the stars occupy in this HR Diagram a rather extended region around the Sun, many of them seem more evolved and older than the Sun, and only 4 of the evolved stars seem younger. The age of some stars in the sample is also discussed in terms of chromospheric activity and Li-content. Our conclusion is much the same as that contained in previous papers we have written on the subject: in spite of a much larger number of stars, we have not been able to nominate a single star of the sample for a ``perfect good solar twin''. Another aim in beginning, 25 years ago, this search for solar analogues, was to have ready a bunch of stars resembling the Sun and analysed spectroscopically in detail, in order that, when planets hunters of solar type stars, finally would have found such a specimen, we would have been able to immediately compare the physical parameters of this star to those of the Sun. We have been lucky enough: one of the good solar analogues we present herewith, is 51 Pegasi (HD 217014) which, according to the very recent observations by Mayor and Queloz (1995), has a planet orbiting around it. And what is more: two other stars possessing planets: 47 Ursae Majoris (HD 95128) and 70 Virginis (HD 117176), have just been discovered by Marcy and Butler (187th Meeting of the AAS, January 1996). One of them, 47 Ursae Majoris, is also included in the list of photometric solar analogues. The other star, 70 Virginis, has only been included after the ``Planets News'', because the colour index (B-V) of this star is slightly higher than the prescribted limit of the selection, (B-V = 0.71, instead, 0.69). It would have been a pity to leave the third '' planet star out of the competition.

  12. Does facial resemblance enhance cooperation?

    Directory of Open Access Journals (Sweden)

    Trang Giang

    Full Text Available Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces. A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system.

  13. Lichenoid Sarcoidosis Resembling Lichen Scrofulosorum


    Thami Gurvinder P; Kanwar Amrinder J


    An old man with lichenoid popular lesions, dyspnoea and bilateral hilar lymphadenopathy resembling lichen scrofulosorum diagnosed as lichenoid sarcofulosorum and therapeutic response to corticosteroids is discussed.

  14. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma. (United States)

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


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

  15. Incidence of and survival from oligodendroglioma in Denmark, 1943-2002

    DEFF Research Database (Denmark)

    Nielsen, Malene Schjønning; Christensen, Helle Collatz; Kosteljanetz, Michael;


    case per 100,000 person-years, but varied somewhat when viewed across isolated periods. Comparison of the incidence rate before and after the introduction of CT scanning did not reveal a significant difference in the incidence rate. The median survival increased from 1.4 years (95% confidence interval......,304 cases of oligodendroglioma were included in the study. We calculated sex- and age-specific incidence rates in 5-year age intervals and for 5-year calendar periods. Overall survival was estimated by the Kaplan-Meier method. In the period 1943-2002, the incidence rate of oligodendroglioma was less than 1......We established the nationwide, population-based incidence of oligodendroglioma in Denmark during 59 years of monitoring and compared the overall survival of patients with oligodendroglial tumors during the periods 1943-1977 and 1978-2002. On the basis of reports in the Danish Cancer Registry, 1...

  16. Anaplastic thyroid carcinoma: a new approach. (United States)

    Simpson, W J


    Less than 10% of patients with anaplastic thyroid carcinoma survive 5 years when treated by operation and conventional irradiation, but survivors who are disease-free at 2 years appear to be cured. The administration of a small number of large radiation fractions (350 to 800 rads) failed to eradicate the local disease in 14 patients, all of whom died within 9 months. Hyperfractionation (100 rads qid at 3-hour intervals) caused complete tumour regression of 6 of 14 patients and partial regression in 7 others; the 1 patient whose tumour failed to respond was treated only once daily. However, the cost was high: two patients died of spinal cord necrosis and a third of pneumonitis due to the unexpected increase in radiation toxicity caused by the concurrent administration of Adriamycin. If an effective systemic treatment can be devised for this disease, hyperfractionation may be capable of eradicating the massive local tumour masses so characteristic of anaplastic thyroid carcinoma.

  17. Incidental anaplastic thyroid carcinoma: A case report

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    Pembegül GÜNEŞ


    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.

  18. Poorly differentiated (anaplastic) seminoma of the testis. (United States)

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


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

  19. Extensive Growth of an Anaplastic Meningioma

    Directory of Open Access Journals (Sweden)

    Hajrullah Ahmeti


    Full Text Available 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.

  20. Clinical analysis of primary anaplastic carcinoma of the small intestine

    Institute of Scientific and Technical Information of China (English)

    Tsutomu Namikawa; Kazuhiro Hanazaki


    Primary anaplastic carcinoma is a rare variant of small intestinal cancer. Most reports of primary anaplastic carcinoma of the small intestine are isolated case reports, therefore the clinicopathological features, therapeutic management, and surgical outcome of this tumor type remain unclear. This review analyzes the available clinical characteristics of primary anaplastic carcinoma of the small intestine and investigates key differences from differentiated adenocarcinoma of the small intestine. A Medline search was performed using the keywords 'small intestine' and 'anaplastic carcinoma' or 'undifferentiated carcinoma'. Additional articles were obtained from references with in the papers identified by the Medline search. The literature revealed a poor prognosis for patients who underwent surgical resection for anaplastic carcinoma of the small intestine, which gave a 3-year overall survival rate of 10.8% and a median survival time of 5.0 mo. The literature suggests that anaplastic carcinoma is markedly more aggressive than differentiated adenocarcinoma of the small intestine. Surgical resection with the aim of complete tumor removal provides the only beneficial therapeutic option for patients with anaplastic carcinoma of the small intestine, because chemotherapy and radiation therapy have no significant effect on the rate of survival. However, despite complete tumor resection, most patients with anaplastic carcinoma of the small intestine are at great risk of disease recurrence. Multicenter clinical trials are expected to provide additional therapeutic strategies and establish the efficacy of multimodality adjuvant therapy. This report also highlights the importance of a systematic diagnostic approach for anaplastic carcinoma of the small intestine.

  1. Phase II Pediatric Study With Dabrafenib in HGG Patients (United States)


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

  2. Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade "oligodendroglioma". (United States)

    Sasaki, Hikaru; Zlatescu, Magdalena C; Betensky, Rebecca A; Johnk, Loki B; Cutone, Andrea N; Cairncross, J Gregory; Louis, David N


    Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumors. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed us to postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade oligodendroglioma. Central neuropathological review divided the series equally into 22 cases with classical oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22 classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular processes) was associated with 1p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity. As a result, such objective molecular genetic analyses should be incorporated into patient management and into clinical trials of low-grade diffuse gliomas.

  3. Oncolytic HSV-1716 in Treating Younger Patients With Refractory or Recurrent High Grade Glioma That Can Be Removed By Surgery (United States)


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

  4. Oligodendrogliomas: estudo anatomopatológico e clínico de 15 casos Oligodendroglioma: a pathological and clinical study of 15 cases

    Directory of Open Access Journals (Sweden)



    Full Text Available Oligodendrogliomas correspondem a 4-5% dos tumores primários do sistema nervoso central apresentando crescimento infiltrativo e lento. Relatamos os achados anatomopatológicos e clínicos de 15 casos de oligodendrogliomas. Oito pacientes eram do sexo masculino e 7 do feminino. As idades oscilaram entre 17 e 66 anos, apresentando média de 39,73 anos. A sintomatologia apresentada correspondeu ao crescimento expansivo, sendo cefaléia (60% e crises convulsivas (60% os sintomas mais frequentes. O lobo frontal (n=6 foi o sítio anatômico mais acometido, seguido pelo parietal (n=2, temporal (n=1 e occipital (n=1. Cinco pacientes foram submetidos a ressecção total do tumor e 10 pacientes a exerese parcial; dentre estes, 3 foram submetidos a radioterapia adjuvante, 1 a quimioterapia e 1 a quimio e radioterapia. Evidenciou-se taxa de recidiva tumoral total de 60% em período médio de 32 meses de acompanhamento. Cinco recidivas tumorais ocorreram nos pacientes submetidos apenas ao tratamento cirúrgico e quatro nos pacientes submetidos a quimio ou radioterapia adjuvante. Estes achados aproximam-se dos encontrados na literatura, auxiliando na compreensão do comportamento biológico deste raro tumor cerebral.Oligodendrogliomas account for 4-5% of primary central nervous system tumours with a slow and infiltrative growth. We report the clinical and pathological findings of 15 cases of oligodendrogliomas. Eight patients were males and 7 were females. The ages ranged between 17 and 66 years, with a mean of 39.73 years. The symptoms reflected the growth and topography of the tumours; migraine (60% and seizures (60% were the most frequent symptoms. Frontal (n=6, parietal (n=2, temporal (n=1 and occipital (n=1 lobes were affected. Five patients undergone total resection of the tumor and 10 were submitted to partial resection, from which 3 received adjuvant radiotherapy, 1 adjuvant chemotherapy and 1 chemotherapy and radiotherapy. The overall recurrence

  5. Loss of heterozygosity of chromosome 1p/19q and p53 protein expression in oligodendroglioma%少突胶质细胞瘤染色体1p/19 q杂合性缺失与p53蛋白表达的相关性研究

    Institute of Scientific and Technical Information of China (English)

    熊佶; 刘颖; 李超; 朱静静; 叶诸榕; 毛颖; 汪寅


    Objective To study the status of loss of heterozygosity ( LOH) of chromosome lp/19q and p53 protein expression in oligodendroglioma,as compared to astrocytoma.Methods One hundred and ninety-one cases of glioma of different histologic types and grades,including 116 cases of low-grade of oligodendroglioma ( 86 paraffin-embedded and 30 fresh tissues) ,45 cases of anaplastic oligodendroglioma (all paraffin-embedded tissues) and 30 cases of astrocytoma of various grades ( all paraffin-embedded tissues),were enrolled into the study.The LOH of chromosome lp/19q was investigated by polymerase chain reaction ( PCR) -based microsatellite analysis.The p53 protein expression was demonstrated by immunohistochemical staining.Results The rates of lp loss, 19q loss and lp/19q loss were 69.8% ,64%,and 57.0% respectively in the 86 paraffin-embedded low-grade oligodendroglioma samples,as compared to 71.1%,60.0% and 55.6% respectively in the 45 paraffin-embedded anaplastic oligodendroglioma samples.There was no difference of LOH of lp/19q between low-grade oligodendroglioma and anaplastic oligodendroglioma (P > 0.05).In the 30 cases of low-grade oligodendroglioma with fresh tissues available,the rates of lp loss,19q loss and lp/19q loss were 70.0%,63.3% and 60.0% respectively.The LOH of lp/19q between paraffin-embedded and fresh samples was not statistically significant (P >0.05).In the 30 cases of astrocytoma,the rates of lp loss,19q loss and lp/19q loss were 23.3%,33.3% and 20.0% respectively,which were significantly less than those in oligodendroglioma (P 0.05).30例WHO Ⅱ级少突胶质细胞瘤新鲜标本染色体1p缺失率为70.0%(21/30)、19q缺失率为63.3%(19/30)、1p/19q联合缺失率为60.0%(18/30),与石蜡标本的缺失率比较差异无统计学意义(P>0.05).30例星形细胞起源的肿瘤染色体对应三种缺失率分别为23.3%(7/30)、33.3%(10/30)及20.0%(6/30),与少突胶质细胞瘤差异有统计学意义(P<0.05).86例WHO Ⅱ

  6. Oligodendroglioma anaplásico en el nervio óptico de un perro.


    Pedregosa Morales, J.R.


    Los gliomas son tumores no neuronales del tejido nervioso. En el Sistema Nervioso Central (SNC) dependiendo de su origen se clasifican en astrocitomas, oligodendrogliomas, tumores mixtos (oligoastrocitomas), ependimomas y papilomas de plexos coroideos. La retina y el nervio óptico pertenecen al SNC. Aunque las neoplasias primarias de la retina y el nervio óptico son bastante infrecuentes, son los meningiomas los tumores primarios más comunes siendo los gliomas más raros.

  7. Primary spinal cord oligodendroglioma:a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Thara Tunthanathip; Thakul Oearsakul


    Background:Primary spinal cord oligodendroglioma is extremely rare.In an extensive review of this disease,53 cases were reported.Furthermore,the authors summarize the characteristics of the primary spinal cord oligodendroglioma;chronological presentation,neurological imaging,treatment and the outcome obtained in the present case as well as review the literature.Case Presentation:A 46-year-old male who had progressive neck pain for a year.Magnetic resonance imaging showed an intramedullary mass from level C2 to T4.A radical resection was performed.Histology revealed oligodendroglioma.Thereafter,the patient was treated with adjuvant radiotherapy.A year later,tumor developed recurrence.The patinet died in 3 years and 6 months.Conclusions:The available data of this disease was limited.Base on 11 published papers and the present case,surgical resection is the treatment of choice although recurrence of the tumor tends to occur after partial resection with or without radiotherapy.From the literature,the management of the recurrent disease is still surgery.Moreover,Temozolomide may be an advantage in recurrent situations.

  8. Oligodendroglioma arising in a mature cystic ovarian teratoma in a child. (United States)

    Büyükka Bay, Sema; Corapcioglu, Funda; Kavurt, Sumru; Müezzinoğlu, Bahar; Anik, Yonca; Tugay, Melih


    In childhood mature cystic teratomas are the most common type of ovarian germ cell tumors. Tumors of neuroepithelial origin are extremely rare in mature teratomas. To the authors' knowledge, this is the first case report oligodendroglioma arising in a mature cystic ovarian teratoma in children. A 13-year-old girl presented with a history of pelvic pain for 2 months. An ultrasound examination showed a monolateral multicystic, calcific ovarian mass, measuring approximately 6 x 5 cm, arising in the left over and adnexia, suggesting a teratoma. An exploratorative laparotomy and ooferectomy were performed. On histopatological examination, various samples from cystic areas had mature tissues from all 3 germ cell layers, including skin, bone, bronchial structures, and cerebellum. Sections from solid areas showed uniform population of monotonous, rounded cells with indistinct cytoplasm and having perinuclear halo (fried-egg appearance) on a fibrillary, neuropilic background. Microcalcifications as calcospherites were noted in the stroma. Based on the typical morphological features, the cased was diagnosed as mature cystic teratoma with low-grade oligodendroglioma. To the authors' knowledge, there are a few reports in the literature of an oligodendroglioma arising in an ovarian teratoma in adults and this presented patient is the first case in childhood.

  9. Pathobiology of Anaplastic Large Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Pier Paolo Piccaluga


    Full Text Available The authors revise the concept of anaplastic large cell lymphoma (ALCL in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

  10. Anaplastic Medullary Ependymoma Presenting as Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Nicolas Nicastro


    Full Text Available A-41-year old man presented with violent thunderclap headache and a bilateral proprioceptive sensibility deficit of the upper limbs. Cerebral CT scan and MRI were negative. Lumbar puncture confirmed subarachnoid hemorrhage (SAH, but cerebral angiography was negative. Three months later, the patient presented with paraparesis, and a thorough work-up revealed a diffuse, anaplastic extramedullary C7-D10 ependymoma with meningeal carcinomatosis considered the source of hemorrhage. The patient went through a D5-D8 laminectomy, temozolomide chemotherapy, and radiotherapy. The situation remained stable for a few months. In this paper, we would like to emphasize that spinal masses should be considered in cases of SAH with negative diagnostic findings for aneurysms or arteriovenous malformation.

  11. Diffuse Hepatic and Spleen Uptake of Tc-99m MDP on Bone Scintigraphy Resembling Liver-Spleen Scintigraphy in a Patient of Plasma Cell Tumor. (United States)

    Ravanbod, Mohammad Reza; Nemati, Reza; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid


    The present case demonstrates a diffuse intense hepatic and, to a lesser degree, spleen, Tc-99m MDP uptake on a routine bone scintigraphy resembling liver-spleen imaging. A 49-year-old female with a history of anaplastic plasma cell tumor and suffering from bone pain was referred for bone scintigraphy to evaluate possible bone metastases. The bone scintigraphy showed diffuse hepatic and spleen uptake of Tc-99m MDP resembling liver-spleen imaging. Furthermore, bone uptake of Tc-99m MDP was significantly diminished and there were no abnormal foci throughout the skeleton. The bone scintigraphy of the present case of an anaplastic plasma cell tumor suggests the possible presence of amyloidosis.

  12. Anaplastic Thyroid Carcinoma: Computed Tomographic Differentiation from Other Thyroid Masses

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    Lee, Jun Won; Yoon, Dae Young; Choi, Chul Soon; Chang, Suk Ki; Yun, Eun Joo; Seo, Young Lan; Rho, Young-Soo; Jin Cho, Sung; Kim, Keon Ha (Depts. of Radiology, Otorhinolaryngology, and Pathology, Kangdong Seong-Sim Hospital, Hallym Univ. College of Medicine, Seoul (KR))


    Background: Anaplastic thyroid carcinoma is rare but is one of the most aggressive malignancies. Therefore, accurate diagnosis is important in order to provide appropriate therapy. Purpose: To establish useful computed tomographic (CT) criteria for differentiating anaplastic carcinoma from other thyroid masses. Material and Methods: The CT scans of nine patients with anaplastic carcinomas were retrospectively reviewed and compared with those of 32 patients with papillary carcinomas (n = 12) or benign lesions (n = 20) exceeding a maximum diameter of 2.0 cm. Image analysis was performed according to the following CT parameters: size, margin (well defined or ill defined), composition (cystic, mixed, or solid), mean attenuation value, ratio of attenuation of the mass to that of the adjacent muscle (M/m attenuation ratio), necrosis (present or absent), and calcification (stippled, nodular, or absent) of the thyroid mass; and tumor-spreading patterns including the presence of surrounding normal thyroid tissue in the involved lobe, involvement of the contralateral thyroid lobe, extension into the adjacent structures, and cervical lymphadenopathy. Results: Anaplastic carcinomas appeared as large (average 4.6 cm), solid (100%), and ill-defined (88.9%) masses accompanied by necrosis (100%), nodular calcification (44.4%), direct invasion into the adjacent organs (55.6%), and cervical lymph node involvement (77.8%). Tumor necrosis was the most valuable parameter in differentiating anaplastic carcinomas from other thyroid masses. Patient age (>70 years) and low attenuation value on postcontrast scan (attenuation value <100 HU, or M/m attenuation ratio <1.3) are also helpful predictors for anaplastic carcinoma. Conclusion: If a patient is older than 70 years of age and has a large necrotic thyroid mass of low attenuation, anaplastic carcinoma should be included in the differential diagnosis

  13. Oligodendroglioma cístico e positividade das reações para cisticercose relato de caso

    Directory of Open Access Journals (Sweden)

    Svetlana Agapejev


    Full Text Available São poucos os estudos sobre gliomas «low-grade». Os oligodendrogliomas representam de 1,3 a 10% dos tumores intracerebrais. A neurocisticercose é uma das mais graves parasitoses do SNC, com evidente polimorfismo clínico e laboratorial. O objetivo deste estudo é relatar o caso de um doente com cefaléia, perda progressiva da visão, alteração do comportamento e, provas imunológicas positivas para cisticercose no líquido cístico e cefalorra-queano. Após tentativas para tratamento da neurocisticercose, sem muito sucesso, foi submetido a craniotomia frontal para exérese de tumor cístico, que revelou tratar-se de oligodendroglioma. Discutem-se aspectos relacionados aos possíveis mecanismos para associação de neurocisticercose e oligodendroglioma.

  14. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

    Directory of Open Access Journals (Sweden)

    Lee A D Cooper

    Full Text Available The Cancer Genome Atlas Project (TCGA has produced an extensive collection of '-omic' data on glioblastoma (GBM, resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt, which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6, but also among 75 grade II and grade III samples (p  =  2.65e-4. This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4. Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor

  15. [KI-1-positive, anaplastic, large-cell lymphoma related to Hodgkin's disease]. (United States)

    Veiga, M; Fresno, M F; Pérez del Río, M J; García, I; Madrigal, B; Herrero, A


    We report a case of lymphoma associated with lung carcinoma that shows morphological and immunohistochemical features of anaplastic large cell Ki-1 positive lymphoma and Hodgkin's disease, with positivity for Ki-1 (CD-30) (characteristic of both lymphomas) and Leu-M1 (CD-15) (normally dosent absent in anaplastic lymphoma). This subtype of lymphoma is designated anaplastic large-cell Hodgkin's related lymphoma (ALCL related to HD) and is considered by some authors as a secondary anaplastic large-cell lymphoma.

  16. ALK1-Negative Anaplastic Large Cell Lymphoma of the Breast from a Nonprosthesis Cyst

    Directory of Open Access Journals (Sweden)

    Christopher Mulligan, MBBS


    Full Text Available Summary: Anaplastic large cell lymphoma of the breast is a rare malignancy associated with prosthetic breast implants. We present a case of a woman with no prior history of breast implants who developed anaplastic lymphoma kinase-1 negative anaplastic large cell lymphoma on a background of a previous benign cyst aspiration.

  17. Leukemic phase of anaplastic lymphoma kinase positive, anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Vijaya S Gadage


    Full Text Available Anaplastic large cell lymphoma (ALCL is a distinct type of CD30+ T/null-cell non-Hodgkin′s lymphoma that frequently involves nodal and extranodal sites. The presence of leukemic phase in ALCL is extremely rare and occurs exclusively with ALK1-positive ALCL. We describe two patients with ALK1-positive ALCL who developed a leukemic phase with rapid progression of the disease. Immunophenotypic pattern assessed on peripheral blood by flow cytometry revealed CD45, CD30, and CD25 positivity in both cases but NPM-ALK1 was expressed in only one case. Both patients developed leukemic phase as a terminal event of the disease and we share the immunophenotypic features of both cases.

  18. Oligodendroglioma cells shed microvesicles which contain TRAIL as well as molecular chaperones and induce cell death in astrocytes. (United States)

    Lo Cicero, Alessandra; Schiera, Gabriella; Proia, Patrizia; Saladino, Patrizia; Savettieri, Giovanni; Di Liegro, Carlo Maria; Di Liegro, Italia


    Microvesicles (MVs) shed from G26/24 oligodendroglioma cells were previously reported to cause a reproducible, dose-dependent, inhibitory effect on neurite outgrowth, and eventually neuronal apoptosis, when added to primary cultures of rat cortical neurons. These effects were reduced but not abolished by functional monoclonal antibodies against Fas-L. In order to investigate whether MVs contain other factors able to induce cell death, we tested them for TRAIL and found clear evidence of its presence in the vesicles. This finding suggests the possibility that Fas-L and TRAIL cooperate in inducing brain cell death. Aimed at understanding the route through which the vesicles deliver their messages to the target cells, we labeled oligodendroglioma cells with radioactive methionine and then added the labeled vesicles shed from tumor cells to unlabeled astrocytes in culture. Here we report that labeled proteins were delivered to the test cells. In order to investigate whether astrocytes, like neurons, are sensitive to oligodendroglioma-derived vesicles, MVs were prepared from media conditioned by G26/24 oligodendroglioma cells and added to primary cultures of rat cortical astrocytes. These cells were clearly more resistant than neurons to microvesicle-induced damage: a high dose (40 µg) of shed MVs induced cell death in only about 40% of astrocytes. Finally, we demonstrated that Hsp70 is specifically enriched in MVs which also contain, even if at lower level, the Hsc70 constitutive chaperone.

  19. Anaplastic Thyroid Cancer: A Review of Epidemiology, Pathogenesis, and Treatment

    Directory of Open Access Journals (Sweden)

    Govardhanan Nagaiah


    Full Text Available Anaplastic thyroid cancer (ATC is an uncommon malignancy of the thyroid. Only 1-2% of thyroid cancers are anaplastic, but the disease contributes to 14–50% of the mortality with a median survival of 3 to 5 months. Most patients diagnosed with this disease are 65 years of age or older. The incidence of anaplastic thyroid cancer is decreasing worldwide. Most patients present with a rapidly growing neck mass, dysphagia, or voice change. We performed a comprehensive literature search using PubMed focusing on the treatment of anaplastic thyroid cancer including historical review of treatment and outcomes and investigations of new agents and approaches. A total of sixteen chart review and retrospective studies and eleven prospective studies and/or clinical trials were reviewed. The current standard therapeutic approach is to consider the disease as systemic at time of diagnosis and pursue combined modality therapy incorporating cytoreductive surgical resection where feasible and/or chemoradiation either concurrently or sequentially. Doxorubicin is the most commonly used agent, with a response rate of 22%. Several new agents are currently under investigation. Referral of patients for participation in clinical trials is needed.

  20. NOTCH2 is neither rearranged nor mutated in t(1;19 positive oligodendrogliomas.

    Directory of Open Access Journals (Sweden)

    Magdalena Benetkiewicz

    Full Text Available The combined deletion of 1p and 19q chromosomal arms is frequent in oligodendrogliomas (OD and has recently been shown to be mediated by an unbalanced t(1;19 translocation. Recent studies of 1p/19q co-deleted OD suggest that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be involved in this rearrangement. The objective of the present study was to analyze the NOTCH2 locus either as a chromosomal translocation locus that may be altered by the 1p/19q recurrent rearrangement or as a gene that may be inactivated by a two hit process. We performed an array-CGH analysis of 15 ODs presenting 1p/19q co-deletion using a high-density oligonucleotide microarray spanning 1p and 19q pericentromeric regions with 377 bp average probe spacing. We showed that the 1p deletion extends to the centromere of chromosome 1 and includes the entire NOTCH2 gene. No internal rearrangement of this gene was observed. This strongly suggests that the t(1;19 translocation does not lead to an abnormal NOTCH2 structure. The analysis of the entire NOTCH2 coding sequence was performed in four cases and did not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic characteristics of a tumor suppressor gene. Finally, the detailed analysis of chromosome 19 pericentromeric region led to the identification of two breakpoint clusters at 19p12 and 19q11-12. Interestingly, these two regions share a large stretch of homology. Together with previous observations of similarities between chromosome 1 and 19 alphoid sequences, this suggests that the t(1;19 translocation arises from complex intra and interchromosomal rearrangements.This is the first comprehensive deletion mapping by high density oligo-array of the 1p/19q co-deletion in oligodendroglioma tumors using a methodological approach superior to others previously applied. As such this paper provides clear evidence that the NOTCH2 gene is not physically rearranged by t(1;19 translocation of

  1. Pediatric infratentorial ependymoma: prognostic significance of anaplastic histology. (United States)

    Phi, Ji Hoon; Wang, Kyu-Chang; Park, Sung-Hye; Kim, Il Han; Kim, In-One; Park, Kyung Duk; Ahn, Hyo Seop; Lee, Ji Yeoun; Son, Young-Je; Kim, Seung-Ki


    Pediatric infratentorial ependymomas are difficult to cure. Despite the availability of advanced therapeutic modalities for brain tumors, total surgical resection remains the most important prognostic factor. Recently, histological grade emerged as an independent prognostic factor for intracranial ependymoma. We retrospectively reviewed the treatment outcome of 33 pediatric patients with infratentorial ependymoma. Progression-free survival (PFS) and overall survival (OS) rates were calculated and relevant prognostic factors were analyzed. Fourteen patients (42%) were under the age of 3 at diagnosis. Gross total resection was achieved in 16 patients (49%). Anaplastic histology was found in 13 patients (39%). Adjuvant therapies were delayed until progression in 12 patients (36%). Actuarial PFS rates were 64% in the first year and 29% in the fifth year. Actuarial OS rates were 91% in the first year and 71% in the fifth year. On univariate analysis, brainstem invasion (P = 0.047), anaplastic histology (P = 0.004), higher mitotic count (P = 0.001), and higher Ki-67 index (P = 0.004) were significantly related to a shorter PFS. Gross total resection (P = 0.029) and a greater age at diagnosis (P = 0.033) were significantly related to a longer PFS. On multivariate analysis, anaplastic histology alone was significantly related to a shorter PFS (P = 0.023). Gross total resection (P = 0.039) was significantly related to a longer overall survival (OS) on multivariate analysis. Anaplastic histology and gross total resection were the most important clinical factors affecting PFS and OS, respectively. Anaplastic histology, mitotic count, and Ki-67 index can be used as universal and easily available prognostic parameters in infratentorial ependymomas.

  2. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Delphine Lamoral-Theys


    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.

  4. Renal Clear Cell Sarcoma - Anaplastic Variant: A Rare Entity. (United States)

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


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

  5. Research progresses in the pathogenesis of anaplastic large cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lan Shi; Xiao-Wen Tang; De-Pei Wu


    Anaplastic large cell lymphoma (ALCL) is a distinct subset of T-cell non-Hodgkin's lymphoma. As a consequence of its low incidence, general pathogenic consideration of ALCL is lacking. In this review, we summarize the pathogenesis, epidemiology, clinical manifestations, and treatment of ALCL, so as to better understand key stages of the development of this disease and provide valuable information for future treatment.

  6. [Improving the management of rare brain cancers with the POLA network]. (United States)

    Terziev, Robert; Ravin, Mylène; Carpentier, Catherine; Dehais, Caroline


    The national POLA network is dedicated to the management of certain rare brain tumours, mainly anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and glioblastomas with oligodendroglioma component. The nursing team and the patient are at the heart of the organisation.

  7. p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors (United States)


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

  8. Timely topic: anaplastic lymphoma kinase (ALK) spreads its influence. (United States)

    Cheuk, W; Chan, J K


    Anaplastic lymphoma kinase (ALK) is normally not expressed in human tissues except selected sites in the nervous system. Its expression and constitutive activation as a result of a chromosomal translocation involving 2p23 plays a pivotal role in the genesis of anaplastic large cell lymphoma. ALK expression has been instrumental in defining a homogeneous subset from the category of anaplastic large cell lymphoma, characterised by occurrence in young patients, primary systemic presentation, favorable prognosis, a broad morphological spectrum, nuclear and/or cytoplasmic immunostaining for ALK protein, and a number of possible fusion partner genes such as NPM, ATIC, TFG, TPM3 and CLTCL. Recently ALK has been implicated in the genesis of another tumour type, the inflammatory myofibroblastic tumours. The ALK-positive examples occur in children and young adults, involving a variety of sites, such as the abdomen, mesentery, liver, bladder, mediastinum, lung and bone. The partner genes identified in some cases are TPM3 (tropomyosin 3) and TPM4 (tropomyosin 4). These molecular findings also further support the neoplastic nature of at least a subset of inflammatory myofibroblastic tumours.

  9. Multiple ureterolithiasis resembling steinstrasse: An unusual presentation


    Praveen Kumar Pandey; Suruchi Shukla; Anup Kumar Kundu; Pramod Kumar Sharma; Mukesh Kumar Vijay


    Steinstrasse or “stone street” is an expected complication after extracorporeal shock wave lithotripsy in patients with high stone burden. However, there are published reports of multiple ureterolithiasis resembling steinstrasse in patients with distal renal tubular acidosis. Here we report an uncommon case of a 60-year-old woman who presented with right renal calculi. Her right ureter was studded with multiple calculi up to the vesicoureteric junction. The affected right kidney was nonfuncti...

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

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


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

  11. Spinal cord glioneuronal tumor with neuropil-like islands with 1p/19q deletion in an adult with low-grade cerebral oligodendroglioma. (United States)

    Fraum, Tyler J; Barak, Stephanie; Pack, Svetlana; Lonser, Russell R; Fine, Howard A; Quezado, Martha; Iwamoto, Fabio M


    Glioneuronal tumor with neuropil-like islands (GTNI) is considered a rare variant of astrocytoma, characterized by discrete aggregates of cells expressing neuronal markers that punctuate a GFAP-positive glial background. Of the 24 published GTNI cases, only two occurred in adult spinal cords; none occurred concurrent with another CNS tumor; and none of those tested exhibited the 1p/19q deletion typical of oligodendroglioma. A 48-year-old man without significant past medical history was diagnosed with a WHO grade II oligodendroglioma by stereotactic biopsy of a lesion discovered after the patient suffered a generalized tonic-clonic seizure. By FISH analysis, this tumor exhibited the 1p/19q deletion present in up to 80% of oligodendrogliomas. The patient received 14 monthly cycles of temozolomide, and his cerebral tumor had a minor response. When the patient subsequently reported progressive paresthesias of his lower extremities, an MRI revealed an enhancing, cystic tumor of the thoracic spinal cord that was diagnosed as GTNI by histological analysis. By FISH analysis, this lesion exhibited the same 1p/19q deletion present in the concurrent cerebral oligodendroglioma. This case of a spinal cord GTNI with 1p/19q deletions constitutes the third report of a spinal cord GTNI in an adult patient; the first report of a GTNI in an individual with a separate CNS neoplasm; and the first report of a GTNI with 1p/19q deletions. This case establishes a potential genetic kinship between GTNI and oligodendroglioma that warrants further investigation.

  12. Anaplastic thyroid carcinoma with rhabdomyoblastic differentiation : A case report with a good clinical outcome

    NARCIS (Netherlands)

    Olthof, Marijke; Persoon, Adrienne C. M.; Plukker, John T. M.; van der Wal, Jacqueline E.; Links, Thera P.


    Anaplastic thyroid carcinoma is a rare and highly malignant disease. Usually, this type of tumor is irresectable, and almost all patients die within 1 year after diagnosis. We present a case of anaplastic thyroid carcinoma with rhabdomyoblastic differentiation and good therapeutic outcome. A 76-year

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

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie


    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 angioimm...

  14. Low-grade glioma: supratentorial astrocytoma, oligodendroglioma, and oligoastrocytoma in adults. (United States)

    Ashby, Lynn S; Shapiro, William R


    Low-grade glioma is not a single diagnosis but a category of biologically diverse neoplasms. They are indolent, progressive, and, following anaplastic transformation, invariably fatal. Neuro-oncologists have not established a treatment standard for these tumors. However, it is clear that "low-grade" is not synonymous with "benign," and treatment is required sometime in the course of the disease. Previously, achieving a consensus had been limited by a lack of class I evidence. Physicians treated patients based on retrospective series and personal experience. Currently, results from prospective clinical trials are becoming available. These studies have provided data that may serve as treatment guidelines. Additional results regarding the identification of prognostic variables have raised more questions to be answered. Attention is now directed to the importance of translational research to better define these neoplasms. In the future, it will be necessary to distinguish among low-grade gliomas and identify therapies that may differ between them.

  15. The effect of low level laser on anaplastic thyroid cancer (United States)

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


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

  16. Myelopathy following hyperfractionated accelerated radiotherapy for anaplastic thyroid carcinoma. (United States)

    Wong, C S; Van Dyk, J; Simpson, W J


    From 1975 to 1982, 32 patients with a diagnosis of anaplastic carcinoma of the thyroid were entered into a protocol of hyperfractionated accelerated radiotherapy. The tumor dose was 30-45 Gy at 1 Gy per fraction given 4 times a day at 3-h intervals. The results were disappointing with a median survival of less than 6 months. Two patients developed radiation myelopathy at 8 and 13 months, total spinal cord dose being 39.9 and 48.3 Gy, respectively. The risk of spinal cord damage was much higher than expected. The possible radiobiological causes and clinical implications are discussed.

  17. Intravntricular anaplastic hemangiopericytoma: CT and MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Bo Hwa; Moon, Jin Il; Baek, Hye Jin; Cho, Soo Buem; Bae, Kyung Soo; Jeon, Kyung Nyeo [Dept. of Radiology, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, Changwon (Korea, Republic of)


    Intracranial hemangiopericytomas (HPC) are uncommon tumors, and their intraventricular occurrence is even rarer. Although the histopathologic findings in HPC are distinct, the diagnosis of intraventricular HPC can be difficult owing to its rarity and nonspecific clinicoradiologic manifestations. Here we present a case of intraventricular anaplastic HPC in a 20-year-old female patient, confirmed on histopathologic examination. We suggest that HPC should be considered in the differential diagnosis of space-occupying lesions of the ventricles. This article also highlights a situation in which clinical suspicion led to a meticulous radiologic review.

  18. Dual anaplastic large cell lymphoma mimicking meningioma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keun Ho; Kim, Ki Hwan; Lee, Ghi Jai; Lee, Hye Kyung; Shim, Jae Chan; Lee, Kyoung Eun; Suh, Jung Ho [Seoul Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Lee, Chae Heuck [Dept. of Neurosurgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of)


    Anaplastic large cell lymphoma (ALCL) is a rare T cell lymphoma composed of CD30-positive lymphoid cells. Most ALCLs present as nodal disease, with skin, bone, soft tissue, lung, and liver as common extranodal sites. ALCL rarely occurs in the central nervous system and is even more infrequent in the dura of the brain. We report a case of dural-based ALCL secondary to systemic disease in a 17-year-old male that mimicked meningioma on magnetic resonance imaging and angiography.

  19. Multiple ureterolithiasis resembling steinstrasse: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Pandey


    Full Text Available Steinstrasse or “stone street” is an expected complication after extracorporeal shock wave lithotripsy in patients with high stone burden. However, there are published reports of multiple ureterolithiasis resembling steinstrasse in patients with distal renal tubular acidosis. Here we report an uncommon case of a 60-year-old woman who presented with right renal calculi. Her right ureter was studded with multiple calculi up to the vesicoureteric junction. The affected right kidney was nonfunctional and was managed by nephroureterectomy.

  20. Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas. (United States)

    Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao


    The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80, CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs.

  1. A case of Primary Bone Anaplastic Large Cell Lymphoma (United States)

    Kim, Kyung Hyun; Jung, Yun Hwa; Han, Chi Wha; Woo, In Sook; Son, Jong ho


    Patient: Female, 52 Final Diagnosis: Primary bone anaplastic large cell lymphoma Symptoms: Bone pain Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: Anaplastic large cell lymphoma (ALCL) is a relatively rare subtype of non-Hodgkin’s lymphoma (NHL). Like other types of NHL, ALCL primarily involves the nodal area, and sometimes it can involve several extra-nodal sites such as skin, soft tissue, and lungs. However, extensive bone involvement in cases of ALCL is very rare whether it is primary or secondary. Without nodular involvement, ALCL can be misdiagnosed as bone tumor or metastatic carcinoma such as lung, breast, or prostate cancer, which frequently spread to bone. Case Report: A 52-year-old woman with generalized pain and 2 months of fever of unknown origin presented to our institution. After extensive evaluation, only multiple osteolytic bone lesions with periosteal soft tissue reaction were identified. Repeated core needle biopsy revealed only inflammatory cells with histiocytic reactions. After pathologic and chromosomal analysis of sufficient tissue, which was acquired from incisional biopsy, primary bone ALCL was confirmed. Conclusions: Clinicians should keep in mind that ALCL can present with extensive bone involvement without nodal involvement. PMID:27729639

  2. Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression. (United States)

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


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

  3. ALK signaling and target therapy in anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Fabrizio eTabbo


    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  4. Anaplastic myeloma presenting as mandibular swelling: Diagnosis by cytology

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    K Subitha


    Full Text Available Multiple myeloma is a disease resulting from clonal proliferation of plasma cells. A disease of the elderly, jaw lesions are seen in 14% of patients affected with myeloma. Rarely the oral and maxillofacial lesions can be the first manifestation of the disease. We report the case of a 75-year-old man who presented with mandibular swelling. Fine-needle aspiration cytology was done from the swelling and smears were suggestive of anaplastic myeloma, which is a rare and aggressive variant of myeloma. The diagnosis of a plasmacytoma was confirmed by biopsy. Further workup of the patient revealed osteolytic lesions in skull, M band in electrophoresis and evidence of renal failure. Peripheral smear and bone marrow findings were also consistent with myeloma.


    Directory of Open Access Journals (Sweden)

    E. V. Chernyshova


    Full Text Available ALK-positive anaplastic large cell lymphoma is a heterogeneous group of mature T-cell non-Hodgkin lymphoma, and is characterized by CD30/Ki-1 expression. Recently, value of various prognostic factors is investigated. These include clinical, histological and molecular genetic changes associated with different signaling pathways activation. Some features of the mechanism of action of anaplastic lymphoma kinases and targeted therapies possibilities addressed in this review.

  6. Microwave-assisted antigen retrieval and incubation with cox-2 antibody of archival paraffin-embedded human oligodendroglioma and astrocytomas. (United States)

    Temel, Sehime G; Minbay, F Zehra; Kahveci, Zeynep; Jennes, Lothar


    Immunohistochemistry is an important tool that is often used for the diagnosis of pathologies; however, the length of time required to process the tissue is relatively long. Furthermore, the quality and sensitivity of immunohistochemical staining is affected by formalin fixation which results in variable loss of antigenicity, known as masking effect. Here we assess the effect of microwave irradiation on the incubation time required to obtain high quality immunohistochemical staining for cox-2 using archival formalin-fixed, paraffin-embedded human oligodendrogliomas and astrocytomas. The results show that intermittent microwave irradiation during the incubation with the primary antibody reduced the time requirement to 5 min while the staining quality was indistinguishable from 1 or 24 h long incubations. Thus, the use of this procedure results in a significant saving of time which is important for a timely diagnosis of pathological conditions that await treatment.

  7. Primary anaplastic large T cell lymphoma of central nervous system

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    ZHANG Yan


    Full Text Available Background Primary anaplastic large T cell lymphoma (ALCL of central nervous system (CNS can occur in people of all ages, and is usually unrelated with immunodeficiency. It is often misdiagnosed as meningitis, especially tuberculous meningitis, on clinical practice and imaging examination. In pathological diagnosis, the morphological changes of primary ALCL of CNS are similar to the systemic ALCL and the anaplastic lymphoma kinase-1 (ALK-1 can be positive or negative. Being misdiagnosed as meningitis, hormone therapy with glucocorticoid before biopsy is always used, and massive necrosis and a lot of histocyte proliferation and phagocytosis can be found under histological findings. Therefore, when the material is not enough, primary ALCL of CNS is often misdiagnosed as cerebral infarction or malignant histocytosis and so on. This paper reports a case of primary ALCL of CNS and makes a review of relevant literature, so as to summarize the clinical manifestations and elevate the recognition of clinicians and pathologists on this disease. Methods and Results A 12-year-old boy was admitted because of fever, worsening headache, numbness and weakness of right limbs. MRI showed local gyri swelling and abnormal enhancement of pia mater in the right parietal lobe, expanding to the right temporal lobe, and pia mater enhancement in the left parietal lobe. The right temporo-parietal lobe lesion biopsy revealed irregularly shaped tumor cells of large size, rich and eosinophilic cytoplasm and horseshoe-shaped or kidney-shaped nuclei. Immunohistochemical examination showed tumor cells positive for CD3, CD45RO, CD30, ALK-1 and epithelial membrane antigen (EMA, and negative for CD20 and CD79a. Conclusion Primary ALCL of CNS is an extremely rare tumor which is usually misdiagnosed as meningitis according to clinical and imaging examinations. Therefore, for those patients who are considered as meningitis but with poor treatment effect and replase of illness, brain

  8. Composite ALK-negative anaplastic large cell lymphoma and small lymphocytic lymphoma involving the right inguinal lymph node. (United States)

    Persad, Paul; Pang, Changlee S


    Anaplastic large cell lymphoma and small lymphocytic lymphoma are two lymphoid malignancies with completely distinct morphologies and natural histories. We present a rare case of composite anaplastic large cell lymphoma and small lymphocytic lymphoma in an inguinal lymph node of an otherwise healthy 47-year-old male patient. Immunohistochemical and molecular studies identified the two populations clearly. Their separation is imperative as anaplastic large cell lymphoma can be an aggressive neoplasm and easily overlooked in cases of small lymphocytic lymphoma with a small population of anaplastic large cell lymphoma cells.

  9. 不同级别少突胶质细胞瘤影像病理对照%Correlative analysis between imaging manifestations and pathological features of oligodendrogliomas in different grades

    Institute of Scientific and Technical Information of China (English)

    赵君; 周俊林; 董驰


    cases had cystic degeneration; 8 cases had bleeding and 5 cases had peritumoral edema. Anaplastic oligodendrogliomas (WHO III grade) were found in 22 cases with a median age of 32 years. Most of the tumors occurred in cortex and medulla junction of frontal,parietal and temporal lobes,with clear boundary. On CT images,10 cases was slightly low-density,12 cases were mixed density. On T1WI,19 cases were low signal and 3 cases were iso-intense. 19 patients showed high signal on T2W1. On enhanced CT scan,2 cases showed mild enhancement and 20 cases showed significant enhancement. 3 cases had calcification; 12 cases had cystic necrosis; nine cases had hemorrhage and 22 cases had peritumoral edema. Conclusions: Cystic necrosis,hemorrhage,edema and enhancement were more common in anaplastic o!igodendrogliomas(WHO III grade) than in glioblastoma. These imaging features contribute to tumor classification before surgery,and treatment planning for the tumor.

  10. Anaplastic meningioma: progression from atypical and chordoid morphotype with morphologic spectral variation at recurrence. (United States)

    Bollag, Roni J; Vender, John R; Sharma, Suash


    The current WHO 2007 classification divides meningiomas into a 3-grade prognostic hierarchy. Recent literature evokes two pathways to disease progression in meningiomas akin to a comparable paradigm in gliomas, but without similar prognostic connotation: de novo anaplastic meningioma (better prognosis), and transformed meningioma (worse prognosis). We present two adult cases of transformed meningiomas that display a spectrum of morphologic progression. Case 1 at presentation showed a random admixture of meningothelial, atypical and anaplastic meningioma. The tumor recurred as anaplastic meningioma. Case 2 presented as a chordoid meningioma, but recurred as anaplastic meningioma mainly at the invasive front in transition with residual chordoid pattern. Of interest, portions of tumor also showed papillary configuration. In accordance with the dire prognosis for anaplastic meningioma, both patients succumbed to their disease within 2 months of recurrence. The present study highlights two main points: First, that proper recognition of focal high-grade areas in a heterogeneous low-grade meningioma (case 1) provides critical morphologic clues to spatial histologic progression and predicts aggressive biologic behavior, as evidenced by progression to frankly anaplastic meningioma at recurrence. Second, the presence of papillary in addition to anaplastic areas, in the recurrence of a previously diagnosed chordoid meningioma supports the ostensibly heightened transforming potential of grade II meningiomas, but also reflects on the morphologic heterogeneity of high-grade meningiomas, and their potentially diverse pathways of progression. We propose that grading of meningiomas as outlined by WHO is of more critical prognostic import than histologic sub-typing, and must include a thorough survey of the tumor-brain interface. Future molecular genetic correlates, akin to those characterized in gliomas, could help stratify prognostic subcategories to refine meningioma grading, and

  11. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

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    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)


    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

  12. O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy. (United States)

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


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

  13. Paucicellular variant of anaplastic thyroid carcinoma: A diagnostic pitfall in thyroid pathology

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    Reetika Sharma


    Full Text Available Paucicellular variant is a rare variant of anaplastic carcinoma. Anaplastic thyroid carcinomas usually creates no problems in histologic diagnosis because of the obvious invasive growth, high cellularity, and marked degree of anaplasia, but paucicellular variant of anaplastic carcinoma is problematic in diagnosis because of its histologic mimicry to benign lesions, e.g. Riedel disease and fibrous variant of Hashimoto thyroiditis, i.e. prominent fibrosis and low cellularity. It is important to distinguish it from these two lesions because both are reactive conditions with favorable prognosis while anaplastic carcinoma is a malignant condition with poor prognosis. We present a case of 45-year-old female presented with a history of thyroid swelling for 10 years. The cytological diagnosis was given as colloid goiter while histopathological examination turned out to be paucicellular variant of anaplastic carcinoma thyroid. To conclude paucicellular variant is the entity to which all pathologists should be familiar and should know differential diagnosis while dealing with any fibrosed lesion of the thyroid.

  14. Nonconventional papillary thyroid carcinomas with pleomorphic tumor giant cells: a diagnostic pitfall with anaplastic carcinoma. (United States)

    Hommell-Fontaine, Juliette; Borda, Angela; Ragage, Florence; Berger, Nicole; Decaussin-Petrucci, Myriam


    The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

  15. Expression and sub-cellular localization of leucine-rich repeats and immunoglobulin-like domains are related to antioxidant enzymes in human ependymoma and oligodendroglioma

    Institute of Scientific and Technical Information of China (English)

    Wei Yi; Lin Liu; Okechi Humphrey; Qianxue Chen; Shulan Huang


    The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 (LRIG1) and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.

  16. 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

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    Marcelo E. Corti


    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

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

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    Zeliha Esin Celik


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

  18. Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas. (United States)

    Boi, Michela; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco


    The currently used 2008 World Health Organization classification recognizes two types of systemic anaplastic large T cell lymphoma according to ALK protein expression in tumour cells. First, the 'anaplastic large cell lymphoma, ALK positive' (ALK(+) ALCL) that is characterized by the presence of ALK gene rearrangements and consequent ALK protein expression, and, second, the 'anaplastic large cell lymphoma, ALK negative' (ALK(-) ALCL) that is a provisional entity lacking ALK protein expression but cannot be distinguished morphologically from ALK(+) ALCL. In this review we summarize the current knowledge on the genetic lesions and biological features that underlie the pathogenesis of ALK(+) and the ALK(-) ALCL and that can lead to the use of targeted anti-cancer agents.

  19. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient (United States)

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


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

  20. Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult. (United States)

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


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

  1. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird". (United States)

    de Herder, Wouter W


    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology.

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

  3. 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 (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

  4. miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. (United States)

    Matsuyama, Hironori; Suzuki, Hiroshi I; Nishimori, Hikaru; Noguchi, Masaaki; Yao, Takashi; Komatsu, Norio; Mano, Hiroyuki; Sugimoto, Koichi; Miyazono, Kohei


    Many transformed lymphoma cells show immune-phenotypes resembling the corresponding normal lymphocytes; thus, they provide a guide for proper diagnosis and present promising routes to improve their pathophysiologic understanding and to identify novel therapeutic targets. However, the underlying molecular mechanism(s) of these aberrant immune-phenotypes is largely unknown. Here, we report that microRNA-135b (miR-135b) mediates nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-driven oncogenicity and empowers IL-17-producing immunophenotype in anaplastic large cell lymphoma (ALCL). NPM-ALK oncogene strongly promoted the expression of miR-135b and its host gene LEMD1 through activation of signal transducer and activator of transcription (STAT) 3. In turn, elevated miR-135b targeted FOXO1 in ALCL cells. miR-135b introduction also decreased chemosensitivity in Jurkat cells, suggesting its contribution to oncogenic activities of NPM-ALK. Interestingly, miR-135b suppressed T-helper (Th) 2 master regulators STAT6 and GATA3, and miR-135b blockade attenuated IL-17 production and paracrine inflammatory response by ALCL cells, indicating that miR-135b-mediated Th2 suppression may lead to the skewing to ALCL immunophenotype overlapping with Th17 cells. Furthermore, antisense-based miR-135b inhibition reduced tumor angiogenesis and growth in vivo, demonstrating significance of this "Th17 mimic" pathway as a therapeutic target. These results collectively illuminated unique contribution of oncogenic kinase-linked microRNA to tumorigenesis through modulation of tumor immune-phenotype and microenvironment.

  5. Anaplastic carcinoma of pancreas:report of 6 cases and literature review

    Institute of Scientific and Technical Information of China (English)

    SHAO Cheng-hao; HU Xian-gui; GAO Li; TANG Yan; LIU Rui; ZHANG Yi-jie; ZHOU Ying-qi


    Objective:To investigate clinicopathological features,diagnosis and treatment of anaplastic carcinoma of the pancreas and to review relevant literature on this entity. Methods :A retrospective clinical analysis was made in 6 cases of anaplastic pancreatic carcinomas admitted from 1989 to 2001. Results:Anaplastic pancreatic carcinoma was found in 5 men and 1 woman with a mean age of 61.5 years. Tumor location was in the head of the pancreas in 3 patients,body and tail in 3 cases. Tumors were surgically resected in all patients, by pancreaticoduodenectomy in 1, by pancreaticoduodenectomy combined resection and reconstruction of superior mesenteric vein(SMV) in 1 ,by pancreaticoduodenectomy combined resection and reconstruction of SMV and superior mesenteric artery(SMA) in 1,by distal pancreatectomy in 2,by distal pancreatectomy combined total gastrotectomy in 1. Liver metastasis was found in one patient. Follow-up suggested the prognosis was poor with a mean survival of 5.5 months after operation. All patients were dead with tumor recurrence and liver metastasis. Conclusion:Histologically,anaplastic pancreatic carcinoma is characterized by pleomorphic cell carcinoma consisting of pleomorphic giant/small cells and spindle cells ,or osteoclast-like giant cell tumor composed of pleomorphic small cells,or pleomorphic giant cell carcinoma with osteoclastoid giant cells,and demonstrates aggressive biological behavior. Invasions to adjoined organ and metastasis are usual. The prognosis of this tumor appears to be very poor.

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

    Directory of Open Access Journals (Sweden)

    Heidegger S


    Full Text Available Simon Heidegger,1 Ambros Beer,2 Eva Geissinger,3 Andreas Rosenwald,3 Christian Peschel,1 Ingo Ringshausen,1 Ulrich Keller11III Medical Department, 2Nuclear Medicine Department, Technische Universität München, Munich, Germany; 3Institute of Pathology, University of Würzburg, Würzburg, GermanyAbstract: Anaplastic large cell lymphoma (ALCL is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone. However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.Keywords: anaplastic large cell lymphoma (ALCL, refractory/relapsed lymphoma, anti-CD30 drug conjugate, DHAP

  7. Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy



    A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The...

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

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    Hassan Huwait


    Full Text Available 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.

  9. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo. (United States)

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J


    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris.

  10. The challenge of unravelling family resemblance related to illness behaviour.

    NARCIS (Netherlands)

    Cardol, M.; Groenewegen, P.P.; Spreeuwenberg, P.; Dijk, L. van; Bosch, W. van den; Bakker, D.H. de


    Background: Efforts to promote health or prevent disease may conflict with patients’ habits at home. Irrespective of the national setting, families are important social contexts in which illness occurs and resolves. Family members resemble each other in their illness behaviour, even across generatio

  11. The Resemblances Between Wuthering Height and Jane Eyre

    Institute of Scientific and Technical Information of China (English)

    Li yichun


    Large difference in style from appearance, "Jane Evre"and "Wuthering Heights" have greet resemblance in reality. As the principal expressions: The protagonist's pursuing for individual value and vindicating of personal dignity; The writer's pursuit of an ideal love; The works" creative method of illusion and symbolism.

  12. Cytokeratin positive anaplastic large cell lymphoma: Difficulty in differentiation from metastatic carcinoma

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    Nishat Afroz


    Full Text Available Cytokeratin and epithelial membrane antigen (EMA are usually included in the first panel of immunomarkers used to differentiate metastatic carcinoma from lymphoma in cases presenting with enlarged lymph nodes. While carcinomas are cytokeratin and EMA positive, most lymphomas are negative for the above. However, recently few cases of cytokeratin positive lymphomas have also been reported. Here, we describe a very rare case of cytokeratin positive anaplastic large cell lymphoma (ALCL masquerading as a poorly differentiated carcinoma. Simultaneously, we also discuss the differential diagnosis and difficulty in differentiation from metastatic carcinoma in such a scenario. Review of literature shows that this is probably the first case report of anaplastic lymphoma kinase negative-ALCL seen in a young adult.

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

    Directory of Open Access Journals (Sweden)

    Zizzi A


    Full Text Available Maurizio Iacoangeli,1 Alessandro Di Rienzo,1 Roberto Colasanti,1 Lorenzo Alvaro,1 Niccolò Nocchi,1 Gabriele Polonara,2 Lucia Giovanna Maria Di Somma,1 Antonio Zizzi,3 Marina Scarpelli,3 Massimo Scerrati11Department of Neurosurgery, 2Department of Radiology, Section of Neuroradiology, 3Department of Pathology, Università Politecnica delle Marche, Umberto I General Hospital, Ancona, ItalyAbstract: The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a "cure" and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment.Keywords: multiple primary intracranial tumors, vestibular schwannoma, oligodendroglioma, indolent low grade gliomas, incidentaloma, surgery

  14. NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis. (United States)

    Briançon-Marjollet, Anne; Balenci, Laurent; Fernandez, Manuel; Estève, François; Honnorat, Jérôme; Farion, Régine; Beaumont, Marine; Barbier, Emmanuel; Rémy, Chantal; Baudier, Jacques


    Gliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunohistological and immunocytochemical analyses were used to further characterize low-grade rat gliomas at different stages of evolution. We showed that early low-grade gliomas have characteristics of oligodendroglioma-like tumors and exclusively contain NG2-expressing slow dividing precursor cells, which express early markers of oligodendroglial lineage. These tumor-derived precursors failed to fully differentiate into oligodendrocytes and exhibited multipotential abilities in vitro. Moreover, a few glioma NG2+ cells are resistant to radiotherapy and may be responsible for tumor recurrence, frequently observed in humans. Overall, these findings suggest that transformed multipotent NG2 glial precursor cell may be a potential cell of origin in the genesis of rat ENU-induced oligodendroglioma-like tumors. This work may open up new perspectives for understanding biology of human gliomas.

  15. High angiogenic potential in an in vivo rat corneal model is associated with shorter disease-free survival in low-grade oligodendrogliomas. (United States)

    Ozkan, Abdulkadir; Guduk, Mustafa; Atabay, Kutay Deniz; Uyar, Süheyla Bozkurt; Seker, Askin; Konya, Deniz; Pamir, M Necmettin; Kilic, Turker


    This study aimed to examine the association between time to tumor recurrence, angiogenic potential and tumor contrast-enhancement. Tumor samples were taken from 20 patients with low-grade oligodendroglioma and examined for their angiogenic potential using an in vivo rat corneal model of angiogenesis. Patients were evaluated for tumor contrast enhancement prior to surgical excision using MRI and they were followed for tumor recurrence. Patients who had tumors without contrast enhancement had longer disease-free survival (median time to tumor recurrence, 72 months) compared to those who had tumors with contrast enhancement (median, 42 months; p=0.0068). Based on corneal angiogenesis assay results, a high angiogenic potential was associated with a significantly shorter disease-free survival. Our findings suggest that radiological contrast enhancement and a high angiogenic potential based on an in vivo corneal angiogenesis assay were related to a shorter disease-free survival. This might have important prognostic implications in patients with low-grade oligodendrogliomas.

  16. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

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    Moira Ragazzi


    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  17. Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma

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    Seema Kaushal


    Full Text Available A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131 ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

  18. Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report and Literature Review. (United States)

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


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

  19. ALK-positive anaplastic large cell lymphoma with soft tissue involvement in a young woman

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    Gao KH


    Full Text Available Kehai Gao, Hongtao Li, Caihong Huang, Huazhuang Li, Jun Fang, Chen Tian Department of Orthopaedics, Yidu Central Hospital, Shandong, People’s Republic of China Introduction: Anaplastic large cell lymphoma (ALCL is a type of non-Hodgkin lymphoma that has strong expression of CD30. ALCL can sometimes involve the bone marrow, and in advanced stages, it can produce destructive extranodal lesions. But anaplastic large cell lymphoma kinase (ALK+ ALCL with soft tissue involvement is very rare.Case report: A 35-year-old woman presented with waist pain for over 1 month. The biopsy of soft tissue lesions showed that these cells were positive for ALK-1, CD30, TIA-1, GranzymeB, CD4, CD8, and Ki67 (90%+ and negative for CD3, CD5, CD20, CD10, cytokeratin (CK, TdT, HMB-45, epithelial membrane antigen (EMA, and pan-CK, which identified ALCL. After six cycles of Hyper-CVAD/MA regimen, she achieved partial remission. Three months later, she died due to disease progression.Conclusion: This case illustrates the unusual presentation of ALCL in soft tissue with a bad response to chemotherapy. Because of the tendency for rapid progression, ALCL in young adults with extranodal lesions are often treated with high-grade chemotherapy, such as Hyper-CVAD/MA. Keywords: anaplastic large cell lymphoma, ALK+, soft tissue involvement, Hyper-CVAD/MA

  20. A case of tonsillar anaplastic large cell lymphoma-anaplastic lymphoma kinase negative: An unusual site of involvement with review of literature

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    Umesh Das


    Full Text Available We present this unusual case of the clinical importance of a 50-year-old male patient who presented with foreign body sensation in the throat and halitosis of 20 days duration. On examination, there were no palpable lymph nodes and oral cavity revealed an ulcero proliferative growth over the right tonsil. Computed tomography of the paranasal sinuses and neck revealed a heterogeneously enhancing mass involving the right tonsil measuring 3.8 cm × 3 cm. Biopsy of the tonsillar mass was suggestive of anaplastic large cell lymphoma (ALCL with neoplastic large cells positive for CD30, epithelial membrane antigen and CD3 and negative for Tdt, CD56, anaplastic lymphoma kinase (ALK and cytokeratin. A diagnosis of ALK negative ALCL Stage IA was made and the patient was started on chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks. He received six cycles of chemotherapy followed by 33 gray involved region radiotherapy and reassessment showed total regression of the tonsillar lesion. The patient is in complete remission and now under follow-up for the last 2 years

  1. Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated signaling and anaplastic large cell lymphoma growth. (United States)

    Riera, Ludovica; Lasorsa, Elena; Ambrogio, Chiara; Surrenti, Nadia; Voena, Claudia; Chiarle, Roberto


    Most anaplastic large cell lymphomas (ALCL) express oncogenic fusion proteins derived from chromosomal translocations or inversions of the anaplastic lymphoma kinase (ALK) gene. Frequently ALCL carry the t(2;5) translocation, which fuses the ALK gene to the nucleophosmin (NPM1) gene. The transforming activity mediated by NPM-ALK fusion induces different pathways that control proliferation and survival of lymphoma cells. Grb2 is an adaptor protein thought to play an important role in ALK-mediated transformation, but its interaction with NPM-ALK, as well as its function in regulating ALCL signaling pathways and cell growth, has never been elucidated. Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. An intact SH3 domain at the C terminus of Grb2 was required for Tyr(160) phosphorylation. Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). Finally, shRNA knockdown experiments showed that Grb2 regulates primarily the NPM-ALK-mediated phosphorylation of SHP2 and plays a key role in ALCL cell growth.

  2. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma. (United States)

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


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

  3. Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas

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    Nicholas M Kelly


    Full Text Available Abstract Background Oligodendroglioma (ODG and oligoastrocytoma (OAC are diffusely infiltrating primary brain tumors whose pathogenesis remains unclear. We previously identified a group of genes whose expression was inversely correlated with survival in a cohort of patients with glioblastoma (GBM, and some of these genes are also reportedly expressed in ODG and OAC. We examined the expression patterns and localization of these survival-associated genes in ODG and OAC in order to analyze their possible roles in the oncogenesis of these two tumor types. Methods We used UniGene libraries derived from GBM and ODG specimens to examine the expression levels of the transcripts for each of the 50 GBM survival-associated genes. We used immunohistochemistry and cDNA microarrays to examine expression of selected survival-associated genes and Id4, a gene believed to control the timing of oligodendrocyte development. The expression of FABP7 and Id4 and the survival of patients with ODG and OAC were also analyzed. Results Transcripts of most survival-associated genes as well as Id4 were present in both GBM and ODG tumors, whereas protein expression of Id4 and one of the survival-associated genes, brain-type fatty acid-binding protein (FABP7, was present in cells with astrocytic features, including reactive and neoplastic astrocytes, but not in neoplastic oligodendrocytes. Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC. Id4 and FABP7 expression, however, did not correlate with the clinical outcome of patients with ODG or OAC tumors. Conclusion Expression of Id4 and some of our previously identified GBM survival-associated genes is present in developing or mature oligodendrocytes. However, protein expression of Id4 and FABP7 in GBM, ODG, and OAC suggests that this group of functionally important genes might demonstrate two patterns of expression in these glioma subtypes: one group is universally expressed in


    Directory of Open Access Journals (Sweden)

    Indawan Syahri


    Full Text Available Abstract: Politeness principles are universally utilized by the speakers of any language when realizing various speech acts. However, the speakers of particular languages relatively apply politeness due to the cultural norms embedded. The present study attempts to delineate how the Indonesian learners of English (ILE apply the politeness principles in request realizations. Specifically it devotes to the types of politeness strategies applied and resemblance of the indirectness in politeness strategies in requesting acts. The FTAs and indirectness are the theoretical bases used to trace the typologies of both politeness and request strategies. The data werere collected by means of certain elicitation techniques, i.e. DCTs and Role-plays. The analyses werere done through three stages; determining request strategies, politeness strategies, and resemblance of indirectness in politeness. The results show that the indirectness generally is parallel to politeness. Besides, some pragmatic transfers are found in terms of applying native-culture norms in realizing target speech acts.

  5. Resemblance Argument” and Controversies over Mimesis

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    Nives Delija


    Full Text Available Contrary to the common interpretation of Platonic art that supports the view that it is ontologically and gnoseologically irrelevant because it is mainly defined by mimetic concept as a mere imitation of the material world, and is therefore banished from the Republic, we will offer some different interpretations. Namely, it is possible to show that mimetic principle is not the reason why Plato condemns art, and that the notion of artistic mimesis in fact stems from the metaphysical notion of mimesis as approximation or gradual resemblance to the paradigm. In this case artistic mimesis achieves higher ontological authenticity and imitates the ideal by means of the sensory. Parmenides’ “resemblance argument” may constitute a serious obstacle for the acceptance of, on the one hand, the idea of the relation of resemblance (homoiotes between Forms and particulars, that is between the paradigm and its image, and on the other hand it may question the idea of approximation in which mimetic principle has metaphysical foundation. However, when Form is seen as a synthetic unity of many things (hen epi pollon, it then represents the right standpoint for the explanation of the phenomena, and it becomes questionable when it is placed on the same level with its exemplars. If the relation of resemblance between the paradigm and its image is determined by the “dynamic”, and not by “symmetric resemblance” in which both parts are on the same level of ontological authenticity, then the view of philosophical mimesis as approximation on which relies artistic mimetic concept is legitimate.

  6. A lethal syndrome resembling branchio-oculo-facial syndrome. (United States)

    Hing, A V; Torack, R; Dowton, S B


    Branchio-oculo-facial syndrome, a recently delineated autosomal dominant condition, is characterized by branchial cleft sinuses, ocular anomalies, and unusual facial appearance. A patient with branchial cleft fistulae, microphthalmia, nasomaxillary dysplasia, in addition to cardiac and CNS malformation (holoprosencephaly and meningo-encephalocele), is described. Although many features of this lethal malformation complex resemble those seen in the branchio-oculo-facial syndrome, the complex may represent a new multiple malformation syndrome.

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


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

  8. Yoga Therapy in Treating Patients With Malignant Brain Tumors (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

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

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    Gema Mira-Perceval Juan


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

  10. Multiple oligodendroglioma with pseudoprogression

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    Junko Matsuyama


    Full Text Available A 72 year-old male hospitalized with aphasia, abnormal behavior, and rapidlyprogressive dementia.Magnetic resonance imaging (MRI enhanced by contrast media demonstrated multiplebrain tumors in left parietal lobe and left paraventricular region. Biopsy was performed,andhistopathological examination and genetical evaluation revealed anaplasticoligodendroglioma. Local radiation 50Gy was given, and Temozolomide via orallyadministered for 42 days. After the chemoradiotherapy, even though the parietal tumorshowed lessening of the size, enlargement of the tumor in the left paraventricularregion was observed, and we considered that phenomenon was pseudoprogression. 5courses of Temozolomide therapy was added, but cerebellar tumor appeared andenlarged with hydrocephalus, and died 1 year and 3 months after the firsthospitalization.

  11. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma

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    Gunchan Paul


    Full Text Available Soma (Carisoprodol is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene.

  12. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma (United States)

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh


    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene. PMID:27625493

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

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


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

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

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


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

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

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


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

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

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


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


    NARCIS (Netherlands)

    van der Laan, Bernard F.A.M.; FREEMAN, JL; TSANG, RW; ASA, SL


    The sequence of tumorigenesis in the thyroid is unclear. It has been proposed that anaplastic carcinomas of the thyroid develop by dedifferentiation in pre-existing differentiated carcinomas. We reviewed all anaplastic and insular (poorly differentiated) thyroid carcinomas in a consultation practice

  18. Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis. (United States)

    Kuwabara, Yoshimitsu; Sato, Atsuki; Abe, Hiroko; Abe, Sumino; Kawai, Naoki; Takeshita, Toshiyuki


    A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.

  19. Resemblance operations and conceptual complexity in animal metaphors

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    Aneider Iza Ervitia


    Full Text Available For over thirty years cognitive linguists have devoted much effort to the study of metaphors based on the correlation of events in human experience to the detriment of the more traditional notion of resemblance metaphor, which exploits perceived similarities among objects. Grady (1999 draws attention to this problem and calls for a more serious study of the latter type of metaphor. The present paper takes up this challenge on the basis of a small corpus of ‘animal’ metaphors in English, which are essentially based on resemblance. Contrary to previous analyses by cognitive linguists (e.g. Lakoff & Turner 1989, Ruiz de Mendoza Ibáñez, 1998, who claim that such metaphors are based on a single mapping generally involving comparable behavioral attributes, I will argue that we have a more complex situation which involves different patterns of conceptual interaction. In this respect, I have identified cases of (i animal metaphors interacting with high-level (i.e. grammatical metaphors and metonymies, of (ii (situational animal metaphors whose source domains are constructed metonymically (cf. Goossens 1990; Ruiz de Mendoza Ibáñez & Díez Velasco 2002, and of (iii animal metaphors interacting with other metaphors thereby giving rise to metaphoric amalgams (cf. Ruiz de Mendoza Ibáñez & Galera Masegosa 2011.

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

    LENUS (Irish Health Repository)

    Kelleher, Fergal C


    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

  1. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda


    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  2. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer]. (United States)

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


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

  3. Disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural disease: case report. (United States)

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


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

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

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    Laura S. Lourdes


    Full Text Available 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.

  5. Differentiated human stem cells resemble fetal, not adult, β cells. (United States)

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


    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β 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 β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.


    Directory of Open Access Journals (Sweden)


    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


    Directory of Open Access Journals (Sweden)

    Aneider Iza Ervitia


    Full Text Available

    For over thirty years cognitive linguists have devoted much effort to the study of metaphors based on the correlation of events in human experience to the detriment of the more traditional notion of resemblance metaphor, which exploits perceived similarities among objects. Grady (1999 draws attention to this problem and calls for a more serious study of the latter type of metaphor. The present paper takes up this challenge on the basis of a small corpus of ‘animal’ metaphors in English, which are essentially based on resemblance. Contrary to previous analyses by cognitive linguists (e.g. Lakoff & Turner 1989, Ruiz de Mendoza Ibáñez, 1998, who claim that such metaphors are based on a single mapping generally involving comparable behavioral attributes, I will argue that we have a more complex situation which involves different patterns of conceptual interaction. In this respect, I have identified cases of (i animal metaphors interacting with high-level (i.e. grammatical metaphors and metonymies, of (ii (situational animal metaphors whose source domains are constructed metonymically (cf. Goossens 1990; Ruiz de Mendoza Ibáñez & Díez Velasco 2002, and of (iii animal metaphors interacting with other metaphors thereby giving rise to metaphoric amalgams (cf. Ruiz de Mendoza Ibáñez & Galera Masegosa 2011.

  8. Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death. (United States)

    Zamo, Alberto; Chiarle, Roberto; Piva, Roberto; Howes, Jennifer; Fan, Yan; Chilosi, Marco; Levy, David E; Inghirami, Giorgio


    The anaplastic lymphoma kinase (ALK) gene is characteristically translocated in Anaplastic Large Cell Lymphomas (ALCL) and the juxtaposition of the ALK gene to multiple partners results in its constitutive protein tyrosine kinase activity. We show here that expression of activated ALK induces the constitutive phosphorylation of Stat3 in transfected cells as well as in primary human ALCLs. Furthermore, immunohistochemical studies demonstrate that among distinct human B and T cell lymphomas, activation of Stat3 nuclear translocation is uniquely associated with ALK expression. NPM-ALK also binds and activates Jak3; however, Jak3 is not required for Stat3 activation or for cell transformation in vitro. Moreover, src family kinases are not necessary for NPM-ALK-mediated Stat3 activation or transformation, suggesting that Stat3 may be phosphorylated directly by ALK. To evaluate relevant targets of ALK-activated Stat3, we investigated the regulation of the anti-apoptotic protein Bcl-x(L) and its role in cell survival in NPM-ALK positive cells. NPM-ALK expression caused enhanced Bcl-x(L) transcription, largely mediated by Stat3. Increased expression of Bcl-x(L) provided sufficient anti-apoptotic signals to protect cells from treatment with specific inhibitors of the Jaks/Stat pathway or the Brc-Abl kinase. These studies support a pathogenic mechanism whereby stimulation of anti-apoptotic signals through activation of Stat3 contributes to the successful outgrowth of ALK positive tumor cells.

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

    Directory of Open Access Journals (Sweden)

    Chen X


    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

  10. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation (United States)

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


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

  11. PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma. (United States)

    Boi, Michela; Rinaldi, Andrea; Kwee, Ivo; Bonetti, Paola; Todaro, Maria; Tabbò, Fabrizio; Piva, Roberto; Rancoita, Paola M V; Matolcsy, András; Timar, Botond; Tousseyn, Thomas; Rodríguez-Pinilla, Socorro Maria; Piris, Miguel A; Beà, Sílvia; Campo, Elias; Bhagat, Govind; Swerdlow, Steven H; Rosenwald, Andreas; Ponzoni, Maurilio; Young, Ken H; Piccaluga, Pier Paolo; Dummer, Reinhard; Pileri, Stefano; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco


    Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK(-)ALCL, and in 29% of all ALCL cases with a clinical implication.

  12. Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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.

  14. Ovarian mucinous cystic tumor with sarcoma-like mural nodules and multifocal anaplastic carcinoma: a case report. (United States)

    Zheng, Jinfeng; Geng, Ming; Li, Peifeng; Li, Yi; Cao, Yongcheng


    A 48-year-old woman presented with left abdominal pain and fullness. Computed tomography scan revealed a multicystic mass with multifocal mural nodules. Histologic examination showed a mucinous cystic tumor with cystadenoma, borderline malignant cystadenoma and cystadenocarcinoma, which were associated with sarcoma-like mural nodules (SLMNs) and multifocal anaplastic carcinoma. Mural nodules showed a positive reaction for CD56 and vimentin, but were negative for cytokeratin 7 and SMA. She underwent postoperative chemotherapy and is currently under follow-up; no recurrence or metastases were found in the first year of follow-up. Ovarian mucinous cystic tumor with SLMNs and foci of anaplastic carcinoma is extremely rare. To our knowledge, this case reports the most complex neoplastic and reactive components. Our findings shed some light on the pathogenesis of this rather rare carcinoma. We think that the formation of SLMNs may be the result of the reactive proliferation of undifferentiated mesenchymal cells, while the anaplastic carcinoma may be derived from mucinous epithelium. Moreover, because of difficulties encountered in their differential diagnosis, we think that the existence of foci of anaplastic carcinoma along with SLMNs necessitates careful histologic and immunohistochemical analysis of mural nodules for the determination of treatment and prognosis.

  15. Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis

    DEFF Research Database (Denmark)

    Vindeløv, L L; Hansen, H H; Christensen, I J


    Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination...

  16. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951.

    NARCIS (Netherlands)

    Idbaih, A.; Dalmasso, C.; Kouwenhoven, M.; Jeuken, J.W.M.; Carpentier, C.; Gorlia, T.; Kros, J.M.; French, P.; Teepen, J.; Broet, P.; Delattre, O.; Mokhtari, K.; Sanson, M.; Delattre, J.Y.; Bent, M. van den; Hoang-Xuan, K.


    Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify ne

  17. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

    NARCIS (Netherlands)

    A. Idbaih (Ahmed); C. Dalmasso (Cyril); M.C.M. Kouwenhoven (Mathilde); J. Jeuken (Judith); C. Carpentier (Catherine); T.S. Gorlia (Thierry); J.M. Kros (Johan); P.J. French (Pim); J.L.J.M. Teepen; P. Broët (Philippe); O. Delattre (Olivier); K. Mokhtari (Karima); M. Sanson (Marc); M.J. van den Bent (Martin); K. Hoang-Xuan (Khe)


    textabstractDespite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To

  18. A Para-Canalicular Abscess Resembling an Inflamed Chalazion

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    Diamantis Almaliotis


    Full Text Available Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis. When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  19. A neural network dynamics that resembles protein evolution (United States)

    Ferrán, Edgardo A.; Ferrara, Pascual


    We use neutral networks to classify proteins according to their sequence similarities. A network composed by 7 × 7 neurons, was trained with the Kohonen unsupervised learning algorithm using, as inputs, matrix patterns derived from the bipeptide composition of cytochrome c proteins belonging to 76 different species. As a result of the training, the network self-organized the activation of its neurons into topologically ordered maps, wherein phylogenetically related sequences were positioned close to each other. The evolution of the topological map during learning, in a representative computational experiment, roughly resembles the way in which one species evolves into several others. For instance, sequences corresponding to vertebrates, initially grouped together into one neuron, were placed in a contiguous zone of the final neural map, with sequences of fishes, amphibia, reptiles, birds and mammals associated to different neurons. Some apparent wrong classifications are due to the fact that some proteins have a greater degree of sequence identity than the one expected by phylogenetics. In the final neural map, each synaptic vector may be considered as the pattern corresponding to the ancestor of all the proteins that are attached to that neuron. Although it may be also tempting to link real time with learning epochs and to use this relationship to calibrate the molecular evolutionary clock, this is not correct because the evolutionary time schedule obtained with the neural network depends highly on the discrete way in which the winner neighborhood is decreased during learning.

  20. A para-canalicular abscess resembling an inflamed chalazion. (United States)

    Almaliotis, Diamantis; Nakos, Elias; Siempis, Thomas; Koletsa, Triantafyllia; Kostopoulos, Ioannis; Chatzipantazi, Maria; Karampatakis, Vasileios


    Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis). When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  1. Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib (United States)

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


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

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

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    Nikolić Branka


    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

  3. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis (United States)

    Li, Shi-jun; Wang, Tao; Wang, Lin; Pang, Zhan-qi; Ma, Ben; Li, Ya-wen; Yang, Jian; Dong, He


    Abstract Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias. A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone. The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia. As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess. PMID:27057898

  4. Predator-Resembling Aversive Conditioning for Managing Habituated Wildlife

    Directory of Open Access Journals (Sweden)

    Elsabé Louise Kloppers


    Full Text Available Wildlife habituation near urban centers can disrupt natural ecological processes, destroy habitat, and threaten public safety. Consequently, management of habituated animals is typically invasive and often includes translocation of these animals to remote areas and sometimes even their destruction. Techniques to prevent or reverse habituation and other forms of in situ management are necessary to balance ecological and social requirements, but they have received very little experimental attention to date. This study compared the efficacy of two aversive conditioning treatments that used either humans or dogs to create sequences resembling chases by predators, which, along with a control category, were repeatedly and individually applied to 24 moderately habituated, radio-collared elk in Banff National Park during the winter of 2001-2002. Three response variables were measured before and after treatment. Relative to untreated animals, the distance at which elk fled from approaching humans, i.e., the flight response distance, increased following both human and dog treatments, but there was no difference between the two treatments. The proportion of time spent in vigilance postures decreased for all treatment groups, without differences among groups, suggesting that this behavior responded mainly to seasonal effects. The average distance between elk locations and the town boundary, measured once daily by telemetry, significantly increased for human-conditioned elk. One of the co-variates we measured, wolf activity, exerted counteracting effects on conditioning effects; flight response distances and proximity to the town site were both lower when wolf activity was high. This research demonstrates that it is possible to temporarily modify aspects of the behavior of moderately habituated elk using aversive conditioning, suggests a method for reducing habituation in the first place, and provides a solution for Banff and other jurisdictions to manage

  5. Gait analysis in a mouse model resembling Leigh disease. (United States)

    de Haas, Ria; Russel, Frans G; Smeitink, Jan A


    Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.

  6. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case. (United States)

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


    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.

  7. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

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    Vibhu Mendiratta


    Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

  8. Implant-associated anaplastic large cell lymphoma of the breast: Insight into a poorly understood disease. (United States)

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


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

  9. Primary pancreatic anaplastic large cell lymphoma, ALK negative:A case report

    Institute of Scientific and Technical Information of China (English)

    Christos G Savopoulos; NE Tsesmeli; GD Kaiafa; AT Zantidis; MT Bobos; AI Hatzitolios; ST Papavramidis; IS Kostopoulos


    We present the fourth case of a primary pancreatic anaplastic large cell lymphoma (ALCL), ALK-. An 80-year-old man was admitted to our clinic for further investigation of a fever of unknown origin. He noted anorexia, weight loss and fatigue. His laboratory tests showed anemia and a great elevation of ESR, LDH, and β2 microglobulin. In CT and MRI scan, a soft tissue mass in the pancreas was observed. A repeated endoscopy after his admission revealed an ulcerated mass-like deformity of the duodenal bulb. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant pancreatic mass extending to the adjacent organs. Duodenal and surgical biopsies identified an ALCL of T-cell lineage, ALK-. The patient died in the Intensive Care Unit due to hemodynamic instability.Our case is the first one indicating that primary pancreatic lymphoma should be suspected in a patient with pancreatic mass and elevated serum LDH and β2 microglobulin.

  10. Anaplastic carcinoma of the pancreas: Case report and literature review of reported cases in Japan (United States)

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


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

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

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    Oscar Mauricio Aguilar Mejía


    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

  12. Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep.

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    Lei Bai


    Full Text Available Though evidence is mounting that a major function of sleep is to maintain brain plasticity and consolidate memory, little is known about the molecular pathways by which learning and sleep processes intercept. Anaplastic lymphoma kinase (Alk, the gene encoding a tyrosine receptor kinase whose inadvertent activation is the cause of many cancers, is implicated in synapse formation and cognitive functions. In particular, Alk genetically interacts with Neurofibromatosis 1 (Nf1 to regulate growth and associative learning in flies. We show that Alk mutants have increased sleep. Using a targeted RNAi screen we localized the negative effects of Alk on sleep to the mushroom body, a structure important for both sleep and memory. We also report that mutations in Nf1 produce a sexually dimorphic short sleep phenotype, and suppress the long sleep phenotype of Alk. Thus Alk and Nf1 interact in both learning and sleep regulation, highlighting a common pathway in these two processes.

  13. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

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    Swaroop Revannasiddaiah


    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  14. Anaplastic large cell lymphoma ALK-negative clinically mimicking alcoholic hepatitis – a review

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    Fernando Peixoto Ferraz de Campos


    Full Text Available Anaplastic large cell lymphoma (ALCL, described less than 30 years ago by Karl Lennert and Herald Stein in Kiel, West Germany, is a T-cell or null non-Hodgkin lymphoma, with distinctive morphology (hallmark cells, prominent sinus and/or perivascular growth pattern, characteristic immunophenotype (CD30+, cytotoxic granules protein+, CD3–/+ and specific genetic features as translocations involving the receptor tyrosine kinase called anaplastic lymphoma kinase (ALK on 2p23 and variable partners genes, which results in the expression of ALK fusion protein. The absence of ALK expression is also observed and is associated with poorer prognosis that seen with ALK expression. ALK-negative ALCL is more frequent in adults, with both nodal and extra nodal clinical presentation and includes several differential diagnoses with other CD30+ lymphomas. Liver involvement by ALCL is rare and is generally seen as mass formation; the diffuse pattern of infiltration is even more unusual. The authors present a case of a 72-year-old man who presented clinical symptoms of acute hepatic failure. The patient had a long history of alcohol abuse and the diagnosis of alcoholic hepatitis was highly considered, although the serum lactic dehydrogenase (LDH value was highly elevated. The clinical course was fulminant leading to death on the fourth day of hospitalization. Autopsy demonstrated diffuse neoplastic hepatic infiltration as well as splenic, pulmonary, bone marrow, and minor abdominal lymph nodes involvement by the tumor. Based on morphological, immunophenotypical, and immunohistochemical features, a diagnosis of ALK- negative ALCL was concluded. When there is marked elevation of LDH the possibility of lymphoma, ALCL and other types, should be the principal diagnosis to be considered.

  15. Facial resemblance to emotions: group differences, impression effects, and race stereotypes. (United States)

    Zebrowitz, Leslie A; Kikuchi, Masako; Fellous, Jean-Marc


    The authors used connectionist modeling to extend previous research on emotion overgeneralization effects. Study 1 demonstrated that neutral expression male faces objectively resemble angry expressions more than female faces do, female faces objectively resemble surprise expressions more than male faces do, White faces objectively resemble angry expressions more than Black or Korean faces do, and Black faces objectively resemble happy and surprise expressions more than White faces do. Study 2 demonstrated that objective resemblance to emotion expressions influences trait impressions even when statistically controlling possible confounding influences of attractiveness and babyfaceness. It further demonstrated that emotion overgeneralization is moderated by face race and that racial differences in emotion resemblance contribute to White perceivers' stereotypes of Blacks and Asians. These results suggest that intergroup relations may be strained not only by cultural stereotypes but also by adaptive responses to emotion expressions that are overgeneralized to groups whose faces subtly resemble particular emotions.

  16. Features Resembling Pseudotachylyte at Enchanted Rock Batholith, Texas (United States)

    Buchanan, P. C.; Degenhardt, J. J., Jr.; Reid, A. M.


    Enchanted Rock batholith in central Texas is a granitic pluton of ~250 km^2 area [1]. The batholith intrudes Precambrian metamorphic rocks and is dated by Rb-Sr at 1,048+/-34 m.y. [2]. Plutonic rocks are exposed in a series of exfoliation domes located along the southeastern edge of the batholith. Numerous subvertical fractures occur along the outer margins of the intrusion and, in a few cases, between exfoliation domes. A number of these fractures contain veins described as pseudotachylytes by Barnes [3]. In hand specimen, the veins resemble pseudotachylytes, forming a branching network and containing angular fragments of local country rock in a fine-grained matrix that locally exhibits an apparent flow texture. Some smaller veins appear to have been injected into host rock. The veins range in width up to ~30 cm with boundaries which are sharp and smooth with undulating surfaces. Thin (~4-5 cm) aplite dikes cut the granite and generally show small amounts of displacement where intersected by the fracture veins (maximum measured apparent displacement ~75 cm). Matrix material in veins includes fragments of quartz, feldspar, biotite, and opaques. Matrix biotite is generally associated with opaques and occurs as numerous, tiny, oriented flakes between fragments of feldspar and quartz in areas which are darker than surrounding matrix. The flow-like textures of matrix materials are defined by these darker areas which are elongated subparallel to fracture direction. The finer-grained matrix biotite apparently derives from comminution of larger grains from host rock. Larger clasts include rock fragments and fragments of alkali feldspar and quartz, with a tendency for the larger fragments to concentrate in the centers of veins. Clasts are irregular in shape and are commonly angular and rarely contorted. Rock fragments are derived from host rock and also include "breccia within breccia" fragments. Single-mineral fragments display evidence of strain; quartz commonly shows

  17. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome. (United States)

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie


    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal.

  18. Acute spontaneous tumor lysis in anaplastic large T-cell lymphoma presenting with hyperuricemic acute renal failure. (United States)

    Hsu, Hsiang-Hao; Huang, Chiu-Ching


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

  19. Prognostic significance of NPM-ALK fusion transcript overexpression in ALK-positive anaplastic large-cell lymphoma. (United States)

    Li, Chunmei; Takino, Hisashi; Eimoto, Tadaaki; Ishida, Takashi; Inagaki, Atsushi; Ueda, Ryuzo; Suzuki, Ritsuro; Yoshino, Tadashi; Nakagawa, Atsuko; Nakamura, Shigeo; Inagaki, Hiroshi


    In anaplastic large-cell lymphomas positive for anaplastic lymphoma kinase (ALK) protein, the ALK gene is most commonly fused to the NPM gene, and less commonly to TPM3, TFG, ATIC, and other rare genes. Although this lymphoma is generally associated with a favorable clinical outcome, 25% of the patients die of the disease within 5 years. In this study, we developed three assays, all of which can be used with archival formalin-fixed, paraffin-embedded tissues: (1) a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay for various X-ALK fusion genes, (2) a 5' rapid amplification of cDNA ends (RACE) assay to identify unknown fusion partners, and (3) a real-time RT-PCR assay to quantify the amount of the NPM-ALK fusion transcript. In 26 cases of ALK(+) anaplastic large-cell lymphoma, the RT-PCR assay showed that the ALK was fused to NPM in 21 cases, to TPM3 in three, and to TFG in one. The 5' RACE assay detected ATIC-ALK fusion in the remaining case. The real-time quantitative RT-PCR assay showed that the NPM-ALK transcript was over expressed in four of 20 quantifiable cases. Patients with NPM-ALK overexpression showed a significantly unfavorable overall survival compared with those with a low expression of this transcript. The RT-PCR and 5' RACE assays developed here may be useful for identification of known and unknown gene partners fused to the ALK gene. Overexpression of the NPM-ALK fusion transcript may be associated with a poor prognosis of the patients with ALK(+) anaplastic large-cell lymphomas.

  20. Ovarian mucinous cystic tumor of borderline malignancy with a mural nodule of anaplastic spindle cell carcinoma: a case report. (United States)

    Yamazaki, Hitoshi; Matsuzawa, Akiyo; Shoda, Takashi; Iguchi, Hiroyoshi; Kyushima, Noriyuki


    Ovarian cystic tumors with a mural nodule are a rare entity. We report a case of a mural nodule of anaplastic spindle cell carcinoma in an ovarian mucinous cystic tumor of borderline malignancy. The patient was a 45-years-old Japanese woman who presented with an ovarian cyst. She suffered from mature cystic teratoma of both ovaries 9 years before the present history. Image analysis and laboratory data showing a high serum CA19-9 level suggested ovarian malignancy. She underwent bilateral salpingo-oophorectomy with hysterectomy and omentectomy. There was a mural nodule in the ovarian mucinous cystic lesion. Microscopically, the nodule was composed of spindle-shaped cells with severe nuclear atypia. Immunohistochemical analysis allowed the cells to be categorized as anaplastic spindle cell carcinoma. Fifteen months after the operation the patient is alive without any clinical findings of tumor recurrence. To the best of our knowledge in the English literature, this is the first report of a mural nodule of an anaplastic spindle cell carcinoma within an ovarian mucinous cystic borderline tumor harboring previously confirmed cystic teratoma.

  1. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

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    Maher Kurdi


    Full Text Available 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.

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

    Roskoski, Robert


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

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

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    Wang Yan-Fang


    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

  4. Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene

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    Haberkom, U. [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Dept. of Nuclear Medicine, Univ. of Heidelberg (Germany); Altmann, A.; Jiang, S.; Morr, I.; Mahmut, M. [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Eisenhut, M. [Dept. of Nuclear Medicine, Univ. of Heidelberg (Germany)


    Human thyroperoxidase (hTPO) is critical for the accumulation of iodide in thyroid tissues. Poorly differentiated and anaplastic thyroid tumours which lack thyroid-specific gene expression fail to accumulate iodide and, therefore, do not respond to iodine-131 therapy. We consequently investigated whether transfer of the hTPO gene is sufficient to restore the iodide-trapping capacity in undifferentiated thyroid and non-thyroid tumour cells. The human anaplastic thyroid carcinoma cell lines C643 and SW1736, the rat Morris hepatoma cell line MH3924A and the rat papillary thyroid carcinoma cell line L2 were used as in vitro model systems. Employing a bicistronic retroviral vector based on the myeloproliferative sarcoma virus for the transfer of the hTPO and the neomycin resistance gene, the C643 cells and SW1736 cells were transfected while the L2 cells and MH3924A cells were infected with retroviral particles. Seven recombinant C643 and seven SW1736 cell lines as well as four recombinant L2 and four MH3924A cell lines were established by neomycin selection. They were studied for hTPO expression using an antibody-based luminescence kit, followed by determination of the enzyme activity in the guaiacol assay and of the iodide uptake capacity in the presence of Na{sup 125}I. Genetically modified cell lines expressed up to 1,800 times more hTPO as compared to wild type tumour cells. The level of hTPO expression varied significantly between individual neomycin-resistant cell lines, suggesting that the recombinant retroviral DNA was integrated at different sites of the cellular genome. The accumulation of iodide, however, was not significantly enhanced in individual recombinant cell lines, irrespective of low or high hTPO expression. Moreover, there was no correlation between hTPO expression and enzyme activity in individual cell lines. The transduction of the hTPO gene per se is not sufficient to restore iodide trapping in non-iodide-concentrating tumour cells. Future

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

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


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

  6. Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients

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    Wang, Yinyan; Jiang, Tao [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Wang, Kai; Li, Shaowu; Ma, Jun [Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China); Wang, Jiangfei [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Dai, Jianping [Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China)


    Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients. (orig.)

  7. Targeting TGF-β1 suppresses survival of and invasion by anaplastic thyroid carcinoma cells (United States)

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


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

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

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    Li MA


    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.

  9. Anaplastic carcinoma of the pancreas: Is there a role for palliative surgical procedure?

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan


    Full Text Available Anaplastic carcinoma (AC or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF. Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  10. Infectious Mimicry Complicates Diagnosis in Hemophagocytic Syndrome Caused by Anaplastic Large-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Michael J. Peluso


    Full Text Available Hemophagocytic syndrome (HPS arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL. This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS—first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

  11. Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall. (United States)

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


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

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

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    Arai Hajime


    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.

  13. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Margarita Baka


    Full Text Available A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL, whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months, pyrazinamide (the first 2 months, and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

  14. Radiation-induced anaplastic ependymoma mimicking a skull base meningioma: A case report (United States)



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

  15. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report (United States)

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


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

  16. Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas. (United States)

    Niu, Hai-Tao; Zhou, Qi-Ming; Wang, Fang; Shao, Qiong; Guan, Yuan-Xiang; Wen, Xi-Zhi; Chen, Li-Zhen; Feng, Qi-Sheng; Li, Wei; Zeng, Yi-Xin; Zhang, Xiao-Shi


    Acral and mucosal melanomas, the two most common subtypes of melanoma in China, exhibit different genetic alterations and biologic behavior compared with other subtypes of melanomas. The purpose of this study was to identify the genetic alterations in patients with acral or mucosal melanomas in southern China. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) analysis, polymerase chain reaction (PCR), and quantitative real-time reverse transcriptase PCR (qRT-PCR) were used to assess the anaplastic lymphoma kinase (ALK) break points. Furthermore, a mass spectrometry-based genotyping platform was used to analyze 30 acral melanomas and 28 mucosal melanomas to profile 238 known somatic mutations in 19 oncogenes. ALK break points were identified in four acral cases (6.9%). Eight (13.8%) cases harbored BRAF mutations, six (10.3%) had NRAS mutations, four (6.9%) had KIT mutations, two (3.5%) had EGFR mutations, two (3.5%) had KRAS mutations, two (3.5%) had MET mutations, one (1.7%) had an HRAS mutation, and one (1.7%) had a PIK3CA mutation. Two cases exhibited co-occurring mutations, and one case with a BRAF mutation had a translocation in ALK. This study represents a comprehensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from southern China. These data have implications for both clinical trial designs and therapeutic strategies.

  17. Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy: Report of a case and a review of the literature

    Institute of Scientific and Technical Information of China (English)

    Kenichi Hakamada; Takuya Miura; Akitoshi Kimura; Masaki Nara; Yoshikazu Toyoki; Shunij Narumi; Mutsuo Sasak


    Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.

  18. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas (United States)


    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

  19. The Texas Adoption Project: adopted children and their intellectual resemblance to biological and adoptive parents. (United States)

    Horn, J M


    Intelligence test scores were obtained from parents and children in 300 adoptive families and compared with similar measures available for the biological mothers of the same adopted children. Results supported the hypothesis that genetic variability is an important influence in the development of individual differences for intelligence. The most salient finding was that adopted children resemble their biological mothers more than they resemble the adoptive parents who reared them from birth. A small subset of the oldest adopted children did not resemble their biological mothers. The suggestion that the influence of genes declines with age is treated with caution since other adoption studies report a trend in the opposite direction.

  20. {sup 18}F-fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Poisson, Thomas [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Service de Medecine Nucleaire, Hopital Bichat, Paris (France); Deandreis, Desiree; Leboulleux, Sophie; Lumbroso, Jean; Baudin, Eric [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Bidault, Francois [Institut Gustave Roussy and University Paris-Sud XI, Department of Radiology, Villejuif Cedex (France); Bonniaud, Guillaume [Institut Gustave Roussy and University Paris-Sud XI, Department of Medical Physics, Villejuif Cedex (France); Baillot, Sylvain; Auperin, Anne [Institut Gustave Roussy and University Paris-Sud XI, Department of Epidemiology, Villejuif Cedex (France); Ghuzlan, Abir Al [Institut Gustave Roussy and University Paris-Sud XI, Department of Pathology, Villejuif Cedex (France); Travagli, Jean-Paul [Institut Gustave Roussy and University Paris-Sud XI, Department of Endocrine Surgery, Villejuif Cedex (France); Schlumberger, Martin [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Institut Gustave Roussy, Service de Medecine Nucleaire et de Cancerologie Endocrinienne, Villejuif (France)


    Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients the value of {sup 18}F-FDG PET/CT compared with total body computed tomography (CT) using intravenous contrast material for initial staging, prognostic assessment, therapeutic monitoring and follow-up. Twenty consecutive ATC patients underwent PET/CT for initial staging. PET/CT was performed again during follow-up. The gold standard was progression on imaging follow-up (CT or PET/CT) or confirmation with another imaging modality. A total of 265 lesions in 63 organs were depicted in 18 patients. Thirty-five per cent of involved organs were demonstrated only with PET/CT and one involved organ only with CT. In three patients, the extent of disease was significantly changed with PET/CT that demonstrated unknown metastases. Initial treatment modalities were modified by PET/CT findings in 25% of cases. The volume of FDG uptake ({>=}300 ml) and the intensity of FDG uptake (SUV{sub max} {>=}18) were significant prognostic factors for survival. PET/CT permitted an earlier assessment of tumour response to treatment than CT in 4 of the 11 patients in whom both examinations were performed. After treatment with combined radiotherapy and chemotherapy, only the two patients with a negative control PET/CT had a confirmed complete remission at 14 and 38 months; all eight patients who had persistent FDG uptake during treatment had a clinical recurrence and died. FDG PET/CT appears to be the reference imaging modality for ATC at initial staging and seems promising in the early evaluation of treatment response and follow-up. (orig.)

  1. Treatment and Prognosis of Anaplastic Thyroid Carcinoma: A Clinical Study of 50 Cases (United States)

    Long, Zhen; Wei, Fan-Qin; Zhuang, Shi-Min; Sun, Xiao-Mei; Xie, Liang-En; Mu, Jia-Sheng; Zhang, Guan-Ping; Fan, Yi


    Introduction Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC. Materials and Methods The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model. Results The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis. Conclusion Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis. PMID:27760217

  2. CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin.

    Directory of Open Access Journals (Sweden)

    Susan Friedman

    Full Text Available BACKGROUND: Anaplastic thyroid cancer (ATC is one of the most lethal human malignancies. Its rapid onset and resistance to conventional therapeutics contribute to a mean survival of six months after diagnosis and make the identification of thyroid-cancer-initiating cells increasingly important. METHODOLOGY/PRINCIPAL FINDINGS: In prior studies of ATC cell lines, CD133(+ cells exhibited stem-cell-like features such as high proliferation, self-renewal and colony-forming ability in vitro. Here we show that transplantation of CD133(+ cells, but not CD133(- cells, into immunodeficient NOD/SCID mice is sufficient to induce growth of tumors in vivo. We also describe how the proportion of ATC cells that are CD133(+ increases dramatically over three months of culture, from 7% to more than 80% of the total. This CD133(+ cell pool can be further separated by flow cytometry into two distinct populations: CD133(+/high and CD133(+/low. Although both subsets are capable of long-term tumorigenesis, the rapidly proliferating CD133(+/high cells are by far the most efficient. They also express high levels of the stem cell antigen Oct4 and the receptor for thyroid stimulating hormone, TSHR. Treating ATC cells with TSH causes a three-fold increase in the numbers of CD133(+ cells and elicits a dose-dependent up-regulation of the expression of TSHR and Oct4 in these cells. More importantly, immunohistochemical analysis of tissue specimens from ATC patients indicates that CD133 is highly expressed on tumor cells but not on neighboring normal thyroid cells. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first report indicating that CD133(+ ATC cells are solely responsible for tumor growth in immunodeficient mice. Our data also give a unique insight into the regulation of CD133 by TSH. These highly tumorigenic CD133(+ cells and the activated TSH signaling pathway may be useful targets for future ATC therapies.

  3. Anaplastic thyroid carcinoma and foscarnet use in a multitarget treatment documented by 18F-FDG PET/CT (United States)

    Giannetta, Elisa; Isidori, Andrea M.; Durante, Cosimo; Di Gioia, Cira; Longo, Flavia; Tombolini, Vincenzo; Bulzonetti, Nadia; Graziadio, Chiara; Pofi, Riccardo; Gianfrilli, Daniele; Verrienti, Antonella; Carletti, Raffaella; Filetti, Sebastiano; Lenzi, Andrea; Baroli, Alberto


    Abstract Rationale: The case reported the rapid remission of disease recurrence achieved adding foscarnet, a DNA polymerase inhibitor that interacts with fibroblast growth factor 2, to low molecular weight heparin and sunitinib for the first time in a patient with an anaplastic thyroid cancer (ATC). Patient concerns: A 65-year-old woman with a multinodular goiter referred for a rapid enlargement of a nodule. Histological examination revealed an ATC with a little area of papillary thyroid cancer (PTC). The patient was resistant to selective single-target treatment. DIagnoses: Immunophenotyping and gene analyses found a significant increase in FGF2 and FGFR1 expression in the primary ATC area (FGF2 = 38.2 ± 6.2% in ATC vs 34.6 ± 6.0% in the differentiated area of PTC, P FGFR4 in ATC. Low molecular wight heparin and Sunitinib were coadministere to limiti metastatic progression and on neck tumor masse, respectively. Outcomes: The rationale for the clinical response to this innovative multitarget association with foscarnet is based on the histological and genetic finding that fibroblast growth factors and their receptor super-family are up-regulated in the primary anaplastic thyroid tumor and in the metastatic lymph node of our patient. Lessons: We propose that fibroblast growth factors and their receptor super-family play a key role as potential therapeutic targets in anaplastic thyroid cancer and the positive relevance of this suggestion for patient care, especially for an individualized management. PMID:28178124

  4. CD13-positive anaplastic large cell lymphoma of T-cell origin--a diagnostic and histogenetic problem. (United States)

    Popnikolov, N K; Payne, D A; Hudnall, S D; Hawkins, H K; Kumar, M; Norris, B A; Elghetany, M T


    The expression of myelomonocytic-associated antigens in anaplastic large cell lymphomas (ALCLs), particularly those presenting in extranodal sites, can make their distinction from extramedullary myeloid cell tumors (EMCTs) or histiocytic tumors problematic. Yet, this distinction is clinically significant because of its therapeutic and prognostic implications. Herein, we describe a case of extranodal anaplastic lymphoma kinase-positive CD30-positive ALCL of T-cell origin in a 12-year-old boy, which was initially called an EMCT because of the expression of CD13 and HLA-DR detected by flow cytometry and the absence of other T-cell-related surface markers. However, the detection of cytoplasmic CD3 by flow cytometry prompted further studies. The tumor was composed of large cells with abundant slightly eosinophilic vacuolated cytoplasm and ovoid or reniform nuclei with a few small nucleoli. Using immunohistochemistry, the tumor was positive for CD45, CD30, CD45RO, and CD43 with a strong cytoplasmic and nuclear anaplastic lymphoma kinase stain. The tumor cells showed a T-cell clonal genotype. Electron microscopy revealed no ultrastructural features of myelomonocytic or histiocytic origin. The patient responded well to the chemotherapy and was in complete remission for 10 months at the time of submission of this manuscript. Review of the literature showed inconsistencies regarding the diagnosis, nomenclature, and, therefore, treatment and prognosis of these tumors. In addition, the CD13 expression in ALCL raises some histogenetic questions and may indicate origin from a pluripotent stem cell, misprogramming during malignant transformation, or a microenvironmental effect on lymphoid cell expression of surface antigens. Therefore, ALCL should be considered in the differential diagnosis of EMCTs or histiocytic tumors, particularly when surface marker lineage assignment is ambiguous.

  5. Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib

    DEFF Research Database (Denmark)

    Rossing, Henrik H; Grauslund, Morten; Urbanska, Edyta M;


    , the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations......Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase...... inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However...

  6. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan


    Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector...... known STATs was consistently tyrosine phosphorylated in these cell lines. In addition, malignant cells in tissue sections from all (10 of 10) ALK+ TCL patients expressed tyrosine-phosphorylated STAT3. Transfection of BaF3 cells with NPM/ALK resulted in tyrosine phosphorylation of STAT3. Furthermore...

  7. Poor response to gefitinib in lung adenocarcinoma with concomitant epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement. (United States)

    Zhou, Jianya; Zheng, Jing; Zhao, Jing; Sheng, Yihong; Ding, Wei; Zhou, Jianying


    A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant ALK rearrangement and exon 19 (E746-A750del) EGFR mutation. The ALK rearrangement was confirmed not only in the primary tumor biopsy specimen, but also in the pleural effusion cell block by reverse transcriptase-polymerase chain reaction (RT-PCR), Ventana ALK immunohistochemistry assay, and fluorescence in situ hybridization. No clinical benefit using chemotherapy or EGFR tyrosine kinase inhibitor gefitinib was obtained in this case.

  8. Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study. (United States)

    Langenhof, M Rohaa; Komdeur, Jan; Oldehinkel, Albertine J


    This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We modelled the association between perceived parental warmth and rejection at age eleven and personality resemblance to parents at about age sixteen. Parenting experienced during early adolescence was related to the degree and direction in which adolescents resembled their parents five years later in life. Rejection, especially from fathers, significantly predicted a smaller resemblance to both the parents. Girls were more strongly affected by parental quality than boys, and there was some indication that adolescents responded in opposite ways to parenting from mothers and fathers. This study is a first step in uncovering the complex interplay between parenting, gender, and the current generation's ability to develop personality traits independent from the previous generation.

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

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


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

  10. Who resembles whom? Mimetic and coincidental look-alikes among tropical reef fishes. (United States)

    Robertson, D Ross


    Studies of mimicry among tropical reef-fishes usually give little or no consideration to alternative explanations for behavioral associations between unrelated, look-alike species that benefit the supposed mimic. I propose and assess such an alternative explanation. With mimicry the mimic resembles its model, evolved to do so in response to selection by the mimicry target, and gains evolved benefits from that resemblance. In the alternative, the social-trap hypothesis, a coincidental resemblance of the model to the "mimic" inadvertently attracts the latter to it, and reinforcement of this social trapping by learned benefits leads to the "mimic" regularly associating with the model. I examine three well known cases of supposed aggressive mimicry among reef-fishes in relation to nine predictions from these hypotheses, and assess which hypothesis offers a better explanation for each. One case, involving precise and complex morphological and behavioral resemblance, is strongly consistent with mimicry, one is inconclusive, and one is more consistent with a social-trap based on coincidental, imprecise resemblance. Few cases of supposed interspecific mimicry among tropical reef fishes have been examined in depth, and many such associations may involve social traps arising from generalized, coincidental resemblance. Mimicry may be much less common among these fishes than is generally thought.

  11. 少突胶质细胞瘤影像学表现与临床病理分析%Imaging features of oligodendrogliomas and the analysis of clinic and pathology

    Institute of Scientific and Technical Information of China (English)

    陈杨宗; 谢福荣; 李鹏; 杨登法


    Objective: To improve the recognition of oligodendrogliomas by studying the imaging features and analyzing the clinic and pathology of oligodendroglioma. Methods: The CT,MR findings of 20 pathologically proven oligodendrogliomas were retrospectively analyzed. All these 20 cases underwent contrast MR scans, nine of them also underwent CT scan before surgery. Results: All these 20 cases had supratentorial single lesion. There were 13 cases of grade Ⅱ and 7 cases of grade Ⅲ, respectively. CT and MR features of oligodendrogliomas were as follows:①The frontal lobes were most often involved, which accounted for 65.0%. ② The size of grade Ⅲ tumors was larger than that of grade Ⅱ , and the mean of the maximum diameter was 55.6 mm and 42.7 mm, respectively. ③The modality of oligodendrogliomas showed mass, like round and irregular lobulated. The tumors were usually heterogeneous but had relatively low intensity on Tl WI and high intensity on T2 WI, four of them calcified.④ Cystic-appearing regions were commonly found in the mass,57.1% of grade HI and 46.2% of grade Ⅱ tumors had cystic lesion. ⑤Peritumoral edema was found in the most cases,which accounted for 70.0%. ⑥After contrast,60.0% cases were enhanced and the pattern of the enhancement was various. Conclusion: Imaging features of oligodendrogliomas are characteristic, they can improve accuracy of the diagnosis and grading of oligodendroglioma in most cases after recognizing the imaging features.hanced ad the pat%目的:分析颅内少突胶质细胞瘤的影像学表现及临床、病理的特点,以提高对本病的认识.方法:对20例经手术病理证实的颅内少突胶质细胞瘤的CT、MR表现及病理改变进行回顾性分析.所有患者术前行MR平扫加增强扫描,9例行CT平扫.结果:20例均为单发病灶,年龄27 - 58岁,病变均位于幕上脑实质内.其中Ⅱ级少突胶质细胞瘤13例,Ⅲ级7例.其CT、MR上表现为:①额叶发病率最高,占65.0%;②Ⅲ级

  12. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. (United States)

    Huang, Wei-Sheng; Liu, Shuangying; Zou, Dong; Thomas, Mathew; Wang, Yihan; Zhou, Tianjun; Romero, Jan; Kohlmann, Anna; Li, Feng; Qi, Jiwei; Cai, Lisi; Dwight, Timothy A; Xu, Yongjin; Xu, Rongsong; Dodd, Rory; Toms, Angela; Parillon, Lois; Lu, Xiaohui; Anjum, Rana; Zhang, Sen; Wang, Frank; Keats, Jeffrey; Wardwell, Scott D; Ning, Yaoyu; Xu, Qihong; Moran, Lauren E; Mohemmad, Qurish K; Jang, Hyun Gyung; Clackson, Tim; Narasimhan, Narayana I; Rivera, Victor M; Zhu, Xiaotian; Dalgarno, David; Shakespeare, William C


    In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

  13. Down-regulation of transcription elogation factor A (SII like 4 (TCEAL4 in anaplastic thyroid cancer

    Directory of Open Access Journals (Sweden)

    Miyamoto Shizuyo


    Full Text Available Abstract Background Anaplastic thyroid cancer (ATC is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC. However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII-like 4 (TCEAL4, encodes a member of the transcription elongation factor A (SII-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously. Methods To investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue. Results Expression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested. Conclusion To our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required.

  14. A North American brain tumor consortium phase II study of Poly-ICLC for adult patients with recurrent anaplastic gliomas (United States)

    Butowski, Nicholas; Lamborn, Kathleen R.; Lee, Bee L; Prados, Michael D.; Cloughesy, Timothy; DeAngelis, Lisa M.; Abrey, Lauren; Fink, Karen; Lieberman, Frank; Mehta, Minesh; Robins, H. Ian; Junck, Larry; Salazar, Andres M.; Chang, Susan M.


    Purpose This phase II study was designed to determine the objective response rate and 6-month progression free survival of adult patients with recurrent supratentorial anaplastic glioma when treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). Methods and Materials This was an open-labeled, single arm phase II study. Patients were treated with poly-ICLC alone. Patients may have had treatment for no more than two prior relapses. Treatment with poly-ICLC continued until tumor progression. Results 55 patients were enrolled in the study. 10 were ineligible after central review of pathology. 11% of patients (5 of 45) had a radiographic response. Time to progression was known for 39 patients and 6 remain on treatment. The estimated 6-month progression free survival was 24%. The median survival time was 43 weeks. Conclusions Poly-ICLC was well tolerated, but there was no improvement in 6-month progression free survival compared to historical database nor was there an encouraging objective radiographic response rate. Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents such as temozolomide. PMID:18850068

  15. Reactive oxygen species and lipoxygenases regulate the oncogenicity of NPM-ALK-positive anaplastic large cell lymphomas. (United States)

    Thornber, K; Colomba, A; Ceccato, L; Delsol, G; Payrastre, B; Gaits-Iacovoni, F


    The chimera nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the tyrosine kinase activity of which is constitutively upregulated, is the causative agent of 75% of the anaplastic large-cell lymphomas (ALCLs). We have demonstrated that NPM-ALK induces the production of reactive oxygen species (ROS) by a pathway involving the arachidonic acid-metabolizing enzymes of the lipoxygenase (LOX) family. The use of the LOX inhibitor nordihydroguaiaretic acid (NDGA) and of the anti-oxidant N-acetylcysteine (NAC) demonstrated that ROS are important in maintaining the ALK kinase active. Consistent with this, NDGA treatment resulted in the inhibition of key pathways, such as Akt, signal transducer and activator of transcription factor 3 (STAT3) and extracellular signal-regulated kinase (ERK), which are involved in NPM-ALK antiapoptotic and pro-mitogenic functions. Conversely, the stress-activated kinase p38, described in some instances as a mediator of apoptosis, was activated. Interestingly, 5-LOX, an isoform involved in many cancers, was found to be activated in NPM-ALK(+) cells. Functional studies have shown that transforming properties, namely proliferation and resistance to apoptosis, were abrogated by treatment with either NDGA or the 5-LOX inhibitor (N-(3-phenoxycinnamyl)-acetohydroxamic acid) (BW A4C). Together, these data point to the ROS/LOX pathway as a potential new target for therapy in NPM-ALK-positive tumors.

  16. Silibinin suppresses NPM-ALK, potently induces apoptosis and enhances chemosensitivity in ALK-positive anaplastic large cell lymphoma. (United States)

    Molavi, Ommoleila; Samadi, Nasser; Wu, Chengsheng; Lavasanifar, Afsaneh; Lai, Raymond


    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), an oncogenic fusion protein carrying constitutively active tyrosine kinase, is known to be central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK+ALCL). Here, it is reported that silibinin, a non-toxic naturally-occurring compound, potently suppressed NPM-ALK and effectively inhibited the growth and soft agar colony formation of ALK+ALCL cells. By western blots, it was found that silibinin efficiently suppressed the phosphorylation/activation of NPM-ALK and its key substrates/downstream mediators (including STAT3, MEK/ERK and Akt) in a time- and dose-dependent manner. Correlating with these observations, silibinin suppressed the expression of Bcl-2, survivin and JunB, all of which are found to be upregulated by NPM-ALK and pathogenetically important in ALK+ALCL. Lastly, silibinin augmented the chemosensitivity of ALK+ALCL cells to doxorubicin, particularly the small cell sub-set expressing the transcriptional activity of Sox2, an embryonic stem cell marker. To conclude, the findings suggest that silibinin might be useful in treating ALK+ALCL.

  17. Analysis of human T-cell lymphotropic virus in CD25+ anaplastic large cell lymphoma in children. (United States)

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


    Anaplastic large cell lymphoma (ALCL) is recognized as 2 distinct diseases: anaplastic lymphoma kinase (ALK)+ ALCL and ALK- ALCL. ALK+ ALCL occurs in younger patients and has a better prognosis. Human T-cell lymphotropic virus (HTLV-1) is linked to the development of adult T-cell leukemia/lymphoma (ATLL), which frequently expresses CD25. CD25 is significantly expressed in childhood ALCL. In Brazil, HTLV-1 infection is endemic, and vertical transmission is responsible for spread to children. Of HTLV-1 carriers, 90% or more remain asymptomatic. Some cases of adult HTLV-1-related lymphomas have characteristics of ALCL but are considered CD30+ ATLL subtypes. No similar cases have been described in children. We analyzed 33 cases of pediatric ALCL, CD25+ and CD25-, for proviral HTLV-1 DNA. All cases corresponded to the common histologic ALCL type and were CD30+ in virtually all neoplastic cells. ALK expression was observed in 31 (94%) of 33 cases; CD25 was positive in 27 (82%), including 1 ALK- ALCL case. There was a strong positive correlation between ALK and CD25 expression. None of the cases showed proviral HTLV-1 DNA. ALCL in children has no relationship with HTLV-1; the frequent CD25 expression must be explained by a mechanism different from that in ATLL.

  18. A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation. (United States)

    Abate, F; Todaro, M; van der Krogt, J-A; Boi, M; Landra, I; Machiorlatti, R; Tabbò, F; Messana, K; Abele, C; Barreca, A; Novero, D; Gaudiano, M; Aliberti, S; Di Giacomo, F; Tousseyn, T; Lasorsa, E; Crescenzo, R; Bessone, L; Ficarra, E; Acquaviva, A; Rinaldi, A; Ponzoni, M; Longo, D L; Aime, S; Cheng, M; Ruggeri, B; Piccaluga, P P; Pileri, S; Tiacci, E; Falini, B; Pera-Gresely, B; Cerchietti, L; Iqbal, J; Chan, W C; Shultz, L D; Kwee, I; Piva, R; Wlodarska, I; Rabadan, R; Bertoni, F; Inghirami, G


    Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.

  19. A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in an HIV Patient Treated with CHOP

    Directory of Open Access Journals (Sweden)

    Jorge Hurtado-Cordovi


    Full Text Available Anaplastic large cell lymphoma (ALCL is the second most common malignancy of T-cell phenotype. This case report describes an unusual rapidly progressing cutaneous anaplastic large T-cell lymphoma in an HIV patient. Our patient is a twenty-year-old African American male with perinatally acquired HIV who presented with a 2×2 centimeter necrotic lesion in the right 1st toe; however, 2-3 weeks later multiple smaller lesions appeared on the anterior aspect of the right foot, ankle, and thigh. Biopsy showed cells strongly positive for CD3 and CD30 and negative for CD56 and the ALK gene product. CT of the chest, abdomen, and pelvis was negative for extracutaneous involvement favoring cutaneous ALCL. Patient was treated with 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone chemotherapy and went into complete remission. Due to the aggressive course that this malignancy follows in HIV patients we suggest prompt treatment with systemic therapy.

  20. Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy (United States)

    Buetti-Dinh, Antoine; O’Hare, Thomas


    A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance. PMID:27669408

  1. Influence of insurance status and income in anaplastic astrocytoma: an analysis of 4325 patients. (United States)

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


    To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.

  2. Older Adults' Trait Impressions of Faces Are Sensitive to Subtle Resemblance to Emotions. (United States)

    Franklin, Robert G; Zebrowitz, Leslie A


    Younger adults (YA) attribute emotion-related traits to people whose neutral facial structure resembles an emotion (emotion overgeneralization). The fact that older adults (OA) show deficits in accurately labeling basic emotions suggests that they may be relatively insensitive to variations in the emotion resemblance of neutral expression faces that underlie emotion overgeneralization effects. On the other hand, the fact that OA, like YA, show a 'pop-out' effect for anger, more quickly locating an angry than a happy face in a neutral array, suggests that both age groups may be equally sensitive to emotion resemblance. We used computer modeling to assess the degree to which neutral faces objectively resembled emotions and assessed whether that resemblance predicted trait impressions. We found that both OA and YA showed anger and surprise overgeneralization in ratings of danger and naiveté, respectively, with no significant differences in the strength of the effects for the two age groups. These findings suggest that well-documented OA deficits on emotion recognition tasks may be more due to processing demands than to an insensitivity to the social affordances of emotion expressions.

  3. From similitude to success: The effects of facial resemblance on perceptions of team effectiveness. (United States)

    Wang, Ze; He, Xin; Liu, Fan


    Scant empirical research has focused on how impressions of teams are formed based on members' collective appearance, even though team photos are omnipresent in visual communications and teamwork is a common theme to elicit positive responses. Across 4 studies, we show that a subtle increase in the facial resemblance among team members enhances observers' evaluations of team effectiveness. This resemblance effect is mediated by perceived cooperative intent among team players. Furthermore, we demonstrate a reversal of the resemblance effect through the moderating role of information valence and extend the finding from team perception to behavioral intention. These results hold across different manipulations, contexts, stimuli, and sample characteristics. Collectively, this research presents the first empirical evidence that inferences based on facial morphology persist well beyond evaluations of individuals to influence the way a team, as a whole, is perceived.

  4. Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma. (United States)

    Bohling, Sandra D; Jenson, Stephen D; Crockett, David K; Schumacher, Jonathan A; Elenitoba-Johnson, Kojo S J; Lim, Megan S


    Anaplastic large cell lymphoma (ALCL) comprises a group of non-Hodgkin lymphomas characterized by the expression of the CD30/Ki-1 antigen. A subset of ALCL is characterized by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2. While the most common translocation is the t(2;5)(p23;q35) involving the nucleophosmin (NPM) gene on chromosome 5, up to 12 other translocations partners of the ALK gene have been identified. One of these is the t(1;2)(q25;p23) which results in the formation of the chimeric protein TPM3-ALK. While several of the signaling pathways induced by NPM-ALK have been elucidated, those involved in ALCLs harboring TPM3-ALK are largely unknown. In order to investigate the expression profiles of ALCLs carrying the NPM-ALK and TPM3-ALK fusions, we carried out cDNA microarray analysis of two ALCL tissue samples, one expressing the NPM-ALK fusion protein and the other the TPM3-ALK fusion protein. RNA was extracted from snap-frozen tissues, labeled with fluorescent dyes and analyzed using cDNAs microarray containing approximately 9,200 genes and expressed sequence tags (ESTs). Quantitative fluorescence RT-PCR was performed to validate the cDNA microarray data on nine selected gene targets. Our results show a significant overlap of genes deregulated in the NPM-ALK and TPM-ALK positive lymphomas. These deregulated genes are involved in diverse cellular functions, such as cell cycle regulation, apoptosis, proliferation, and adhesion. Interestingly, a subset of the genes was distinct in their expression pattern in the two types of lymphomas. More importantly, many genes that were not previously associated with ALK positive lymphomas were identified. Our results demonstrate the overlapping and unique transcriptional patterns associated with the NPM-ALK and TPM3-ALK fusions in ALCL.

  5. Adding Chemotherapy to Radiation Improves Survival for Some Patients with Rare Brain Cancer (United States)

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

  6. Anaplastic lymphoma kinase-positive lung adenocarcinoma patient with development of sick sinus syndrome while on targeted treatment with crizotinib. (United States)

    Jiang, Hao; Li, Mei-Mei; Jin, Shu-Xian


    The anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are younger and have never smoked, while pathologically are predominately adenocarcinomas. Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to. We now describe a case of ALK positive NSCLC patient with development of sick sinus syndrome (SSS) while on targeted treatment with crizotinib. A 46-year-old non-smoking woman with right hilar mass and underwent transesophageal endoscopic ultrasonography lymph node biopsy showed low differentiation adenocarcinoma, immunohistochemistry (IHC) of tumor samples revealed the ALK overexpression. The severe sinus bradycardia and RR interval prolongation were detected 3 months after crizotinib treatment, she underwent pacemaker implantation. Although the severe sinus bradycardia and RR interval prolongation were unusual adverse effects, physicians should be aware of these side effects when using crizotinib.

  7. Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report (United States)

    Ungaro, Antonio; Orsi, Franco; Casadio, Chiara; Galdy, Salvatore; Spada, Francesca; Cella, Chiara Alessandra; Tonno, Clementina Di; Bonomo, Guido; Vigna, Paolo Della; Murgioni, Sabina; Frezza, Anna Maria; Fazio, Nicola


    We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient’s clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma. PMID:27170835

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

    Directory of Open Access Journals (Sweden)

    Graf N


    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

  9. Locally advanced breast implant associated anaplastic large cell lymphoma: A case report of successful treatment with radiation and chemotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Fleighton Estes


    Full Text Available The development of breast implant associated anaplastic large cell lymphoma (ALCL is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can become more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy.

  10. Conjugal plasmid transfer in Streptomyces resembles bacterial chromosome segregation by FtsK/SpoIIIE


    Vogelmann, Jutta; Ammelburg, Moritz; Finger, Constanze; Guezguez, Jamil; LINKE, Dirk; Flötenmeyer, Matthias; Stierhof, York-Dieter; Wohlleben, Wolfgang; Muth, Günther


    Most bacteria share virulence and resistance genes by transferring single-stranded DNA through a type IV secretion system. Streptomycetes, however, exchange dsDNA, using a system found to closely resemble machineries for prokaryotic chromosome segregation or DNA translocation during spore formation.

  11. Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study

    NARCIS (Netherlands)

    Langenhof, M Rohaa; Komdeur, Jan; Oldehinkel, Albertine J


    This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We

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

    NARCIS (Netherlands)

    Nielsen, M.; Vachon, C.M.; Scott, C.G.; Chernoff, K.; Karemore, G.; Karssemeijer, N.; Lillholm, M.; Karsdal, M.A.


    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 exami

  13. A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Mads; Karemore, Gopal; Loog, Marco


    Objective: We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker. Methods: A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior...

  14. Startle eye-blink modulation by facial self-resemblance and current mood. (United States)

    Finke, Johannes B; Larra, Mauro F; Schilling, Thomas M; Lass-Hennemann, Johanna; Blumenthal, Terry D; Schächinger, Hartmut


    Although salient stimuli are known to modulate startle eye-blink responses, and one's own face is considered of particular salience, effects of facial self-resemblance on startle responsiveness have not been systematically investigated. For the present study, pictures from the FACES database (rated as neutral) were digitally morphed to resemble the participants' (N=37) faces to varying degrees (25-50-75%). Perceptually matched geometrical shapes served as a control condition. At SOAs of either 300ms or 3000ms after picture onset, startle responses were elicited by white noise (50ms, 105dB), and recorded at the orbicularis oculi via EMG. Prior to the experiment, self-reported mood was assessed by means of the PANAS. Relative to non-face stimuli, the presentation of faces reduced startle magnitude at short, but not long, lead intervals. Furthermore, for probes presented at a SOA of 300ms, a linear decrease in startle magnitude with higher levels of self-resemblance was observed, presumably reflecting higher salience of the self-face. The startle modulating effect of self-resembling faces during longer lead intervals was moderated by the participants' current mood: negative affect predicted stronger patterns of attenuation, which might be interpreted as an increase in self-focus resulting from more negative mood.

  15. Family resemblance in fat intake, nutrition attitudes and beliefs: a study among three generations of women.

    NARCIS (Netherlands)

    Stafleu, A.


    In this thesis nutrition attitudes, beliefs, and fat intake in three generations of women are described. The aim of the study was twofold: the development of methods, and to study family resemblance in food habits. Based on literature study and qualitative pilot studies a questionnaire on beliefs an

  16. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. (United States)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara; Boeri Erba, Elisabetta; Boccalatte, Francesco; Mohammed, Shabaz; Jensen, Ole N; Palestro, Giorgio; Inghirami, Giorgio; Chiarle, Roberto


    Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542 of Shp2 mainly stained ALK-positive cells. In ALCL cell lines, Shp2-constitutive phosphorylation was dependent on NPM-ALK, as it significantly decreased after short hairpin RNA (shRNA)-mediated NPM-ALK knock down. In addition, only the constitutively active NPM-ALK, but not the kinase dead NPM-ALK(K210R), formed a complex with Shp2, Gab2, and growth factor receptor binding protein 2 (Grb2), where Grb2 bound to the phosphorylated Shp2 through its SH2 domain. Shp2 knock down by specific shRNA decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and of the tyrosine residue Y416 in the activation loop of Src, resulting in impaired ALCL cell proliferation and growth disadvantage. Finally, migration of ALCL cells was reduced by Shp2 shRNA. These findings show a direct involvement of Shp2 in NPM-ALK lymphomagenesis, highlighting its critical role in lymphoma cell proliferation and migration.

  17. NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma. (United States)

    Galietta, Annamaria; Gunby, Rosalind H; Redaelli, Sara; Stano, Paola; Carniti, Cristiana; Bachi, Angela; Tucker, Philip W; Tartari, Carmen J; Huang, Ching-Jung; Colombo, Emanuela; Pulford, Karen; Puttini, Miriam; Piazza, Rocco G; Ruchatz, Holger; Villa, Antonello; Donella-Deana, Arianna; Marin, Oriano; Perrotti, Danilo; Gambacorti-Passerini, Carlo


    The oncogenic fusion tyrosine kinase nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) induces cellular transformation in anaplastic large-cell lymphomas (ALCLs) carrying the t(2;5) chromosomal translocation. Protein-protein interactions involving NPM/ALK are important for the activation of downstream signaling pathways. This study was aimed at identifying novel NPM/ALK-binding proteins that might contribute to its oncogenic transformation. Using a proteomic approach, several RNA/DNA-binding proteins were found to coimmunoprecipitate with NPM/ALK, including the multifunctional polypyrimidine tract binding proteinassociated splicing factor (PSF). The interaction between NPM/ALK and PSF was dependent on an active ALK kinase domain and PSF was found to be tyrosine-phosphorylated in NPM/ALK-expressing cell lines and in primary ALK(+) ALCL samples. Furthermore, PSF was shown to be a direct substrate of purified ALK kinase domain in vitro, and PSF Tyr293 was identified as the site of phosphorylation. Y293F PSF was not phosphorylated by NPM/ALK and was not delocalized in NPM/ALK(+) cells. The expression of ALK fusion proteins induced delocalization of PSF from the nucleus to the cytoplasm and forced overexpression of PSF-inhibited proliferation and induced apoptosis in cells expressing NPM/ALK. PSF phosphorylation also increased its binding to RNA and decreased the PSF-mediated suppression of GAGE6 expression. These results identify PSF as a novel NPM/ALK-binding protein and substrate, and suggest that PSF function may be perturbed in NPM/ALK-transformed cells.

  18. Postoperative spindle cell nodules of genitourinary tract resembling sarcomas. A report of eight cases. (United States)

    Proppe, K H; Scully, R E; Rosai, J


    Eight cases of proliferative spindle cell nodules that developed 5 weeks to 3 months after operations on the lower genital tract of four women, and the lower urinary tract of four men, are described. The lesions ranged up to 4 cm in diameter, resembled spindle cell sarcomas on microscopical examination, and were initially interpreted as such in most of the cases. Six of the lesions were treated by local excision alone, and two by a radical surgical procedure, followed by radiation therapy in one case. The six patients whose lesions were treated inadequately on the assumption that they were sarcomas were free of disease 9-60 months (average, 28 months) postoperatively, and the two men who were treated by radical procedures were well 18 and 60 months later. The microscopic features, the unusual clinical setting, and the favorable prognosis of these lesions suggest that they were examples of a hitherto undescribed form of benign reactive lesion resembling a sarcoma.

  19. Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax. (United States)

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


    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.

  20. Parent-child resemblance in weight status and its correlates in the United States.

    Directory of Open Access Journals (Sweden)

    Yinghui Liu

    Full Text Available BACKGROUND: Few studies have examined parent-child resemblance in body weight status using nationally representative data for the US. DESIGN: We analyzed Body Mass Index (BMI, weight status, and related correlates for 4,846 boys, 4,725 girls, and their parents based on US nationally representative data from the 2006 and 2007 Medical Expenditure Panel Survey (MEPS. Pearson partial correlation coefficients, percent agreement, weighted kappa coefficients, and binary and multinomial logistic regression were used to examine parent-child resemblance, adjusted for complex sampling design. RESULTS: Pearson partial correlation coefficients between parent and child's BMI measures were 0.15 for father-son pairs, 0.17 for father-daughter pairs, 0.20 for mother-son pairs, and 0.23 for mother-daughter pairs. The weighted kappa coefficients between BMI quintiles of parent and child ranged from -0.02 to 0.25. Odds ratio analyses found children were 2.1 (95% confidence interval (CI: 1.6, 2.8 times more likely to be obese if only their father was obese, 1.9 (95% CI: 1.5, 2.4 times more likely if only their mother was obese, and 3.2 (95% CI: 2.5, 4.2 times more likely if both parents were obese. CONCLUSIONS: Parent-child resemblance in BMI appears weak and may vary across parent-child dyad types in the US population. However, parental obesity status is associated with children's obesity status. Use of different measures of parent-child resemblance in body weight status can lead to different conclusions.

  1. On Resemblance Between the Protagonists in Wuthering Heights and the Author——Emily Bront?

    Institute of Scientific and Technical Information of China (English)



    Wuthering Heights has been puzzling readers in many respects.People have been wondering how an unmarried lady like Emily Bront?could create the most intense,the most beautiful and at the same time the most horrible love story and where her experience came from.This article makes attempt to compare the resemblance between the protagonists and the author to discuss the source of the story’s creation and answer the above questions.

  2. Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity. (United States)

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


    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.

  3. Brain metastasis of ALK positive anaplastic large cell lymphoma after a long-term disease free survival in an old adult (United States)

    Wang, Cai-Xia; Wang, Hai; Li, Jie; Ma, Heng-Hui; Yu, Bo; Shi, Shan-Shan; Zhou, Xiao-Jun; Shi, Qun-Li


    Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma composed of CD30-positive cells and now recognized as three different entities: primary cutaneous ALCL, primary systemic anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and primary ALK-negative (ALK-) ALCL. ALK+ ALCL is supposed to have a better prognosis than ALK- ALCL. It is rarely metastasized to other sites, especially to the central nervous system (CNS). Herein, we present a rare case of systemic ALK+ ALCL which metastasized to the brain after a long-term disease free survival in an adult. Neuroimaging revealed a well-enhanced mass in the left frontal lobe. And it was completely resected. The results of the pathological and immunohistochemical studies were consistent with the metastasized ALK+ ALCL. The clinical findings, pathologic characteristics and treatment are described. PMID:24696735

  4. Facial Resemblance Exaggerates Sex-Specific Jealousy-Based Decisions1

    Directory of Open Access Journals (Sweden)

    Steven M. Platek


    Full Text Available Sex differences in reaction to a romantic partner's infidelity are well documented and are hypothesized to be attributable to sex-specific jealousy mechanisms which are utilized to solve adaptive problems associated with risk of extra-pair copulation. Males, because of the risk of cuckoldry become more upset by sexual infidelity, while females, because of loss of resources and biparental investment tend to become more distressed by emotional infidelity. However, the degree to which these sex-specific reactions to jealousy interact with cues to kin are completely unknown. Here we investigated the interaction of facial resemblance with decisions about sex-specific jealousy scenarios. Fifty nine volunteers were asked to imagine that two different people (represented by facial composites informed them about their romantic partner's sexual or emotional infidelity. Consistent with previous research, males ranked sexual infidelity scenarios as most upsetting and females ranked emotional infidelity scenarios most upsetting. However, when information about the infidelity was provided by a face that resembled the subject, sex-specific reactions to jealousy were exaggerated. This finding highlights the use of facial resemblance as a putative self-referent phenotypic matching cue that impacts trusting behavior in sexual contexts.

  5. 131I therapy for hyperthyroidism and consequent appearing of anaplastic carcinoma of the thyroid: simple case-report or real pathophysiologic link?

    Directory of Open Access Journals (Sweden)

    G. Scanelli


    Full Text Available BACKGROUND 131I is usually employed for the therapy of hyperfunctioning thyroid diseases. This β-emitting radioisotope acts releasing its radiations in small tissue volumes, but it is mandatory to consider, also for the small doses, the carcinogenic risk, well documented with the high 131I dosages used to cure differentiated thyroid cancers. METHODS We describe a case of anaplastic thyroid carcinoma appeared 4 years after therapy with 131I for Graves’ disease. The patient was treated both surgically and with thyonamides for Graves’ disease 20 years before; thereafter she underwent simple nephrectomy owing to Grawitz disease. After some years of well being, she was treated with 131I for a relapse of Graves’ disease. Four years later, she was treated with interleukin-2 and TNF-α, owing to distant metastases (pancreas, liver and lung of Grawitz cancer. Some months later, because of a rapid enlargement of the thyroid gland, she was thyroidectomized and anaplastic thyroid cancer was histologically documented. DISCUSSION AND CONCLUSIONS It is very difficult to investigate the possible transformation of a benign thyroid lesion to a malignant one, and data from the literature are conflicting. Fractioned doses of 131I are known to induce less cancers than high doses: they allow DNA to repair. Nevertheless, in patients with altered or non valid genetic repair’s mechanisms (i.e. patients with p53 mutations and, for this reason, prone to develop cancers, even low doses of 131I can induce carcinogenetic effects. In a patient with a history of cancer, who subsequently develops hyperthyroidism, even low doses of 131I can induce anaplastic thyroid cancer; in these subjects, therefore, other treatments than 131I could be preferred for the therapy of Graves’ disease. In our peculiar case, moreover, some studies have noteworthy demonstrated that certain cytokines (IL-1, TGF-β1 e TNF-α can, rather than inhibit, induce anaplastic thyroid cancer cells

  6. Integrated phosphoproteomic and metabolomic profiling reveals NPM-ALK-mediated phosphorylation of PKM2 and metabolic reprogramming in anaplastic large cell lymphoma. (United States)

    McDonnell, Scott R P; Hwang, Steven R; Rolland, Delphine; Murga-Zamalloa, Carlos; Basrur, Venkatesha; Conlon, Kevin P; Fermin, Damian; Wolfe, Thomas; Raskind, Alexander; Ruan, Chunhai; Jiang, Jian-Kang; Thomas, Craig J; Hogaboam, Cory M; Burant, Charles F; Elenitoba-Johnson, Kojo S J; Lim, Megan S


    The mechanisms underlying the pathogenesis of the constitutively active tyrosine kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expressing anaplastic large cell lymphoma are not completely understood. Here we show using an integrated phosphoproteomic and metabolomic strategy that NPM-ALK induces a metabolic shift toward aerobic glycolysis, increased lactate production, and biomass production. The metabolic shift is mediated through the anaplastic lymphoma kinase (ALK) phosphorylation of the tumor-specific isoform of pyruvate kinase (PKM2) at Y105, resulting in decreased enzymatic activity. Small molecule activation of PKM2 or expression of Y105F PKM2 mutant leads to reversal of the metabolic switch with increased oxidative phosphorylation and reduced lactate production coincident with increased cell death, decreased colony formation, and reduced tumor growth in an in vivo xenograft model. This study provides comprehensive profiling of the phosphoproteomic and metabolomic consequences of NPM-ALK expression and reveals a novel role of ALK in the regulation of multiple components of cellular metabolism. Our studies show that PKM2 is a novel substrate of ALK and plays a critical role in mediating the metabolic shift toward biomass production and tumorigenesis.

  7. Resembling a viper: implications of mimicry for conservation of the endangered smooth snake. (United States)

    Valkonen, Janne K; Mappes, Johanna


    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

  8. Right atrial aneurysm with downward displacement of the anterior leaflet that resembled Ebstein's anomaly. (United States)

    Yamauchi, Sanae; Suzuki, Yasuyuki; Daitoku, Kazuyuki; Kimura, Masaomi; Okumura, Ken; Fukuda, Ikuo


    A 13-year-old boy presented with right atrial aneurysm and downward displacement of the anterior leaflet in the tricuspid valve into the right ventricle, without tricuspid valve regurgitation. Paroxysmal atrial flutter was caused by an abnormal electrical re-entry circuit, which could not be treated using catheter radiofrequency ablation. Therefore, the patient underwent surgical ablation and resection of the enlarged right atrial wall. The anterior leaflet of the tricuspid valve was plastered and displaced downward into the right ventricle, which resembled Ebstein's anomaly. Pathological evaluation revealed a thin wall that contained fibrous tissue with lipomatous degeneration and few muscular elements. No postoperative arrhythmia was observed.

  9. The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met. (United States)

    Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Heiden, Katherine B; Xing, Mingzhao; Li, Yi; Prinz, Richard A; Xu, Xiulong


    The sonic hedgehog (Shh) pathway is highly activated in thyroid neoplasms and promotes thyroid cancer stem-like cell phenotype, but whether the Shh pathway regulates thyroid tumor cell motility and invasiveness remains unknown. Here, we report that the motility and invasiveness of two anaplastic thyroid tumor cell lines, KAT-18 and SW1736, were inhibited by two inhibitors of the Shh pathway (cyclopamine and GANT61). Consistently, the cell motility and invasiveness was decreased by Shh and Gli1 knockdown, and was increased by Gli1 overexpression in KAT-18 cells. Mechanistic studies revealed that Akt and c-Met phosphorylation was decreased by a Gli1 inhibitor and by Shh and Gli1 knockdown, but was increased by Gli1 overexpression. LY294002, a PI-3 kinase inhibitor, and a c-Met inhibitor inhibited the motility and invasiveness of Gli1-transfected KAT-18 cells more effectively than the vector-transfected cells. Knockdown of Snail, a transcription factor regulated by the Shh pathway, led to decreased cell motility and invasiveness in KAT-18 and SW1736 cells. However, key epithelial-to-mesenchymal transition (EMT) markers including E-cadherin and vimentin as well as Slug were not affected by cyclopamine and GANT61 in either SW1736 or WRO82, a well differentiated follicular thyroid carcinoma cell line. Our data suggest that the Shh pathway-stimulated thyroid tumor cell motility and invasiveness is largely mediated by AKT and c-Met activation with little involvement of EMT.

  10. Like father, like son: young children's understanding of how and why offspring resemble their parents. (United States)

    Solomon, G E; Johnson, S C; Zaitchik, D; Carey, S


    4 studies investigated the broad claim that preschoolers understand biological inheritance. In Study 1, 4-7-year-old children were told a story in which a boy was born to one man and adopted by another. The biological father was described as having one set of features (e.g., green eyes) and the adoptive father as having another (e.g., brown eyes). Subjects were asked which man the boy would resemble when he grew up. Preschoolers showed little understanding that selective chains of processes mediate resemblance to parents. It was not until age 7 that children substantially associated the boy with his biological father on physical features and his adoptive father on beliefs. That is, it was not until age 7 that children demonstrated that they understood birth as part of a process selectively mediating the acquisition of physical traits and learning or nurturance as mediating the acquisition of beliefs. In Study 2, subjects were asked whether, as a boy grew up, various of his features could change. Children generally shared our adult intuitions, indicating that their failure in Study 1 was not due to their having a different sense of what features can change. Studies 3 and 4 replicated Study 1, with stories involving mothers instead of fathers and with lessened task demands. Taken together, the results of the 4 studies refute the claim that preschoolers understand biological inheritance. The findings are discussed in terms of whether children understand biology as an autonomous cognitive domain.

  11. Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

    Directory of Open Access Journals (Sweden)

    Marijn A Distel

    Full Text Available Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017 and their siblings (N = 1,266, parents (N = 3,064 and spouses (N = 939 from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26% and dominant genetic (24%; 95% CI 17-31% factors. Environmental influences (55%; 95% CI 51-60% explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance. There was no effect of cultural transmission from parents to offspring.

  12. Intrathecal baclofen withdrawal resembling serotonin syndrome in an adolescent boy with cerebral palsy. (United States)

    Salazar, Maria L; Eiland, Lea S


    Intrathecal baclofen (ITB) is increasingly being used to reduce spasticity among children with cerebral palsy, dystonia, and spinal cord injuries. However, complications such as withdrawal, which is a potentially life-threatening condition, can occur. Intrathecal baclofen withdrawal should be differentiated with autonomic dysreflexia, malignant hyperthermia, neuroleptic malignant syndrome, and serotonin syndrome. We report a case of ITB withdrawal secondary to low residual volume in the pump reservoir and resembling serotonin syndrome in an adolescent with cerebral palsy. He presented with agitation, diaphoresis, increasing spasticity, rigidity, jitteriness, hyperreflexia, clonus, tachycardia, hypertension, and rhabdomyolysis. Treatment consisted of emergent refilling of the pump, intravenous diazepam, and oral cyproheptadine. We also emphasize the importance of prompt recognition of ITB withdrawal among high-risk patients.

  13. Westermarck, Freud, and the incest taboo: does familial resemblance activate sexual attraction? (United States)

    Fraley, R Chris; Marks, Michael J


    Evolutionary psychological theories assume that sexual aversions toward kin are triggered by a nonconscious mechanism that estimates the genetic relatedness between self and other. This article presents an alternative perspective that assumes that incest avoidance arises from consciously acknowledged taboos and that when awareness of the relationship between self and other is bypassed, people find individuals who resemble their kin more sexually appealing. Three experiments demonstrate that people find others more sexually attractive if they have just been subliminally exposed to an image of their opposite-sex parent (Experiment 1) or if the face being rated is a composite image based on the self (Experiment 2). This finding is reversed when people are aware of the implied genetic relationship (Experiment 3). These findings have implications for a century-old debate between E. Westermarck and S. Freud, as well as contemporary research on evolution, mate choice, and sexual imprinting.

  14. The heat-pipe resembling action of boiling bubbles in endovenous laser ablation. (United States)

    van der Geld, Cees W M; van den Bos, Renate R; van Ruijven, Peter W M; Nijsten, Tamar; Neumann, H A Martino; van Gemert, Martin J C


    Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100 degrees C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100 degrees C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100 degrees C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall.

  15. Ethionamide-induced pellagroid dermatitis resembling lichen simplex chronicus: A report of two cases

    Directory of Open Access Journals (Sweden)

    Gaurav Garg


    Full Text Available Pellagra is a niacin deficiency disorder characterized clinically by diarrhea, dermatitis, and dementia. However, few drugs also cause pellagroid dermatitis. Recently, we encountered two cases of pellagroid dermatitis; both were on second line of antituberculosis drugs. Case 1 was of multidrug-resistant pulmonary tuberculosis. Patient was on ethionamide since one year before developing pellagroid dermatitis. Case 2 was of central nervous system tuberculoma and was on second line of antitubercular drugs. This patient was on ethionamide and isoniazid (INH since six months before developing pellagroid dermatitis. This patient had previously taken first line of antituberculous therapy, inclusive of INH, for 1 year without any dermatitis. The skin lesions in both patients were symmetric hyperpigmented thickened plaques with prominent skin markings resembling lichen simplex chronicus. Nicotinamide 300 mg in three divided doses healed the lesions completely within 4 weeks and 3 weeks in first and second patient, respectively.

  16. A universal, easy-to-apply light-quality index based on natural light spectrum resemblance (United States)

    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


    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.

  17. Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex. (United States)

    Basile, Angelo; Onetti-Muda, Andrea; Giannakakis, Konstantinos; Faraggiana, Tullio; Aresu, Luca


    A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion.

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

    DEFF Research Database (Denmark)

    Nielsen, Mads; Vachon, Celine M.; Scott, Christopher G.


    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...

  19. Silica deposits on Mars with features resembling hot spring biosignatures at El Tatio in Chile (United States)

    Ruff, Steven W.; Farmer, Jack D.


    The Mars rover Spirit encountered outcrops and regolith composed of opaline silica (amorphous SiO2.nH2O) in an ancient volcanic hydrothermal setting in Gusev crater. An origin via either fumarole-related acid-sulfate leaching or precipitation from hot spring fluids was suggested previously. However, the potential significance of the characteristic nodular and mm-scale digitate opaline silica structures was not recognized. Here we report remarkably similar features within active hot spring/geyser discharge channels at El Tatio in northern Chile, where halite-encrusted silica yields infrared spectra that are the best match yet to spectra from Spirit. Furthermore, we show that the nodular and digitate silica structures at El Tatio that most closely resemble those on Mars include complex sedimentary structures produced by a combination of biotic and abiotic processes. Although fully abiotic processes are not ruled out for the Martian silica structures, they satisfy an a priori definition of potential biosignatures.

  20. Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures. (United States)

    Jahodova, Alena; Krsek, Pavel; Komarek, Vladimir; Kudr, Martin; Kyncl, Martin; Zamecnik, Josef; Tichy, Michal


    We report a girl with a drug-resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled "wet dog shake" seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure-free for the three years following resection. [Published with video sequences].

  1. American alligator proximal pedal phalanges resemble human finger bones: Diagnostic criteria for forensic investigators. (United States)

    Ferraro, Joseph V; Binetti, Katie M


    A scientific approach to bone and tooth identification requires analysts to pursue the goal of empirical falsification. That is, they may attribute a questioned specimen to element and taxon only after having ruled out all other possible attributions. This requires analysts to possess a thorough understanding of both human and non-human osteology, particularly so for remains that may be morphologically similar across taxa. To date, forensic anthropologists have identified several potential 'mimics' for human skeletal remains, including pig teeth and bear paws. Here we document another possible mimic for isolated human skeletal elements--the proximal pedal phalanges of American alligators (Alligator mississippiensis) closely resemble the proximal and intermediate hand phalanges of adult humans. We detail morphological similarities and differences between these elements, with the goal of providing sufficient information for investigators to confidently falsify the hypothesis that a questioned phalanx is derived from an American alligator.

  2. An insulinoma with clinical and electroencephalographic features resembling complex partial seizures

    Institute of Scientific and Technical Information of China (English)

    Shuang WANG; Hai-tao HU; Shu-qun WEN; Zhong-jin WANG; Bao-rong ZHANG; Mei-ping DING


    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 pharmacoresistant epilepsy. After the insulinoma was found and surgically removed, her EEG turned normal and she was seizure-free during the 4-year follow-up. This report highlights the need for careful reassessment of all seizures refractory to medication, even for the patients associated with epileptiform discharges on EEG.

  3. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma (United States)

    Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.


    Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

  4. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

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    Shao, Mingchen; Geng, Yiwei [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Xi, Ying [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Wei, Sidong [Liver Transplantation Hepatobiliary Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Wang, Liuxing; Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Ma, Wang, E-mail: [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China)


    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells.

  5. Malignant transformation of mature T cells after gammaretrovirus mediated transfer of nucleophosmin-anaplastic lymphoma kinase oncogene

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    Ashok Kumar


    Full Text Available Background: Gene therapy has been in use to cure hereditary and acquired diseases by incorporating the desired gene into the cells with the help of gammaretroviral vectors. Despite the success of this therapy in X-linked severe combined immunodeficiency syndrome, few patients developed leukemia as a major adverse event due to retroviral insertional mutagenesis within stem cells. In experimental animals also, retroviral-mediated gene transfer technique resulted in the development of leukemia. On the other hand, evidence suggests that mature T cells (TC are relatively resistant to transformation even after retroviral-mediated transfer of potent oncogenes Tcl1, ΔTrkA and LMO2 with no reported side effects yet. Aims: To further address the safety issue for TC use in gene therapy, this study investigated susceptibility of mature polyclonal TC to malignant transformation by the retroviral-mediated transfer of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK oncogene. Materials and Methods: Wild-type mature TC, isolated from C57BL/6 donor mice (genetic background Ly5.1 were transduced with gamma-retroviral vectors encoding the potent TC oncogene NPM-ALK or the control vector enhanced green fluorescent protein eGFP. The cells were then transplanted into RAG-1 deficient recipient mice (genetic background Ly5.2. Results: Two out of five mice from NPM-ALK oncogene group developed leukemia/lymphoma after latency periods (153 and 250 days, respectively. None of the mice from the control group developed any malignancy throughout the observational period. Conclusion: Mature polyclonal TC are relatively susceptible to malignant transformation after gamma-retroviral mediated transfer of NPM-ALK oncogene; hence safety of TC use in gene therapy should be further investigated to avoid the possible side-effect of development of leukemia/lymphoma.

  6. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients (United States)

    Miranda, Roberto N.; Aladily, Tariq N.; Prince, H. Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E.; Amin, Mitual B.; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S.; Shifrin, David A.; O'Malley, Dennis P.; Cheah, Chan Y.; Bacchi, Carlos E.; Gualco, Gabriela; Li, Shiyong; Keech, John A.; Hochberg, Ephram P.; Carty, Matthew J.; Hanson, Summer E.; Mustafa, Eid; Sanchez, Steven; Manning, John T.; Xu-Monette, Zijun Y.; Miranda, Alonso R.; Fox, Patricia; Bassett, Roland L.; Castillo, Jorge J.; Beltran, Brady E.; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H.; Medeiros, L. Jeffrey


    Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. PMID:24323027

  7. Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma (United States)

    Wurster, K D; Hummel, F; Richter, J; Giefing, M; Hartmann, S; Hansmann, M-L; Kreher, S; Köchert, K; Krappmann, D; Klapper, W; Hummel, M; Wenzel, S-S; Lenz, G; Janz, M; Dörken, B; Siebert, R; Mathas, S


    Apart from its unique histopathological appearance with rare tumor cells embedded in an inflammatory background of bystander cells, classical Hodgkin lymphoma (cHL) is characterized by an unusual activation of a broad range of signaling pathways involved in cellular activation. This includes constitutive high-level activity of nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), activator protein-1 (AP-1) and interferon regulatory factor (IRF) transcription factors (TFs) that are physiologically only transiently activated. Here, we demonstrate that inactivation of the putative ubiquitin E3-ligase PDLIM2 contributes to this TF activation. PDLIM2 expression is lost at the mRNA and protein levels in the majority of cHL cell lines and Hodgkin and Reed–Sternberg (HRS) cells of nearly all cHL primary samples. This loss is associated with PDLIM2 genomic alterations, promoter methylation and altered splicing. Reconstitution of PDLIM2 in HRS cell lines inhibits proliferation, blocks NF-κB transcriptional activity and contributes to cHL-specific gene expression. In non-Hodgkin B-cell lines, small interfering RNA-mediated PDLIM2 knockdown results in superactivation of TFs NF-κB and AP-1 following phorbol 12-myristate 13-acetate (PMA) stimulation. Furthermore, expression of PDLIM2 is lost in anaplastic large cell lymphoma (ALCL) that shares key biological aspects with cHL. We conclude that inactivation of PDLIM2 is a recurrent finding in cHL and ALCL, promotes activation of inflammatory signaling pathways and thereby contributes to their pathogenesis. PMID:27538486

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

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    Georgi Tchernev


    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-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30 + cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.

  9. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

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    Gan, Gregory N., E-mail: [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)


    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  10. Brentuximab vedotin in children and adolescents with Hodgkin’s lymphoma and anaplastic large cell lymphoma – literature review and own experience

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    N. V. Myakova


    Full Text Available Despite significant advances in the treatment of lymphomas in children remain a small proportion of patients with refractory or recurrent disease. An effective approach to the treatment of such patients – not only is the second line chemotherapy, but the use of the new targeted therapies. An example of this approach is the use of brentuximab vedotin (antibody-drug conjugate directed to the CD30 in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Literature review and own experience of using this drug in children are describes in this article.

  11. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors (United States)


    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

  12. Aberrant anaplastic lymphoma kinase activity induces a p53 and Rb-dependent senescence-like arrest in the absence of detectable p53 stabilization.

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    Fiona Kate Elizabeth McDuff

    Full Text Available Anaplastic Lymphoma Kinase (ALK is a receptor tyrosine kinase aberrantly expressed in a variety of tumor types, most notably in Anaplastic Large Cell Lymphoma (ALCL where a chromosomal translocation generates the oncogenic fusion protein, Nucleophosmin-ALK (NPM-ALK. Whilst much is known regarding the mechanism of transformation by NPM-ALK, the existence of cellular defence pathways to prevent this pathological process has not been investigated. Employing the highly tractable primary murine embryonic fibroblast (MEF system we show that cellular transformation is not an inevitable consequence of NPM-ALK activity but is combated by p53 and Rb. Activation of p53 and/or Rb by NPM-ALK triggers a potent proliferative block with features reminiscent of senescence. While loss of p53 alone is sufficient to circumvent NPM-ALK-induced senescence and permit cellular transformation, sole loss of Rb permits continued proliferation but not transformation due to p53-imposed restraints. Furthermore, NPM-ALK attenuates p53 activity in an Rb and MDM2 dependent manner but this activity is not sufficient to bypass senescence. These data indicate that senescence may constitute an effective barrier to ALK-induced malignancies that ultimately must be overcome for tumor development.

  13. NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma. (United States)

    Pearson, Joel D; Lee, Jason K H; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J


    Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The normal cellular counterpart of this malignancy is presumed to be the cytotoxic T lymphocyte (CTL), and this presumption is partly based on the observation that these tumour cells often express cytotoxic granules containing Granzyme B (GzB) and Perforin. Chromosomal translocations involving the gene encoding for the ALK tyrosine kinase are also characteristic of ALK+ ALCL, and the resulting fusion proteins (e.g. NPM-ALK) initiate signalling events important in ALK+ ALCL pathogenesis. These events include the elevated expression of JunB; an AP-1 family transcription factor that promotes ALK+ ALCL proliferation. In this report we demonstrate that JunB is a direct transcriptional activator of GzB and that GzB transcription is also promoted by NPM-ALK. We found that Perforin expression was not regulated by JunB, but was promoted by NPM-ALK in some cell lines and inhibited by it in others. In conclusion, our study makes the novel observation that signalling through NPM-ALK and JunB affect the expression of cytotoxic molecules in ALK+ ALCL. Moreover, these findings demonstrate the expression of GzB and Perforin in this lymphoma is not solely due its presumed CTL origin, but that oncogenic signalling is actively influencing the expression of these proteins.

  14. Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK(+) anaplastic large cell lymphoma. (United States)

    Hamedani, Farid Saei; Cinar, Munevver; Mo, Zhicheng; Cervania, Melissa A; Amin, Hesham M; Alkan, Serhan


    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is an aberrant fusion gene product with tyrosine kinase activity and is expressed in substantial subset of anaplastic large cell lymphomas (ALCL). It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3). Although NPM-ALK(+) ALCL overall shows a better prognosis, there is a sub-group of patients who relapses and is resistant to conventional chemotherapeutic regimens. NPM-ALK is a potential target for small molecule kinase inhibitors. Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression. In this study, we have investigated the in vitro effects of Crizotinib in ALCL cell line with NPM-ALK fusion. Crizotinib induced marked downregulation of STAT3 phosphorylation, which was associated with significant apoptotic cell death. Apoptosis induction was attributed to caspase-3 cleavage and marked downregulation of the Bcl-2 family of proteins including MCL-1. These findings implicate that Crizotinib has excellent potential to treat patients with NPM-ALK(+) ALCL through induction of apoptotic cell death and downregulation of major oncogenic proteins in this aggressive lymphoma.

  15. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. (United States)

    Damm-Welk, Christine; Mussolin, Lara; Zimmermann, Martin; Pillon, Marta; Klapper, Wolfram; Oschlies, Ilske; d'Amore, Emanuele S G; Reiter, Alfred; Woessmann, Wilhelm; Rosolen, Angelo


    Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival.

  16. Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas. (United States)

    Colomba, A; Courilleau, D; Ramel, D; Billadeau, D D; Espinos, E; Delsol, G; Payrastre, B; Gaits-Iacovoni, F


    The majority of anaplastic large cell lymphomas (ALCLs) express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion protein, which is oncogenic due to its constitutive tyrosine kinase activity. Transformation by NPM-ALK not only increases proliferation, but also modifies cell shape and motility in both lymphoid and fibroblastic cells. We report that the Rac1 GTPase, a known cytoskeletal regulator, is activated by NPM-ALK in ALCL cell lines (Karpas 299 and Cost) and transfected cells (lymphoid Ba/F3 cells, NIH-3T3 fibroblasts). We have identified Vav3 as one of the exchange factors involved in Rac1 activation. Stimulation of Vav3 and Rac1 by NPM-ALK is under the control of Src kinases. It involves formation of a signaling complex between NPM-ALK, pp60(c-src), Lyn and Vav3, in which Vav3 associates with tyrosine 343 of NPM-ALK via its SH2 domain. Moreover, Vav3 is phosphorylated in NPM-ALK positive biopsies from patients suffering from ALCL, demonstrating the pathological relevance of this observation. The use of Vav3-specific shRNA and a dominant negative Rac1 mutant demonstrates the central role of GTPases in NPM-ALK elicited motility and invasion.

  17. IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells. (United States)

    Shi, Ping; Lai, Raymond; Lin, Quan; Iqbal, Abid S; Young, Leah C; Kwak, Larry W; Ford, Richard J; Amin, Hesham M


    Type I insulin-like growth factor receptor (IGF-IR) tyrosine kinase plays important roles in the pathogenesis of several malignancies. Although it promotes the growth of stimulated hematopoietic cells, a direct role of IGF-IR in malignant lymphoma has not been identified. Anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK(+) ALCL) is a unique type of T-cell lymphoma. Approximately 85% of ALK(+) ALCL cases harbor the translocation t(2;5)(p23;q35), which generates the chimeric oncogene NPM-ALK. In the present study, we explored a possible role of IGF-IR in ALK(+) ALCL. Our results demonstrate that IGF-IR and IGF-I are widely expressed in ALK(+) ALCL cell lines and primary tumors. Importantly, we identified novel reciprocal functional interactions between IGF-IR and NPM-ALK. Antagonism of IGF-IR decreased the viability, induced apoptosis and cell-cycle arrest, and decreased proliferation and colony formation of ALK(+) ALCL cell lines. These effects could be explained by alterations of cell survival regulatory proteins downstream of IGF-IR signaling. Our findings improve current understanding of the biology of IGF-IR and NPM-ALK and have significant therapeutic implications as they identify IGF-IR signaling as a potential therapeutic target in ALK(+) ALCL and possibly other types of malignant lymphoma.

  18. Downregulation of NPM-ALK by siRNA causes anaplastic large cell lymphoma cell growth inhibition and augments the anti cancer effects of chemotherapy in vitro. (United States)

    Hsu, Faye Yuan-yi; Zhao, Yi; Anderson, W French; Johnston, Patrick B


    The fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), results from the chromosome translocation t(2;5)(p23;q25) and is present in 50-70 percent of anaplastic large-cell lymphomas (ALCLs). NPM-ALK is a constitutively activated kinase that transforms cells through stimulating several mitogenic signaling pathways. To examine if the NPM-ALK is a potential therapeutic target in ALCL, we used siRNA to specifically downregulate the expression of the NPM-ALK in ALCL cell lines. In this report, we demonstrated viability loss in t(2;5)-positive ALCL cell lines, SUDHL-1 and Karpas 299 cells, but not in lymphoma cell lines without the chromosome translocation, Jurkat and Granta 519 cells. Further study demonstrated that the downregulation of NPM-ALK resulted in decreased cell proliferation and increased cell apoptosis. When used in combination with chemotherapeutic agents, such as doxorubicin, the inhibition of the NPM-ALK augments the chemosensitivity of the tumor cells. These results revealed the importance of continuous expression of NPM-ALK in maintaining the growth of ALCL cells. Our data also suggested that the repression of the fusion gene might be a potential novel therapeutic strategy for NPM-ALK positive ALCLs.

  19. An unusual clinical presentation resembling superior vena cava syndrome post heart surgery

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    Pellegrini Ronald


    Full Text Available Abstract Background An unusual sequence of post operative events heralded by hemodynamic deterioration followed by dyspnea and rapidly progressive dilatation of superficial neck and facial veins, resembling a superior vena cava syndrome, two days post surgical resection of filamentous aortic valve masses, closure of a patent foramen ovale, and performance of a modified Maze procedure for atrial fibrillation in a patient that presented with transient neurologic findings is presented. Case Presentation Although both clinical findings and hemodynamic derangements completely resolved following tricuspid valve repair aimed to correct the new onset severe tricuspid regurgitation noted post operatively; a clear mechanism was not readily obvious and diagnostic testing data somewhat conflictive. We present a careful retrospective examination of all clinical data and review possible clinical entities that could have been implicated in this particular case and recognize that transesophageal echocardiographic findings were most useful in identifying the best course of action. Conclusion After reviewing all clinical data and despite the inconclusive nature of test results; the retrospective examination of transesophageal echocardiographic findings proved to be most useful in identifying the best course of action. We postulate that in our case, resolution of the suspected pulmonary embolism with anticoagulation and reestablishment of a normal right ventricular geometry with tricuspid valve repair worked in unison in restoring normal hemodynamics and resolving both dyspnea and venous dilatation.

  20. Ad-hoc KEEN-type Waves and their Occasional Resemblance to KdV Waveforms (United States)

    Tyshetskiy, Yuriy; Afeyan, Bedros


    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)

  1. Transformation of Face Transplants: Volumetric and Morphologic Graft Changes Resemble Aging After Facial Allotransplantation. (United States)

    Kueckelhaus, M; Turk, M; Kumamaru, K K; Wo, L; Bueno, E M; Lian, C G; Alhefzi, M; Aycart, M A; Fischer, S; De Girolami, U; Murphy, G F; Rybicki, F J; Pomahac, B


    Facial allotransplantation restores normal anatomy to severely disfigured faces. Although >30 such operations performed worldwide have yielded promising short-term results, data on long-term outcomes remain scarce. Three full-face transplant recipients were followed for 40 months. Severe changes in volume and composition of the facial allografts were noted. Data from computed tomography performed 6, 18 and 36 months after transplantation were processed to separate allograft from recipient tissues and further into bone, fat and nonfat soft tissues. Skin and muscle biopsies underwent diagnostic evaluation. All three facial allografts sustained significant volume loss (mean 19.55%) between 6 and 36 months after transplant. Bone and nonfat soft tissue volumes decreased significantly over time (17.22% between months 6 and 18 and 25.56% between months 6 and 36, respectively), whereas fat did not. Histological evaluations showed atrophy of muscle fibers. Volumetric and morphometric changes in facial allografts have not been reported previously. The transformation of facial allografts in this study resembled aging through volume loss but differed substantially from regular aging. These findings have implications for risk-benefit assessment, donor selection and measures counteracting muscle and bone atrophy. Superior long-term outcomes of facial allotransplantation will be crucial to advance toward future clinical routine.

  2. Manothermosonication of foods and food-resembling systems: effect on nutrient content and nonenzymatic browning. (United States)

    Vercet, A; Burgos, J; López-Buesa, P


    The effect of manothermosonication (MTS), an emergent technology for food preservation, on thiamin, riboflavin, carotenoids, and ascorbic acid was evaluated in milk and orange juice. The effect of both heat treatment and MTS on several compounds produced in nonenzymatic browning in model systems was also studied. MTS does not affect significantly the nutrient content studied. However, it changes the behavior of nonenzymatic browning. No formation of 5-(hydroxymethyl)-2-furfuraldehyde (HMF) was detected in fruit juice model systems after heat and MTS treatments at the experimental conditions used. In a milk-resembling system, free HMF formation by MTS is higher compared to that by heat treatment. As the MTS temperature increases, free HMF production by both treatments equaled on another. For bound HMF the production rate is lower by MTS than by heat treatment under the experimental conditions used. Formation kinetics of brown pigments and that of fluorescent compounds are different for both treatments. Fluorescence and brown pigment production are faster in MTS.

  3. Digital redesign of uncertain interval systems based on time-response resemblance via particle swarm optimization. (United States)

    Hsu, Chen-Chien; Lin, Geng-Yu


    In this paper, a particle swarm optimization (PSO) based approach is proposed to derive an optimal digital controller for redesigned digital systems having an interval plant based on time-response resemblance of the closed-loop systems. Because of difficulties in obtaining time-response envelopes for interval systems, the design problem is formulated as an optimization problem of a cost function in terms of aggregated deviation between the step responses corresponding to extremal energies of the redesigned digital system and those of their continuous counterpart. A proposed evolutionary framework incorporating three PSOs is subsequently presented to minimize the cost function to derive an optimal set of parameters for the digital controller, so that step response sequences corresponding to the extremal sequence energy of the redesigned digital system suitably approximate those of their continuous counterpart under the perturbation of the uncertain plant parameters. Computer simulations have shown that redesigned digital systems incorporating the PSO-derived digital controllers have better system performance than those using conventional open-loop discretization methods.

  4. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human. (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel


    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  5. Uterine tumor resembling ovarian sex cord tumor. Case report and review of literature. (United States)

    Stefanovic, A; Jeremic, K; Kadija, S; Mitrovic, M; Filimonovic, D; Jankovic-Raznatovic, S; Tavcar, J


    A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord markers, as well as hormone receptors. The authors present a case of a 59-year-old multiparous woman admitted to the Institute of Gynecology and Obstetrics Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of 100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas sized 54 x 69 mm located in fundus with secondary changes. She underwent abdominal hysterectomy with adnexectomy. Microscopic examination revealed submucosal uterine tumor with variabile histological organization that had anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10 HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and ER(+). The poly phenotypic immunophenotype can be useful in differential diagnosis from other neoplasms but also suggests an origin of UTROSCT from uncommitted stem cell enabling for multidirectional differentiation.

  6. Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis. (United States)

    Augustin, Iris; Gross, Julia; Baumann, Daniel; Korn, Claudia; Kerr, Grainne; Grigoryan, Tamara; Mauch, Cornelia; Birchmeier, Walter; Boutros, Michael


    Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

  7. Pulmonary Extramedullary Hematopoiesis in a Patient with Chronic Asthma Resembling Lung Cancer: A Case Report

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    Massood Hosseinzadeh


    Full Text Available Background. Extramedullary hematopoiesis is most often seen in reticuloendothelial organs specially spleen, liver, or lymph nodes, and it is rarely seen in lung parenchyma. Almost all reported cases of pulmonary extramedullary hematopoiesis occurred following myeloproliferative disorders specially myelofibrosis. Other less common underlying causes are thalassemia syndromes and other hemoglobinopathies. There was not any reported case of pulmonary extramedullary hematopoiesis in asthmatic patients in the medical literature. Case. Here we reported a 65-year-old lady who was a known case of bronchial asthma with recent developed right lower lobe lung mass. Chest X-ray and CT studies showed an infiltrating mass resembling malignancy. Fine needle aspiration cytology of mass revealed pulmonary extramedullary hematopoiesis. The patient followed for 10 months with serial physical examination and laboratory evaluations which were unremarkable. Conclusion. Extramedullary hematopoiesis of lung parenchyma can be mistaken for lung cancer radiologically. Although previous reported cases occurred with myelofibrosis or hemoglobinopathies, we are reporting the first case of asthma-associated extramedullary hematopoiesis.

  8. Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates. [Sponges

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    Jacob, M.H.


    The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by (/sup 3/H)thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with (/sup 3/H)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 (/sup 3/H)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 invertebrates.

  9. Human endomembrane H sup + pump strongly resembles the ATP-synthetase of Archaebacteria

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    Suedhof, T.C.; Stone, D.K.; Johnston, P.A.; Xie, Xiaosong (Univ. of Texas Southwestern Medical Center, Dallas (USA)); Fried, V.A. (Saint Jude Children' s Research Hospital, Memphis, TN (USA))


    Preparations of mammalian H{sup +} pumps that acidify intracellular vesicles contain eight or nine polypeptides, ranging in size from 116 to 17 kDa. Biochemical analysis indicates that the 70- and 58-kDa polypeptides are subunits critical for ATP hydrolysis. The amino acid sequences of the major catalytic subunits (58 and 70 kDa) of the endomembrane H{sup +} pump are unknown from animal cells. The authors report here the complete sequence of the 58-kDa subunit derived from a human kidney cDNA clone and partial sequences of the 70- and 58-kDa subunits purified from clathrin-coated vesicles of bovine brain. The amino acid sequences of both proteins strongly resemble the sequences of the corresponding subunits of the vacuolar H{sup +} pumps of Archaebacteria, plants, and fungi. The archaebacterial enzyme is believed to use a H{sup +} gradient to synthesize ATP. Thus, a common ancestral protein has given rise to a H{sup +} pump that synthesizes ATP in one organism and hydrolyzes it in another and is highly conserved from prokaryotes to humans. The same pump appears to mediate the acidification of intracellular organelles, including coated vesicles, lysosomes, and secretory granules, as well as extracellular fluids such as urine.

  10. Primary uterine cervix melanoma resembling malignant peripheral nerve sheath tumor: a case report. (United States)

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


    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.

  11. Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

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    Nitrini Ricardo


    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.

  12. Resemblance Coefficient Based Intrapulse Feature Extraction Approach for Radar Emitter Signals

    Institute of Scientific and Technical Information of China (English)

    ZHANGGexiang; JINWeidong; HULaizhao


    Radar emitter signal recognition plays an important role in electronic intelligence and electronic support measure systems. To enhance accurate recognition rate of advanced radar emitter signals to meet the requirement of modern electronic warfare, Resemblance coefficient (RC) approach is proposed to extract features from radar emitter signals with different intrapulse modulation laws. Definition of RC is given. Properties and advantages of RC are analyzed. Feature extraction algorithm using RC is described in detail. The noise-suppression performances of RC features are also analyzed. Subsequently, neural networks are used to design classifiers. Because RC contains the change and distribution information of amplitude, phase and frequency of radar emitter signals, RC can reflect the intrapulse modulation laws effectively. The results of theoretical analysis and simulation experiments show that RC features have good characteristic of not being sensitive to noise. 9 radar emitter signals are chosen to make the experiment of RC feature extraction and automatic recognition. A large number of experimental results show that good accurate recognition rate can be achieved using the proposed approach. It is proved to be a valid and practical approach.

  13. On Learning Natural-Science Categories That Violate the Family-Resemblance Principle. (United States)

    Nosofsky, Robert M; Sanders, Craig A; Gerdom, Alex; Douglas, Bruce J; McDaniel, Mark A


    The general view in psychological science is that natural categories obey a coherent, family-resemblance principle. In this investigation, we documented an example of an important exception to this principle: Results of a multidimensional-scaling study of igneous, metamorphic, and sedimentary rocks (Experiment 1) suggested that the structure of these categories is disorganized and dispersed. This finding motivated us to explore what might be the optimal procedures for teaching dispersed categories, a goal that is likely critical to science education in general. Subjects in Experiment 2 learned to classify pictures of rocks into compact or dispersed high-level categories. One group learned the categories through focused high-level training, whereas a second group was required to simultaneously learn classifications at a subtype level. Although high-level training led to enhanced performance when the categories were compact, subtype training was better when the categories were dispersed. We provide an interpretation of the results in terms of an exemplar-memory model of category learning.

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

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


    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

  15. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy. (United States)

    Shin, Jacob Y; Diaz, Aidnag Z


    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  16. In vitro identification and characterization of CD133(pos cancer stem-like cells in anaplastic thyroid carcinoma cell lines.

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    Giovanni Zito

    Full Text Available BACKGROUND: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs. Anaplastic Thyroid Carcinoma (ATC is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively. These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg. Furthermore, ARO/CD133(pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos in comparison to ARO/CD133(neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos when compared with ARO/CD133(neg cells. CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos cells in ATC cell lines. ARO/CD133(pos cells exhibit stem cell-like features--such as high proliferation, self-renewal ability, expression of OCT-4--and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest

  17. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis: A Case Report. (United States)

    Li, Shi-Jun; Wang, Tao; Wang, Lin; Pang, Zhan-Qi; Ma, Ben; Li, Ya-Wen; Yang, Jian; Dong, He


    Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias.A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone.The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia.As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess.

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

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    Muirhead William


    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

  19. Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus. (United States)

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


    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.

  20. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity (United States)

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


    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 metabolism 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. PMID:20126342

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

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    Adriano Senatore

    Full Text Available 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.

  2. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis

    NARCIS (Netherlands)

    Kruithof, E; Baeten, D; De Rycke, L; Vandooren, B; Foell, D; Roth, J; Canete, JD; Boots, AM; Veys, EM; De Keyser, F


    At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/ axial forms belonging to SpA and polyarticular forms resembl

  3. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

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    Antonietta R. Farina


    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

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

    Energy Technology Data Exchange (ETDEWEB)

    Enig, B.; Winther, E.; Hessov, I.

    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. 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.

  5. Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature. (United States)

    Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M


    Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC.

  6. A Unique “Composite” PTLD with Diffuse Large B-Cell and T/Anaplastic Large Cell Lymphoma Components Occurring 17 Years after Transplant

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    Kristin La Fortune


    Full Text Available Posttransplant lymphoproliferative disorder (PTLD comprises a spectrum ranging from polyclonal hyperplasia to aggressive monoclonal lymphomas. The majority of PTLDs are of B-cell origin while T-cell PTLDs and Hodgkin lymphoma-like PTLDs are uncommon. Here, we report a unique case of a 56-year-old man in whom a lymphoma with two distinct components developed as a duodenal mass seventeen years following a combined kidney-pancreas transplant. This PTLD, which has features not previously reported in the literature, consisted of one component of CD20 positive and EBV negative monomorphic diffuse large B-cell lymphoma. The other component showed anaplastic morphology, expressed some but not all T-cell markers, failed to express most B-cell markers except for PAX5, and was diffusely EBV positive. Possible etiologies for this peculiar constellation of findings are discussed and the literature reviewed for “composite-like” lymphomas late in the posttransplant setting.

  7. NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma. (United States)

    Leventaki, Vasiliki; Drakos, Elias; Medeiros, L Jeffrey; Lim, Megan S; Elenitoba-Johnson, Kojo S; Claret, Francois X; Rassidakis, George Z


    Anaplastic large-cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35), resulting in aberrant expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). We show that in 293T and Jurkat cells, forced expression of active NPM-ALK, but not kinase-dead mutant NPM-ALK (210K>R), induced JNK and cJun phosphorylation, and this was linked to a dramatic increase in AP-1 transcriptional activity. Conversely, inhibition of ALK activity in NPM-ALK(+) ALCL cells resulted in a concentration-dependent dephosphorylation of JNK and cJun and decreased AP-1 DNA-binding. In addition, JNK physically binds NPM-ALK and is highly activated in cultured and primary NPM-ALK(+) ALCL cells. cJun phosphorylation in NPM-ALK(+) ALCL cells is mediated by JNKs, as shown by selective knocking down of JNK1 and JNK2 genes using siRNA. Inhibition of JNK activity using SP600125 decreased cJun phosphorylation and AP-1 transcriptional activity and this was associated with decreased cell proliferation and G2/M cell-cycle arrest in a dose-dependent manner. Silencing of the cJun gene by siRNA led to a decreased S-phase cell-cycle fraction associated with upregulation of p21 and downregulation of cyclin D3 and cyclin A. Taken together, these findings reveal a novel function of NPM-ALK, phosphorylation and activation of JNK and cJun, which may contribute to uncontrolled cell-cycle progression and oncogenesis.

  8. Martian alkaline basites chemically resemble basic rocks of the Lovozero alkaline massif, Kola peninsula (United States)

    Kochemasov, G.

    " (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

  9. Opposite-sex siblings decrease attraction, but not prosocial attributions, to self-resembling opposite-sex faces. (United States)

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


    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.

  10. From FRA to RFN: How the Family Resemblance Approach Can Be Transformed for Science Curriculum Analysis on Nature of Science (United States)

    Kaya, Ebru; Erduran, Sibel


    The inclusion of Nature of Science (NOS) in the science curriculum has been advocated around the world for several decades. One way of defining NOS is related to the family resemblance approach (FRA). The family resemblance idea was originally described by Wittgenstein. Subsequently, philosophers and educators have applied Wittgenstein's idea to problems of their own disciplines. For example, Irzik and Nola adapted Wittgenstein's generic definition of the family resemblance idea to NOS, while Erduran and Dagher reconceptualized Irzik and Nola's FRA-to-NOS by synthesizing educational applications by drawing on perspectives from science education research. In this article, we use the terminology of "Reconceptualized FRA-to-NOS (RFN)" to refer to Erduran and Dagher's FRA version which offers an educational account inclusive of knowledge about pedagogical, instructional, curricular and assessment issues in science education. Our motivation for making this distinction is rooted in the need to clarify the various accounts of the family resemblance idea.The key components of the RFN include the aims and values of science, methods and methodological rules, scientific practices, scientific knowledge as well as the social-institutional dimensions of science including the social ethos, certification, and power relations. We investigate the potential of RFN in facilitating curriculum analysis and in determining the gaps related to NOS in the curriculum. We analyze two Turkish science curricula published 7 years apart and illustrate how RFN can contribute not only to the analysis of science curriculum itself but also to trends in science curriculum development. Furthermore, we present an analysis of documents from USA and Ireland and contrast them to the Turkish curricula thereby illustrating some trends in the coverage of RFN categories. The results indicate that while both Turkish curricula contain statements that identify science as a cognitive-epistemic system, they

  11. Socioeconomic and Demographic Factors for Spousal Resemblance in Obesity Status and Habitual Physical Activity in the United States

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    Hsin-Jen Chen


    Full Text Available Studies suggested that the married population has an increased risk of obesity and assimilation between spouses’ body weight. We examined what factors may affect married spouses’ resemblance in weight status and habitual physical activity (HPA and the association of obesity/HPA with spouses’ sociodemoeconomic characteristics and lifestyles. Medical Expenditure Panel Survey data of 11,403 adult married couples in the US during years 2006–2008 were used. Absolute-scale difference and relative-scale resemblance indices (correlation and kappa coefficients in body mass index (BMI and HPA were estimated by couples’ socioeconomic and demographic characteristics. We found that spousal difference in BMI was smaller for couples with a lower household income, for who were both unemployed, and for older spouses. Correlation coefficient between spouses’ BMI was 0.24, differing by race/ethnicity and family size. Kappa coefficient for weight status (obesity: BMI ≥ 30, overweight: 30 > BMI ≥ 25 was 0.11 and 0.35 for HPA. Never-working women’s husbands had lower odds of obesity than employed women’s husbands (OR = 0.69 (95% CI = 0.53–0.89. Men’s unemployment status was associated with wives’ greater odds of obesity (OR = 1.31 (95% CI = 1.01–1.71. HPA was associated with men’s employment status and income level, but not with women’s. The population representative survey showed that spousal resemblance in weight status and HPA varied with socioeconomic and demographic factors.

  12. Two-dimensional proteome reference map of Rhizobium tropici PRF 81 reveals several symbiotic determinants and strong resemblance with agrobacteria. (United States)

    Gomes, Douglas Fabiano; Batista, Jesiane Stefania da Silva; Torres, Adalgisa Ribeiro; de Souza Andrade, Diva; Galli-Terasawa, Lygia Vitoria; Hungria, Mariangela


    Rhizobium tropici strain PRF 81 is used in commercial inoculants for common-bean crops in Brazil because of its high efficiency in nitrogen fixation and, as in other strains belonging to this species, its tolerance of environmental stresses, representing a useful biological alternative to chemical nitrogen fertilizers. In this study, a proteomic reference map of PRF 81 was obtained by two-dimensional gel electrophoresis and MALDI-TOF/TOF-TOF mass spectrometry. In total, 115 spots representing 109 different proteins were successfully identified, contributing to a better understanding of the rhizobia-legume symbiosis and supporting, at proteomics level, a strong resemblance with agrobacteria.

  13. Efficacy of electrical stimulation of retinal ganglion cells with temporal patterns resembling light-evoked spike trains. (United States)

    Wong, Raymond C S; Garrett, David J; Grayden, David B; Ibbotson, Michael R; Cloherty, Shaun L


    People with degenerative retinal diseases such as retinitis pigmentosa lose most of their photoreceptors but retain a significant proportion (~30%) of their retinal ganglion cells (RGCs). Microelectronic retinal prostheses aim to bypass the lost photoreceptors and restore vision by directly stimulating the surviving RGCs. Here we investigate the extent to which electrical stimulation of RGCs can evoke neural spike trains with statistics resembling those of normal visually-evoked responses. Whole-cell patch clamp recordings were made from individual cat RGCs in vitro. We first recorded the responses of each cell to short sequences of visual stimulation. These responses were converted to trains of electrical stimulation that we then presented to the same cell via an epiretinal stimulating electrode. We then quantified the efficacy of the electrical stimuli and the latency of the evoked spikes. In all cases, spikes were evoked with sub-millisecond latency (0.55 ms, median, ON cells, n = 8; 0.75 ms, median, OFF cells, n = 6) and efficacy ranged from 0.4-1.0 (0.79, median, ON cells; 0.97, median, OFF cells). These data demonstrate that meaningful spike trains, resembling normal responses of RGCs to visual stimulation, can be reliably evoked by epiretinal prostheses.

  14. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

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    Preisinger Rudolf


    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  15. Epigenetic silencing of the proapoptotic gene BIM in anaplastic large cell lymphoma through an MeCP2/SIN3a deacetylating complex. (United States)

    Piazza, Rocco; Magistroni, Vera; Mogavero, Angela; Andreoni, Federica; Ambrogio, Chiara; Chiarle, Roberto; Mologni, Luca; Bachmann, Petra S; Lock, Richard B; Collini, Paola; Pelosi, Giuseppe; Gambacorti-Passerini, Carlo


    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.

  16. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis

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    Walter Arancio


    Full Text Available It has been suggested that cancer stem cells (CSC may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2, in the control cell cycle (TP53, CCND1, and in mitochondrial activity (COX8A. The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated.

  17. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

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    Maria Graziella Catalano


    Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

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

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    Rocco Piazza


    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.

  19. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib. (United States)

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi


    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

  20. Silicone-induced granuloma of breast implant capsule (SIGBIC): similarities and differences with anaplastic large cell lymphoma (ALCL) and their differential diagnosis (United States)

    Fleury, Eduardo de Faria Castro; Rêgo, Milena Morais; Ramalho, Luciana Costa; Ayres, Veronica Jorge; Seleti, Rodrigo Oliveira; Ferreira, Carlos Alberto Pecci; Roveda, Decio


    Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL) is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease.

  1. Primary cutaneous CD8 + CD30 + anaplastic large cell lymphoma: An unusual case with a high Ki-67 index-A short review

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    Jitendra G Nasit


    Full Text Available Primary cutaneous anaplastic large cell lymphoma (PCALCL is a part of the spectrum of CD30 + cutaneous lymphoproliferative disorder, characterized by variable degrees of CD2, CD3, CD4 and CD5 expression by lymphoid cells. PCALCLs with an expression of cytotoxic phenotype (CD8 + and cytotoxic proteins are uncommon. Cutaneous CD8 + CD30 + lymphoproliferative lesions are difficult to classify, diagnose and may be the cause of misdiagnose. CD8 + PCALCL must be distinguished from CD8 + mycosis fungoides, lymphomatoid papulosis type D and primary cutaneous aggressive epidermotropic CD8 + T-cell lymphoma. Usually CD8 + PCALCL is an indolent disease with a favorable prognosis, except few cases can show poor outcomes. The high Ki-67 index points toward advanced PCALCL. Treatment modalities include surgical excision, radiotherapy and clinical monitoring. Chemotherapy is reserved for disseminated disease. We report a 59-year-old male presented with rapid development of multiple painful reddish-brown plaques and nodular ulcerative skin lesions over the left thigh region since 2 months. A diagnosis of CD8 + PCALCL with a high Ki-67 index was made on the basis of histology and immunohistochemistry, in co-relation with clinical presentation.

  2. Involvement of cysteine-rich protein 61 in the epidermal growth factor-induced migration of human anaplastic thyroid cancer cells. (United States)

    Chin, Li-Han; Hsu, Sung-Po; Zhong, Wen-Bin; Liang, Yu-Chih


    Anaplastic thyroid cancer (ATC) is among the most aggressive types of malignant cancer. Epidermal growth factor (EGF) plays a crucial role in the pathogenesis of ATC, and patients with thyroid carcinoma typically exhibit increased cysteine-rich protein 61 (Cyr61). In this study, we found that EGF treatment induced cell migration, stress fiber formation, Cyr61 mRNA and protein expressions, and Cyr61 protein secretion in ATC cells. The recombinant Cyr61 protein significantly induced cell migration; however, inhibition of Cyr61 activity by a Cyr61-specific antibody abrogated EGF-induced cell migration. EGF treatment also affected epithelial-to-mesenchymal transition (EMT)-related marker protein expression, as evidenced by an increase in vimentin and a decrease in E-cadherin expression. Inhibition of Cyr61 expression by Cyr61 siRNA decreased cell migration and reversed the EMT-related marker protein expression. EGF treatment increased the phosphorylation of the extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), and finally activated Cyr61 promoter plasmid activity. Our results suggest that Cyr61 is induced by EGF through the ERK/CREB signal pathway and that it plays a crucial role in the migration and invasion of ATC cells; moreover, Cyr61 might be a therapeutic target for metastatic ATC.

  3. Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation. (United States)

    Capdevila, Laia; Cros, Sara; Ramirez, Jose-Luis; Sanz, Carolina; Carrato, Cristina; Romeo, Margarita; Etxaniz, Olatz; Hostalot, Cristina; Massuet, Ana; Cuadra, Jose Luis; Villà, Salvador; Balañà, Carmen


    Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.

  4. STAT1 is phosphorylated and downregulated by the oncogenic tyrosine kinase NPM-ALK in ALK-positive anaplastic large-cell lymphoma. (United States)

    Wu, Chengsheng; Molavi, Ommoleila; Zhang, Haifeng; Gupta, Nidhi; Alshareef, Abdulraheem; Bone, Kathleen M; Gopal, Keshav; Wu, Fang; Lewis, Jamie T; Douglas, Donna N; Kneteman, Norman M; Lai, Raymond


    The tumorigenicity of most cases of ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL) is driven by the oncogenic fusion protein NPM-ALK in a STAT3-dependent manner. Because it has been shown that STAT3 can be inhibited by STAT1 in some experimental models, we hypothesized that the STAT1 signaling pathway is defective in ALK+ ALCL, thereby leaving the STAT3 signaling unchecked. Compared with normal T cells, ALK+ ALCL tumors consistently expressed a low level of STAT1. Inhibition of the ubiquitin-proteasome pathway appreciably increased STAT1 expression in ALK+ ALCL cells. Furthermore, we found evidence that NPM-ALK binds to and phosphorylates STAT1, thereby promoting its proteasomal degradation in a STAT3-dependent manner. If restored, STAT1 is functionally intact in ALK+ ALCL cells, because it effectively upregulated interferon-γ, induced apoptosis/cell-cycle arrest, potentiated the inhibitory effects of doxorubicin, and suppressed tumor growth in vivo. STAT1 interfered with the STAT3 signaling by decreasing STAT3 transcriptional activity/DNA binding and its homodimerization. The importance of the STAT1/STAT3 functional interaction was further highlighted by the observation that short interfering RNA knockdown of STAT1 significantly decreased apoptosis induced by STAT3 inhibition. Thus, STAT1 is a tumor suppressor in ALK+ ALCL. Phosphorylation and downregulation of STAT1 by NPM-ALK represent other mechanisms by which this oncogenic tyrosine kinase promotes tumorigenesis.

  5. The ALK inhibitor ASP3026 eradicates NPM-ALK⁺ T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model. (United States)

    George, Suraj Konnath; Vishwamitra, Deeksha; Manshouri, Roxsan; Shi, Ping; Amin, Hesham M


    NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK⁺ solid tumors. However, NPM-ALK⁺ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK⁺ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK⁺ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK⁺ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK⁺ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials.

  6. Identification of a novel crosstalk between casein kinase 2α and NPM-ALK in ALK-positive anaplastic large cell lymphoma. (United States)

    Armanious, Hanan; Gelebart, Pascal; Anand, Mona; Lai, Raymond


    It was previously reported that β-catenin contributes to the tumorigenesis of ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), and the oncogenic effects of β-catenin in these tumors are promoted by NPM-ALK, an abnormal fusion protein characteristic of ALK(+)ALCL. In this study, we hypothesized that NPM-ALK promotes the oncogenic activity of β-catenin via its functional interactions with the Wnt canonical pathway (WCP). To test this hypothesis, we examined if NPM-ALK modulates the gene expression of various members in the WCP. Using a Wnt pathway-specific oligonucleotide array and Western blots, we found that the expression of casein kinase 2α (CK2α) was substantially downregulated in ALK(+)ALCL cells in response to siRNA knockdown of NPM-ALK. CK2α is biologically important in ALK(+)ALCL, as its inhibition using 4,5,6,7-tetrabromobenzotriazole or siRNA resulted in a significant decrease in cell growth and a substantial decrease in the β-catenin protein level. Furthermore, CK2α co-immunoprecipitated with NPM-ALK and regulated its level of serine phosphorylation, a feature previously shown to correlate with the oncogenic potential of this fusion protein. To conclude, this study has revealed a novel crosstalk between NPM-ALK and CK2α, and our data supports the model that these two molecules work synergistically to promote the tumorigenicity of these lymphomas.

  7. U.S. Food and Drug Administration approval summary: brentuximab vedotin for the treatment of relapsed Hodgkin lymphoma or relapsed systemic anaplastic large-cell lymphoma. (United States)

    de Claro, R Angelo; McGinn, Karen; Kwitkowski, Virginia; Bullock, Julie; Khandelwal, Aakanksha; Habtemariam, Bahru; Ouyang, Yanli; Saber, Haleh; Lee, Kyung; Koti, Kallappa; Rothmann, Mark; Shapiro, Marjorie; Borrego, Francisco; Clouse, Kathleen; Chen, Xiao Hong; Brown, Janice; Akinsanya, Lara; Kane, Robert; Kaminskas, Edvardas; Farrell, Ann; Pazdur, Richard


    The U.S. Food and Drug Administration (FDA) describes the accelerated approval of brentuximab vedotin for patients with relapsed Hodgkin lymphoma and relapsed systemic anaplastic large-cell lymphoma (sALCL). FDA analyzed the results of two single-arm trials, enrolling 102 patients with Hodgkin lymphoma and 58 patients with sALCL. Both trials had primary endpoints of objective response rate (ORR) and key secondary endpoints of response duration and complete response (CR) rate. For patients with Hodgkin lymphoma, ORR was 73% (95% CI, 65-83%); median response duration was 6.7 months, and CR was 32% (95% CI, 23-42%). For patients with sALCL, ORR was 86% (95% CI, 77-95%), median response duration was 12.6 months, and CR was 57% (95% CI, 44-70%). The most common adverse reactions were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting. FDA granted accelerated approval of brentuximab vedotin for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplantation (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates, and for the treatment of patients with sALCL after failure of at least one prior multiagent chemotherapy regimen.

  8. Undifferentiated (Anaplastic Carcinoma of the Pancreas with Osteoclast-Like Giant Cells Showing Various Degree of Pancreas Duct Involvement. A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Vlad Maksymov


    Full Text Available Context Undifferentiated (anaplastic carcinoma of the pancreas with osteoclast-like giant cells is exceedingly rare. The prognosis of undifferentiated carcinoma is worse than that of poorly differentiated ductal adenocarcinoma of the pancreas; however, undifferentiated carcinoma with osteoclast-like giant cells might have a more favorable prognosis. Case report We report the case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, showing an intraductal growth pattern with various degree of pancreas duct involvement in the different areas. As a result, we were able to demonstrate the entire spectrum of changes, ranging from the early, minimal intraluminal growth to the partial or complete occlusion of the branches of the main pancreatic duct, and finally invasion and formation of the large necrotic/degenerated cysts. Conclusions Our findings support the epithelial origin of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. In early stages, the affected pancreatic duct epithelium was intermingled with nonepithelial component and had an immunoprofile distinctive from the epithelial lining of the uninvolved (normal pancreatic ducts. Distinctive immunoprofile (CK 5/6, p63 and p53 positive of the epithelial component and p63 and p53 positivity of the nonepithelial component should be explained and further investigated in the similar cases. Our findings support prior assertions that undifferentiated carcinoma of the pancreas with osteoclast-like giant cells may develop from carcinoma in situ within the main pancreatic duct or its branches

  9. Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

    Directory of Open Access Journals (Sweden)

    Gaiser Timo


    Full Text Available Abstract Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL. We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    Muñoz-de-Toro Mónica


    Full Text Available 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 this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis. Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling

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

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    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)


    ''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.)

  12. Entropy generation in a channel resembling gas turbine cooling passage: Effect of rotation number and density ratio on entropy generation

    Indian Academy of Sciences (India)

    M Basha; M Al-Qahtani; B S Yilbas


    Flow into a passage resembling a gas turbine blade cooling passage is considered and entropy generation rate in the passage is examined for unique rotation number and density ratios. In the simulations, leading and trailing walls of the passage are assumed to be at constant temperature. A control volume approach is introduced to discretize the governing equations of flow, heat transfer, and entropy generation. Reynolds stress turbulence model is accommodated in the simulation to account for the turbulence. The study is extended to include two rotational speeds and three density ratios. The passage aspect ratio is kept 10:1. It is found that volumetric entropy generation rate attains high values at passage inlet due to attainment of high temperature gradient in this region. Increasing rotation number and density ratio enhances volumetric entropy generation rate in the passage.

  13. An analysis on equal width quantization and linearly separable subcode encoding-based discretization and its performance resemblances

    Directory of Open Access Journals (Sweden)

    Lim Meng-Hui


    Full Text Available Abstract Biometric discretization extracts a binary string from a set of real-valued features per user. This representative string can be used as a cryptographic key in many security applications upon error correction. Discretization performance should not degrade from the actual continuous features-based classification performance significantly. However, numerous discretization approaches based on ineffective encoding schemes have been put forward. Therefore, the correlation between such discretization and classification has never been made clear. In this article, we aim to bridge the gap between continuous and Hamming domains, and provide a revelation upon how discretization based on equal-width quantization and linearly separable subcode encoding could affect the classification performance in the Hamming domain. We further illustrate how such discretization can be applied in order to obtain a highly resembled classification performance under the general Lp distance and the inner product metrics. Finally, empirical studies conducted on two benchmark face datasets vindicate our analysis results.

  14. Human Glioma–Initiating Cells Show a Distinct Immature Phenotype Resembling but Not Identical to NG2 Glia (United States)

    Barrantes-Freer, Alonso; Kim, Ella; Bielanska, Joanna; Giese, Alf; Mortensen, Lena Sünke; Schulz-Schaeffer, Walter J.; Stadelmann, Christine; Brück, Wolfgang


    Abstract Glioma-initiating cells (GICs) represent a potential important therapeutic target because they are likely to account for the frequent recurrence of malignant gliomas; however, their identity remains unsolved. Here, we characterized the cellular lineage fingerprint of GICs through a combination of electrophysiology, lineage marker expression, and differentiation assays of 5 human patient-derived primary GIC lines. Most GICs coexpressed nestin, NG2 proteoglycan, platelet-derived growth factor receptor-α, and glial fibrillary acidic protein. Glioma-initiating cells could be partially differentiated into astrocytic but not oligodendroglial or neural lineages. We also demonstrate that GICs have a characteristic electrophysiologic profile distinct from that of well-characterized tumor bulk cells. Together, our results suggest that GICs represent a unique type of cells reminiscent of an immature phenotype that closely resembles but is not identical to NG2 glia with respect to marker expression and functional membrane properties. PMID:23481707

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

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    Hakyemez, Bahattin [Uludag University Medical School, Department of Radiology, Bursa (Turkey); Bursa State Hospital, Department of Radiology, Bursa (Turkey); Yildirim, Nalan; Erdogan, Cueneyt; Parlak, Mufit [Uludag University Medical School, Department of Radiology, Bursa (Turkey); Kocaeli, Hasan; Korfali, Ender [Uludag University Medical School, Department of Neurosurgery, Bursa (Turkey)


    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 metastases showed a type 3 curve. (orig.)

  16. Transient global ischemia in rats yields striatal projection neuron and interneuron loss resembling that in Huntington's disease. (United States)

    Meade, C A; Figueredo-Cardenas, G; Fusco, F; Nowak, T S; Pulsinelli, W A; Reiner, A


    The various types of striatal projection neurons and interneurons show a differential pattern of loss in Huntington's disease (HD). Since striatal injury has been suggested to involve similar mechanisms in transient global brain ischemia and HD, we examined the possibility that the patterns of survival for striatal neurons after transient global ischemic damage to the striatum in rats resemble that in HD. The perikarya of specific types of striatal interneurons were identified by histochemical or immunohistochemical labeling while projection neuron abundance was assessed by cresyl violet staining. Projectionneuron survival was assessed by neurotransmitter immunolabeling of their efferent fibers in striatal target areas. The relative survival of neuron types was determined quantitatively within the region of ischemic damage, and the degree of fiber loss in striatal target areas was quantified by computer-assisted image analysis. We found that NADPHd(+) and cholinergic interneurons were largely unaffected, even in the striatal area of maximal damage. Parvalbumin interneurons, however, were as vulnerable as projection neurons. Among immunolabeled striatal projection systems, striatoentopeduncular fibers survived global ischemia better than did striatopallidal or striatonigral fibers. The order of vulnerability observed in this study among the striatal projection systems, and the resistance to damage shown by NADPHd(+) and cholinergic interneurons, is similar to that reported in HD. The high vulnerability of projection neurons and parvalbumin interneurons to global ischemia also resembles that seen in HD. Our results thus indicate that global ischemic damage to striatum in rat closely mimics HD in its neuronal selectivity, which supports the notion that the mechanisms of injury may be similar in both.

  17. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. (United States)

    Kruithof, Elli; Baeten, Dominique; De Rycke, Leen; Vandooren, Bernard; Foell, Dirk; Roth, Johannes; Cañete, Juan D; Boots, Annemieke M; Veys, Eric M; De Keyser, Filip


    At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/axial forms belonging to SpA and polyarticular forms resembling rheumatoid arthritis (RA). To address this issue with regard to peripheral synovitis, we compared the synovial characteristics of PsA with those of ankylosing spondylitis (AS)/undifferentiated SpA (USpA) and RA, and compared the synovium of oligoarticular versus polyarticular PsA. Synovial biopsies were obtained from patients with RA, nonpsoriatic SpA (AS + USpA), and oligoarticular and polyarticular PsA. The histological analysis included examination(s) of the lining layer thickness, vascularity, cellular infiltration, lymphoid aggregates, plasma cells and neutrophils. Also, we performed immunohistochemical assessments of CD3, CD4, CD8, CD20, CD38, CD138, CD68, CD163, CD83, CD1a, CD146, alphaVbeta3, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, S100A12, intracellular citrullinated proteins and major histocompatibility complex (MHC)-human cartilage (HC) gp39 peptide complexes. Comparing SpA (PsA + AS + USpA) with RA, vascularity, and neutrophil and CD163+ macrophage counts were greater in SpA (P polyarticular PsA, no significant differences were noted. Moreover, intracellular citrullinated proteins and MHC-HC gp39 peptide complexes, which are specific markers for RA, were observed in neither oligoarticular nor polyarticular PsA. Taken together, these data indicate that the synovial histopathology of PsA, either oligoarticular or polyarticular, resembles that of other SpA subtypes, whereas both groups can be differentiated from RA on the basis of these same synovial features, suggesting that peripheral synovitis in PsA belongs to the SpA concept.

  18. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus (United States)

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo


    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  19. ALK and c-myc gene of anaplastic large cell lymphoma%间变性大细胞淋巴瘤的ALK和c-myc基因研究

    Institute of Scientific and Technical Information of China (English)

    于冉; 周春菊; 陈刚; 高子芬; 时云飞; 石岩; 谢建兰; 周小鸽; 宫丽平


    目的 探讨间变性大细胞淋巴瘤(ALCL)中间变性淋巴瘤激酶(ALK)基因与c-myc基因的分子遗传学改变.方法 收集原发系统性ALCL石蜡包埋组织标本72例,利用间期荧光原位杂交(FISH)技术检测ALCL肿瘤组织中ALK和c-myc基因结构与数目的变化.结果 72例ALCL中,ALK阳性者42例,40例存在涉及ALK基因的染色体易位,其中17例同时伴有ALK基因的多拷贝;ALK阴性的30例均未发现ALK基因的易位,但其中14例存在ALK基因的多拷贝.ALK基因多拷贝的发生率在ALK阳性与阴性组中的差异无统计学意义(P>0.05).72例病例中,均未发现涉及c-myc基因的染色体易位,但其中24例存在c-myc基因的多拷贝.结论 大部分ALCL伴有ALK基因的异常(75.0%).以涉及ALK基因的染色体易位最为多见(55.6%),ALK基因多拷贝也是ALCL较为常见的遗传学改变(43.1%).前者只出现于ALK阳性ALCL中,后者既可出现在ALK阳性也可出现在ALK阴性的ALCL中.ALCL中不见或罕见涉及c-myc基因的染色体易位,但c-myc基因多拷贝的现象较为常见(33.3%).%Objective To investigate the molecular genetic changes of anaplastic lymphoma kinase (ALK) gene and c-myc gene in anaplastic large cell lymphoma (ALCL). Methods The structural aberrations and changes of copy numbers in ALK and c-myc genes in 72 paraffin-embedded ALCL specimens were detected by interphase fluorescence in situ hybridization (FISH). Results Among 72 ALCL specimens, ALK protein was expressed in 42, ALK gene translocation was detected in 40 specimens in which extra copies of ALK gene were detected in 17. ALK gene translocation was not found in all 30 ALK negative specimens, but extra copies of ALK gene were detected in 14 cases. The difference of incidence rates of extra copies in ALK gene between ALK positive and ALK negative specimens was not significant (P>0.05). c-myc gene translocation was not found in any of 72 ALCL specimens, but extra copies were detected in 24

  20. Destaining of Diff-Quik stained cytologic smears is not necessary for the detection of anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma by fluorescence in situ hybridization

    Directory of Open Access Journals (Sweden)

    Weisheng Xu


    Full Text Available Background: Anaplastic lymphoma kinase (ALK gene rearrangement analysis by fluorescence in situ hybridization (FISH is one of the standard molecular tests for targeted therapy of lung adenocarcinoma. However, insufficient cell block cellularity may impede molecular testing. A recent study showed that Diff-Quik (DQ stained cytology smear is suitable for ALK by FISH. Aims: The aim of our study was to observe the impact of destaining intervals on the quality of FISH signals and determine if DQ smears without destaining would allow FISH analysis. Materials and Methods: Thirty-five DQ smears from 27 cases of lung adenocarcinoma were analyzed for ALK gene rearrangement by FISH. Twenty three DQ smears were destained for different intervals, including 30 s (13 cases, 1 min (6 cases, or 2 min (4 cases. Twelve DQ smears were not subjected to destaining. For further validation, FISH signals in 8 smears and 6 cell blocks were compared with the paired destained DQ smears. The signal quality was semi-quantified and analyzed with Chi-squared test. Results: Of the total 27 selected cases, three (11% were positive for ALK gene rearrangement, whereas 24 (89% were negative. FISH signal was satisfactory in all DQ smears. There was no significant difference in the quality of signal among smears with different destaining intervals (P = 0.55 or between smears with and without destaining (P = 0.41. DQ smears without destaining showed identical FISH results and similar or better signals as compared with paired destained smears and cell blocks in all cases. Conclusions: Duration of destaining intervals does not impact the quality of FISH signal on DQ smears. Destaining of DQ smears is not necessary for ALK by FISH.

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

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


    SU6656 is a small-molecule indolinone that selectively inhibits Src family kinase and induces death of cancer cells. The aim of the present study was to investigate the influence of SU6656 on cell survival and to assess the role of p21 and PI3K/Akt signaling in cell survival resulting from SU6656 treatment in anaplastic thyroid carcinoma (ATC) cells. When 8505C, CAL62, and FRO ATC cells were treated with SU6656, the viability of 8505C and CAL62 ATC cells decreased only after treatment with SU6656 at a dosage of 100 μM for 72 h, while the viability of FRO ATC cells decreased after treatment with SU6656 in a concentration- and time-dependent manner. Cell viability was not changed by pretreatment with the broad-spectrum caspase inhibitor z-VAD-fmk. Phospho-Src protein levels were reduced, and p21 protein levels were elevated. Phospho-ERK1/2 protein levels were multiplied without alteration of total ERK1/2, total Akt, and phospho-Akt protein levels. Regarding FRO ATC cells, the decrement of cell viability, the increment of cleaved PARP-1 protein levels, and the decrement of phospho-Src protein levels were shown in p21 siRNA- or LY294002-pretreated cells compared to SU6656-treated control cells. ERK1/2 siRNA transfection did not affect cell viability and protein levels of cleaved PARP-1, p21, and Akt. In conclusion, these results suggest that SU6656 induces caspase-independent death of FRO ATC cells by overcoming the resistance mechanism involving p21 and Akt. Suppression of p21 and Akt enhances the cytotoxic effect of SU6656 in FRO ATC cells.

  2. Clinicopathologic characteristics andtherapeutic responses ofChinese patients withnon-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

    Institute of Scientific and Technical Information of China (English)

    ShaFu; HaiYunWang; FangWang; MaYanHuang; LingDeng; XiaoZhang; ZuLuYe; JianYong Shao


    Introduction:The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6%of lung adenocarcinoma cases and deifnes a molecular subgroup of tumors characterized by clinical sensitivity toALK inhibitors such as crizotinib. This study aimed to identify the relationship betweenALK rearrangement and the clinico‑pathologic characteristics of non‑small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy toALK rearrangement in NSCLC patients. Methods:A total of 487 lung cancer patients who underwent testing forALK rearrangement in our department were included in this study.ALK rearrangement was examined by using lfuorescence insitu hybridization (FISH) assay. Results:Among the 487 patients, 44 (9.0%) were diagnosed withALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non‑smokers and of a young age (≤58years old), the frequency ofALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non‑adenocarcinoma tumor type (P=0.006), poorly differentiated tumors (P=0.001), advanced‑stage tumors (P<0.001), smoking history (P=0.008), and wild‑type epidermal growth factor receptor (EGFR) (P=0.008). Moreover, patients with poorly differentiated and advanced‑stage tumors had a shorter time to cancer progression compared with those with well differentiated (P=0.023) and early‑stage tumors (P=0.001), respectively. Conclusions:ALK‑rearranged NSCLC tends to occur in younger individuals who are either non‑smokers or light smokers with adenocarcinoma. Patients withALK rearrangement might beneift fromALK inhibitor therapy.

  3. Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma. (United States)

    Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Keiko; Kagotani, Akiko; Iwai, Muneo; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Yoshida, Takashi; Okabe, Hidetoshi


    IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4-related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder.

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

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E., E-mail: [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Schulz-Ertner, Daniela [Radiologisches Institut, Markuskrankenhaus Frankfurt, Frankfurt am Main (Germany); Debus, Juergen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Deimling, Andreas von; Hartmann, Christian [Department of Neuropathology, Institute for Pathology, University Hospital of Heidelberg, Heidelberg (Germany); Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg (Germany)


    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  5. Late intervention with anti-BRAF(V600E) therapy induces tumor regression in an orthotopic mouse model of human anaplastic thyroid cancer. (United States)

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


    Human anaplastic thyroid cancer (ATC) is a lethal disease with an advanced clinical presentation and median survival of 3 months. The BRAF(V600E) 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 BRAF(V600E) and TP53(R248G) mutations. Immunocompromised mice were randomized to receive the selective anti-BRAF(V600E) inhibitor, PLX4720, or vehicle by oral gavage 28 d after tumor implantation, 1 wk before all animals typically die due to widespread metastatic lung disease and neck compressive symptoms in this model. Mice were euthanized weekly to evaluate tumor volume and metastases. Control mice showed progressive tumor growth and lung metastases by 35 d after tumor implantation. At that time, all control mice had large tumors, were cachectic, and were euthanized due to their tumor-related weight loss. PLX4720-treated mice, however, showed a significant decrease in tumor volume and lung metastases in addition to a reversal of tumor-related weight loss. Mouse survival was extended to 49 d in PLX4720-treated animals. PLX4720 treatment inhibited cell cycle progression from 28 d to 49 d in vivo. PLX4720 induces striking tumor regression and reversal of cachexia in an in vivo model of advanced thyroid cancer that harbors the BRAF(V600E) mutation.

  6. Diagnostic and therapeutic issues for patients with advanced non‑small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (review). (United States)

    Di Maio, Massimo; De Marinis, Filippo; Hirsch, Fred R; Gridelli, Cesare


    The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.

  7. 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)

    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)


    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

  8. The tyrosine 343 residue of nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) is important for its interaction with SHP1, a cytoplasmic tyrosine phosphatase with tumor suppressor functions. (United States)

    Hegazy, Samar A; Wang, Peng; Anand, Mona; Ingham, Robert J; Gelebart, Pascal; Lai, Raymond


    The cytoplasmic tyrosine phosphatase SHP1 has been shown to inhibit the oncogenic fusion protein nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK), and loss of SHP1 contributes to NPM-ALK-mediated tumorigenesis. In this study, we aimed to further understand how SHP1 interacts and regulates NPM-ALK. We employed an in vitro model in which GP293 cells were transfected with various combinations of NPM-ALK (or mutants) and SHP1 (or mutants) expression vectors. We found that SHP1 co-immunoprecipitated with NPM-ALK, but not the enzymatically inactive NPM-ALK(K210R) mutant, or the mutant in which all three functionally important tyrosine residues (namely, Tyr(338), Tyr(342), and Tyr(343)) in the kinase activation loop (KAL) of ALK were mutated. Interestingly, whereas mutation of Tyr(338) or Tyr(342) did not result in any substantial change in the NPM-ALK/SHP1 binding (assessed by co-immunoprecipitation), mutation of Tyr(343) abrogated this interaction. Furthermore, the NPM-ALK/SHP1 binding was readily detectable when each of the remaining 8 tyrosine residues known to be phosphorylated were mutated. Although the expression of SHP1 effectively reduced the level of tyrosine phosphorylation of NPM-ALK, it did not affect that of the NPM-ALK(Y343F) mutant. In soft agar clonogenic assay, SHP1 expression significantly reduced the tumorigenicity of NPM-ALK but not that of NPM-ALK(Y343F). In conclusion, we identified Tyr(343) of NPM-ALK as the crucial site for mediating the NPM-ALK/SHP1 interaction. Our results also support the notion that the tumor suppressor effects of SHP1 on NPM-ALK are dependent on its ability to bind to this oncogenic protein.

  9. ALK kinase domain mutations in primary anaplastic large cell lymphoma: consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Federica Lovisa

    Full Text Available ALK inhibitor crizotinib has shown potent antitumor activity in children with refractory Anaplastic Large Cell Lymphoma (ALCL and the opportunity to include ALK inhibitors in first-line therapies is oncoming. However, recent studies suggest that crizotinib-resistance mutations may emerge in ALCL patients. In the present study, we analyzed ALK kinase domain mutational status of 36 paediatric ALCL patients at diagnosis to identify point mutations and gene aberrations that could impact on NPM-ALK gene expression, activity and sensitivity to small-molecule inhibitors. Amplicon ultra-deep sequencing of ALK kinase domain detected 2 single point mutations, R335Q and R291Q, in 2 cases, 2 common deletions of exon 23 and 25 in all the patients, and 7 splicing-related INDELs in a variable number of them. The functional impact of missense mutations and INDELs was evaluated. Point mutations were shown to affect protein kinase activity, signalling output and drug sensitivity. INDELs, instead, generated kinase-dead variants with dominant negative effect on NPM-ALK kinase, in virtue of their capacity of forming non-functional heterocomplexes. Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation. Functional changes in ALK kinase activity induced by both point mutations and structural rearrangements were resolved by molecular modelling and dynamic simulation analysis, providing novel insights into ALK kinase domain folding and regulation. Therefore, these data suggest that NPM-ALK pre-therapeutic mutations may be found at low frequency in ALCL patients. These mutations occur randomly within the ALK kinase domain and affect protein activity, while preserving responsiveness to crizotinib.

  10. ALK kinase domain mutations in primary anaplastic large cell lymphoma: consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors. (United States)

    Lovisa, Federica; Cozza, Giorgio; Cristiani, Andrea; Cuzzolin, Alberto; Albiero, Alessandro; Mussolin, Lara; Pillon, Marta; Moro, Stefano; Basso, Giuseppe; Rosolen, Angelo; Bonvini, Paolo


    ALK inhibitor crizotinib has shown potent antitumor activity in children with refractory Anaplastic Large Cell Lymphoma (ALCL) and the opportunity to include ALK inhibitors in first-line therapies is oncoming. However, recent studies suggest that crizotinib-resistance mutations may emerge in ALCL patients. In the present study, we analyzed ALK kinase domain mutational status of 36 paediatric ALCL patients at diagnosis to identify point mutations and gene aberrations that could impact on NPM-ALK gene expression, activity and sensitivity to small-molecule inhibitors. Amplicon ultra-deep sequencing of ALK kinase domain detected 2 single point mutations, R335Q and R291Q, in 2 cases, 2 common deletions of exon 23 and 25 in all the patients, and 7 splicing-related INDELs in a variable number of them. The functional impact of missense mutations and INDELs was evaluated. Point mutations were shown to affect protein kinase activity, signalling output and drug sensitivity. INDELs, instead, generated kinase-dead variants with dominant negative effect on NPM-ALK kinase, in virtue of their capacity of forming non-functional heterocomplexes. Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation. Functional changes in ALK kinase activity induced by both point mutations and structural rearrangements were resolved by molecular modelling and dynamic simulation analysis, providing novel insights into ALK kinase domain folding and regulation. Therefore, these data suggest that NPM-ALK pre-therapeutic mutations may be found at low frequency in ALCL patients. These mutations occur randomly within the ALK kinase domain and affect protein activity, while preserving responsiveness to crizotinib.

  11. Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation. (United States)

    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


    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-κB- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-Rβ, 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-κB, was significantly suppressed by lobatin B most likely due to its NF-κB-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-κB, thereby not affecting normal cells with low constitutive NF-κB activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this

  12. The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma (United States)

    Vastolo, Viviana; Di Somma, Sarah; Scamardella, Eloise; Gigantino, Vincenzo; Franco, Renato; Marone, Gianni; Portella, Giuseppe


    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy. PMID:26625205

  13. Muscle-type nicotinic receptor modulation by 2,6-dimethylaniline, a molecule resembling the hydrophobic moiety of lidocaine

    Directory of Open Access Journals (Sweden)

    Armando Alberola-Die


    Full Text Available To identify the molecular determinants responsible for lidocaine blockade of muscle-type nAChRs, we have studied the effects on this receptor of 2,6-dimethylaniline (DMA, which resembles lidocaine’s hydrophobic moiety. Torpedo marmorata nAChRs were microtransplanted to Xenopus oocytes and currents elicited by ACh (IACh, either alone or co-applied with DMA, were recorded. DMA reversibly blocked IACh and, similarly to lidocaine, exerted a closed-channel blockade, as evidenced by the enhancement of IACh blockade when DMA was pre-applied before its co-application with ACh, and hastened IACh decay. However, there were marked differences among its mechanisms of nAChR inhibition and those mediated by either the entire lidocaine molecule or diethylamine (DEA, a small amine resembling lidocaine’s hydrophilic moiety. Thereby, the IC50 for DMA, estimated from the dose-inhibition curve, was in the millimolar range, which is one order of magnitude higher than that for either DEA or lidocaine. Besides, nAChR blockade by DMA was voltage-independent in contrast to the increase of IACh inhibition at negative potentials caused by the more polar lidocaine or DEA molecules. Accordingly, virtual docking assays of DMA on nAChRs showed that this molecule binds predominantly at intersubunit crevices of the transmembrane-spanning domain, but also at the extracellular domain. Furthermore, DMA interacted with residues inside the channel pore, although only in the open-channel conformation. Interestingly, co-application of ACh with DEA and DMA, at their IC50s, had additive inhibitory effects on IACh and the extent of blockade was similar to that predicted by the allotopic model of interaction, suggesting that DEA and DMA bind to nAChRs at different loci. These results indicate that DMA mainly mimics the low potency and non-competitive actions of lidocaine on nAChRs, as opposed to the high potency and voltage-dependent block by lidocaine, which is emulated by the


    Energy Technology Data Exchange (ETDEWEB)

    Faherty, Jacqueline K. [Department of Astronomy, Universidad de Chile Cerro Calan, Las Condes (Chile); Rice, Emily L.; Cruz, Kelle L.; Nunez, Alejandro [Department of Astrophysics , American Museum of Natural History, Central Park West at 79th Street, New York, NY 10034 (United States); Mamajek, Eric E., E-mail:, E-mail: [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile)


    We present parallax and proper motion measurements, near-infrared spectra, and Wide-field Infrared Survey Explorer photometry for the low surface gravity L5{gamma} dwarf 2MASS J035523.37+113343.7 (2M0355). We use these data to evaluate photometric, spectral, and kinematic signatures of youth as 2M0355 is the reddest isolated L dwarf yet classified. We confirm its low-gravity spectral morphology and find a strong resemblance to the sharp triangular shaped H-band spectrum of the {approx}10 Myr planetary-mass object 2M1207b. We find that 2M0355 is underluminous compared to a normal field L5 dwarf in the optical and Mauna Kea Observatory J, H, and K bands and transitions to being overluminous from 3 to 12 {mu}m, 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 2M1207b and HR8799bcd. We calculate UVW space velocities and find that the motion of 2M0355 is consistent with young disk objects (<2-3 Gyr) and it shows a high likelihood of membership in the AB Doradus association.

  15. Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis. (United States)

    Greer, K A; Wong, A K; Liu, H; Famula, T R; Pedersen, N C; Ruhe, A; Wallace, M; Neff, M W


    Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

  16. 2MASSJ035523.51+113337.4: A Young, Dusty, Nearby, Isolated Brown Dwarf Resembling A Giant Exoplanet

    CERN Document Server

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


    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 ...

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

    Paech, Christian; Gebauer, Roman Antonin


    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.

  18. Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting. (United States)

    Meng, Fanfei; Asghar, Sajid; Xu, Yurui; Wang, Jianping; Jin, Xin; Wang, Zhilin; Wang, Jing; Ping, Qineng; Zhou, Jianping; Xiao, Yanyu


    Many nanoparticle matrixes have been demonstrated to be efficient in brain targeting, but there are still certain limitations for them. To overcome the shortcomings of the existing nanoparticulate systems for brain-targeted delivery, a lipoprotein resembling protein-free nanostructured lipid carrier (PS80-NLC) loaded with curcumin was constructed and assessed for in vitro and in vivo performance. Firstly, single factor at a time approach was employed to investigate the effects of various formulation factors. Mean particle sizes of ≤100nm, high entrapment efficiency (EE, about 95%) and drug loading (DL, >3%) were obtained for the optimized formulations. In vitro release studies in the presence of plasma indicated stability of the formulation under physiological condition. Compared with NLC, PS80-NLC showed noticeably higher affinity for bEnd.3 cells (1.56 folds greater than NLC) but with lower uptake in macrophages. The brain coronal sections showed strong and widely distributed fluorescence intensity of PS80-NLC than that of NLC in the cortex. Ex vivo imaging studies further confirmed that PS80-NLC could effectively permeate BBB and preferentially accumulate in the brain (2.38 times greater than NLC). The considerable in vitro and in vivo performance of the safe and biocompatible PS80-NLC makes it a suitable option for further investigations in brain targeted drug delivery.

  19. Solution structures of the linear leaderless bacteriocins enterocin 7A and 7B resemble carnocyclin A, a circular antimicrobial peptide. (United States)

    Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; McKay, Ryan T; van Belkum, Marco J; McMullen, Lynn M; Vederas, John C


    Leaderless bacteriocins are a class of ribosomally synthesized antimicrobial peptides that are produced by certain Gram-positive bacteria without an N-terminal leader section. These bacteriocins are of great interest due to their potent inhibition of many Gram-positive organisms, including food-borne pathogens such as Listeria and Clostridium spp. We now report the NMR solution structures of enterocins 7A and 7B, leaderless bacteriocins recently isolated from Enterococcus faecalis 710C. These are the first three-dimensional structures to be reported for bacteriocins of this class. Unlike most other linear Gram-positive bacteriocins, enterocins 7A and 7B are highly structured in aqueous conditions. Both peptides are primarily α-helical, adopting a similar overall fold. The structures can be divided into three separate α-helical regions: the N- and C-termini are both α-helical, separated by a central kinked α-helix. The overall structures bear an unexpected resemblance to carnocyclin A, a 60-residue peptide that is cyclized via an amide bond between the C- and N-termini and has a saposin fold. Because of synergism observed for other two-peptide leaderless bacteriocins, it was of interest to probe possible binding interactions between enterocins 7A and 7B. However, despite synergistic activity observed between these peptides, no significant binding interaction was observed based on NMR and isothermal calorimetry.

  20. Bruck 88 : a young star cluster with an old age resemblance in the outskirts of the Small Magellanic Cloud

    CERN Document Server

    Piatti, Andrés E


    We present spectroscopic and photometric results for the Small Magellanic Cloud (SMC) cluster Bruck 88. From the comparison of the cluster integrated spectrum with template cluster spectra we found that the Milky Way globular cluster template spectra are the ones which best resemble it. However, the extracted cluster colour magnitude diagram reveals that Bruck 88 is a young cluster (log(t) = 8.1 +- 0.1). The derived cluster age is compatible with the presence of a Bright Red Giant (BRG) star located ~ 2.6 arcsec in the sky from the cluster centre. We serendipitously observed HW 33, a star cluster located ~ 3 arcmin to the south-east from Bruck 88. We obtained for the cluster the same age than Bruck 88 and surprisingly, a BRG star located within the cluster radius also appears to be compatible with the cluster age. We estimated the MK type of the BRG star in the Bruck 88 field to be in the range G9 II/Ib - K1 III. By combining the spectrum of a star within this MK type range with a 100-150 Myr template cluster...

  1. Local Analogs for High-redshift Galaxies: Resembling the Physical Conditions of the Interstellar Medium in High-redshift Galaxies

    CERN Document Server

    Bian, Fuyan; Dopita, Michael; Juneau, Stephanie


    We present a sample of local analogs for high-redshift galaxies selected in the Sloan Digital Sky Survey (SDSS). The physical conditions of the interstellar medium (ISM) in these local analogs resemble those in high-redshift galaxies. These galaxies are selected based on their positions in the [OIII]/H$\\beta$ versus [NII]/H$\\alpha$ nebular emission-line diagnostic diagram. We show that these local analogs share similar physical properties with high-redshift galaxies, including high specific star formation rates (sSFRs), flat UV continuums and compact galaxy sizes. In particular, the ionization parameters and electron densities in these analogs are comparable to those in $z\\simeq2-3$ galaxies, but higher than those in normal SDSS galaxies by $\\simeq$0.6~dex and $\\simeq$0.9~dex, respectively. The mass-metallicity relation (MZR) in these local analogs shows $-0.2$~dex offset from that in SDSS star-forming galaxies at the low mass end, which is consistent with the MZR of the $z\\sim2-3$ galaxies. We compare the lo...

  2. Production and Distribution of 44Ti and 56Ni in a Three-dimensional Supernova Model Resembling Cassiopeia A

    CERN Document Server

    Wongwathanarat, A; Mueller, E; Pllumbi, E; Wanajo, S


    The spatial and velocity distributions of nuclear species synthesized in the innermost regions of core-collapse supernovae (SNe) can yield important clues about explosion asymmetries and the operation of the still disputed explosion mechanism. Recent observations of radioactive 44Ti with high-energy satellite telescopes (NuSTAR, INTEGRAL) have measured gamma-ray line details, which provide direct evidence of large-scale explosion asymmetries in Supernova 1987A, and in Cassiopeia A (Cas A) even by mapping of the spatial brightness distribution (NuSTAR). Here, we discuss a three-dimensional (3D) simulation of a neutrino-driven explosion, using a parametrized neutrino engine, whose 44Ti distribution is mostly concentrated in one hemisphere pointing opposite to the neutron-star (NS) kick velocity. Both exhibit intriguing resemblance to the observed morphology of the Cas A remnant, although neither progenitor nor explosion were fine-tuned for a perfect match. Our results demonstrate that the asymmetries observed i...

  3. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

    Directory of Open Access Journals (Sweden)

    Sandy A van Gool

    Full Text Available We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs differentiating towards chondrocytes as an alternative model for the human growth plate (GP. Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  4. A new mouse model resembling human diabetic nephropathy: uncoupling of VEGF with eNOS as a novel pathogenic mechanism. (United States)

    Nakagawa, T


    Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.

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

  6. Risk factors for oligodendroglial tumors: a pooled international study

    DEFF Research Database (Denmark)

    McCarthy, Bridget J; Rankin, Kristin M; Aldape, Ken


    (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history...

  7. Successful treatment of low-grade oligodendroglial tumors with a chemotherapy regimen of procarbazine, lomustine, and vincristine

    NARCIS (Netherlands)

    Stege, Elize M Biemond-ter; Kros, Johan M; de Bruin, Hein G; Enting, R H; van Heuvel, Irene; Looijenga, Leendert H J; van der Rijt, Carin D D; Smitt, Peter A E Sillevis; van den Bent, Martin J


    BACKGROUND: Anaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low-grade OD. The authors retrosp

  8. 间变性淋巴瘤激酶抑制剂的研究进展%Advances in research on anaplastic lympgoma kinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    陈雅琳; 李巍; 汪天洋; 周雪琴; 刘东志


    研究发现非小细胞肺癌的形成与多种致癌突变密切相关,其中间变性淋巴瘤激酶重排备受关注,针对棘皮动物微管相关蛋白质4-间变性淋巴瘤激酶融合基因的抑制剂克唑替尼对于治疗晚期ALK阳性非小细胞肺癌患者是有效的,2011年获得美国食品药品监督管理局批准上市,但出现了耐药性,第二代间变性淋巴瘤激酶抑制剂的出现,克服了耐药机制,并显示出治疗非小细胞肺癌患者的活性。本论文按化学结构的不同介绍了克唑替尼、Ceritinib、Alectinib 、Brigatinib、RXDX-101、PF-06463922、ASP3026、X-396、CEP-37440等间变性淋巴瘤激酶抑制剂及临床研究等,为非小细胞肺癌的靶向治疗药物的开发提供了参考。%Researchers have found that multiple oncogenic driver multations are closely related with the progression and prognosis of NSCLC.In the era of molecular targeted treatment,rearrangements in anaplastic lymphoma kinase(ALK)gene and echinoderm microtubule-associated protein-like 4 (EML4)gene were applied in patients with non-small cell lung cancer(NSCLC). Crizotinib,an ALK inhibitor,is effective in treating advanced ALK-positive NSCLC,and the US Food and Drug Administration(FDA)approved it for treating ALK-positive NSCLC. Several mechanisms of acquired resistance to crizotinib have recently been reported. Second-generation ALK inhibitors were developed to overcome these resistance mechanisms and showed activity againstALKpositive NSCLC. The latest development of crizotinib,ceritinib,alectinibetc. were reviewed.

  9. Novel covalent modification of human anaplastic lymphoma kinase (ALK and potentiation of crizotinib-mediated inhibition of ALK activity by BNP7787

    Directory of Open Access Journals (Sweden)

    Parker AR


    Full Text Available Aulma R Parker,1 Pavankumar N Petluru,1 Vicki L Nienaber,2 Min Zhao,1 Philippe Y Ayala,1 John Badger,2 Barbara Chie-Leon,2 Vandana Sridhar,2 Cheyenne Logan,2 Harry Kochat,1 Frederick H Hausheer1 1BioNumerik Pharmaceuticals, Inc., San Antonio, TX, USA; 2Zenobia Therapeutics, Inc., La Jolla, CA, USA Abstract: BNP7787 (Tavocept, disodium 2,2’-dithio-bis-ethanesulfonate is a novel, investigational, water-soluble disulfide that is well-tolerated and nontoxic. In separate randomized multicenter Phase II and Phase III clinical trials in non-small-cell lung cancer (NSCLC patients, treatment with BNP7787 in combination with standard chemotherapy resulted in substantial increases in the overall survival of patients with advanced adenocarcinoma of the lung in the first-line treatment setting. We hypothesized that BNP7787 might interact with and modify human anaplastic lymphoma kinase (ALK. At least seven different variants of ALK fusions with the gene encoding the echinoderm microtubule-associated protein-like 4 (EML4 are known to occur in NSCLC. EML4–ALK fusions are thought to account for approximately 3% of NSCLC cases. Herein, we report the covalent modification of the kinase domain of human ALK by a BNP7787-derived mesna moiety and the functional consequences of this modification in ALK assays evaluating kinase activity. The kinase domain of the ALK protein crystallizes as a monomer, and BNP7787-derived mesna-cysteine adducts were observed at Cys 1235 and Cys 1156. The BNP7787-derived mesna adduct at Cys 1156 is located in close proximity to the active site and results in substantial disorder of the P-loop and activation loop (A-loop. Comparison with the P-loop of apo-ALK suggests that the BNP7787-derived mesna adduct at Cys 1156 interferes with the positioning of Phe 1127 into a small pocket now occupied by mesna, resulting in a destabilization of the loop's binding orientation. Additionally, in vitro kinase activity assays indicate that BNP7787

  10. Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly. (United States)

    Inoue, Takashi; Ogawa, Masaharu; Mikoshiba, Katsuhiko; Aruga, Jun


    The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

  11. White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection. (United States)

    Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching


    The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

  12. Specificity of lectin-immobilized fluorescent nanospheres for colorectal tumors in a mouse model which more resembles the clinical disease (United States)

    Kitamura, Tokio; Sakuma, Shinji; Shimosato, Moe; Higashino, Haruki; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Hiwatari, Ken-ichiro; Kumagai, Hironori; Morimoto, Naoki; Koike, Seiji; Tobita, Etsuo; Hoffman, Robert M.; Gore, John C.; Pham, Wellington


    We are investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of this study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to more resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real-time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration of them from the anus. When the luminal side of the colon was washed with PBS, most of the nanospheres drained away. However, fluorescence persisted in areas where the cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor specific and bound to tumors even after vigorously washing. The nanospheres non-specifically bound to normal mucosa were easily removed through mild washing. Results indicate that the nanospheres accompanied by colonoscopy will be a clinically-valuable diagnostic tool for the early stage primary colon carcinoma. PMID:24976331

  13. A data collection method resembling continuous-mode SPECT. Use of two-degree step projection data

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Yasuyuki; Shinbata, Hiroyuki [Ehime Prefectural Central Hospital (Japan); Shinohara, Hisashi


    Continuous-mode SPECT can be characterized by the collection of data using movable detectors. We examined the effects of movement of the detector on SPECT images. Projection data collected in step mode at a sampling angle of 2 degrees were serially added, and images at sampling angles of 4, 6, 8, and 10 degrees were reconstructed. In this manner, data were collected using a method resembling continuous-mode SPECT. Our experiment using phantoms revealed that, as the sampling angle increased, the resolution of hot spots in the periphery of the columnar phantom decreased slightly, and that the relationship between the sampling angle and the variance of the data in a given direction of projection was defined by a regression equation of y=0.51x+47.66 (r=0.98). When a myocardial phantom was used, the imaged area of the defect created in the anterior wall increased as the sampling angle increased (y=12.63x+78.54; r=0.99), when the imaged area at a sampling angle of 2 degrees was set at 100%. No changes were observed in the ability to obtain images of the area near the center of the columnar phantom, the ability to obtain images of the defect in the inferior wall of the myocardial phantom, or the quality of the image of normal myocardium obtained by Tc-99m Tetrofosmin SPECT. These results suggest that although this method is not equivalent to continuous-mode SPECT, its resolution in the tangential direction and its ability to image in this direction are affected by the movement of the detectors and that these effects are associated with the sampling angle. (author)

  14. Acetylene Resembling Effect of Ethylene on Seed Germination: Evaluating the Effect of Acetylene Released from Calcium Carbide

    Directory of Open Access Journals (Sweden)



    Full Text Available Some vegetable seeds need a very long time to germinate. In these kinds of seeds the second phase of germination is very long. As acetylene’s chemical structure is almost similar to the gaseous hormone ethylene, its’ physiological effect on seed germination should be very similar as well. Therefore, an experiment was established in order to enhance seed germination, by treating seeds with acetylene released from interaction of calcium carbide (CaC2 with water (H2O. A simple system was designed for efficient and proper use of gaseous acetylene resulted from the two substrates interaction, which conducted the produced gas obtained inside the interaction chamber into a sealed container wherein seeds were floating in water. This experiment aimed to evaluate the effect of one concentration of acetylene with different exposure periods (between 1 to 8 hours on parsley, celery and Swees chard seeds’ germination (chosen as late germinating vegetables. The effect of acetylene on seed germination speed and percent was investigated. There were significant differences in both percent and speed of germination within the various treatments. By floating for 3, 5 and 3 hours for parsley, celery and Swiss chard respectively, the highest germination rates were observed. The highest germination speed was achieved by 5, 5 and 3 hours floating respectively for parsley, celery and Swiss chard. Based on the results obtained, the current experiment suggests that acetylene has positive effect on enhancing seed germination of named vegetables, and played the role of ethylene, its effects resembling in regard to seed germination process.

  15. Rhythmicity in mice selected for extremes in stress reactivity: behavioural, endocrine and sleep changes resembling endophenotypes of major depression.

    Directory of Open Access Journals (Sweden)

    Chadi Touma

    Full Text Available BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD. Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called 'stress reactivity' (SR mouse model consists of three separate breeding lines selected for either high (HR, intermediate (IR, or low (LR corticosterone increase in response to stressors. METHODOLOGY/PRINCIPLE FINDINGS: In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period, resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice. CONCLUSION/SIGNIFICANCE: Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may

  16. A Comparative Study of Film Title Translation in Chinese Mainland, Hong Kong and Taiwan--From the Perspective of Spiritual Resemblance

    Institute of Scientific and Technical Information of China (English)



    Due to different social systems, economic development and cultural phenomenon in Chinese mainland, Hong Kong and Taiwan, one foreign film title may generate into various translation texts. Therefore,“one country, three-translation” phenomenon has come into being. This paper, combined with Spiritual Resemblance, attempts to analyze this phenomenon so as to better promote the film title translation.

  17. Does My Baby Really Look Like Me? Using Tests for Resemblance between Parent and Child to Teach Topics in Categorical Data Analysis (United States)

    Froelich, Amy G.; Nettleton, Dan


    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…

  18. 原发系统型间变性大细胞淋巴瘤间变性淋巴瘤激酶基因异常与其融合蛋白表达及预后分析%Anaplastic lymphoma kinase gene abnormality and the expression of its fusion protein in primary systemic anaplastic large cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    时云飞; 刘翠苓; 周春菊; 宫丽平; 董丽娜; 李敏; 黄欣; 高子芬


    目的:回顾性研究原发系统型间变性大细胞淋巴瘤(primary systemic anaplastic large cell lymphoma,S-ALCL)间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合蛋白表达及ALK基因异常情况,探讨两者关系及预后意义.方法:收集北京大学基础医学院病理学系淋巴瘤研究室及北京儿童医院28例确诊S-ALCL的病例,重新进行常规形态观察,复习及补充必要免疫组化标记以核实诊断.采用EnVision法进行免疫组织化学染色(immu-nohistochemical stainining,IHC).应用ALK-1单克隆抗体检测ALK融合蛋白表达,应用位点特异性间期荧光原位杂交(locus specific interphase fluorescence in situ hybridization,LSI-FISH)方法检测石蜡包埋组织中肿瘤细胞ALk基因断裂及其他异常情况.收集临床资料,随访.结果:8例S-ALCL病例IHC检测ALK-1蛋白阳性19例,阴性9例.用LSI-FISH法检测到ALK基因断裂14例,其余14例无ALK基因断裂的病例中,5例呈2个拷贝,9例呈多个拷贝.全部病例中有完整随访的共22例,随访截止时16例生存,6例死亡,生存期0.5~36.0个月,平均生存期12.8个月;1年累计生存率73.9%.ALk基因多个完整拷贝者1年累计生存率仅47.6%,预后相对较差.结论:-ALcL病例肿瘤细胞有ALK-1融合蛋白表达,在S-ALCL诊断中高度特异.S-ALCL病例ALK基因的异常改变很复杂,ALK-l融合蛋白表达与ALK基因断裂不完全吻合.S-ALCL中ALK基因异常的不同类型间预后可能有差异.ALK基因呈多个完整拷贝病例的预后可能更差.

  19. Analysis on the clinicopathology characteristics of anaplastic large cell lymphoma%间变性大细胞淋巴瘤临床病理分析

    Institute of Scientific and Technical Information of China (English)

    王刚平; 田胜花; 梁粉花


    目的 研究间变性大细胞淋巴瘤(ALCL)的临床病理特征、免疫表型,以提高诊断水平.方法 回顾性分析19例ALCL的临床、病理形态学资料和免疫组织化学,CD30、ALK、CD43、CD45RO、EMA和TIA-1检测结果.结果 19例均为原发系统型ALCL,其中男性11例,女性8例,年龄2~71岁,平均26岁.16例(84.2%)出现B症状,14例(73.7%)结外侵犯.肿瘤细胞沿淋巴窦生长或散在分布,均可见标志性肿瘤细胞,CD+3019例(100%),ALK(+)15例(78.9%),EMA(+)10例(52.6%),TIA-1(+)14例(73.7%),ALK、EMA和TIA-1同时阴性2例(10.5%).重新诊断17例(89.5%)正确.结论 ALCL表现多样,大部分患者经临床、组织病理学和免疫标记特征综合判断可作出相应诊断,CD30、ALK、EMA、TIA-1对鉴别诊断有帮助.%Objective To investigate the clinicopathology characteristics, immunopheotypic of anaplastic large cell lymphoma (ALCL) in order to improve its diagnostic and therapeutic accuracy. Methods The clinical, immunophenotypic and histopathologie features of 19 cases ALCL were retrospectively studied. The expression of CD30, ALK, CD43, CD45RO, EMA and TIA-1 was detected using EnVision immunohistochemical technique. Results All patients were primary systemic ALCL. Among the 19 patients, 11 were males and 8were females. The age ranged from 2 to 71 years, average age 26 years old. It shows a broad morphologic spectrum of the tumor cell and the hallmark cells characterized by sheets of large lymphoid cells withchromatin-poor horseshoe-shaped nuclei containing multiple nucleoli were encountered in all ALCL variants. 16patients (84.2 %) showed B-symptoms, and extranodal involvement was present in 14 (73.7 % ).Immunohistochemical study showed that the tumor cells expressed CD30 (100 %), ALK (78.9 %), EMA(52.6 %), TIA-1 (73.7 %) and 2 cases (10.5 %) neither expressed ALK, nor EMA,TIA-1.17 cases were reached the correct diagnosis according to combination of clinic, histological and immunological features

  20. {sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)


    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

  1. Research progress of IDH1 and IDH2 mutations in gliomas

    Directory of Open Access Journals (Sweden)

    Shan-shan ZHANG


    Full Text Available The gene mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2 mainly occur in astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma and secondary glioblastoma. The IDH1/2 gene mutation can alter proteinase function, consume α-ketoglutarate and nicotinamide adenine dinucleotide phosphate-reduced (NADPH and thus produce carcinogenic metabolite, 2-hydroxyglutarate. The intracellular accumulation of 2-hydroxyglutarate will induce a series of downstream effects which may result in the development of gliomas mentioned above. Both IDH1/2 mutations and other concomitant hereditary variations are biomarkers for differential diagnosis and IDH1/2 mutations are also independent factors for the prognosis of gliomas. The molecular targeting therapy for IDH1/2 mutations has become the research focus of glioma treatment. This review summarizes the recent progress of this field. DOI: 10.3969/j.issn.1672-6731.2015.11.017

  2. Critique of Wittgenstein's Theory of "Family Resemblance"%对维特根斯坦"家族相似"理论的批判

    Institute of Scientific and Technical Information of China (English)



    @@ 维特根斯坦在中提出了著名的"家族相似"(family resemblance)的"语言游戏"观,以此来否定和消解传统哲学中的"本质主义".维氏的这一理论影响极为广泛,并被奉为是对形而上学教条的重大理论突破.

  3. Forensic facial approximation assessment: can application of different average facial tissue depth data facilitate recognition and establish acceptable level of resemblance? (United States)

    Herrera, Lara Maria; Strapasson, Raíssa Ananda Paim; da Silva, Jorge Vicente Lopes; Melani, Rodolfo Francisco Haltenhoff


    Facial soft tissue thicknesses (FSTT) are important guidelines for modeling faces from skull. Amid so many FSTT data, Forensic artists have to make a subjective choice of a dataset that best meets their needs. This study investigated the performance of four FSTT datasets in the recognition and resemblance of Brazilian living individuals and the performance of assessors in recognizing people, according to sex and knowledge on Human Anatomy and Forensic Dentistry. Sixteen manual facial approximations (FAs) were constructed using three-dimensional (3D) prototypes of skulls (targets). The American method was chosen for the construction of the faces. One hundred and twenty participants evaluated all FAs by means of recognition and resemblance tests. This study showed higher proportions of recognition by FAs conducted with FSTT data from cadavers compared with those conducted with medical imaging data. Targets were also considered more similar to FAs conducted with FSTT data from cadavers. Nose and face shape, respectively, were considered the most similar regions to targets. The sex of assessors (male and female) and the knowledge on Human Anatomy and Forensic Dentistry did not play a determinant role to reach greater recognition rates. It was possible to conclude that FSTT data obtained from imaging may not facilitate recognition and establish acceptable level of resemblance. Grouping FSTT data by regions of the face, as proposed in this paper, may contribute to more accurate FAs.

  4. From FRA to RFN, or How the Family Resemblance Approach Can Be Transformed for Science Curriculum Analysis on Nature of Science (United States)

    Kaya, Ebru; Erduran, Sibel


    The inclusion of Nature of Science (NOS) in the science curriculum has been advocated around the world for several decades. One way of defining NOS is related to the family resemblance approach (FRA). The family resemblance idea was originally described by Wittgenstein. Subsequently, philosophers and educators have applied Wittgenstein's idea to problems of their own disciplines. For example, Irzik and Nola adapted Wittgenstein's generic definition of the family resemblance idea to NOS, while Erduran and Dagher reconceptualized Irzik and Nola's FRA-to-NOS by synthesizing educational applications by drawing on perspectives from science education research. In this article, we use the terminology of "Reconceptualized FRA-to-NOS (RFN)" to refer to Erduran and Dagher's FRA version which offers an educational account inclusive of knowledge about pedagogical, instructional, curricular and assessment issues in science education. Our motivation for making this distinction is rooted in the need to clarify the various accounts of the family resemblance idea.The key components of the RFN include the aims and values of science, methods and methodological rules, scientific practices, scientific knowledge as well as the social-institutional dimensions of science including the social ethos, certification, and power relations. We investigate the potential of RFN in facilitating curriculum analysis and in determining the gaps related to NOS in the curriculum. We analyze two Turkish science curricula published 7 years apart and illustrate how RFN can contribute not only to the analysis of science curriculum itself but also to trends in science curriculum development. Furthermore, we present an analysis of documents from USA and Ireland and contrast them to the Turkish curricula thereby illustrating some trends in the coverage of RFN categories. The results indicate that while both Turkish curricula contain statements that identify science as a cognitive-epistemic system, they

  5. 间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤泛发性皮肤侵犯一例%Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma with generalized cutaneous involvement:a case report

    Institute of Scientific and Technical Information of China (English)

    孙春秋; 唐旭; 王松; 沈宏


    A rare case of anaplastic lymphoma kinase(ALK)-negative anaplastic large cell lymphoma (ALCL)with generalized cutaneous involvement is reported in a 37-year-old man.Seven months prior to the presentation,he developed a goose egg-sized mass in his right thigh without obvious triggers,which gradually grew and no significant discomfort was felt.Diffuse and nonpitting edema gradually appeared in his right thigh and hip.Two months prior to the presentation,multiple dark red papules,nodules,and plaques emerged over the body surface with erosions and ulcers of varying size arising on some of the plaques.Laboratory examination revealed reduced albumin and significantly elevated lactate dehydrogenase in serum.B-mode sonography showed swelling and mutual fusion of superficial lymph nodes,and color Doppler flow imaging revealed markedly increased branch blood flow signals in lymph nodes.Computed tomography(CT)displayed generalized swelling of lymph nodes associated with soft-tissue edema in the right thigh and perineal region,as well as extensive enlargement of epigastric and mediastinal lymph nodes.Pathological examination of the skin lesion revealed a dense dermal infiltrate with mononuclear cells,some of which presented with cellular atypia and atypical nuclear division.Immunohistochemistry of the skin lesion showed that the mononuclear cells stained positive for CD3,CD8,CD30(80% positive),CD4,CD45RO and granzyme B,but negative for CD56,ALK and T cell intracellular antigen-1(TIA-1).Pathology of lymph nodes indicated that the lymph node structure was completely destroyed with a diffuse growth of tumor cells,which were larger than common large cell lymphoma cells,and contained basophilic or bi-color abundant cytoplasm,deviating,horseshoe-,kidney-shaped,or lobulated cell nuclei,sparse nuclear chromatin and single or multiple small basophilic nucleoli.Angiogenesis,stromal fibrosis and infiltration of varying number of plasma cells and lymphocytes were seen in pathological

  6. Dedifferentiation in Gastrointestinal Stromal Tumor to an Anaplastic KIT Negative Phenotype – a Diagnostic Pitfall. Morphologic and Molecular Characterization of 8 Cases Occurring either de-novo or after Imatinib Therapy (United States)

    Antonescu, Cristina R; Romeo, Salvatore; Zhang, Lei; Nafa, Khedoudja; Hornick, Jason L.; Nielsen, G. Petur; Mino-Kenudson, Mari; Huang, Hsuan-Ying; Mosquera, Juan-Miguel; Dei Tos, Paolo A; Fletcher, Christopher D.M.


    Most GISTs can be recognized by their monotonous cytologic features and overexpression of KIT oncoprotein. Altered morphology and loss of CD117 reactivity has been described previously after chronic imatinib treatment; however, this phenomenon has not been reported in imatinib-naïve tumors. Eight patients with abrupt transition from a classic CD117-positive spindle cell GIST to an anaplastic CD117-negative tumor were investigated for underlying molecular mechanisms of tumor progression. Pathologic and molecular analysis was performed on each of the two components. Genomic DNA PCR for KIT, PDGFRA, BRAF and KRAS hot spot-mutations and FISH for detecting KIT gene copy number alterations were performed. TP53 mutational analysis was performed in 5 cases. There were 7 males and 1 female, with an age range of 23–65 years. Five of the primary tumors were located in the stomach, while one case each originated in small bowel, colon and rectum. In 3 patients, the dedifferentiated component occurred in the setting of imatinib-resistance, while the remaining 5 occurred de novo. The dedifferentiated component had an anaplastic appearance, including one angiosarcomatous phenotype, with high mitotic activity and necrosis, and showed complete loss of CD117 (8/8) and CD34 (5/8) expression, and de novo expression of either cytokeratin (4/8) or desmin (1/8). There was no difference in the KIT genotype between the two components. However, two imatinib-resistant tumors showed co-existence of KIT exon 11 and exon 13 mutations. FISH showed loss of one KIT gene in 3 cases and low level amplification of KIT in 2 other cases in the CD117-negative component, compared to the CD117-positive area. TP53 mutation was identified in 1/5 cases tested, being present in both components. In summary, dedifferentiation in GIST may occur either de novo or after chronic imatinib exposure and can represent a diagnostic pitfall. This phenomenon is not related to additional KIT mutations, but might be

  7. The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein

    Directory of Open Access Journals (Sweden)

    Pearson Joel D


    Full Text Available Abstract Background Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90 plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40, is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines. Methods NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined. Results We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to

  8. Molecular analysis of a case of nevus of ota showing progressive evolution to melanoma with intermediate stages resembling cellular blue nevus. (United States)

    Gerami, Pedram; Pouryazdanparast, Pedram; Vemula, Swapna; Bastian, Boris C


    Nevus of Ota is a variant of congenital nevus, which is morphologically paucicellular and resembles a common blue nevus. Although nevus of Ota is a risk factor for uveal melanoma in white people, the development of cutaneous melanoma within nevus of Ota is a very rare occurrence with only a few reported cases. We present a case of a long-standing nevus of Ota, with radiologic imaging demonstrating a large retro-orbital mass and a biopsy showing melanoma. The histopathology of the eye exenteration specimen illustrated various stages of melanocytic progression including areas resembling a nevus of Ota, blue nevus, cellular blue nevus, and melanoma. There was heterogeneity in the overtly malignant sections with some areas displaying expansile nodules of blander appearing spindled cells, whereas other areas were composed of epithelioid cells with higher mitotic counts and zones of necrosis. The extensive lesion also infiltrated the soft tissue and bone. We performed gene mutation analysis for GNAQ, BRAF, NRAS, and KIT and fluorescence in situ hybridization (FISH) targeting commonly altered chromosomal loci in melanoma and comparative genomic hybridization (CGH). Copy number changes typical of melanoma were identified by both FISH and CGH in the morphologically malignant areas illustrating the relationship of tumor progression and the progressive acquisition of genetic aberrations.

  9. Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma. (United States)

    Damm-Welk, Christine; Busch, Kerstin; Burkhardt, Birgit; Schieferstein, Jutta; Viehmann, Susanne; Oschlies, Ilske; Klapper, Wolfram; Zimmermann, Martin; Harbott, Jochen; Reiter, Alfred; Woessmann, Willi


    Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large-cell lymphoma (ALCL). We evaluated the presence, extent, and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK-positive ALCL at diagnosis using qualitative and quantitative polymerase chain reaction (PCR) for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 10(4) copies ABL (NCNs). BM was analyzed from 80 patients and PB from 52. BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histologic subtype. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-Rs): CI-R was 50% +/- 10% for 38 PCR-positive and 15% +/- 7% for 42 PCR-negative patients (P NPM-ALK in BM had a CI-R of 71% +/- 14% compared with a CI-R of 18% +/- 6% for 59 patients with 10 or fewer NCNs (P < .001). PB PCR results led to a similar grouping. Thus, quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%.

  10. IL-2R common gamma-chain is epigenetically silenced by nucleophosphin-anaplastic lymphoma kinase (NPM-ALK) and acts as a tumor suppressor by targeting NPM-ALK. (United States)

    Zhang, Qian; Wang, Hong Yi; Liu, Xiaobin; Bhutani, Gauri; Kantekure, Kanchan; Wasik, Mariusz


    Anaplastic lymphoma kinase (ALK), physiologically expressed only by certain neural cells, becomes highly oncogenic, when aberrantly expressed in nonneural tissues as a fusion protein with nucleophosphin (NPM) and other partners. The reason why NPM-ALK succeeds in transforming specifically CD4(+) T lymphocytes remains unknown. The IL-2R common γ-chain (IL-2Rγ) is shared by receptors for several cytokines that play key roles in the maturation and growth of normal CD4(+) T lymphocytes and other immune cells. We show that IL-2Rγ expression is inhibited in T-cell lymphoma cells expressing NPM-ALK kinase as a result of DNA methylation of the IL-2Rγ gene promoter. IL-2Rγ promoter methylation is induced in malignant T cells by NPM-ALK. NPM-ALK acts through STAT3, a transcription factor that binds to the IL-2Rγ gene promoter and enhances binding of DNA methyltransferases (DNMTs) to the promoter. In addition, STAT3 suppresses expression of miR-21, which selectively inhibits DNMT1 mRNA expression. Reconstitution of IL-2Rγ expression leads to loss of the NPM-ALK protein and, consequently, apoptotic cell death of the lymphoma cells. These results demonstrate that the oncogenic tyrosine kinase NPM-ALK induces epigenetic silencing of the IL-2Rγ gene and that IL-2Rγ acts as a tumor suppressor by reciprocally inhibiting expression of NPM-ALK.

  11. Quantitative PCR detection of NPM/ALK fusion gene and CD30 gene expression in patients with anaplastic large cell lymphoma--residual disease monitoring and a correlation with the disease status. (United States)

    Kalinova, Marketa; Krskova, Lenka; Brizova, Helena; Kabickova, Edita; Kepak, Tomas; Kodet, Roman


    Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of malignant lymphoproliferative diseases with a consistent expression of the cytokine receptor CD30. ALCL is frequently associated with a NPM/ALK fusion gene which is found in up to 75% of pediatric ALCLs. Real-time quantitative RT-PCR (RQ-RT-PCR) of NPM/ALK and CD30 gene expression was employed to analyze minimal residual disease (MRD) in 10 patients with NPM/ALK positive ALCL in 79 follow-up bone marrow (BM) and/or peripheral blood (PB) samples. In all BM samples from relapses and/or closely before a relapse, BM samples revealed NPM/ALK and CD30 positivity in at least one of the iliac BM trephines. Five out of nine relapses were preceded or were accompanied by minimally half log increased NPM/ALK levels in the BM. We found that RQ-RT-PCR of the CD30 expression is not suitable for MRD detection--only two relapses were accompanied by an increase of the CD30 level above a level which was detected in BM/PB samples from healthy individuals. RQ-RT-PCR of NPM/ALK expression is a promising and rapid approach for monitoring MRD.

  12. 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. (United States)

    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


    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.

  13. Low-grade oligodendroglioma: current treatments and future hopes. (United States)

    Lwin, Zarnie; Gan, Hui K; Mason, Warren P


    Current treatment modalities for low-grade gliomas include surgery, radiotherapy and chemotherapy. Management of these ultimately incurable tumors remains controversial, particularly the timing and extent of surgery, and the optimal sequence of radiotherapy and chemotherapy thereafter. Two ongoing Phase III trials should provide definitive answers to some of these controversial issues in the treatment of low-grade gliomas and confirm the impact of molecular predictors of response and outcome. This review will discuss recent progress and topical issues in the treatment of low-grade gliomas.

  14. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, C; Ladelund, S; Rambech, E


    BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome...... staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects....

  15. Curriculum Innovation: Difference and Resemblance (United States)

    Hanley, Una; Torrance, Harry


    How do teachers respond to a mathematics curriculum innovation? This paper reports some of the findings from a UK Research Council (ESRC)-funded project investigating how teachers in English secondary schools (students aged 12-16 years) responded to innovation. A Gatsby Foundation funded program implemented new materials; the project investigated…

  16. Spinal myoclonus resembling belly dance. (United States)

    Kono, I; Ueda, Y; Araki, K; Nakajima, K; Shibasaki, H


    A 63-year-old man presented with an 11-month history of progressive myoclonus in the right abdominal wall. Administration of clonazepam reduced the frequency and amplitude. When the therapy was discontinued, the frequency and amplitude of the myoclonus increased, and synchronous and weak myoclonus also was observed in the left abdomen. The trunk was twisted just after the appearance of the abdominal myoclonus associated with myoclonic jerks spreading from the rostral to caudal paraspinal muscles. Later in the clinical course, the myoclonus became stimulus sensitive and was induced by tendon tap given anywhere on the body, with the latency ranging from 50 to 150 ms irrespective of the sites of tapping. Myoclonus seen in the abdominal wall was segmental and considered to be of spinal origin. The reflex myoclonus had a 150-ms refractory period. It can be postulated that increased excitability of anterior horn cells at a certain segment might make a spino-bulbo-spinal reflex manifest at the corresponding segment. This myoclonus is considered to be a new form of spinal reflex myoclonus, because the abdominal myoclonic jerk seems to trigger another myoclonic jerk involving the paraspinal muscles.

  17. Biosynthetic mechanism for L-Gulose in main polar lipids of Thermoplasma acidophilum and possible resemblance to plant ascorbic acid biosynthesis. (United States)

    Yamauchi, Noriaki; Nakayama, Yusuke


    L-Gulose is a very rare sugar, but appears as a sugar component of the main polar lipids characteristic in such a thermophilic archaeon as Thermoplasma acidophilum that lives without cell walls in a highly acidic environment. The biosynthesis of L-gulose in this thermophilic organism was investigated with deuterium-labeling experiments. L-Gulose was found to be biosynthesized from D-glucose via stepwise stereochemical inversion at C-2 and C-5. The involvement of an epimerase related to GDP-mannose 3,5-epimerase, the key enzyme of plant ascorbate biosynthesis, was also suggested in this C-5 inversion. The resemblance of L-gulose biosynthesis in archaea and plants might be suggested from these results.

  18. The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man. (United States)

    de Tommaso, M; Libro, G; Guido, M; Sciruicchio, V; Puca, F


    Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

  19. Review of the Article by Orlando Lourenco:Piaget and Vygotsky: Many resemblances, and a crucial difference(NewIdeasinPsychology 30 (2012 P. 281-295

    Directory of Open Access Journals (Sweden)

    Alexeyeva G.V.


    Full Text Available 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: 1the origins of knowledge and motor of development; 2 influence of equal vs. those based on authorities relations on child development and learning; 3 the more appropriate method for studying developmental changes; 4the importance of the distinction between true vs. necessary knowledge;5 the role of transformation vs. transmission in the development and learning phenomena.

  20. Permian ginkgophyte fossils from the Dolomites resemble extant O-ha-tsuki aberrant leaf-like fructifications of Ginkgo biloba L

    Directory of Open Access Journals (Sweden)

    Kustatscher Evelyn


    Full Text Available Abstract Background Structural elucidation and analysis of fructifications of plants is fundamental for understanding their evolution. In case of Ginkgo biloba, attention was drawn by Fujii in 1896 to aberrant fructifications of Ginkgo biloba whose seeds are attached to leaves, called O-ha-tsuki in Japan. This well-known phenomenon was now interpreted by Fujii as being homologous to ancestral sporophylls. The common fructification of Ginkgo biloba consists of 1-2 (rarely more ovules on a dichotomously divided stalk, the ovules on top of short stalklets, with collars supporting the ovules. There is essentially no disagreement that either the whole stalk with its stalklets, collars and ovules is homologous to a sporophyll, or, alternatively, just one stalklet, collar and ovule each correspond to a sporophyll. For the transition of an ancestral sporophyll resembling extant O-ha-tsuki aberrant leaves into the common fructification with stalklet/collar/ovule, evolutionary reduction of the leaf lamina of such ancestral sporophylls has to be assumed. Furthermore, such ancestral sporophylls would be expected in the fossil record of ginkgophytes. Results From the Upper Permian of the Bletterbach gorge (Dolomites, South Tyrol, Italy ginkgophyte leaves of the genus Sphenobaiera were discovered. Among several specimens, one shows putatively attached seeds, while other specimens, depending on their state of preservation, show seeds in positions strongly suggesting such attachment. Morphology and results of a cuticular analysis are in agreement with an affiliation of the fossil to the ginkgophytes and the cuticle of the seed is comparable to that of Triassic and Jurassic ones and to those of extant Ginkgo biloba. The Sphenobaiera leaves with putatively attached seeds closely resemble seed-bearing O-ha-tsuki leaves of extant Ginkgo biloba. This leads to the hypothesis that, at least for some groups of ginkgophytes represented by extant Ginkgo biloba, such

  1. The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide. (United States)

    Strowd, Roy E; Abuali, Inas; Ye, Xiaobu; Lu, Yao; Grossman, Stuart A


    Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA.

  2. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling. (United States)

    Staber, Philipp B; Vesely, Paul; Haq, Naznin; Ott, Rene G; Funato, Kotaro; Bambach, Isabella; Fuchs, Claudia; Schauer, Silvia; Linkesch, Werner; Hrzenjak, Andelko; Dirks, Wilhelm G; Sexl, Veronika; Bergler, Helmut; Kadin, Marshall E; Sternberg, David W; Kenner, Lukas; Hoefler, Gerald


    Anaplastic large cell lymphomas (ALCLs) are highly proliferating tumors that commonly express the AP-1 transcription factor JunB. ALK fusions occur in approximately 50% of ALCLs, and among these, 80% have the t(2;5) translocation with NPM-ALK expression. We report greater activity of JunB in NPM-ALK-positive than in NPM-ALK-negative ALCLs. Specific knockdown of JUNB mRNA using small interfering RNA and small hairpin RNA in NPM-ALK-expressing cells decreases cellular proliferation as evidenced by a reduced cell count in the G2/M phase of the cell cycle. Expression of NPM-ALK results in ERK1/2 activation and transcriptional up-regulation of JUNB. Both NPM-ALK-positive and -negative ALCL tumors demonstrate active ERK1/2 signaling. In contrast to NPM-ALK-negative ALCL, the mTOR pathway is active in NPM-ALK-positive lymphomas. Pharmacological inhibition of mTOR in NPM-ALK-positive cells down-regulates JunB protein levels by shifting JUNB mRNA translation from large polysomes to monosomes and ribonucleic particles (RNPs), and decreases cellular proliferation. Thus, JunB is a critical target of mTOR and is translationally regulated in NPM-ALK-positive lymphomas. This is the first study demonstrating translational control of AP-1 transcription factors in human neoplasia. In conjunction with NPM-ALK, JunB enhances cell cycle progression and may therefore represent a therapeutic target.

  3. Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method. (United States)

    Zhao, Jing; Zhao, Jin-Yin; Chen, Zhi-Xia; Zhong, Wei; Li, Long-Yun; Liu, Li-Cheng; Hu, Xiao-Xu; Chen, Wei-Jun; Wang, Meng-Zhao


    Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/μl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/μl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

  4. Cytological Diagnosis of Bilateral Breast Implant-Associated Lymphoma of the ALK-Negative Anaplastic Large-Cell Type. Clinical Implications of Peri-Implant Breast Seroma Cytological Reporting. (United States)

    Granados, Rosario; Lumbreras, Eva M; Delgado, Manuel; Aramburu, José A; Tardío, Juan C


    The cytological examination of peri-prosthetic breast effusions allowed the diagnosis of bilateral breast-implant ALK-negative anaplastic large cell lymphoma (BI-ALCL) in the case reported. Ten years after reconstructive surgery with bilateral breast implants, a large unilateral seroma developed and was cytologically analyzed. The presence of CD30 and CD4-positive large-sized atypical lymphoid cells exhibiting horseshoe-shaped nuclei and a brisk mitotic activity rendered the diagnosis of BI-ALCL. Similar cells were seen in the peri-prosthetic fluid intraoperatively collected from the contralateral breast. Although initial histological analysis of the capsulectomy specimens showed unilateral tumor, the cytological findings prompted a more thorough tissue sampling, resulting in the diagnosis of bilateral disease. BI-ALCL usually follows an indolent clinical course; however, there are reported cases with an aggressive behavior. While the presence of bilateral disease is a putative risk factor for a bad prognosis, the small number of cases reported precludes a definitive assessment of this risk. Since most BI-ALCL present with late seromas, cytologic analysis of these effusions in women with breast implants should be mandatory. Cytology is a safe tool for diagnosis and follow-up of patients with breast implant-related late seromas, sometimes proven more sensitive than histological analysis. Complete bilateral capsulectomy and a detailed histological analysis should follow a cytological diagnosis of BI-ALCL in a breast effusion in order to avoid false negative diagnoses. Our case constitutes the first published report of a bilateral BI-ALCL diagnosed by cytology. Diagn. Cytopathol. 2016;44:623-627. © 2016 Wiley Periodicals, Inc.

  5. 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.

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    Filipa Bernardino

    Full Text Available 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.

  6. Amberstripe scad Decapterus muroadsi (Carangidae) fish ingest blue microplastics resembling their copepod prey along the coast of Rapa Nui (Easter Island) in the South Pacific subtropical gyre. (United States)

    Ory, Nicolas Christian; Sobral, Paula; Ferreira, Joana Lia; Thiel, Martin


    An increasing number of studies have described the presence of microplastics (≤5mm) in many different fish species, raising ecological concerns. The factors influencing the ingestion of microplastics by fish remain unclear despite their importance to a better understanding of the routes of microplastics through marine food webs. Here, we compare microplastics and planktonic organisms in surface waters and as food items of 20 Amberstripe scads (Decapterus muroadsi) captured along the coast of Rapa Nui (Easter Island) to assess the hypothesis that fish ingest microplastics resembling their natural prey. Sixteen (80%) of the scad had ingested one to five microplastics, mainly blue polyethylene fragments that were similar in colour and size to blue copepod species consumed by the same fish. These results suggest that planktivorous fish, as a consequence of their feeding behaviour as visual predators, are directly exposed to floating microplastics. This threat may be exacerbated in the clear oceanic waters of the subtropical gyres, where anthropogenic litter accumulates in great quantity. Our study highlights the menace of microplastic contamination on the integrity of fragile remote ecosystems and the urgent need for efficient plastic waste management.

  7. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition. (United States)

    González-Alonso, Adrián; Ramírez-Tortosa, César L; Varela-López, Alfonso; Roche, Enrique; Arribas, María I; Ramírez-Tortosa, M Carmen; Giampieri, Francesca; Ochoa, Julio J; Quiles, José L


    An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

  8. The variable expressivity and incomplete penetrance of the twist-null heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome. (United States)

    Bourgeois, P; Bolcato-Bellemin, A L; Danse, J M; Bloch-Zupan, A; Yoshiba, K; Stoetzel, C; Perrin-Schmitt, F


    Most targeted gene mutations are recessive and analyses of gene function often focus on homozygous mutant phenotypes. Here we describe parts of the expression pattern of M-twist in the head of developing wild-type mice and present our analysis of the phenotype of heterozygous twist- null animals at around birth and in adults. A number of twist -null heterozygous mice present skull and limb defects and, in addition, we observed other malformations, such as defects in middle ear formation and the xyphoïd process. Our study is of interest to understand bone formation and the role of M-twist during this process, as within the same animal growth of some bones can be accelerated while for others it can be delayed. Moreover, we show here that expressivity of the mouse mutant heterozygous phenotype is dependent on the genetic background. This information might also be helpful for clinicians, since molecular defects affecting one allele of the human H-twist ( TWIST ) gene were identified in patients affected with Saethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable, although most patients present craniofacial and limb malformations resembling those seen in mutant mice. Thus the mutant mouse twist -null strain might be a useful animal model for SCS. The twist -null mutant mouse model, combined with other mutant mouse strains, might also help in an understanding of the etiology of morphological abnormalities that appear in human patients affected by other syndromes.

  9. Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

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    Amanda Natália Lucchesi


    Full Text Available Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC and 30 untreated diabetic (UD rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.

  10. A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome. (United States)

    Kim, Eun Na; Kim, Gu-Hwan; Kim, Jiyoon; Park, In Ah; Shin, Jin Ho; Chai, Yun; Kim, Kyu-Rae


    We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1-7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations.

  11. Narcissism Guides Mate Selection: Humans Mate Assortatively, as Revealed by Facial Resemblance, following an Algorithm of “Self Seeking Like”

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    Liliana Alvarez


    Full Text Available Theoretical studies suggest that mating and pair formation is not likely to be random. Computer simulations suggested that sex among genetically complex organisms requires mate choice strategies for its evolutionary maintenance, to reduce excessive genetic variance produced by out-crossing. One strategy achieving this aim efficiently in computer simulations is assortative mating modeled as “self seeking like”. Another one is selection of “good genes”. Assortative mating increases the probability of finding a genetically similar mate, without fomenting inbreeding, achieving assortative mating without hindering the working of other mate selection strategies which aim to maximize the search for “good genes”, optimizing the working of sex in evolutionary terms. Here we present indirect evidence that in a significant proportion of human reproductive couples, the partners show much higher facial resemblances than can be expected by random pair formation, or as the outcome of “matching for attractiveness” or the outcome of competition for the most attractive partner accessible, as had been previously assumed. The data presented is compatible with the hypothesis derived from computer simulations, that human mate selection strategies achieve various aims: “self seeking like” (including matching for attractiveness and mating with the best available genes.

  12. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

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    Carlos Wong-Baeza


    Full Text Available Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

  13. On the Issue of Education on Resembling Single-parent Family%类单亲家庭教育问题探究

    Institute of Scientific and Technical Information of China (English)



      The problem of resembling single-parent families may be more serious because of their recessive state. Family, social and schools should be full cooperation to reduce the adverse effects of sin-gle-parent families. According to the common question, we can orga-nize the schools for parents, purify socio-cultural, tell children how to interact in a bid to develop better and not let the occupational factors and the living conditions of the parents affecting a child's development.%  类单亲家庭教育问题因其隐性存在结果可能更为严重。家庭社会学校应该加强合作减少类单亲家庭的不良影响。针对比较常见的教育问题,可以从举办家长学校、净化社会文化、教会孩子交往等方面入手,培养身心健康的孩子,尽量不让家长的职业因素和生活状态影响到孩子的发展。

  14. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Directory of Open Access Journals (Sweden)

    Adrián González-Alonso


    Full Text Available An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

  15. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation. (United States)

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars


    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  16. Inhibitory serpins from wheat grain with reactive centers resembling glutamine-rich repeats of prolamin storage proteins. Cloning and characterization of five major molecular forms. (United States)

    Ostergaard, H; Rasmussen, S K; Roberts, T H; Hejgaard, J


    Genes encoding proteins of the serpin superfamily are widespread in the plant kingdom, but the properties of very few plant serpins have been studied, and physiological functions have not been elucidated. Six distinct serpins have been identified in grains of hexaploid bread wheat (Triticum aestivum L.) by partial purification and amino acid sequencing. The reactive centers of all but one of the serpins resemble the glutamine-rich repetitive sequences in prolamin storage proteins of wheat grain. Five of the serpins, classified into two protein Z subfamilies, WSZ1 and WSZ2, have been cloned, expressed in Escherichia coli, and purified. Inhibitory specificity toward 17 proteinases of mammalian, plant, and microbial origin was studied. All five serpins were suicide substrate inhibitors of chymotrypsin and cathepsin G. WSZ1a and WSZ1b inhibited at the unusual reactive center P(1)-P(1)' Gln-Gln, and WSZ2b at P(2)-P(1) Leu-Arg-one of two overlapping reactive centers. WSZ1c with P(1)-P(1)' Leu-Gln was the fastest inhibitor of chymotrypsin (k(a) = 1.3 x 10(6) m(-1) s(-1)). WSZ1a was as efficient an inhibitor of chymotrypsin as WSZ2a (k(a) approximately 10(5) m(-1) s(-1)), which has P(1)-P(1)' Leu-Ser-a reactive center common in animal serpins. WSZ2b inhibited plasmin at P(1)-P(1)' Arg-Gln (k(a) approximately 10(3) m(-1) s(-1)). None of the five serpins inhibited Bacillus subtilisin A, Fusarium trypsin, or two subtilisin-like plant serine proteinases, hordolisin from barley green malt and cucumisin D from honeydew melon. Possible functions involving interactions with endogenous or exogenous proteinases adapted to prolamin degradation are discussed.

  17. Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme. (United States)

    Casarini, D E; Plavinik, F L; Zanella, M T; Marson, O; Krieger, J E; Hirata, I Y; Stella, R C


    Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.

  18. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. (United States)

    Balan, Sreekumar; Ollion, Vincent; Colletti, Nicholas; Chelbi, Rabie; Montanana-Sanchis, Frédéric; Liu, Hong; Vu Manh, Thien-Phong; Sanchez, Cindy; Savoret, Juliette; Perrot, Ivan; Doffin, Anne-Claire; Fossum, Even; Bechlian, Didier; Chabannon, Christian; Bogen, Bjarne; Asselin-Paturel, Carine; Shaw, Michael; Soos, Timothy; Caux, Christophe; Valladeau-Guilemond, Jenny; Dalod, Marc


    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.

  19. 子宫性索样肿瘤临床病理观察%Clinicopathologic features of uterine tumor resembling ovarian sex-cord-like tumors

    Institute of Scientific and Technical Information of China (English)



    Objective:To investigate the clinicopathological features of uterine tumor resembling ovarian sex-cord tumor review and its behaviour prognsis. Methods:The clinicopathological data was analysed in 3 case of uterine sex cord-like tumors with review of the literature. Results:The tumor cells were arranged in sheets with formation of small cords, trabeculaes, or solid tubules structures. The tumor cells expressed the most recently identified marks of sex cord defferentiation (calretinin, Melan A, CD99, and inhibin) and smooth muscle (desmin and smooth muscle actin), with coexpression of cytokeratin. Conclusion:The unusual uterine sex cord-like tumors are polyphenotypic neoplasms with true sex cord differentiation ,whose definite diagnosis should be based on the histopathological and immunohistochemical feature to exclude other tumor.%目的:探讨子宫性索样肿瘤的临床病例特征、生物学行为及预后。方法:分析3例子宫性索样肿瘤的临床和病理资料,并复习相关文献。结果:肿瘤细胞排列呈小索状、小条状、实性管状结构。免疫组化染色显示肿瘤细胞表达性索标记(calretinin、Melan A、CD99和inhibin)、平滑肌和上皮标记。结论:子宫性索样肿瘤是少见的含真正性索成分的多表型肿瘤,确诊依赖于病理形态特点及免疫组化标记。

  20. Sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines

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    Lam Wan L


    Full Text Available Abstract Background Hodgkin lymphoma (HL and Anaplastic Large Cell Lymphoma (ALCL, are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428 and ALCL cell lines (DEL and SR-786 in order to identify disease-associated gene copy number gains and losses. Results Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55% were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45% were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23. Conclusion This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3 in KMH2 and L428 (HL and DEL (ALCL cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling

  1. The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide (United States)

    Abuali, Inas; Ye, Xiaobu; Lu, Yao; Grossman, Stuart A.


    Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan–Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23–43). Survival was longer in the post-2004 cohort (37 mo, 24–64) than pre-2004 (27 mo, 19–40; HR 0.75, 0.53–1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44–0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA

  2. Anaplastic lymphoma kinase gene alteration in gastric signet ring cell carcinoma%间变性淋巴瘤激酶融合基因在胃印戒细胞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    赵瑞华; 姜文静; 张伟杰; 周亚楠; 宗红


    目的 观察间变性淋巴瘤激酶(ALK)融合基因在胃印戒细胞癌患者中的表达,探讨ALK融合基因与胃癌临床病理的关系.方法 搜集177例我院病理检查确诊的胃印戒细胞癌患者的组织标本,采用免疫组织化学染色(IHC)法观察ALK蛋白的表达.随后,针对ALK蛋白阳性的病理标本,采用荧光原位杂交技术(FISH)验证其ALK基因重排.结果 IHC显示177例胃印戒细胞癌中4例(2.3%)ALK蛋白表达阳性.4例ALK蛋白表达阳性的患者FISH检测均为阳性.结论 IHC及FISH为检测胃印戒细胞癌ALK表达的可靠方法,ALK阳性的胃印戒细胞癌患者的肿瘤浸润性可能更强,确诊时淋巴结阳性率高,人类表皮生长因子受体-2 (HER-2)多为阴性.%Objective To investigate the frequency of anaplastic lymphoma kinase (ALK) alterations in patients with gastric signet ring cell carcinoma (SRC) and the correlations between ALK alterations and the clinicopathological features.Methods The expression of ALK protein was determined in paraffin-embedded tissue specimens (FFPE) from 177 pathologically confirmed SRC patients by Ventana immunohistochemistry (IHC).The patients with positive ALK detected by IHC were assayed in ALK rearrangement by fluorescence in situ hybridization (FISH).Results We assessed 4 of 177 cases (2.3%) as positive by IHC.Three of the 4 patients had T4 tumors and positive nodal status,and rest one had metastasis.All of them were human epidermalgrowth factor receptor-2 (HER-2) negative.All of the 4 patients were positive for ALK rearrangement using the standard criteria of FISH.Conclusion Ventana IHC and FISH were both of the reliable approaches in SRC patients.Patients with positive ALK seemed to have deep infiltration and positive lymph nodes and negative HER-2.

  3. mRNA decay proteins are targeted to poly(A+ RNA and dsRNA-containing cytoplasmic foci that resemble P-bodies in Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Itzel López-Rosas

    Full Text Available In higher eukaryotes, mRNA degradation and RNA-based gene silencing occur in cytoplasmic foci referred to as processing bodies (P-bodies. In protozoan parasites, the presence of P-bodies and their putative role in mRNA decay have yet to be comprehensively addressed. Identification of P-bodies might provide information on how mRNA degradation machineries evolved in lower eukaryotes. Here, we used immunofluorescence and confocal microscopy assays to investigate the cellular localization of mRNA degradation proteins in the human intestinal parasite Entamoeba histolytica and found evidence of the existence of P-bodies. Two mRNA decay factors, namely the EhXRN2 exoribonuclease and the EhDCP2 decapping enzyme, were localized in cytoplasmic foci in a pattern resembling P-body organization. Given that amoebic foci appear to be smaller and less rounded than those described in higher eukaryotes, we have named them "P-body-like structures". These foci contain additional mRNA degradation factors, including the EhCAF1 deadenylase and the EhAGO2-2 protein involved in RNA interference. Biochemical analysis revealed that EhCAF1 co-immunoprecipitated with EhXRN2 but not with EhDCP2 or EhAGO2-2, thus linking deadenylation to 5'-to-3' mRNA decay. The number of EhCAF1-containing foci significantly decreased after inhibition of transcription and translation with actinomycin D and cycloheximide, respectively. Furthermore, results of RNA-FISH assays showed that (i EhCAF1 colocalized with poly(A(+ RNA and (ii during silencing of the Ehpc4 gene by RNA interference, EhAGO2-2 colocalized with small interfering RNAs in cytoplasmic foci. Our observation of decapping, deadenylation and RNA interference proteins within P-body-like foci suggests that these structures have been conserved after originating in the early evolution of eukaryotic lineages. To the best of our knowledge, this is the first study to report on the localization of mRNA decay proteins within P

  4. Primary anaplastic large T cell lymphoma of central nervous system%中枢神经系统原发性间变性大细胞淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    刘腾飞; 韩慧霞; 黎相照; 张彦


    研究背景 中枢神经系统原发性间变性大细胞淋巴瘤可发生于各年龄阶段,通常与免疫缺陷无关,临床及影像学检查易误诊为脑膜炎症性病变,尤其是结核性脑膜炎.而在病理诊断上,形态与中枢神经系统以外的间变性大细胞淋巴瘤相似,间变性淋巴瘤激酶1 可呈阳性或阴性.由于易误诊为脑膜炎而于组织活检前应用糖皮质激素治疗,造成组织学观察呈现大片坏死,以及大量组织细胞增生和吞噬现象,故在取材不够全面时易误诊为脑梗死或恶性组织细胞增生性疾病等.本文结合1 例12 岁中枢神经系统原发性间变性大细胞淋巴瘤患儿的临床资料,通过相关文献回顾,总结该病发病特点和临床表现,以提高临床及病理医师对该病的认识.方法 与结果12 岁男性患儿,临床表现为发热、头痛,伴右侧肢体麻木、无力.MRI 检查右侧顶叶局部脑回肿胀及软脑膜异常强化,并累及右侧颞叶;左侧顶叶软脑膜异常强化.右侧颞顶叶病变组织活检肿瘤细胞体积较大且形态不规则,胞质丰富、嗜伊红,可见马蹄形和肾形核.免疫组织化学检测肿瘤细胞CD3、CD45RO、CD30、间变性淋巴瘤激酶1 和上皮膜抗原表达阳性,CD20 和CD79a 表达阴性.结论 间变性大细胞淋巴瘤是中枢神经系统的罕见病理亚型,临床及影像学极易误诊为脑膜炎症性病变.因此,对临床考虑为脑膜炎,但治疗效果差、病情反复的患者,应尽早进行脑组织活检或反复脑脊液细胞学检查,尤其是脑组织活检为明确诊断之重要手段.%Background Primary anaplastic large T cell lymphoma (ALCL) of central nervous system (CNS) can occur in people of all ages, and is usually unrelated with immunodeficiency. It is often misdiagnosed as meningitis, especially tuberculous meningitis, on clinical practice and imaging examination. In pathological diagnosis, the morphological changes of primary ALCL of CNS

  5. 芝麻染色体核型及似近系数分析%Analysis of Sesame Karyotype and Resemblance-near Coefficient

    Institute of Scientific and Technical Information of China (English)

    张海洋; 苗红梅; 李春; 魏利斌; 马琴


    芝麻(Sesamum indicum L.)是世界上最古老的油料作物之一,在植物进化中具有重要地位.以8个二倍体栽培种、4个四倍体栽培种以及2个野生种S.radiatum Schum & Thonn和S.schinzianum Asch.为材料,比较分析了芝麻不同种的核型特征.结果表明:栽培种与野生种的核型及结构具有明显的差异,栽培种的着丝点类型有m、sm和st,臂比均值(AAR)为2.11-2.25,核型不对称系数(AKC)为66.05%-66.99%,核型分2B、3A和3B三类;野生种S.radiatum和S.schinzianum仅有M和m两种着丝点类型,AAR值分别为1.09和1.08,AKC为52.12%和51.68%,核型分1B和1A两类.核型聚类结果表明,野生种与栽培种的似近系数范围介于0.027-0.107之间,亲缘关系较远;与地理来源相比,种皮颜色能够显示不同种间的进化地位,推测芝麻进化方向为野生种→栽培种黑芝麻→栽培种白芝麻.%Sesame is one of the oldest oil crops and has an important place in plant evolution. We compared the chromosome types and karyotypes of 8 diploid and 4 tetraploid materials of Sesamum indicum L. and 2 wild species, S. ra-diatum Schum & Thonn and S. schinzianum Asch. The species significantly differed in karyotype and chromosome variables. S. indicum centromere types were m, sm and st; the average arm ratio (AAR) was 2.11 to 2.25, asymmetric karyotype coefficients (AKC) were 66.05% to 66.99%, and the karyotypes belonged to 2B, 3A and 3B. However, S. ra-diatum and S. schinzianum exhibited only M and m centromere types; the AAR was 1.09 and 1.08, respectively; AKC was 52.12% and 51.68%, respectively; and karyotypes were 1B and 1A, respectively. Karyotype clustering revealed that the resemblance-near coefficient between S. indicum and the wild species was 0.027 to 0.107, which indicates a remote genetic relationship. Furthermore, seed coat color was more suitable for sesame evolution estimation than was geographic origin. The evolution direction of sesame was from wild species to

  6. 皮肤原发性CD30阳性间变性大细胞淋巴瘤%Primary cutaneous CD30-positive anaplastic large cell lymphoma analysis

    Institute of Scientific and Technical Information of China (English)

    石群立; 周晓军; 燕晓雯; 印洪林; 徐新宇; 张彤; 社本擀博; 钱斌


    目的对10例皮肤原发性CD30阳性间变性大细胞淋巴瘤(ALCL)进行临床及组织病理学研究,为临床病理早期诊断提供依据.方法采用组织病理学及免疫组织化学法(LCA、 CD20、CD30、CD45RO、CD68、EMA、CK和HMB45)对10例皮肤原发性CD30阳性ALCL进行观察.结果组织病理学示瘤细胞体积大,呈多形性、圆形或椭圆形,胞浆丰富,核大,核分裂像多,常见R-S样细胞和多核巨细胞,核仁明显.免疫组化标记CD30 阳性,其中6例同时表达CD45RO, 1例表达CD20,非T非B表达3例.随访发现2例因肿瘤转移死亡,2例复发,6例无复发.结论皮肤原发性CD30阳性ALCL是具有独特形态特点且预后较好的肿瘤.组织病理学特征及CD30阳性在鉴别诊断时具有重要意义.%Objective To examine 10 cases with primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL), analyze their clinical manifestations and pathological and immunohistochemical features, and improve early diagnosis of this disease. Methods We studied the morphological characteristics of primary cutaneous CD30-positive ALCL using histopathological methods. Leukocyte common antigen (LCA), CD20, CD30, CD45RO, CD68, epithelial membrane antigen (EMA), cytokeratin (CK) and HMB45 antibodies were used to determine the expression of their respective antigens from routine paraffin samples of the patients. Results Ten patients (7 men and 3 women, aged 31 to 84 years) complained of subcutaneous masses or papular eruptions over their lower trunks and extremities. Histopathologically, the lesions were composed of numerous large round or oval pleomorphic cells. The cytoplasm was usually abundant, amphophilic or basophilic, and finely vacuolated. Nuclei were commonly eccentrically localized and lobated or horseshoed in shape, and multinucleated giant cells and Reed-Sternberg-like cells were seen. Nucleoli were generally multiple and large. Of the 10 patients, tumor cells displayed positive antigen

  7. Anaplastic lymphoma kinase-positive adenocarcinoma of lung:a cytopathologic analysis%间变性淋巴瘤激酶阳性肺腺癌细胞病理学特点初探

    Institute of Scientific and Technical Information of China (English)

    陈颖; 杨文韬; 宋以菊; 曾欢; 张静; 柏乾明; 周晓燕; 平波; 高丽丽; 王彦丽; 桂贤; 张皓; 王龙富; 顾良宏; 冯丽青; 吴佳文


    Objective To study the cytomorphologic features of anaplastic lymphoma kinase ( ALK )-rearranged pulmonary adenocarcinoma.Methods The morphologic features in 153 pulmonary adenocarcinoma cytology specimens encountered during the period from September, 2011 to April, 2015 in Shanghai Cancer Hospital were retrospectively reviewed.Fluorescence in-situ hybridization ( FISH) and/or immunohistochemistry ( Ventana D5F3) for ALK gene rearrangement were carried out.The samples studied included 34 pleural effusion specimens, 40 endobronchial ultrasound-guided transbronchial needle aspirates ( EBUS-TBNA) and 79 fine needle aspirates of palpable masses on body surface.Results Thirty-nine cases (25.5%) of ALK-rearranged samples were identified by FISH and/or immunohistochemistry, including 3 cases diagnosed by FISH and 36 cases by both technologies.The median age of the ALK-positive group was 50 years, significantly younger than that of the ALK-negative group (60 years old,P=0.002) .Only 4 of the ALK-positive patients were smokers, which was significantly less than that of the ALK-negative group (P<0.01).In ALK-positive group, 3 cases showed cribriform pattern with prominent nucleoli, 3 cases showed cribriform pattern with mucin-rich cells and 8 cases showed extracellular mucus with mucin-rich cells.The above cytomorphologic patterns were significantly less common in ALK-negative tumors ( P <0.01 ) . Conclusions ALK-rearranged lung adenocarcinoma is associated with certain distinctive morphologic patterns, including cribriform architecture, presence of prominent nucleoli, mucin-rich cells and extracellular mucus, which can be observed in cytology specimens ( including conventional smears and cell block sections) .These findings, when combined with clinical features, may give clues to detection of ALK-positive cases.%目的探讨间变性淋巴瘤激酶( ALK)基因重排阳性肺腺癌的细胞病理学特点。方法回顾性分析2011年9月至2015年4月在复旦大学

  8. Clinicopathological features of lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangements%间变性淋巴瘤激酶融合基因阳性肺腺癌的临床病理特征

    Institute of Scientific and Technical Information of China (English)

    董宇杰; 周立娟; 王敬慧; 蔡毅然; 穆晶; 张海青


    Objective To analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase( ALK) rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients. Methods Clinicopathological data of 34 cases of ALK⁃positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistochemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method. Results Among the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage ⅠA in 5 patients,ⅠB in one patient,ⅡA in two patients,ⅢA in 16 patients,ⅢB in 5 patients,Ⅳin 4 patients, and one patient of unknown stage. ALK⁃positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with mucin production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet⁃ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation ( L858R at exon 21) . Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months (1.7⁃48.7 months). Conclusions ALK⁃positive tumors as a molecular subtype of lung adenocarcinoma have distinct clinicopathological features. The histological findings of ALK⁃positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet⁃ring cells and cribriform structures. They were rarely co⁃mutated with EGFR mutation.%目的:探讨间变性淋巴瘤激酶( ALK)融合基因阳性肺腺癌的临床病理特征

  9. 卵巢类似性索-间质肿瘤子宫内膜样腺癌临床病理观察%Ovarian endometrioid adenocarcinoma resembling sex-cord tumors: a chlincopathologic study

    Institute of Scientific and Technical Information of China (English)

    马怡晖; 赵庆夏; 李惠翔


    目的 探讨卵巢类似性索-间质肿瘤子宫内膜样腺癌(ovarian endometrial carcinoma resembling sex cord-stromal tumor,ECSCS)的临床病理特征、免疫表型和鉴别诊断.方法 对1例ECSCS进行HE和免疫组化SP染色,并复习相关文献.结果 镜检:肿瘤90%以上区域由胞质透亮的梭形或短梭形细胞构成,其内混有实性条索状或中空小管样结构,类似Sertoli细胞肿瘤;仅有不到10%的区域表现为经典的子宫内膜样腺癌.免疫表型:肿瘤细胞弥漫表达CK、CK7、EMA、ER,不表达α-inhibin、PLAP以及CA125.结论 ECSCS与卵巢性索-间质肿瘤在形态上易混淆.在组织充分取材的基础上仔细寻找镜下经典的子宫内膜样腺癌的结构并结合免疫表型,有助于诊断.%Purpose To investigate the clinicopathological features, immunophenotype and differential diagnosis of ovarian endometrial carcinoma resembling sex cord-stromal tumor ( ECSCS ). Methods One case of ECSCS was studied by HE and immunohistochemical staining and the literatures were reviewed. Results Microscopically, more than 90% of the tumor was composed of spindle/short-spindle cells with clear cytoplasma, which were mixed with solid sheets or some tubular structures resembling Sertoli cell tumor. Less than 10% of the tumor showed typical morphology of endometrioid adenocarcinoma. Immunohistochemical staining demonstrated the tumor cells were diffusely positive for CK, CK7, EMA, ER, while negative for a-inhibin, PLAP and CA125. Conclusions Morphologically , ESCSC is easily confused with ovarian sex-cord tumour. To carefully observe the mass, take enough tissue samples, seek the clue of classical endometrioid adenocarcinoma and employ the necessary immunohistochemical staining is very useful to reach a correct diagnosis.

  10. Coronary fistula resembling patent ductus arteriosus

    Directory of Open Access Journals (Sweden)

    Sgarbieri Ricardo Nilsson


    Full Text Available A 14-year-old girl, presenting with heart failure and a continuous murmur, similar to that of a patent arterial duct, was investigated using echocardiogram and cardiac catheterization revealing a left to right shunt throught a coronary artery fistulae between the first septal branch and the right ventricular outflow tract. The patient was submitted to surgery, occluding the anomalous branch by the suturing of its orifice in the right ventricular outflow tract, under cardiopulmonary bypass. After the operation, cardiac catheterization revealed complete occlusion of the fistula without any residual shunt or compromise to the coronary circulation. In seven years of follow-up the patient is completely free of symptoms.

  11. Family Resemblance in Attitudes to Foods. (United States)

    Rozin, Paul; And Others


    Compares young adults with their parents and explores food preferences and attitudes to food, especially sensitivity to cleanliness and contamination of foods. Results indicate small positive parent-child correlations for food preferences but larger correlations for contamination sensitivity. (Author/AS)

  12. Sullys Hill herd resembles original plains bison (United States)

    US Fish and Wildlife Service, Department of the Interior — This article is on recent findings on Sullys Hill National Game Preserve that show bison brought there nearly a century ago have remained closer to genetically pure...

  13. Primary laryngeal cryptococcosis resembling laryngeal carcinoma. (United States)

    Tamagawa, Shunji; Hotomi, Muneki; Yuasa, Jun; Tuchihashi, Shigeki; Yamauchi, Kazuma; Togawa, Akihisa; Yamanaka, Noboru


    A case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. Histological examination showed pseudoepitheliomatous hyperplasia and severe submucosal inflammation with ovoid budding yeasts by Grocott's stain. A serological study indicated a high titer of cryptococcal antigen. After treating with oral fluconazole for 3 months, her primary lesion of larynx turned to be clear. We implicate a long-term use of steroids as the significant risk factor in developing cryptococcosis of the larynx.

  14. Rat Bite Fever Resembling Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ripa Akter


    Full Text Available Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated.

  15. Detecting Family Resemblance: Automated Genre Classification

    Directory of Open Access Journals (Sweden)

    Yunhyong Kim


    Full Text Available This paper presents results in automated genre classification of digital documents in PDF format. It describes genre classification as an important ingredient in contextualising scientific data and in retrieving targetted material for improving research. The current paper compares the role of visual layout, stylistic features, and language model features in clustering documents and presents results in retrieving five selected genres (Scientific Article, Thesis, Periodicals, Business Report, and Form from a pool of materials populated with documents of the nineteen most popular genres found in our experimental data set.

  16. Crystal structure of YwpF from Staphylococcus aureus reveals its architecture comprised of a β-barrel core domain resembling type VI secretion system proteins and a two-helix pair. (United States)

    Lee, Sang Jae; Lee, Kyu-Yeon; Lee, Ki-Young; Kim, Dong-Gyun; Kim, Soon-Jong; Lee, Bong-Jin


    The ywpF gene (SAV2097) of the Staphylococcus aureus strain Mu50 encodes the YwpF protein, which may play a role in antibiotic resistance. Here, we report the first crystal structure of the YwpF superfamily from S. aureus at 2.5-Å resolution. The YwpF structure consists of two regions: an N-terminal core β-barrel domain that shows structural similarity to type VI secretion system (T6SS) proteins (e.g., Hcp1, Hcp3, and EvpC) and a C-terminal two-helix pair. Although the monomer structure of S. aureus YwpF resembles those of T6SS proteins, the dimer/tetramer model of S. aureus YwpF is distinct from the functionally important hexameric ring of T6SS proteins. We therefore suggest that the S. aureus YwpF may have a different function compared to T6SS proteins.

  17. 灰色相似性栽培理论在杂交稻宜香481配套栽培中的应用%Application of Grey Resemblance Cultivation Theory in Systematic Cultivation of Yixiang481

    Institute of Scientific and Technical Information of China (English)

    严明建; 雷树凡; 胡景涛; 黄文章; 吕直文; 黄成志; 蒲云升


    为了加快新品种的推广应用,通过灰色相似性栽培原理,以17个已有成熟的配套栽培措施的品种为材料,研究了新品种宜香481的高产栽培配套技术。结果表明:宜香481与K优88的各性状指标最为相似,在K优88栽培技术方案的基础上,结合宜香481的特征特性进行简单改良,建立了一套适应宜香481的高产栽培技术方案;且通过2009~2011年连续3 a的生产示范,增产效果显著,平均单产达到9694.5 kg/hm2,比对照区平均增产5.2%,最高产量达9936 kg/hm2。这表明通过灰色相似性栽培原理,来指导水稻新品种利用已有栽培技术实现良种与良法配套是切实可行的。%To promote the popularization and application of new varieties, the high-yielding systematic cultivation technique of new rice variety Yixiang481 was explored based on the grey resemblance cultivation theory, and 17 rice varieties which have mature systematic cultivation technique were taken as comparative materials. The results showed that each character of Yixiang481 were the most similar with that of Kyou88, thus a set of high-yielding systematic cultivation technique for Yixiang481 was established based on the cultivation technique of Kyou88 but simply modified according to the characteristics of Yixiang481. With the high-yielding systematic cultivation technique, Yixiang481 showed a significant yield increasing effect in the production tests from 2009 to 2011, the average yield per unit area reached 9 694.5 kg/hm 2, which average increased by 5.2% in comparison with control area; the highest yield was up to 9 936 kg/hm 2. Therefore, it is feasibility that using grey resemblance cultivation theory to find a suitable systematic cultivation technique for new rice variety based on present cultivation techniques.

  18. AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors (United States)


    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

  19. Clinicopathologic features of uterine tumor resembling ovarian sex-cord tumor%伴性索分化的低度恶性子宫内膜间质肉瘤1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    高福平; 夏月华; 魏谨; 马平


    Objective:To investigate the clinicopathological features of uterine tumor resembling ovarian sex - cold tumor( UTROSCT) and its behaviour and prognosis. Methods: The clinical data was analysed of one case of UTROSCT with review of the literature. Results: Microscopically, the tumor cells were arranged in sheets with forma-tion of small cords, trabeculaes, or solid tubules structures. The tumor cells grew in diffusely infiltrative fashion that in-vaded the myometrium . Immunohistochemically,the cells showed positive for CD10.ER . Ki - 67 labelling index was about 10% . But the cells showed negative for inhibin, MelanA, PAX - 5, Desmin and SMA. Conclusion: UTROSCT is a very rare tumor, definite diagnosis should be based on the histopathological and immunohistochemical features . Its clinical manifestation should also be taken into account.%目的:探讨伴性索分化的低度恶性子宫内膜间质肉瘤的临床病理特征、生物学行为及预后.方法:对1例伴性索分化的低度恶性子宫内膜间质肉瘤的临床、病理和免疫学表型进行观察、分析及文献复习.结果:结合组织学特点及免疫组化结果,诊断为伴性索分化的低度恶性子宫内膜间质肉瘤.结论:伴性索分化的低度恶性子宫内膜间质肉瘤是一种极其少见的现象.其诊断依赖于组织病理学、免疫组化,并须结合其临床资料.

  20. Tomato yellow leaf curl Sardinia virus-resistant tomato plants expressing the multifunctional N-terminal domain of the replication-associated protein show transcriptional changes resembling stress-related responses. (United States)

    Lucioli, Alessandra; Berardi, Alessandra; Gatti, Francesca; Tavazza, Raffaela; Pizzichini, Daniele; Tavazza, Mario


    The N-terminal domain (amino acids 1-130) of the replication-associated protein (Rep130 ) of Tomato yellow leaf curl Sardinia virus (TYLCSV) retains the ability of full-length Rep to localize to the nucleus and to down-regulate C1 transcription when ectopically expressed in plants, both functions being required to inhibit homologous viral replication. In this study, we analysed the effect of Rep130 expression on virus resistance and the plant transcriptome in the natural and agronomically important host species of TYLCSV, Solanum lycopersicum. Tomato plants accumulating high levels of Rep130 were generated and proved to be resistant to TYLCSV. Using an in vitro assay, we showed that plant-expressed Rep130 also retains the catalytic activity of Rep, thus supporting the notion that this protein domain is fully functional. Interestingly, Rep130 -expressing tomatoes were characterized by an altered transcriptional profile resembling stress-related responses. Notably, the serine-type protease inhibitor (Ser-PI) category was over-represented among the 20 up-regulated genes. The involvement of Rep130 in the alteration of host mRNA steady-state levels was confirmed using a distinct set of virus-resistant transgenic tomato plants expressing the same TYLCSV Rep130 , but from a different, synthetic, gene. Eight genes were found to be up-regulated in both types of transgenic tomato and two encoded Ser-PIs. Four of these eight genes were also up-regulated in TYLCSV-infected wild-type tomato plants. Implications with regard to the ability of this Rep domain to interfere with viral infections and to alter the host transcriptome are discussed.

  1. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors.

    Directory of Open Access Journals (Sweden)

    Michael C Burger

    Full Text Available Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV. This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma. In these patients progression-free survival (PFS intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.

  2. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors. (United States)

    Burger, Michael C; Zeiner, Pia S; Jahnke, Kolja; Wagner, Marlies; Mittelbronn, Michel; Steinbach, Joachim P


    Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.

  3. The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67phox (United States)

    Bechor, Edna; Dahan, Iris; Fradin, Tanya; Berdichevsky, Yevgeny; Zahavi, Anat; Rafalowski, Meirav; Federman-Gross, Aya; Pick, Edgar


    The superoxide (O2.-)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b558 (a heterodimer of Nox2 and p22phox), and four cytosolic components, p47phox, p67phox, p40phox, and Rac. The catalytic component, responsible for O2.- generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytosolic components, principally with p67phox. Using a peptide-protein binding assay, we found that Nox2 peptides containing a 369CysGlyCys371 triad (CGC) bound p67phox with high affinity, dependent upon the establishment of a disulfide bond between the two cysteines. Serially truncated recombinant Nox2 DHR proteins bound p67phox only when they comprised the CGC triad. CGC resembles the catalytic motif (CGHC) of protein disulfide isomerases (PDIs). This led to the hypothesis that Nox2 establishes disulfide bonds with p67phox via a thiol-dilsulfide exchange reaction and, thus, functions as a PDI. Evidence for this was provided by the following: 1. Recombinant Nox2 protein, which contained the CGC triad, exhibited PDI-like disulfide reductase activity; 2. Truncation of Nox2 C-terminal to the CGC triad or mutating C369 and C371 to R, resulted in loss of PDI activity; 3. Comparison of the sequence of the DHR of Nox2 with PDI family members revealed three small regions of homology with PDIA3; 4. Two monoclonal anti-Nox2 antibodies, with epitopes corresponding to regions of Nox2/PDIA3 homology, reacted with PDIA3 but not with PDIA1; 5. A polyclonal anti-PDIA3 (but not an anti-PDIA1) antibody reacted with Nox2; 6. p67phox, in which all cysteines were mutated to serines, lost its ability to bind to a Nox2 peptide containing the CGC triad and had an impaired capacity to support oxidase activity in vitro. We propose a model of oxidase assembly in which binding of p67phox to Nox2 via disulfide bonds, by virtue of the intrinsic PDI activity of Nox2, stabilizes the primary interaction between the two components.

  4. The historic Proton Synchrotron (PS) control room is about to start a new life. Opened by Niels Bohr in 1960, the room will be reused by CMS to built its control centre. When finished, it will resemble the CERN Control Centre for LHC operations, located in Prevessin.

    CERN Multimedia

    Husi C.


    The historic Proton Synchrotron (PS) control room is about to start a new life. Opened by Niels Bohr in 1960, the room will be reused by CMS to built its control centre. When finished, it will resemble the CERN Control Centre for LHC operations, located in Prevessin.

  5. Osteossarcoma de mandíbula inicialmente mimetizando lesão do periápice dental: relato de caso Osteosarcoma of mandible initially resembling lesion of dental periapex: a case report

    Directory of Open Access Journals (Sweden)

    Rosilene C. Soares


    the dental periapex, the patient initially underwent endodontic treatment of the tooth involved. Thereafter, in a period of eleven days, a significant increase of the lesion could be observed, resulting in visible facial asymmetry. The occlusal radiographic view showed an area of bone destruction and abnormal bone formation in the region. The external cortical portion showed clear radiopacity resembling sunrays, suggesting the diagnosis of osteosarcoma. The treatment comprised partial mandibulectomy and reconstruction of the area, using bone of the rib and skin graft from the buttock for the oral mucosa involved. Eight months after surgery, there was local recurrence of the lesion and the patient died approximately one year after relapse.

  6. RNAi阻断NPM-ALK基因表达及对大细胞间变性淋巴瘤细胞的影响%Effects of RNA interference on NPM-ALK fusion gene expression in anaplastic large-cell lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    赵艳霞; 顾龙君; 叶启东; 赵金彩


    目的应用RNA干扰技术抑制大细胞间变性淋巴瘤细胞系(Karpas299)中NPM-ALK融合基因表达,观察其对肿瘤细胞生长的影响.方法针对NPM-ALK融合位点设计两个siRNA序列siRNA-I与siRNA-II, 经PCR反应构建含U6启动子siRNA正义和反义线性表达载体,通过脂质体转染Karpas299细胞,应用实时荧光定量RT-PCR、Western blot检测siRNA片段对NPM-ALK mRNA和蛋白表达的抑制作用,MTT、Hoechst荧光染色检测siRNA对肿瘤细胞生长的影响.结果 siRNA-I可导致NPM-ALK mRNA下降约75%(P<0.05),转染72 h后可导致蛋白表达下降;转染siRNA-II细胞NPM-ALK mRNA下降为35%(P<0.05),但蛋白水平无明显改变.转染siRNA-I的细胞可抑制Karpas299细胞的增殖和诱导凋亡发生,siRNA-II则无明显的抑制增殖和诱导凋亡作用.结论含有针对NPM-ALK融合位点特异siRNA序列 的U6表达载体,可特异地抑制NPM-ALK基因mRNA和蛋白的表达,并能抑制大细胞间变性淋巴瘤肿瘤细胞株Karpas299细胞的增殖,导致肿瘤细胞凋亡增加,提示NPM-ALK融合基因的异常表达与大细胞间变性淋巴瘤形成密切相关,为研究NPM-ALK基因功能和大细胞间变性淋巴瘤基因靶向治疗提供了新策略.%Objective To evaluate two small interfering RNAs (siRNAs) on the NPM-ALK fusion gene expression in anaplastic large-cell lymphoma cell line Karpas299, and to study the effect of RNA interference on Karpas299 cells proliferation. Methods Two siRNAs sequences (siRNA- I and siRNA-II) were designed to target the NPM-ALK fusion site in anaplastic large-cell lymphoma cell line Karpas299. An siRNA U6 expression system including U6 RNA-based polymerase III promoter was set up. The two siRNAs designed for down-regulation of the NPM-ALK fusion mRNA were transfected into Karpas299 cells by liposomal transfection reagents. The effect of RNAi on NPM-ALK mRNA expression was detected by real-time RT-PCR and Western blot. The anti-proliferative effects of the si

  7. Therapy-related myelodysplastic syndrome/acute myeloid leukemia after treatment with temozolomide in a patient with glioblastoma multiforme. (United States)

    Kim, Sue Jung; Park, Tae Sung; Lee, Seung Tae; Song, Jaewoo; Suh, Borum; Kim, Se Hoon; Jang, Seon Jung; Lee, Chang Hoon; Choi, Jong Rak


    Therapy-related myelodysplastic syndrome and acute leukemia after treatment with temozolomide have rarely been described in the literature. Only 10 cases in association with temozolomide have been documented. The cases included anaplastic astrocytoma (4 cases), anaplastic oligodendroglioma (2 cases), low grade astrocytoma (2 cases), low grade oligodendroglioma (1 case), and one case of secondary Philadelphia-positive acute lymphoblastic leukemia in a patient with glioblastoma multiforme. Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia associated with der(1;7)(q10;p10) in a glioblastoma multiforme patient treated with temozolomide. Results of bone marrow morphology, chromosome, and fluorescent in situ hybridization (FISH) analyses, as well as the clinical history, strongly suggest a treatment-related etiology in our case. In past reports, karyotypes in cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia mostly demonstrated abnormalities in chromosomes 5 and 7. However, we report a case of temozolomide-related myelodysplastic syndrome/acute myeloid leukemia with der(1;7)(q10;p10), possibly the first reported case, to the authors' knowledge.

  8. Contribution of 1p, 19q, 9p and 10q Automated Analysis by FISH to the Diagnosis and Prognosis of Oligodendroglial Tumors According to WHO 2016 Guidelines (United States)

    Michaud, Karine; de Tayrac, Marie; D’Astous, Myreille; Duval, Céline; Paquet, Claudie; Samassekou, Oumar; Gould, Peter Vincent; Saikali, Stéphan


    Objective To study the feasibility and the diagnostic and prognostic interest of automated analysis of 1p, 19q, 9p and 10q status by FISH technique in oligodendroglial tumors. Methods We analyzed a retrospective series of 33 consecutive gliomas with oligodendroglial histology (originally diagnosed as 24 oligodendrogliomas and 9 oligoastrocytomas). For all cases, automated FISH analysis of 1p, 19q, 9p and 10q status were performed and compared to clinical and histological data, ATRX, IDH1R132H and alpha-internexin status (studied by immunohistochemistry) and overall survival (OS). Manual analysis of 9p and 10q status were also performed and compared to automated analysis to verify the concordance of the two methods. Results The 33 gliomas were reclassified into 13 low-grade oligodendrogliomas (OII), 10 anaplastic oligodendrogliomas (OIII), 3 diffuse astrocytomas (AII), 3 anaplastic astrocytomas (AIII) and 4 glioblastomas (GBM) according to the WHO 2016 histological criteria. The 1p and/or 19q imbalanced status were restricted to astrocytomas with no correlation to their grade or their OS. Chromosome 9p deletion was restricted to OIII (70%) and GBM (100%) and was correlated with a shorter OS in the total cohort (p = 0.0007), the oligodendroglioma cohort (p = 0.03) and the astrocytoma cohort (p = 0.001). Concordance between 9p manual and automated analysis was satisfactory (81%, κ = 0.69). Chromosome 10q deletion was restricted to GBMs (50%) and was correlated with a poor OS in both the total cohort (p = 0.003) and the astrocytoma (AS) cohort (p = 0.04). Concordance between manual and automated analysis was satisfactory (79%, κ = 0.62). Conclusion Automated analysis of 1p, 19q, 9p and 10q status by FISH is a reliable technique which allows for refined classification of oligodendroglial tumors. 1p and/or 19q imbalanced status is evidence of astrocytic differentiation. 9p deletion is found in high grade oligodendrogliomas and astrocytomas with a poor OS. 10q is

  9. Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, M.; Kunze, S.; Eich, H.T.; Semrau, R.; Mueller, R.P. [Dept. of Radiation Oncology, Univ. of Cologne (Germany)


    Purpose: to evaluate the feasibility, safety and efficacy of daily temozolomide concurrent with postoperative radiotherapy in malignant glioma. Patients and methods: from 11/1999 to 03/2003, n = 81 patients aged 15-72 years (median 52 years, karnofsky score 80-100% in 83%) suffering from primary glioblastoma (n = 47), anaplastic astrocytoma (n = 6), anaplastic oligodendroglioma (n = 16), and recurrent glioma (n = 12) were treated. Patients with primary gliomas received a combination of postoperative radiotherapy (60 Gy/1.8- to 2.0-Gy fractions) and daily oral temozolomide (75 mg/m{sup 2}) at all irradiation days (30-33 doses), while recurrent tumors were treated with 45-60 Gy and temozolomide. Initially, 6/81 patients had daily temozolomide doses of 50 mg/m{sup 2}. Results: in total, 70/81 patients (86%) completed both radio- and chemotherapy. Grade 1 nausea/vomiting was seen in 28%, grade 2 in 11%, grade 3 in 1%. Antiemetics were applied in 41%. Hematologic toxicities were observed as follows: leukopenia grade 3/4 1%, lymphopenia grade 3/4 46%, thrombopenia grade 3/4 1%. Two patients under dexamethasone suffered herpes encephalitis after one and 16 doses of temozolomide (75 mg/m{sup 2}). Median survival was 15 months for glioblastoma. In oligodendroglioma patients, a 4-year survival rate of 78% was observed. Conclusion: postoperative radiochemotherapy with 30-33 daily doses of temozolomide (75 mg/m{sup 2}) is safe in patients with malignant glioma. The combined schedule is effective in oligodendroglioma patients and may prolong survival in glioblastoma. Effort should be taken to minimize corticosteroid doses, since both steroids and temozolomide lead to immunosuppression. (orig.)

  10. Intraoperative direct electrical stimulations of central nervous system during surgery of gliomas near eloquent areas

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    WANG Wei-min


    Full Text Available Objective To report our experiences of direct cortical stimulation in surgery of gliomas located in eloquent areas. Methods Clinical data of 157 patients with gliomas underwent awake craniotomy with the direct electrical stimulation for functional mapping of the eloquent areas were analysed retrospectively. Results Negative cortical stimulation was found in 4 patients, and positive cortical stimulation was achieved in 153 patients (97.45% . Four hundred and ninty -six cortical sites in 139 patients were detected for motor response by direct electrical stimulation, 70 sites in 21 patients for sensory, 112 sites in 91 patients for language (such as counting and naming. The positive areas of counting disturbance were mainly seen at the lower part of left precentral gyri operculum of left inferior frontal gyri, triangular part of left inferior frontal gyri, posterior part of left middle frontal gyri, and posterior part of left superior frontal gyri. Postoperative MRI showed 92 patients (58.60% achieved total resection, 55 cases (35.03% subtotal and 10 cases (6.37% partial. One hundred and ten patients (70.06% were diagnosed as having low grade glimas, including 71 cases of astrocytoma, 26 cases of oligodendroglioma, and 13 cases of mixed astro ? oligodendroglioma, 47 patients (29.94% were high grade gliomas, including 19 cases of glioblastoma, 15 cases of anaplastic astrocytoma, and 13 cases of anaplastic oligodendroglioma. After operation 53 patients (33.76% occurred transient postoperative paralysis, 39 patients (24.84% transient language disturbance and 4 patients (2.55% permanent neurological deficits. Conclusion Intraoperative direct electrical stimulation is a reliable, precise and safety method for functional mapping of the eloquent areas. This technique allows us to achieve 'maximal safety resection' in glioma surgery.

  11. Prognostic significance of the NPM-ALK fusion gene in bone marrow and peripheral blood for patients with anaplastic large cell lymphoma%间变性大细胞淋巴瘤患者骨髓及外周血NPM-ALK融合基因表达与预后的关系

    Institute of Scientific and Technical Information of China (English)

    杨菁; 赵晓曦; 金铃; 段彦龙; 黄爽; 张梦; 张蕊; 周春菊; 张永红


    Objective To investigate the expression of NPM-ALK fusion gene in bone marrow (BM) and peripheral blood (PB) in anaplastic large cell lymphoma (ALCL) patients and its prognostic significance.Methods NPM-ALK fusion gene of 21 BM and 15 PB samples from patients with NPMALK positive ALCL was detected by RT-PCR,and the relationship between NPM-ALK expression and prognosis and clinical characters was evaluated.Results Of the 21 patients,12 cases were male and 9 case were female with a median age of 9 (range,2-14) years old.The median follow-up was 31months.Patients with a positive NPM-ALK expression in BM had a 3-years EFS of (35.6± 18.6)%,compared with (91.7±8.0)% for patients with negative NPM-ALK (P=0.038).The incidence of positive expression in BM was significantly higher in patients who had more than 3 organs involved by tumor (P=0.032).86.7%patients had a concordant results of NPM-ALK expression in PB and BM.Conclusion We could evaluate the minimal disseminated disease of NPM-ALK positive ALCL patients by screening the NPM-ALK fusion gene in BM and PB by RT-PCR.The positive expression is associated with a poor prognosis and could be used for stratification of ALCL.%目的 探讨间变性大细胞淋巴瘤(ALCL)患者骨髓及外周血NPM-ALK融合基因的表达与预后的关系.方法 应用RT-PCR法检测21例ALCL患者骨髓(21份标本)及外周血(15份标本)细胞NPM-ALK融合基因的表达,并对其与患者的预后及临床特征之间的关系进行统计学分析.结果 21例患者中男12例,女9例,中位年龄9(2~14)岁.21例患者中位随访时间31个月.骨髓细胞NPM-ALK阳性患者3年无事件生存率为(35.6±18.6)%,阴性患者为(91.7士8.0)%,差异有统计学意义(P=0.038).患者骨髓细胞NPM-ALK阳性与其有3个以上器官受累(P=0.032)有相关性.86.7%的患者外周血与骨髓NPM-ALK检测结果一致.结论 通过RT-PCR法检测ALCL患者骨髓及外周血NPM-ALK融合基因表达,可以证实患者血

  12. 胃原发间变性大细胞淋巴瘤4例临床病理学特点及预后分析%Analysis of clinicopthologic features and prognosis of 4 cases primary gastric anaplastic large cell lymphomas

    Institute of Scientific and Technical Information of China (English)

    赖玉梅; 黄欣; 刘翠苓; 王小燕; 李敏; 孙琳; 陆伟; 高子芬


    目的 探讨胃原发间变性大细胞淋巴瘤( ALCL)的临床病理学特点及预后.方法 收集经北京大学医学部基础医学院病理学系确诊的4例胃原发ALCL,通过HE染色、免疫组织化学、EB病毒( EBV)编码的小核RNA(EBV-EBER)原位杂交、间期荧光原位杂交技术并结合文献复习,分析其临床病理学特点及预后.结果 男性3例,女性1例;年龄27~87岁,中位年龄58.5岁.大体标本均为胃部巨大溃疡型肿物;镜下见肿瘤细胞多形性明显、体积大的肿瘤细胞弥漫性浸润并破坏胃壁.肿瘤细胞一致性强表达LCA和CD30、CD3e阳性率75%(3/4).ALK蛋白水平及基因水平检测均为阴性(4/4),亦未检测到EBV感染.2例患者接受手术+CHOP方案化疗,1例接受CHOP方案化疗+自体干细胞移植,此3例患者均获得临床完全缓解出院,随访截至2011年11月30日,均未出现肿瘤复发或进展.另1例患者未接受治疗,于确诊后22个月死亡.结论 胃原发ALCL多为ALK阴性,其临床病理学特点及预后与其他部位原发的ALK阴性ALCL基本相同,但CD3e阳性率较高,早期诊断和积极治疗有助于改善患者的预后.%Objective To evaluate clinicopathologic features and prognosis of primary gastric anaplastic large cell lymphomas (ALCL).Methods Clinical data and parafiin blocks of 4 patients diagnosed with primary gastric ALCL were obtained. The diagnosis of all cases was based on the criteria of WHO classification of hematolymphoid neoplasm.Furthermore,chromosomal rearrangement involving ALK gene was detected by interphase fluorescence in situ hybridization (FISH) and Epstein-Barr virus (EBV) status was determined by in situ hybridization(ISH) for EBV-encoded small RNAs (EBERs).Results The patients (3 males and 1 female) were from 27 to 87 years old, with a median age of 58.5 years. All the four cases presented with a solitary ulcerative mass in stomach. Morphologically, the normal architecture of gastric wall was

  13. 全自动免疫组化筛查ALK基因融合非小细胞肺癌及其病理特征%Screen of Non-small Cell Lung Cancer with Anaplastic Lymphoma Kinase Fusion Gene by Automatic Immunohistochemical Method and Its Pathological Features

    Institute of Scientific and Technical Information of China (English)

    冯强; 彭森; 刘霞


    目的 探讨全自动免疫组化筛查间变性淋巴瘤激酶(ALK)基因融合非小细胞肺癌的临床特点及病理特征.方法 选取经病理检查确诊的554例非小细胞肺癌组织,采用Ventana抗ALK试剂和全自动免疫组化(IHC)染色检测ALK状态,分析ALK基因融合非小细胞肺癌的临床特点和病理特征.结果 本次研究的554例非小细胞肺癌患者组织中,共筛选出34例ALK阳性,占6.14%;年龄0.05).组织形态学方面,34例ALK阳性非小细胞肺癌中28例为肺腺癌,6例为非肺腺癌.16例实体型为主腺癌合并黏液产生,7例腺泡型为主腺癌,1例为乳头型为主腺癌,4例为浸润性黏液腺癌,4例为鳞状细胞癌.EGFR基因突变检测显示:仅有1例合并该基因突变,其余均为野生型.9例IHC阳性样本,9例ALK基因融合非小细胞肺癌,9例IHC阴性样本经荧光原位杂交技术检测和RT-PCR检测均为阴性结果,6例IHC染色可能为阳性,经荧光原位杂交技术检测均显示为ALK融合阴性.结论 ALK基因融合肺癌是非小细胞肺癌一新的分子亚型,具有独特的临床表现和病理形态;Ventana抗ALK试剂和IHC染色是检测ALK阳性非小细胞肺癌首选方法,对提高该类型肺癌的检出率及个体化治疗具有重要意义.%Objective To explore the automatic immunohistochemical method for the screen of non-small cell lung cancer with anaplastic lymphoma kinase( ALK) and its clinical pathological features.Methods 554 cases of non-small cell lung cancer diagnosed by pathological examination were enrolled in this study.The status of ALK was detected by Ventana anti ALK reagent and IHC staining, and the clinical characteristics and pathological features of ALK gene were analyzed.Results Among of 554 patients with non-small cell lung cancer,34 cases showed positive ALK(6.14%).The positive rate of the patients under 60 years old(8.69%) was significantly higher than that of the elder patients ( 3 .62%) ( P0.05).The results of

  14. Paternal Harsh Parenting in Relation to Paternal Versus Child Characteristics: The Moderating Effect of Paternal Resemblance Belief%父亲严厉教养与父亲及儿童心理行为特点的关系:父亲与儿童类似性判断的调节作用

    Institute of Scientific and Technical Information of China (English)

    李宏利; 张雷


    本研究分别调查了338名中国父母的严厉教养、抑郁情感与婚姻满意度及其独生子女的情感失调与攻击行为情况.研究结果显示父亲对儿童与自己的类似性判断减弱了父亲严厉教养与儿童的情感失调和攻击行为间的联系,但加强了父亲的严厉教养与抑郁和婚姻不满意度间的关系.这些发现支持了父母教养的进化观点,降低父亲的生殖疑虑可能具有进化适应性,父亲与儿童的类似性判断会提高父亲对儿童的投资.%Based on a sample of 338 Chinese parents and their only children, paternal resemblance belief was found to attenuate the association between paternal harsh parenting and child characteristics, such as emotion dysregulation and aggression, and to strengthen the association between harsh parenting and such paternal characteristics as depressive affect and marital dissatisfaction. These findings support the evolutionary view that, as an adaptation to calm paternity doubt, paternal resemblance belief leads to improved paternal investment.

  15. Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors (United States)


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

  16. World oil market - the future will not resemble the past

    Energy Technology Data Exchange (ETDEWEB)

    Bohi, D.R.

    Developments suggest that, compared to the past, inventory demand will be less influenced by speculation and panic and prices will be less sensitive to uncertainties caused by interruptions in supply. Combined with the hypothesis that OPEC no longer is in a position to exploit supply crises to raise official prices to a new plateau, it may be argued that future price shocks will be more transitory and less dramatic than would be expected on the basis of experience. The author suggests that private and public policymakers would do well to ignore Santayana's dictum that those who cannot remember the past are condemned to repeat it. Too great a devotion to the lessons of the 1970s as far as oil is concerned will prepare us for a skirmish on a battlefield that no longer exists.

  17. Central retinal artery occlusion resembling Purtscher-like retinopathy

    Directory of Open Access Journals (Sweden)

    Etomi T


    Full Text Available Takuji Kurimoto1, Norio Okamoto2, Hidehiro Oku1, Yuko Kanbara1, Tomohiko Etomi1, Masahiro Tonari1, Tsunehiko Ikeda11Department of Ophthalmology, Osaka Medical College, Takatsuki, Japan; 2Okamoto Eye Clinic, Suita, Osaka, JapanAbstract: This paper reports three cases of central retinal artery occlusion (CRAO with Purtscher-like retinopathy and good recovery of visual function. The three cases of CRAO had similar fundus changes, ie, cotton wool patches surrounding the optic disc and whitening of the retina surrounding the fovea with a cherry red spot. Fluorescein angiography showed a delay of arm-to-retina circulation time and a partial defect of choroid circulation. Although the three cases were treated by different regimens of steroid pulse therapy and antiplatelet therapy, visual function recovered well and all disturbances of the retinal and choroid circulations resolved. Although eyes with a CRAO normally have a poor visual prognosis, our three cases responded well to the treatments and recovered good visual function. Thus, cases showing fundus changes similar to our three cases may have a pathogenesis different from that of a complete CRAO.Keywords: central retinal artery occlusion, cotton wool patches, Purtscher retinopathy, steroid therapy

  18. Neurilemoma of the eyelid resembling a recurrent chalazion. (United States)

    Shields, J A; Guibor, P


    A 63-year-old woman was seen with a slowly enlarging mass located on the right lower eyelid, where a "chalazion" had been twice curetted but not studied histologically. An excisional biopsy was performed, and the specimen proved histologically to be a neurilemoma (schwannoma). Although a neurilemoma is extremely rare on the eyelid, this case demonstrates that it should be included in the differential diagnosis of lesions that can clinically masquerade as a chalazion.

  19. Trichoscopy of Noncicatricial Pressure-induced Alopecia Resembling Alopecia Areata (United States)

    Papaiordanou, Francine; da Silveira, Bruno Rebelo Lages; Piñeiro-Maceira, Juan; Pirmez, Rodrigo


    Pressure-induced alopecia is an unusual cause of hair loss, and reports of its trichoscopic features are scarce. In this paper, we describe a case of pressure-induced alopecia in which trichoscopic and histopathological findings overlap with those described for alopecia areata. PMID:27601865

  20. Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Raminder Kaur Khangura


    Full Text Available Although colorectal cancer (CRC is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity.

  1. Angioimmunoblastic T-Cell Lymphoma with Polyarthritis Resembling Rheumatoid Arthritis. (United States)

    Yachoui, Ralph; Farooq, Nouman; Amos, Jonathan V; Shaw, Gene R


    Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL). AITL typically presents with lymphadenopathy, fever, rash, hepatosplenomegaly, and rarely polyarthritis. We report the case of a 50-year-old female who presented with lymphadenopathy, rash, and symmetric polyarthritis. She was later diagnosed with AITL and was treated with chemotherapy with resolution of arthritis. AITL should be suspected in paitents presenting with rheumatoid-like arthritis and diffuse lymphadenopathy.

  2. Two sisters resembling Gorlin-Chaudhry-Moss syndrome. (United States)

    Aravena, Teresa; Passalacqua, Cristóbal; Pizarro, Oscar; Aracena, Mariana


    The Gorlin-Chaudhry-Moss syndrome (GCMS), was describe initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters with craniosynostosis, hypertrichosis, hypoplastic labia majora, dental defects, eye anomalies, patent ductus arteriosus, and normal intelligence. Two other sporadic instances have been documented. Here, we report on two sisters with a condition with some similarities to GCMS as well as some differences, which could represent either previously unreported variability in GCMS, or it may represent a novel disorder.

  3. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.


    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  4. Familial resemblance in religiousness in a secular society

    DEFF Research Database (Denmark)

    Hvidtjørn, Dorte; Petersen, Inge; Hjelmborg, Jacob


    generally considered more religious than the very secular northern European countries. Comparisons of the results are complicated by diverse definitions of religiousness, but several studies indicate that the influence of the family environment is most predominant in early life, whereas genetic influences......It is well known that human behavior and individual psychological traits are moderately to substantially heritable. Over the past decade, an increasing number of studies have explored the genetic and environmental influence on religiousness. These studies originate predominantly from countries...

  5. Visual Timing of Structured Dance Movements Resembles Auditory Rhythm Perception

    Directory of Open Access Journals (Sweden)

    Yi-Huang Su


    Full Text Available Temporal mechanisms for processing auditory musical rhythms are well established, in which a perceived beat is beneficial for timing purposes. It is yet unknown whether such beat-based timing would also underlie visual perception of temporally structured, ecological stimuli connected to music: dance. In this study, we investigated whether observers extracted a visual beat when watching dance movements to assist visual timing of these movements. Participants watched silent videos of dance sequences and reproduced the movement duration by mental recall. We found better visual timing for limb movements with regular patterns in the trajectories than without, similar to the beat advantage for auditory rhythms. When movements involved both the arms and the legs, the benefit of a visual beat relied only on the latter. The beat-based advantage persisted despite auditory interferences that were temporally incongruent with the visual beat, arguing for the visual nature of these mechanisms. Our results suggest that visual timing principles for dance parallel their auditory counterparts for music, which may be based on common sensorimotor coupling. These processes likely yield multimodal rhythm representations in the scenario of music and dance.

  6. Hummingbirds at artificial flowers made to resemble ornithophiles versus melittophiles

    Directory of Open Access Journals (Sweden)

    Wyndee A. Guzman


    Full Text Available Certain floral characteristics are associated with specific pollinators. Hummingbird-pollinated flowers are usually red, lack a landing platform, lack nectar guides, and contain a high amount of dilute sucrose-rich nectar. Here we test hypotheses concerning the reasons for these characters to the extent that they involve hummingbird responses. An array was set up of 16 artificial plants, each with five artificial flowers. (1 Flowers made to differ only in colour elicited a slight preference for red. (2 When colour was associated with nectar offerings, and birds generally learned to visit flowers that provided much more nectar but did not associatively learn differences as little as 2 µL. (3 Birds were offered 8 µL of 12% sucrose versus 2 µL of 48% hexose, and they did not prefer the dilute nectar; they showed no evidence of discerning sucrose from hexose; however, they preferred 48% over 12% sucrose when both were offered in the same quantity. (4 Birds preferred flowers that lacked landing platforms over those with landing platforms. (5 Birds were offered flowers with nectar guides, associated with differing nectar volumes, and they did not associate the higher nectar reward with either flower type. In summary, the feedback from hummingbirds reflects some of the differences between bird- and bee-adapted flowers, but nectar seemed less predictive than expected. Factors other than the behavioural proclivities of hummingbirds, such as adaptation to discourage bees, are discussed as additional causes for the differences between the syndromes. We also discuss significance testing for field experiments involving one unreplicated array.

  7. Meurigite, a new fibrous iron phosphate resembling kidwellite (United States)

    Birch, W.D.; Pring, A.; Self, P.G.; Gibbs, R.B.; Keck, E.; Jensen, M.C.; Foord, E.E.


    Meurigite is a new hydrated potassium iron phosphate related to kidwellite and with structural similarities to other late-stage fibrous ferric phosphate species. It has been found at four localities so far - the Santa Rita mine, New Mexico, U.S.A.; the Hagendorf-Sud pegmatite in Bavaria, Germany; granite pegmatite veins at Wycheproof, Victoria. Australia; and at the Gold Quarry Mine, Nevada, U.S.A. The Santa Rita mine is the designated type locality. Meurigite occurs as tabular, elongated crystals forming spherical and hemispherical clusters and drusy coatings. The colour ranges from creamy white to pale yellow and yellowish brown. At the type locality, the hemispheres may reach 2 mm across, but the maximum diameter reached in the other occurrences is usually less than 0.5 mm. A wide variety of secondary phosphate minerals accompanies meurigite at each locality, with dufrenite, cyrilovite. beraunite, rockbridgeite and leucophosphite amongst the most common. Vanadates and uranates occur with meurigite at the Gold Quarry mine. Electron microprobe analysis and separate determination of H2O and CO2 on meurigite from the type locality gave a composition for which several empirical formulae could be calculated. The preferred formula, obtained on the basis of 35 oxygen atoms, is (K0.85Na0.03)??0.88(Fe7.013+Al0.16Cu0.02)??7.19 (PO4)5.11(CO3)0.20(OH) 6.7??7-7.25H2O, which simplifies to KFe73+(PO4)5(OH) 7??8H2O. Qualitative analyses only were obtained for meurigite from the other localities, due to the softness and openness of the aggregates. Because of the fibrous nature of meurigite, it was not possible to determine the crystal structure, hence the exact stoichiometry remains uncertain. The lustre of meurigite varies from vitreous to waxy for the Santa Rita mine mineral, to silky for the more open sprays and internal surfaces elsewhere. The streak is very pale yellow to cream and the estimated Mohs hardness is about 3. Cleavage is perfect on {001] and fragments from the type material have a mean specific gravity of 2.96. The strongest lines in the X-ray powder pattern for the type material are (dobs,Iobs,hkl) 3.216(100)404; 4.84(90)111; 3.116(80)205; 4.32(70)112; 9.41(60)201; 3.470(60)800. The X-ray data were indexed on the basis of a monoclinic unit cell determined from electron diffraction patterns. The cell parameters, refined by least squares methods, are a